OB Meds

Codeine

Codeine (Lexi-Drugs) ALERT: US Boxed Warning Ultra-rapid metabolism of codeine to morphine: Special Alerts Benzodiazepines and Opioid Medicines Safety AlertAugust 2016 Codeine and Hydrocodone Safety AlertJuly 2016 Opioid Pain Medicine Safety AlertMarch 2016 Safety Alert for Codeine Cough and Cold MedicinesJuly 2015 Pronunciation (KOE deen) Brand Names: CanadaCodeine Contin; PMS-Codeine; ratio-Codeine Pharmacologic CategoryAnalgesic, Opioid; Antitussive Dosing: AdultNote: Codeine 30 mg per 5 mL oral solution has been discontinued in the US for more than 1 year. Cough (off-label use in the US): Oral: Reported doses vary; range: 7.5 to 120 mg/day as a single dose or in divided doses (Bolser 2006; Smith 2010); Note: The American College of Chest Physicians does not recommend the routine use of codeine as an antitussive in patients with upper respiratory infections (Bolser 2006). Pain management (analgesic): Oral: Note: These are guidelines and do not represent the maximum doses that may be required in all patients. Doses should be titrated to pain relief/prevention. Immediate release (tablet, oral solution): Initial: 15 to 60 mg every 4 hours as needed; maximum total daily dose: 360 mg/day; patients with prior opioid exposure may require higher initial doses. Note: The American Pain Society recommends an initial dose of 30 to 60 mg for adults with moderate pain (American Pain Society 2008). Controlled release: Codeine Contin [Canadian product]: Note: Titrate at intervals of ≥48 hours until adequate analgesia has been achieved. Daily doses >600 mg/day should not be used; patients requiring higher doses should be switched to an opioid approved for use in severe pain. In patients who receive both Codeine Contin and an immediate release or combination codeine product for breakthrough pain, the rescue dose of immediate release codeine product should be ≤12.5% of the total daily Codeine Contin dose. Opioid-naive patients: Initial: 50 mg every 12 hours Conversion from immediate release codeine preparations: Immediate release codeine preparations contain ~75% codeine base. Therefore, patients who are switching from immediate release codeine preparations may be transferred to a ~25% lower total daily dose of Codeine Contin, equally divided into 2 daily doses every 12 hours. Conversion from a combination codeine product (eg, codeine with acetaminophen or aspirin): See table: Number of 30 mg Codeine Combination Tablets Daily Initial Dose of Codeine Contin Maintenance Dose of Codeine Contin ≤6 50 mg every 12 h 100 mg every 12 h 7-9 100 mg every 12 h 150 mg every 12 h 10-12 150 mg every 12 h 200 mg every 12 h >12 200 mg every 12 h 200-300 every 12 h (maximum: 300 mg every 12 h) Conversion from another opioid analgesic: Using the patient's current opioid dose, calculate an equivalent daily dose of immediate release codeine. A ~25% lower dose of Codeine Contin should then be initiated, equally divided into 2 daily doses. Discontinuation of therapy:Note: Gradual dose reduction is recommended if clinically appropriate. Initially reduce the total daily dose by 50% and administer equally divided into 2 daily doses for 2 days followed by a 25% reduction every 2 days thereafter. * See Dosage and Administration in AHFS Essentials for additional information. Dosing: GeriatricRefer to adult dosing. Use with caution and consider initiation at the low end of the dosing range; reduced initial dosages may be necessary. Dosing: PediatricNote: Codeine 30 mg per 5 mL oral solution has been discontinued in the US for more than 1 year. Pain management (analgesic) (off-label population): Oral: Note: These are guidelines and do not represent the maximum doses that may be required in all patients. Doses should be titrated to pain relief/prevention.) Immediate release (tablet, oral solution): Initial: 0.5 to 1 mg/kg/dose every 4 hours as needed; maximum: 60 mg/dose (American Pain Society 2008) Controlled-release tablet [Canadian product]: Use is not recommended (has not been studied) Dosing: Renal Impairment US labeling: There are no specific dosage adjustments provided in the manufacturers labeling; however, clearance may be reduced; active metabolites may accumulate. Initiate at lower doses or longer dosing intervals followed by careful titration. Canadian labeling: Immediate release (tablet, oral solution): CrCl >50 mL/minute: No dosage adjustment necessary. CrCl 10 to 50 mL/minute: Administer 75% of dose and titrate carefully as needed. CrCl <10 mL/minute: Administer 50% of dose and titrate carefully as needed. Controlled release: There are no dosage adjustments provided in the manufacturer labeling; however, a reduced dosage is recommended Alternate recommendations: The following guidelines have been used by some clinicians (Aronoff 2007): CrCl 10 to 50 mL/minute: Administer 75% of dose CrCl <10 mL/minute: Administer 50% of dose Dosing: Hepatic ImpairmentThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, initial lower doses or longer dosing intervals followed by careful titration are recommended. Calculations Creatinine Clearance by Cockcroft-Gault Creatinine Clearance by Cockcroft-Gault (SI units) Creatinine Clearance by Cockcroft-Gault with IBW Creatinine Clearance by Cockcroft-Gault with IBW (SI units) Creatinine Clearance by Jelliffe Creatinine Clearance by Sanaka Fentanyl Transdermal Conversion Glomerular Filtration Rate by Abbreviated MDRD Glomerular Filtration Rate by Abbreviated MDRD (SI units) Glomerular Filtration Rate by MDRD Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr) Glomerular Filtration Rate by MDRD (SI units) Glomerular Filtration Rate by Schwartz Use: Labeled IndicationsPain: Management of mild-to-moderately-severe pain * See Uses in AHFS Essentials for additional information. Use: Off-Label Cough in select patients (short-term relief)Level of Evidence [G] Based on the American College of Chest Physicians (ACCP) guidelines on cough suppressant and pharmacologic protussive therapy, the use of codeine (among other central cough suppressants such as dextromethorphan) in patients with chronic bronchitis is recommended for the short-term symptomatic relief of coughing. Restless legs syndrome Level of Evidence [C, G] Evidence from noncontrolled trials suggests that the use of opioids, including codeine, may be of benefit in the treatment of RLS in adults, particularly in those who do not respond to dopaminergics or other therapies. Guideline recommendations are conflicting. American Academy of Sleep Medicine guidelines note that low-level evidences supports use of opioids, including codeine, in the management of RLS. EFNS/ENS/ESRS task force guidelines state evidence is insufficient to make a recommendation regarding opioids. Access Full Off-Label Monograph Level of Evidence Definitions Level of Evidence Scale Clinical Practice Guidelines Patient Safety: "CDC Guideline for Prescribing Opioids for Chronic Pain," 2016 Administration: OralMay administer without regard to meals. Take with food or milk to decrease adverse GI effects. Controlled release tablets: Codeine Contin [Canadian product]: Tablets should be swallowed whole; do not chew, dissolve, or crush. All strengths may be halved, except the 50 mg tablets; half tablets should also be swallowed intact. Storage/Stability Immediate release tablet, oral solution: Store at 15°C to 30°C (59°F to 86°F). Protect from moisture and light. Controlled release tablet [Canadian product]: Store at 15°C to 30°C (59°F to 86°F). Extemporaneously PreparedA 3 mg/mL oral suspension may be made with codeine phosphate powder, USP. Add 600 mg of powder to a 400 mL beaker. Add 2.5 mL of Sterile Water for Irrigation, USP, and stir to dissolve the powder. Mix for 10 minutes while adding Ora-Sweet to make 200 mL; transfer to a calibrated bottle. Stable 98 days at room temperature. Dentinger PJ and Swenson CF, "Stability of Codeine Phosphate in an Extemporaneously Compounded Syrup," Am J Health Syst Pharm, 2007, 64(24):2569-73.[PubMed 18056945] Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience sweating a lot. Have patient report immediately to prescriber severe dizziness, passing out, angina, tachycardia, difficulty breathing, slow breathing, shallow breathing, noisy breathing, confusion, severe fatigue, abnormal heartbeat, hallucinations, mood changes, seizures, severe abdominal pain, severe headache, difficult urination, tremors, vision changes, severe nausea, severe vomiting, severe constipation, severe loss of strength and energy, sexual dysfunction (males), amenorrhea, decreased libido, infertility, signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), or signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss) (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients. Medication Safety Issues Sound-alike/look-alike issues: High alert medication: Medication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication: Oral solution: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM302557.pdf Contraindications Hypersensitivity to codeine or any component of the formulation; respiratory depression in the absence of resuscitative equipment; acute or severe bronchial asthma or hypercarbia; presence or suspicion of paralytic ileus; postoperative pain management in children who have undergone tonsillectomy and/or adenoidectomy Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other opioid analgesics; cor pulmonale; acute alcoholism; delirium tremens; severe CNS depression; convulsive disorders; increased cerebrospinal or intracranial pressure; head injury; obstructive airway disease (in addition to asthma); known or suspected mechanical GI obstruction or any disease that affects bowel transit; suspected surgical abdomen (eg, acute appendicitis or pancreatitis); use with or within 14 days of MAO inhibitors; pregnancy and during labor and delivery; children <12 years of age; Additional product specific contraindications: Codeine Contin: acute pain; intermittent or short duration pain that can be managed with alternative pain medication; breast-feeding Warnings/Precautions Concerns related to adverse effects: • CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). • Constipation: Use may cause or aggravate constipation; chronic use may result in obstructive bowel disease, particularly in those with underlying intestinal motility disorders. May also be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventative measures (eg, stool softener, increased fiber) to reduce the potential for constipation. • Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). • Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone). • Respiratory depression: May cause dose-related respiratory depression. The risk is increased in elderly patients, debilitated patients, and patients with conditions associated with hypoxia, hypercapnia, or upper airway obstruction. Disease-related concerns: • Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions. • Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013). • Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi; may increase amylase/lipase levels. • CNS depression/coma: Avoid use of codeine in patients with CNS depression or coma as these patients are susceptible to intracranial effects of CO2 retention. • Drug abuse: Potential for drug dependency exists. Use in patients with a history of drug abuse or acute alcoholism is contraindicated in the Canadian labeling. Use opioids for chronic pain with caution in patients at increased risk for misuse; factors associated with increased risk include previous substance use disorder, younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]). • Gastrointestinal obstruction: Avoid use in patients with gastrointestinal obstruction, particularly paralytic ileus; chronic use may result in obstructive bowel disease. • Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. May also interfere with pupillary response and consciousness, thereby, affecting neurologic examination. • Hepatic impairment: Use with caution in patients with severe hepatic impairment. • Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]). • Obesity: Use with caution in patients who are morbidly obese. • Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. • Renal impairment: Use with caution in patients with severe renal impairment. • Respiratory disease: Use with caution in patients with preexisting respiratory compromise (hypoxia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages. • Sleep-disordered breathing: Use opioids with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing, including HF and obesity. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]). • Seizure disorders: May induce or aggravate seizures; use with caution in patients with seizure disorders. • Thyroid dysfunction: Use with caution in patients with thyroid dysfunction. Concurrent drug therapy issues: • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. • Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol. In the setting of chronic pain, avoid prescribing opioids and benzodiazepines concurrently whenever possible; epidemiologic studies suggest there is an increased risk for potentially fatal overdose with concurrent use (Dowell [CDC 2016]). Special populations: • CYP2D6 "ultrarapid metabolizers": Use caution in patients with two or more copies of the variant CYP2D6*2 allele; may have extensive conversion to morphine and thus increased opioid-mediated effects. Avoid the use of codeine in these patients; consider alternative analgesics such as morphine or a nonopioid agent (Crews 2012). The occurrence of this phenotype is seen in 0.5% to 1% of Chinese and Japanese, 0.5% to 1% of Hispanics, 1% to 10% of Caucasians, 3% of African-Americans, and 16% to 28% of North Africans, Ethiopians, and Arabs. • Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. • Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]). • Neonates: Neonatal withdrawal syndrome: After chronic maternal exposure to opioids, neonatal withdrawal syndrome may occur in the newborn; monitor neonate closely. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn. Opioid withdrawal syndrome in the neonate, unlike in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts. • Pediatric: [US Boxed Warning]: Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and were found to have evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism. Deaths have also occurred in nursing infants after being exposed to high concentrations of morphine because the mothers were ultra-rapid metabolizers. Use is contraindicated in the postoperative pain management of children who have undergone tonsillectomy and/or adenoidectomy. Dosage form specific issues: • Sulfites: Some preparations contain sulfites which may cause allergic reactions. Other warnings/precautions: • Abuse/misuse/diversion: Healthcare provider should be alert to the potential for abuse, misuse, and diversion. • Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg. NSAIDs, acetaminophen, certain anticonvulsants and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and non-opioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using immediate-release opioids (instead of extended-release/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 morphine milligram equivalents (MME)/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]). • Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms. * See Cautions in AHFS Essentials for additional information. Geriatric ConsiderationsThe elderly may be particularly susceptible to CNS depression and confusion as well as the constipating effects of opioids. Pregnancy Risk FactorC Pregnancy ConsiderationsAdverse events have been observed in animal reproduction studies. Opioid analgesics cross the placenta. In humans, birth defects (including some heart defects) have been associated with maternal use of codeine during the first trimester of pregnancy (Broussard 2011). If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur; monitoring of the neonate is recommended. The minimum effective dose should be used if opioids are needed (Chou 2009). Neonatal abstinence syndrome following opioid exposure may present with autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high pitched crying, increased muscle tone, irritability, seizure, tremor) symptoms (Dow 2012; Hudak 2012). Breast-Feeding ConsiderationsCodeine and its metabolite (morphine) are found in breast milk and can be detected in the serum of nursing infants. The relative dose to a nursing infant has been calculated to be ~1% of the weight-adjusted maternal dose (Spigset 2000). Higher levels of morphine may be found in the breast milk of lactating mothers who are "ultrarapid metabolizers" of codeine; patients with two or more copies of the variant CYP2D6*2 allele may have extensive conversion to morphine and thus increased opioid-mediated effects. In one case, excessively high serum concentrations of morphine were reported in a breast-fed infant following maternal use of acetaminophen with codeine. The mother was later found to be an "ultrarapid metabolizer" of codeine; symptoms in the infant included feeding difficulty and lethargy, followed by death. Caution should be used since most persons are not aware if they have the genotype resulting in "ultra-rapid metabolizer" status. When codeine is used in breast-feeding women, it is recommended to use the lowest dose for the shortest duration of time and observe the infant for increased sleepiness, difficulty in feeding or breathing, or limpness (FDA 2007; Koren 2006). The US labeling recommends that caution be used if administered to a nursing woman. Codeine Contin [Canadian product] is contraindicated in nursing women. According to other guidelines, when treatment is needed for pain in nursing women, other agents should be used; if codeine cannot be avoided it should not be used for >4 days (Kahan 2011; Wong 2011). Briggs' Drugs in Pregnancy & Lactation Codeine Adverse ReactionsFrequency not defined. Cardiovascular: Bradycardia, cardiac arrest, circulatory depression, flushing, hypertension, hypotension, palpitations, shock, syncope, tachycardia Central nervous system: Abnormal dreams, agitation, anxiety, apprehension, ataxia, chills, depression, disorientation, dizziness, drowsiness, dysphoria, euphoria, fatigue, hallucination, headache, increased intracranial pressure, insomnia, nervousness, paresthesia, sedation, shakiness, taste disorder, vertigo Dermatologic: Diaphoresis, pruritus, skin rash, urticaria Gastrointestinal: Abdominal cramps, abdominal pain, anorexia, biliary tract spasm, constipation, diarrhea, nausea, pancreatitis, vomiting, xerostomia Genitourinary: Urinary hesitancy, urinary retention Hypersensitivity: Hypersensitivity reaction Neuromuscular & skeletal: Laryngospasm, muscle rigidity, tremor, weakness Ophthalmic: Blurred vision, diplopia, miosis, nystagmus, visual disturbance Respiratory: Bronchospasm, dyspnea, respiratory arrest, respiratory depression <1%, postmarketing, and/or case reports: Hypogonadism (Brennan 2013; Debono 2011) * See Cautions in AHFS Essentials for additional information. Allergy and Idiosyncratic Reactions Opioid Allergy/Hypersensitivity Toxicology Opioids Metabolism/Transport EffectsSubstrate of CYP2D6 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential Drug Interactions Open Interactions Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy Anticholinergic Agents: May enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy CYP2D6 Inhibitors (Moderate): May diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy CYP2D6 Inhibitors (Strong): May diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Diuretics: Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Risk D: Consider therapy modification HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy MAO Inhibitors: May enhance the adverse/toxic effect of Codeine. Risk C: Monitor therapy Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk X: Avoid combination Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Nalmefene: May diminish the therapeutic effect of Analgesics (Opioid). Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Risk D: Consider therapy modification Naltrexone: May diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk D: Consider therapy modification Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Risk D: Consider therapy modification Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Risk C: Monitor therapy Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy Ramosetron: Analgesics (Opioid) may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Risk C: Monitor therapy Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification Somatostatin Analogs: May decrease the metabolism of Codeine. The formation of two major codeine metabolites (morphine and norcodeine) may be impaired by somatostatin analogs. Risk C: Monitor therapy Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Risk D: Consider therapy modification Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification Test InteractionsSome quinolones may produce a false-positive urine screening result for opioids using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opioid screens by more specific methods should be considered. Genes of Interest Catechol-O-Methyltransferase Cytochrome P450, Family 2, Subfamily D, Polypeptide 6 Monitoring Parameters Pain relief, respiratory and mental status, blood pressure, heart rate; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013) Alternate recommendations: Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and re-checking should be considered at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (Dowell [CDC 2016]). Nursing: Physical Assessment/MonitoringMonitor for effectiveness of pain relief and CNS status prior to treatment and periodically throughout. May cause physical and/or psychological dependence. For inpatients, implement safety measures to prevent falls. Assess patient's physical and/or psychological dependence. Discontinue slowly after prolonged use. Product Availability Codeine 30 mg per 5 mL oral solution has been discontinued in the US for more than 1 year. Controlled SubstanceC-II Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product Solution, Oral, as sulfate: Generic: 30 mg/5 mL (500 mL [DSC]) Tablet, Oral, as sulfate: Generic: 15 mg, 30 mg, 60 mg Dosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling. Solution, Oral, as phosphate: 25 mg/5 mL Tablet, Controlled Release: Codeine Contin: 50 mg, 100 mg, 150 mg, 200 mg Anatomic Therapeutic Chemical (ATC) Classification R05DA04 Generic Available (US)Yes Pricing: US Tablets (Codeine Sulfate Oral) 15 mg (100): $57.73 30 mg (100): $62.15 60 mg (100): $113.83 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of ActionBinds to opioid receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough suppression by direct central action in the medulla; produces generalized CNS depression Pharmacodynamics/Kinetics Onset of action: Oral: Immediate release: 0.5-1 hour Peak effect: Oral: Immediate release: 1-1.5 hours Duration: Immediate release: 4-6 hours Absorption: Oral: Adequate Distribution: ~3-6 L/kg Protein binding: ~7% to 25% Metabolism: Hepatic via UGT2B7 and UGT2B4 to codeine-6-glucuronide, via CYP2D6 to morphine (active), and via CYP3A4 to norcodeine. Morphine is further metabolized via glucuronidation to morphine-3-glucuronide and morphine-6-glucuronide (active). Bioavailability: 53% Half-life elimination: 2.5-3.5 hours Time to peak, plasma: Immediate release: 1 hour; Controlled release [Canadian product]: 3.3 hours Excretion: Urine (~90%, ~10% of the total dose as unchanged drug); feces Dental UseTreatment of postoperative pain * See Uses in AHFS Essentials for additional information. Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Dental Health Professional ConsiderationsIt is recommended that codeine not be used as the sole entity for analgesia because of moderate efficacy along with relatively high incidence of nausea, sedation, and constipation. In addition, codeine has some opioid addiction liability. Codeine in combination with acetaminophen or aspirin is recommended. Maximum effective analgesic dose of codeine is 60 mg (1 grain). Beyond 60 mg increases respiratory depression only. Effects on Dental TreatmentNo significant effects or complications reported (see Dental Health Professional Considerations) Effects on BleedingNo information available to require special precautions Dental Usual DosingPostoperative pain: Adults: Oral (immediate release): 30 mg every 4 to 6 hours as needed; patients with prior opioid exposure may require higher initial doses. Usual range: 15 to 120 mg every 4 to 6 hours as needed Related Information Acute Postoperative Pain Anesthetic Considerations in the Substance-Abusing Patient Beers Criteria − Potentially Inappropriate Medications for Geriatrics Chronic Pain Management Chronic Pain Management (Cancer) Drugs of Abuse Comparison Table Laboratory Detection of Drugs Management of EGFR Inhibitor Toxicities: Dermatologic, Ocular, and Gastrointestinal Oral Medications That Should Not Be Crushed or Altered Index TermsCodeine Phosphate; Codeine Sulfate; Methylmorphine

Hemabate

Carboprost Tromethamine (Lexi-Drugs) ALERT: US Boxed Warning Appropriate use: Experienced physician: Pronunciation (KAR boe prost tro METH a meen) Brand Names: USHemabate Brand Names: CanadaHemabate Pharmacologic CategoryAbortifacient; Prostaglandin Dosing: Adult Refractory postpartum uterine bleeding: IM: Initial: 250 mcg; if needed, may repeat at 15- to 90-minute intervals; maximum total dose: 2 mg (8 doses) Termination of pregnancy: IM: 250 mcg, then 250 mcg at 1.5- to 3.5-hour intervals, depending on uterine response; a 500 mcg dose may be given if uterine response is not adequate after several 250 mcg doses; do not exceed 12 mg total dose or continuous administration for >2 days. Note: A 100 mcg test dose may be considered. * See Dosage and Administration in AHFS Essentials for additional information. Dosing: GeriatricRefer to adult dosing. Dosing: Renal ImpairmentUse with caution in patients with a history of renal disease; use is contraindicated in patients with active renal impairment. Dosing: Hepatic ImpairmentUse with caution in patients with a history of hepatic disease; use is contraindicated in patients with active hepatic impairment. Use: Labeled Indications Termination of pregnancy: For aborting pregnancy between week 13 and 20 of gestation as calculated from the first day of the last normal menstrual period and in the following conditions related to second trimester abortion: Failure of expulsion of the fetus during the course of treatment by another method; premature rupture of membranes in intrauterine methods with loss of drug and insufficient or absent uterine activity; requirement of a repeat intrauterine instillation of drug for expulsion of the fetus; inadvertent or spontaneous rupture of membranes in the presence of a previable fetus and absence of adequate activity for expulsion. Refractory postpartum uterine hemorrhage: Treatment of postpartum hemorrhage due to uterine atony that has not responded to conventional methods of management. Prior treatment should include the use of intravenously (IV) administered oxytocin, manipulative techniques such as uterine massage and, unless contraindicated, intramuscular ergot preparations. * See Uses in AHFS Essentials for additional information. Administration: IMAdminister deep IM (use a tuberculin syringe for termination of pregnancy); rotate site if repeat injections are required. Administration: IVShould only be administered deep IM; do not inject IV Storage/StabilityStore under refrigeration at 2°C to 8°C (36°F to 46°F). Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience nausea, vomiting, or diarrhea (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Contraindications Hypersensitivity to carboprost tromethamine or any component of the formulation; acute pelvic inflammatory disease; active cardiac, pulmonary, renal, or hepatic disease. Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty. Warnings/Precautions Concerns related to adverse effects: • Fever: Transient fever may be observed with treatment and is believed to be due to carboprost's effect on hypothalamic thermoregulation; use caution to distinguish between fever induced by the drug and fever associated with postabortion endometritis. • Gastrointestinal effects: Pretreatment or concomitant use of antiemetic and antidiarrheal agents is recommended to decrease the incidence of gastrointestinal effects. • Hypertension: Increased blood pressure may be observed with treatment; degree of hypertension observed is generally moderate and does not require treatment. Disease-related concerns: • Anemia: Use with caution in patients with anemia. • Asthma: Use with caution in patients with a history of asthma; therapy may cause transient bronchoconstriction. • Cardiovascular disease: Use with caution in patients with cardiovascular disease, including hypotension or hypertension. • Compromised uteri: Use oxytocic agents with caution in patients with compromised (scarred) uterus. • Diabetes: Use with caution in patients with diabetes mellitus. • Hepatic impairment: Use with caution in patients with hepatic disease, including jaundice. • Renal impairment: Use with caution in patients with renal disease. • Seizures: Use with caution in patients with a history of seizure disorder. Dosage form specific issues: • Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling. Other warnings/precautions: • Potent oxytocic agent: [U.S. Boxed Warning] Potent oxytocic agent; use only with strict adherence to recommended dosing. Carboprost should be used only by medically-trained personnel in a hospital which can provide immediate intensive care and acute surgical facilities. * See Cautions in AHFS Essentials for additional information. Pregnancy Risk FactorC Pregnancy ConsiderationsTeratogenic effects were not observed in animal reproduction studies. When used for termination of pregnancy, carboprost is not considered feticidal, but is used to terminate pregnancy due to its ability to stimulate uterine contractions; use is not indicated if the fetus has reached a stage of viability in utero. Complete termination of pregnancy may not be induced in ~20% of cases and should therefore be completed in another way. Breast-Feeding ConsiderationsIt is not known if carboprost is excreted in breast milk. Briggs' Drugs in Pregnancy & Lactation Carboprost Adverse ReactionsFrequency not always defined. Effects due to increased smooth muscle contractility are most common and are generally transient and reversible upon discontinuation of therapy. Cardiovascular: Chest pain, chest tightness, flushing, hypertension, palpitations, septic shock syncope, tachycardia, vasodepressor syncope Central nervous system: Anxiety, chills, choking sensation, disturbed sleep, dizziness, drowsiness, dystonia, headache, increased body temperature (may be drug-induced or due to postabortion endometritis), lethargy, nervousness, paresthesia, shivering, vertigo Dermatologic: Diaphoresis, skin rash Endocrine & metabolic: Fullness of throat, hot flash, increased thirst, thyroid storm Gastrointestinal: Diarrhea (approximately 67%), vomiting (approximately 67%), nausea (approximately 33%), dysgeusia, epigastric pain, gag reflex, hematemesis, hiccups, retching, xerostomia Genitourinary: Breast tenderness, cervical perforation (posterior), endometritis (from intrauterine device [IUD]), gynecological pain (dysmenorrhea-like pain), menometrorrhagia, retained placenta (fragment), urinary tract infection, uterine perforation, uterine rupture, sacculation of uterus Local: Pain at injection site Neuromuscular & skeletal: Back pain, leg cramps, myalgia, torticollis, weakness Ophthalmic: Blepharospasm, blurred vision, eye pain Otic: Tinnitus Respiratory: Asthma, bronchospasm, cough, dry throat, dyspnea, epistaxis, hyperventilation, pulmonary edema, respiratory distress, upper respiratory tract infection, wheezing <1%, postmarketing, and/or case reports: Hypersensitivity reaction (includes anaphylactic shock, anaphylactoid reaction, anaphylaxis, angioedema) * See Cautions in AHFS Essentials for additional information. Metabolism/Transport EffectsNone known. Drug Interactions Open Interactions Oxytocic Agents: Carboprost Tromethamine may enhance the adverse/toxic effect of Oxytocic Agents. Specifically, oxytocic effects may be enhanced. Risk X: Avoid combination Monitoring ParametersTermination of pregnancy: Confirmation of fetal death; cervical exam after termination of pregnancy Nursing: Physical Assessment/MonitoringPremedication with an antiemetic should be considered. Assess for complete expulsion of uterine contents (fetal tissue). Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. Solution, Intramuscular [strength expressed as base]: Hemabate: 250 mcg/mL (1 mL) [contains benzyl alcohol] Anatomic Therapeutic Chemical (ATC) Classification G02AD04 Generic Available (US)No Pricing: US Solution (Hemabate Intramuscular) 250 mcg/mL (1 mL): $297.12 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of ActionCarboprost is an analog of naturally occurring prostaglandin F2 alpha (dinoprost); carboprost stimulates uterine contractility which usually results in expulsion of the products of conception and is used to induce abortion between 13-20 weeks of pregnancy. When used postpartum, hemostasis at the placentation site is achieved through the myometrial contractions produced by carboprost. Pharmacodynamics/KineticsTime to peak, serum: IM: 30 minutes Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Effects on Dental TreatmentNo significant effects or complications reported Effects on BleedingNo information available to require special precautions Index TermsCarboprost; Prostaglandin F2 Alpha Analog; Prostaglandin F2 Analog

Hep B Vaccine

Hepatitis B Vaccine (AHFS Essentials (Adult and Pediatric)) U.S. Brand NamesComvax® (combination); Engerix-B® Adult Formulation; Engerix-B® Pediatric/Adolescent Formulation; Pediarix® (combination); Recombivax HB® Adult Formulation; Recombivax HB® Dialysis Formulation; Recombivax HB® Pediatric/Adolescent Formulation; Twinrix® (combination) SynonymsDTaP-HepB-IPV; HepA-HepB; Hepatitis B Vaccine (Recombinant); Hib-HepB Therapeutic Class80:12 Vaccines Introduction Inactivated (recombinant) vaccine.Ref Hepatitis B vaccine contains hepatitis B surface antigen (HBsAg) and is used to stimulate active immunity to hepatitis B virus (HBV) infection.Ref Commercially available in the US as monovalent vaccines (HepB; Engerix-B®, Recombivax HB®).Ref Also commercially available in a fixed-combination vaccine with Haemophilus influenzae type b (Hib) vaccine (Hib-HepB; Comvax®),Ref in a fixed-combination vaccine with hepatitis A virus vaccine (HepA-HepB; Twinrix®),Ref and in a fixed-combination vaccine that contains diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix®).Ref Uses See the full AHFS monograph for more information. Prevention of Hepatitis B Virus (HBV) Infection Prevention of HBV infection in neonates, children, adolescents, and adults.Ref Acute HBV infection may be self-limited resulting in production of antibody to HBsAg (anti-HBs) and immunity against reinfection; however, it may progress to chronic HBV infection (especially in infants or young children, immunocompromised individuals, patients with diabetes) or fatal, fulminant hepatitis.Ref Case fatality rate is 0.5-1.5% among those with acute HBV infection;Ref highest fatality rates are in adults >60 years of age.Ref Chronic HBV infection develops in ≥90% of infants infected perinatally, 25-50% of children infected at 1-5 years of age, and <5% of those infected at ≥5 years of age.Ref Chronic infection is associated with persistent HBV replication in the liver and may result in liver cirrhosis, liver cancer, liver failure, and death.Ref HBV is transmitted by percutaneous or mucosal exposure to hepatitis B surface antigen-positive (HBsAg-positive) blood, serum, plasma, semen, or salivaRef and can be transmitted perinatally from mother to infant at birth, usually as the result of blood exposures during labor and delivery.Ref USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and American Academy of Family Physicians (AAFP) recommend that all neonates and infants and all previously unvaccinated children and adolescents through 18 years of age be vaccinated against HBV infection, unless contraindicated.Ref(See Contraindications under Cautions.) ACIP, AAFP, American College of Obstetricians and Gynecologists (ACOG), and American College of Physicians (ACP) recommend that all unvaccinated adults at risk for HBV infection be vaccinated against HBV.Ref(See Preexposure Vaccination Against Hepatitis B Virus [HBV] Infection in High-risk Groups under Uses.) ACIP also states that any unvaccinated adult requesting protection from HBV can receive the vaccine, unless contraindicated.Ref(See Contraindications under Cautions.) For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity.Ref For hepatitis B vaccine (HepB vaccine), ACIP states initiate or complete the age-appropriate HepB vaccine series if vaccination history is uncertain or <3 doses were previously given.Ref(See Dosage and Administration.) If child's records indicate ≥3 doses of HepB vaccine, ACIP states that additional doses not necessary if ≥1 dose was given at ≥24 weeks of age; if most recent dose was at <24 weeks, give an additional dose at ≥24 weeks.Ref Regardless of vaccination status, test for HBsAg if individual was born in Asia, Pacific Islands, Africa, or other regions where HBV is highly endemic.Ref AAP recommends serologic testing for HBsAg in all internationally adopted children and states that the HepB vaccine series should be given if such testing is not available and vaccination history is uncertain.Ref Combined active immunization with HepB vaccine and passive immunization with hepatitis B immune globulin (HBIG) is used to prevent perinatal HBV infection in neonates born to women known or suspected to be HBsAg-positive.Ref(See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Uses.) Active immunization with HepB vaccine with or without passive immunization with HBIG is used for HBV postexposure prophylaxis (PEP) in certain individuals exposed to HBV or HBsAg-positive materials (e.g., health-care personnel, sexual assault victims, sexual or intimate contacts of individuals with acute or chronic HBV infection).Ref(See Postexposure Prophylaxis of Hepatitis B Virus [HBV] Infection under Uses.) With the exception of hepatitis D virus (HDV) infection,Ref monovalent HepB vaccine will not prevent hepatitis caused by other viruses known to infect the liver, including hepatitis A virus (HAV), hepatitis C virus (HCV), or hepatitis E virus (HEV).Ref HDV occurs only as a coinfection or superinfection in patients with HBV infection; individuals immune to HBV also should be immune to HDV.Ref When a dose of HepB vaccine and a dose of Haemophilus influenzae type b (Hib) vaccine are both indicated in an infant 6 weeks to 15 months of age born to an HBsAg-negative woman, the commercially available fixed-combination vaccine containing Hib conjugate (meningococcal protein conjugate) vaccine and HepB vaccine (Hib-HepB; Comvax®) can be used.Ref ACIP states this fixed-combination vaccine also may be used to complete the HepB vaccine series in infants 6 weeks to 15 months of age born to HBsAg-positive women†.Ref Comvax should not be used for the initial (birth) dose of HepB vaccine that is indicated in neonates.Ref When there are no contraindications to any of the individual components, the commercially available fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix®) can be used in infants and children 6 weeks through 6 years of age born to HBsAg-negative women.Ref ACIP states this fixed-combination vaccine also may be used to complete the HepB vaccine series in infants ≥6 weeks of age born to HBsAg-positive women†.Ref Pediarix® should not be used for the initial (birth) dose of HepB vaccine that is indicated in neonates.Ref Pediarix® contains diphtheria, tetanus, and pertussis antigens identical to those contained in Infanrix® DTaP vaccine and contains HBV antigen identical to that contained in Engerix-B® HepB vaccine.Ref When vaccination against both HBV and HAV is indicated in adults ≥18 years of age, the commercially available fixed-combination vaccine containing hepatitis A virus vaccine inactivated and HepB vaccine (HepA-HepB; Twinrix®) can be used.Ref Preexposure Vaccination Against Hepatitis B Virus (HBV) Infection in High-risk Groups See the full AHFS monograph for more information. Preexposure vaccination in previously unvaccinated children, adolescents, or adults at risk of exposure to HBsAg-positive materials (e.g., blood, plasma, serum).Ref ACIP recommends preexposure vaccination for all unvaccinated adults in settings in which a high proportion of individuals are likely to be at risk for HBV infection.Ref This includes health-care personnel, selected patients and patient contacts, populations with high risk of infection, individuals at risk because of their sexual practices, military personnel identified as being at increased risk, and other individuals at risk of exposure (e.g., injection drug abusers).Ref In settings in which a high proportion of individuals are likely to be at risk for HBV, ACIP recommends universal vaccination for all adults who have not completed the HepB vaccine series and suggests standing orders to administer the vaccine as part of routine services to all susceptible individuals who visit these settings.Ref This includes facilities that test and treat sexually transmitted diseases (STDs) and HIV, facilities that provide drug abuse treatment and prevention, health-care facilities targeting services for injection drug abusers or men who have sex with men, and correctional facilities.Ref In addition, because not all adults with HBV risk factors visit these settings, ACIP recommends that primary care and specialty medical settings (e.g., physician offices, community health centers, family planning clinics, liver disease clinics, travel clinics) implement standing orders to identify susceptible adults and provide HepB vaccine whenever indicated or requested as part of regular preventive care.Ref Health-care personnel at risk of exposure to blood, blood-contaminated body fluids, other body fluids, and/or needles that might be contaminated with HBsAg are at risk of HBV infection and should be vaccinated against HBV.Ref ACIP and Hospital Infection Control Practices Advisory Committee (HICPAC) recommend HBV vaccination for all such health-care personnel (e.g., physicians, nurses, emergency medical personnel, dental professionals and students, medical and nursing students, phlebotomists, medical and laboratory technicians, hospital volunteers, administrative and support staff in health-care institutions).Ref Ideally, the HepB vaccine series should be completed during medical, dental, nursing, laboratory technology, and other allied health professional training so that immunity is provided before exposure in high-risk environments.Ref(For information on HBV postexposure prophylaxis in unvaccinated health-care personnel, see Postexposure Prophylaxis of Hepatitis B Virus [HBV] Infection under Uses.) Individuals with hemophilia or other congenital bleeding disorders who are seronegative for HBV should be vaccinated against HBV.Ref If immunization against HBV was not initiated at birth, initiate HepB vaccine series at the time hemophilia or other congenital bleeding disorders are diagnosed.Ref Improved donor screening, more effective viral-inactivation procedures, and/or purification or filtration procedures have reduced, but not completely eliminated, the risk of transmission of blood-borne viruses (HBV, HCV, HIV) from plasma-derived clotting factors.Ref The National Hemophilia Foundation's Medical and Scientific Advisory Council (MASAC) recommends postvaccination testing in individuals with hemophiliaRef and states that nonresponders (i.e., those who do not respond to the primary HepB vaccine series) should receive ≥1 additional doses of the vaccine.Ref(See Pre- and Postvaccination Serologic Testing under Cautions.) Patients and staff of hemodialysis, organ transplant, or oncology wards are at high risk of exposure to HBsAg-positive materials and should be vaccinated against HBV.Ref Although seroconversion rates and anti-HBs titers induced by vaccination are lower in hemodialysis patients than in healthy individuals, vaccination provides protection against HBV infection in responders and reduces the need for frequent serologic screening.Ref ACIP recommends identifying potential candidates as early as possible in the course of their renal disease; there is some evidence that higher seroconversion rates and anti-HBs titers are achieved in uremic patients if they are vaccinated before requiring dialysis.Ref Residents and staff of institutions for the developmentally disabled, including those in small (group) residential settings, are at high risk of exposure to HBsAg-positive materials and should be vaccinated.Ref Residents discharged from residential institutions into community settings should be screened for HBsAg so that appropriate measures can be taken to prevent transmission in the community; such measures include both environmental controls and appropriate vaccination.Ref Classroom contacts (teachers or classmates) of aggressive, deinstitutionalized developmentally disabled individuals are at high risk of exposure to HBsAg-positive materials.Ref HBV vaccination of classroom contacts of HBsAg carriers is strongly encouraged when the carrier is aggressive or has special medical problems that increase the risk of exposure to their blood or serous secretions.Ref In addition, staff of nonresidential day-care programs (e.g., schools, sheltered workshops for the developmentally disabled) attended by known HBsAg carriers have a risk of infection comparable to that among health-care personnel and should be vaccinated.Ref Also consider vaccination of other enrollees in such day-care programs.Ref Spouses and nonsexual household and sexual contacts of HBsAg carriers are at high risk of exposure to HBsAg-positive materials.Ref When carriers are identified through routine screening of donated blood, diagnostic testing in hospitals, prenatal screening, screening of refugees from certain areas, or other screening programs, they should be notified of their HBsAg status.Ref Although some unvaccinated spouses and nonsexual household and sexual contacts of HBsAg carriers may develop immunity against HBV infection during continuous, long-term exposure, all such contacts should be tested and those who are susceptible should be vaccinated.Ref Certain US population groups with high endemic rates of HBV (e.g., native Alaskans, Pacific Islanders, refugees from HBV-endemic areas) are at increased risk and should be vaccinated against HBV.Ref Because transmission occurs principally during childhood in such populations, initiation of the HepB vaccine series at birth and completion of the series by 6-12 months of age is particularly important in these groups.Ref Because of high rate of interfamily transmission among children in these populations, vaccination efforts should target all susceptible children and adolescents who have ≥1 parent born in a highly endemic area.Ref Individuals at high risk of HBV because of their sexual practices (e.g., men who have sex with men, individuals with >1 sexual partner in the previous 6 months, sexual partners of HBsAg-positive individuals,Ref female prostitutesRef) and individuals seeking evaluation or treatment for STDs should be vaccinated against HBV.Ref HepB vaccine is recommended for all susceptible adolescent and adult men who have sex with men (homosexual, bisexual), regardless of age or duration of such sexual practices.Ref Travelers to areas with levels of endemic HBV that are intermediate (2-7%) or high (≥8%) are at risk of exposure to the disease.Ref ACIP, CDC, and others recommend preexposure vaccination for previously unvaccinated travelers (neonates, infants, adolescents, adults) traveling to such areas.Ref HBV prevalence is intermediate in South Central and Southwest Asia, Israel, Japan, Eastern and Southern Europe, Russia, and most areas surrounding the Amazon River basin, Honduras, and Guatemala; prevalence is high in Africa, Southeast Asia (including China, Korea, Indonesia, and Philippines), Middle East (except Israel), southern and western Pacific islands, interior Amazon Basin, and certain parts of the Caribbean (e.g., Haiti, Dominican Republic).Ref Morticians and embalmers are at high risk of exposure to HBsAg-positive materials; the manufacturers recommend use of HepB vaccine in these individuals.Ref Military personnel may be at increased risk of exposure to HBV; the manufacturers recommend use of HepB vaccine in these individuals.Ref Prisoners may be at increased risk of exposure to HBV; the manufacturers recommend use of HepB vaccine in these individuals.Ref Public-safety personnel (e.g., police, fire department personnel) may be at risk for occupational exposure to HBV (depending on tasks performed); those who have contact with blood or blood-contaminated body fluids should be vaccinated.Ref Individuals with chronic HCV infection may be at increased risk for HBV exposure and should be vaccinated.Ref Optimal HepB vaccine regimen for such individuals has not been identified; response to HepB vaccine may be reduced in individuals with chronic HCV infection.Ref Individuals addicted to parenterally administered drugs are at high risk of exposure to HBsAg-positive materials and should be vaccinated against HBV as soon as their drug use is identified.Ref Individuals in casual contact with HBsAg carriers in settings such as schools, offices, and business environments are at minimal risk of HBV exposure.Ref ACIP does not recommend routine use of HepB vaccine in these individuals.Ref At child-care centers (other than those for the developmentally disabled), HBV transmission between children or between children and staff has rarely been documented.Ref ACIP states that vaccination of contacts of HBsAg carriers in child-care settings is not necessary unless there are special circumstances that might facilitate transmission (e.g., behavior problems such as biting or scratching, medical conditions such as severe skin disease).Ref Prevention of Perinatal Hepatitis B Virus (HBV) Infection See the full AHFS monograph for more information. Prevention of perinatal HBV infection in neonates born to HBsAg-positive women.Ref A combined regimen that includes active immunization with HepB vaccine and passive immunization with HBIG is 85-95% effective in preventing acute and chronic HBV infection in infants born to women positive for both HBsAg and HBeAg.Ref ACIP and AAP recommend routine serologic screening of all pregnant women during an early prenatal visit (e.g., first trimester) to determine their HBsAg status, even if they were tested previously or have already been vaccinated against HBV.Ref Women who were not tested prenatally, those who engage in behaviors that put them at high risk for HBV (e.g., >1 sex partner in the previous 6 months, HBsAg-positive sex partner, evaluation or treatment for STDs, recent or current injection drug abuse) and those with clinical hepatitis should be tested for HBsAg status when admitted to the hospital for delivery.Ref To prevent perinatal HBV infection, ACIP and AAP recommend that all neonates born to HBsAg-positive women receive a dose of HepB vaccine and a dose of HBIG as soon as possible after birth (within 12 hours of birth), regardless of gestational age or birthweight.Ref For neonates <2 kg, do not count the birth vaccine dose toward completion of the HepB vaccine series; begin usual 3-dose vaccine series when infant is 1 month of age.Ref If maternal HBsAg status is unknown at birth, give infant the first dose of HepB vaccine (within 12 hours of birth).Ref Determine mother's HBsAg status as quickly as possible and, if positive, give infant a dose of HBIG as soon as possible (no later than 7 days of age).Ref For neonates weighing <2 kg, if the mother's HBsAg status cannot be determined within 12 hours of birth, give a dose of HBIG as soon as possible (within 12 hours of birth) and do not count the birth vaccine dose toward completion of the HepB vaccine series; begin usual 3-dose vaccine series when infant is 1 month of age.Ref Postexposure Prophylaxis of Hepatitis B Virus (HBV) Infection See the full AHFS monograph for more information. HBV postexposure prophylaxis (PEP) in certain individuals exposed to HBV or HBsAg-positive materials (e.g., health-care personnel, sexual assault victims, sexual or intimate contacts of individuals with acute or chronic HBV infection).Ref Depending on exposure circumstances, PEP regimen may include combined active immunization with HepB vaccine and passive immunization with HBIG to provide both short- and long-term protection.Ref PEP may be indicated in susceptible, unvaccinated health-care personnel following occupational exposure to blood and other body fluids that might contain HBV.Ref If an occupational exposure to HBV occurs, review vaccination status and vaccine-response status (if known) of exposed individual and HBsAg status of source.Ref(See Table 1.) If exposed individual was not previously vaccinated against HBV, initiate HepB vaccine series as soon as possible (preferably within 24 hours).Ref In addition, if source is found to be HBsAg-positive, give a dose of HBIG as soon as possible (preferably within 24 hours).Ref If exposed individual was previously vaccinated against HBV and is a known responder (serum anti-HBs ≥10 mIU/mL), PEP is not necessary.Ref If exposed individual was previously vaccinated against HBV but is a known nonresponder (serum anti-HBs <10 mIU/mL), PEP is not necessary if source is HBsAg-negative.Ref However, if source is HBsAg-positive or known to be high-risk for HBV, give exposed individual a dose of HBIG and initiate a second HepB vaccine series as soon as possible after exposure.Ref A 2-dose regimen of HBIG (without HepB vaccine) is preferred in individuals who already previously failed to respond to a second vaccine series.Ref If antibody status of exposed individual is unknown, test them for anti-HBs prior to initiation of PEP.Ref If exposed individual is found to be a responder (serum anti-HBs ≥10 mIU/mL), PEP is not necessary.Ref If exposed individual is found to be a nonresponder (anti-HBs levels <10 mIU/mL) and source is HBsAg-positive, give a dose of HBIG and a booster dose of HepB vaccine.Ref If exposed individual is found to be a nonresponder and source is unknown or not available for testing, give a booster dose of HepB vaccine and recheck antibody titer in 1-2 months.Ref Table 1. Postexposure Prophylaxis of HBV following Occupational (Percutaneous or Mucosal) Exposure to BloodRef Treatment when Source Is: Vaccination and Antibody Status of Exposed Individual HBsAg-positive HBsAg-negative Source Unknown or Not Available for Testing Unvaccinated Single HBIG dose (within 24 hours) and initiate hepatitis B vaccine series (within 24 hours) Initiate hepatitis B vaccine series Initiate hepatitis B vaccine series Previously vaccinated Known responder (anti-HBs 10 mIU/mL or greater) No treatment No treatment No treatment Known nonresponder (anti-HBs less than 10 mIU/mL) Single HBIG dose and initiate hepatitis B revaccination series or 2 HBIG doses (first dose as soon as possible; second dose 1 month later) No treatment If known high-risk source, treat as if source were HBsAg-positive Antibody response unknown Test exposed individual for anti-HBs No treatment Test exposed individual for anti-HBs 1. If inadequate, single dose of HBIG and a booster dose of hepatitis B vaccine 1. If inadequate, give a booster dose of hepatitis B vaccine and recheck titer in 1-2 months 2. If adequate, no treatment 2. If adequate, no treatment ACIP and CDC recommend PEP with HepB vaccine for victims of sexual assault (adult, adolescent, child) who are susceptible to HBV.Ref PEP after a sexual assault is not necessary in those who previously received the complete HepB vaccine series.Ref If victim is unvaccinated or incompletely vaccinated and perpetrator is HBsAg-positive, give a dose of HBIG within 14 days of the assault (preferably within 24 hours) and initiate or complete HepB vaccine series.Ref ACIP and CDC recommend PEP with HepB vaccine for sexual or needle-sharing partners and nonsexual household contacts of individuals with chronic HBV infection.Ref Because most HBsAg-positive individuals are identified during routine screening (e.g., blood donation, prenatal evaluation) or clinical evaluation and it may be difficult to identify the time of last contact, use of HBIG is not considered necessary for PEP in contacts of such individuals.Ref A dose of HBIG may be indicated if the most recent sexual exposure to an HBsAg-positive individual occurred within the last 14 days.Ref Consider postvaccination serologic testing in sexual contacts of individuals with chronic HBV infection.Ref Although most are expected to respond to vaccination, initiate a second complete HepB vaccine series in nonresponders.Ref If there is no response to the second vaccine series, provide counsel about abstinence and use of other methods to protect themselves from HBV via sexual transmission.Ref ACIP and CDC recommend that previously unvaccinated sexual partners of individuals with acute HBV infection receive PEP with a dose of HBIG and the initial dose of the HepB vaccine series (within 14 days of the most recent sexual contact).Ref Completion of the vaccine series confers long-term protection in case the individual with acute HBV infection becomes chronically infected.Ref Consider prevaccination serologic testing of sexual partners, but only if it does not delay postexposure vaccination beyond 14 days.Ref AAP recommends that unvaccinated infants <12 months of age in close contact with a mother or other primary caregiver who has acute HBV infection receive combined passive immunization with HBIG and active immunization with HepB vaccine.Ref If the infant previously received a single dose of HepB vaccine, give the second vaccine dose if the interval is appropriate or, if it is too soon to give a vaccine dose, give a dose of HBIG.Ref HBIG is not required if, at the time of exposure, the infant has already received ≥2 doses of HepB vaccine.Ref Other nonsexual household contacts of individuals with acute HBV infection are not at increased risk for infection unless they have other risk factors or are exposed to the blood of the infected patient (e.g., by sharing a toothbrush or razor).Ref However, encourage all household contacts of patients with acute HBV infection to receive HepB vaccine.Ref If the patient with acute HBV infection becomes chronically infected (i.e., remains HBsAg-positive after 6 months), all household contacts should be vaccinated with HepB vaccine.Ref CDC recommends that individuals wounded in bombings or other mass casualty settings who are unvaccinated or have an uncertain vaccination history receive postexposure vaccination with HepB vaccine (without HBIG), unless contraindicated.Ref HepB vaccine generally is warranted in such individuals if they have wounds (penetrating injuries), nonintact skin, or mucous membranes that may have been exposed to blood or body fluids from other individuals.Ref If the vaccine is in short supply, consider that children <17 years of age and health-care personnel are more likely to have previously received the vaccine than other individuals.Ref Responders and other personnel in mass casualty settings should be managed using PEP regimens recommended for occupational exposures to HBV.Ref(See Table 1.) PEP not necessary in individuals who previously received primary immunization with HepB vaccine and have serologic evidence of adequate levels of anti-HBs (≥10 mIU/mL).Ref PEP not necessary in individuals previously infected with HBV; such individuals are immune to reinfection.Ref Dosage and Administration See the full AHFS monograph for more information. Administration See the full AHFS monograph for more information. IM Injection Administer monovalent HepB vaccine (Engerix-B®, Recombivax HB®) by IM injection.Ref May be administered by sub-Q injection when necessary in individuals at risk of hemorrhage following IM injection.Ref(See Individuals with Bleeding Disorders under Cautions.) Do not administer IV or intradermally;Ref there is evidence that intradermal administration may be associated with reduced immunogenicity.Ref Administer fixed-combination vaccine containing Hib vaccine and HepB vaccine (Hib-HepB; Comvax®) by IM injection.Ref Do not administer sub-Q or IV.Ref Administer fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix®) by IM injection.Ref Do not administer sub-Q or IV.Ref Administer fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix®) by IM injection.Ref Do not administer sub-Q or IV.Ref Shake vaccine well immediately prior to administration to provide a uniform, turbid, white suspension.Ref Discard vaccine if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.Ref Do not dilute.Ref Do not mix with any other vaccine or solution.Ref Depending on patient age, administer IM into the deltoid muscle or anterolateral thigh.Ref To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass, the thickness of adipose tissue and muscle at the injection site, and the injection technique.Ref For neonates and young children (up to 12 months of age), IM injections should be made into the anterolateral thigh.Ref For children 1-2 years of age, IM injections should preferably be administered into the anterolateral thigh; the deltoid muscle is an alternative if muscle mass is adequate.Ref For adults, adolescents, and children ≥3 years of age, the deltoid muscle is preferred, although the anterolateral thigh is an alternative.Ref Generally do not administer vaccines into buttock muscle in children because of potential for injection-associated injury to sciatic nerve.Ref Although some experts state that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) can be performed to ensure that a blood vessel has not been entered, ACIP and AAP state this procedure is not required because large blood vessels are not present at recommended IM injection sites.Ref Since syncope may occur following vaccination, observe vaccinee for approximately 15 minutes after the vaccine dose is administered.Ref If syncope occurs, observe the patient until symptoms resolve.Ref Syncope after vaccination occurs most frequently in adolescents and young adults.Ref Monovalent HepB may be given simultaneously with HBIG (using different syringes and different injection sites) when passive immunization is considered necessary in addition to active immunization with the vaccine (e.g., in neonates born to HBsAg-positive women, PEP regimen in certain individuals exposed to HBV or HBsAg-positive materials).Ref May be given simultaneously with other age-appropriate vaccines during the same health-care visit (using different syringes and different injection sites).Ref(See Interactions.) When multiple vaccines are administered during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites.Ref Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.Ref If multiple vaccines must be given into a single limb, the deltoid may be used in older children and adults, but the anterolateral thigh is preferred in infants and younger children.Ref Dosage See the full AHFS monograph for more information. Dose and dosing schedule vary depending on the individual's age and specific vaccine administered, HBsAg status of the mother (for neonates), and presence of underlying disease.RefFollow dosage recommendations for the specific preparation used.Ref Currently available monovalent HepB vaccines (Engerix-B®, Recombivax HB®) generally are considered interchangeable; HepB vaccine series started with one monovalent vaccine may be completed using a different vaccine given in dosage recommended for the specific formulation.Ref Use only monovalent HepB vaccine (Engerix-B®, Recombivax HB®) for the initial (birth) dose in neonates or infants <6 weeks of age.Ref Complete the vaccine series using monovalent or age-appropriate fixed-combination vaccines.Ref The complete HepB vaccine series must be administered to ensure optimal protection.Ref Interruptions resulting in an interval between doses longer than recommended should not interfere with the final immunity achieved; it is not necessary to give additional doses or start the vaccine series over.Ref If the vaccine series is interrupted after the initial dose, give second dose as soon as possible (minimum interval between first and second dose is 4 weeks) and give third dose at least 8 weeks after the second dose (minimum interval between first and third dose is 16 weeks).Ref If only the third dose is delayed, administer as soon as possible.Ref Infants should receive the final dose at ≥24 weeks of age.Ref Pediatric Patients Prevention of Hepatitis B Virus (HBV) Infection (Monovalent Vaccines) Neonates and Infants (Engerix-B®) IM Primary immunization consists of 3 doses.Ref Use pediatric/adolescent formulation containing 10 mcg/0.5 mL.Ref Manufacturer recommends 10-mcg doses at 0, 1, and 6 months.Ref Alternatively, manufacturer recommends a 4-dose regimen consisting of 10-mcg doses at 0, 1, 2, and 12 months.Ref Full-term neonates born to HBsAg-positive women or women with unknown HBsAg status: Give initial dose of 10 mcg within 12 hours of birth.Ref ACIP, AAP, and AAFP recommend that second and third 10-mcg doses be given at 1-2 and 6 months of age, respectively.Ref Give third dose no earlier than 24 weeks of age.Ref(See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Full-term neonates born to HBsAg-negative women: Give initial dose of 10 mcg at birth (before hospital discharge).Ref ACIP, AAP, and AAFP recommend that second and third 10-mcg doses be given at 1-2 and 6-18 months of age, respectively.Ref If not given before hospital discharge, give initial dose no later than 2 months of age.Ref Give third dose no earlier than 24 weeks of age.Ref Preterm neonates weighing <2 kg born to HBsAg-positive women or women with unknown HBsAg status: Give a dose of HepB vaccine and a dose of HBIG as soon as possible after birth (within 12 hours of birth).Ref(See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Do not count this initial (birth) dose toward completion of the HepB vaccine series; initiate usual 3-dose vaccine series when infant is 1 month of age.Ref Preterm neonates weighing <2 kg born to HBsAg-negative women: Give initial dose of 10 mcg at 1 month of age.Ref Initial dose may be given at time of hospital discharge (before 1 month of age) if infant is medically stable and showing consistent weight gain.Ref Give second and third 10-mcg doses at 1-2 and 6-18 months, respectively, after initial dose.Ref Neonates and Infants (Recombivax HB®) IM Primary immunization consists of 3 doses.Ref Use pediatric/adolescent formulation containing 5 mcg/0.5 mL.Ref Manufacturer recommends 5-mcg doses at 0, 1, and 6 months.Ref Full-term neonates born to HBsAg-positive women or women with unknown HBsAg status: Give initial dose of 5 mcg within 12 hours of birth.Ref ACIP, AAP, and AAFP recommend that second and third 5-mcg doses be given at 1-2 and 6 months of age, respectively.Ref Give third dose no earlier than 24 weeks of age.Ref(See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Full-term neonates born to HBsAg-negative women: Give initial dose of 5 mcg at birth (before hospital discharge).Ref ACIP, AAP, and AAFP recommend that second and third 5-mcg doses be given at 1-2 and 6-18 months of age, respectively.Ref If not given before hospital discharge, give initial dose no later than 2 months of age.Ref Give third dose no earlier than 24 weeks of age.Ref Preterm neonates weighing <2 kg born to HBsAg-positive women or women with unknown HBsAg status: Give a dose of HepB vaccine and a dose of HBIG as soon as possible after birth (within 12 hours of birth).Ref(See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Do not count this initial (birth) dose toward completion of the HepB vaccine series; initiate usual 3-dose vaccine series when infant is 1 month of age.Ref Preterm neonates weighing <2 kg born to HBsAg-negative women: Give initial dose of 5 mcg at 1 month of age.Ref Initial dose may be given at time of hospital discharge (before 1 month of age) if infant is medically stable and showing consistent weight gain.Ref Give second and third 5-mcg doses at 1-2 and 6-18 months, respectively, after initial dose.Ref Children ≤10 Years of Age (Engerix-B®) IM Primary immunization (including catch-up vaccination) consists of a series of 3 doses.Ref Use pediatric/adolescent formulation containing 10 mcg/0.5 mLRef Give initial dose of 10 mcg on a selected date.Ref Give second and third 10-mcg doses at 1 and 6 months, respectively, after initial dose.Ref Alternatively, manufacturer states that children ≤10 years of age can receive a 4-dose regimen consisting of 10-mcg doses given on a selected date and at 1, 2, and 12 months after the initial dose, or children 5-10 years of age can receive a 3-dose regimen consisting of 10-mcg doses given on a selected date and at 12 and 24 months after the initial dose.Ref Children ≤10 Years of Age (Recombivax HB®) IM Primary immunization (including catch-up vaccination) consists of 3 doses.Ref Use pediatric/adolescent formulation containing 5 mcg/0.5 mL.Ref Give initial dose of 5 mcg.Ref Give second and third 5-mcg doses at 1 and 6 months, respectively, after initial dose.Ref Adolescents 11-19 Years of Age (Engerix-B®) IM Primary immunization (including catch-up vaccination) consists of a series of 3 doses using the pediatric/adolescent formulation or the adult formulation.Ref If pediatric/adolescent formulation containing 10 mcg/0.5 mL is used, give initial dose of 10 mcg on a selected date.Ref Give second and third 10-mcg doses at 1 and 6 months, respectively, after initial dose.Ref Alternatively, in those 11-16 years of age, manufacturer states that 10-mcg doses can be given on a selected date and at 12 and 24 months after the initial dose.Ref If adult formulation containing 20 mcg/mL is used, give initial dose of 20 mcg on a selected date.Ref Give second and third 20-mcg doses at 1 and 6 months, respectively, after initial dose.Ref Alternatively, manufacturer states that a 4-dose regimen consisting of 20-mcg doses given on a selected date and at 1, 2, and 12 months after the initial dose can be used.Ref Adolescents 11-19 Years of Age (Recombivax HB®) IM Primary immunization (including catch-up vaccination) consists of 3 doses using the pediatric/adolescent formulation.Ref Alternatively, manufacturer states that adolescents 11-15 years of age can receive a 2-dose regimen using the adult formulation.Ref If pediatric/adolescent formulation containing 5 mcg/0.5 mL is used, give initial dose of 5 mcg.Ref Give second and third 5-mcg doses at 1 and 6 months, respectively, after initial dose.Ref If adult formulation containing 10 mcg/mL is used, give 10 mcg dose on a selected date and give second 10-mcg dose 4-6 months later.Ref Prevention of Hepatitis B Virus (HBV) Infection (Combination Vaccines) Infants and Children 6 Weeks to 15 Months of Age (Hib-HepB; Comvax®) IM May be used when primary immunization against Hib and HBV is indicated in infants 6 weeks to 15 months of age born to HBsAg-negative women.Ref ACIP states this vaccine also may be used to complete the HepB vaccine series in infants 6 weeks to 15 months of age born to HBsAg-positive women†.Ref May be used in infants who previously received a dose of monovalent HepB vaccine at or shortly after birth.Ref Manufacturer states that Comvax® can be used in children otherwise scheduled to receive concurrent PedvaxHIB® and Recombivax HB®.Ref Primary immunization consists of a series of 3 doses (0.5 mL) given ideally at 2, 4, and 12-15 months of age.Ref Interval between first 2 doses should be at least 6 weeks and interval between second and third dose should be as close as possible to 8-11 months.Ref Infants and Children 6 Weeks through 6 Years of Age (DTaP-HepB-IPV; Pediarix®) IM May be used when immunization against diphtheria, tetanus, pertussis, HBV, and poliovirus is indicated in infants and children 6 weeks through 6 years of age born to HBsAg-negative women.Ref ACIP states this vaccine also may be used to complete the HepB vaccine series in infants 6 weeks to 15 months of age born to HBsAg-positive women†.Ref May be used to complete the HepB vaccine series in children <7 years of age who have previously received 1 or 2 doses of monovalent HepB vaccine, Infanrix® DTaP vaccine (but not other commercially available DTaP vaccines), and/or monovalent IPV if such children are scheduled to receive the other components of the fixed-combination vaccine.Ref Primary immunization consists of a series of 3 doses (0.5 mL) given at 6- to 8-week intervals (preferably 8 weeks).Ref Initial dose usually given at 2 months of age, but may be given as early as 6 weeks of age.Ref To complete the DTaP and IPV primary vaccination series in children who received a 3-dose primary series of Pediarix®, administer a dose of Infanrix® (DTaP) at 15-18 months of age and a dose of monovalent IPV (IPOL®) at 4-6 years of age.Ref Prevention of Perinatal Hepatitis B Virus (HBV) Infection Neonates Born to HBsAg-positive Women IM Combined passive immunization with HBIG and active immunization with HepB vaccine is indicated.Ref Give a dose of monovalent HepB vaccine and a dose of HBIG (0.5 mL) within 12 hours of birth (using different syringes and different injection sites).Ref Complete the 3-dose HepB vaccine series using usually recommended doses and intervals.Ref (See Prevention of Hepatitis B Virus [HBV] Infection (Monovalent Vaccines) or Prevention of Hepatitis B Virus [HBV] Infection (Combination Vaccines) under Dosage and Administration.) Final dose of the vaccine series should be given at ≥24 weeks of age.Ref For preterm neonates weighing <2 kg at birth, do not count initial (birth) dose of HepB vaccine as part of the 3-dose vaccine series.Ref In addition to the birth dose, give 3 vaccine doses beginning at 1 month of age (total of 4 doses).Ref At 9-18 months of age after completion of the vaccine series, test infant for anti-HBs and HBsAg.Ref If anti-HBs level is <10 mIU/mL and HBsAg is negative, repeat the vaccine series by giving 3 additional doses of HepB vaccine (initial dose on a selected date and second and third dose at 1-2 and 6 months, respectively, after initial dose) and retest for anti-HBs 1-2 months after the third dose.Ref Alternatively, test for anti-HBs 1 month after each dose to determine whether subsequent doses are needed.Ref HBsAg-negative infants with anti-HBs levels ≥10 mIU/mL are protected from HBV and do not need additional doses of HepB vaccine.Ref Neonates Born to Women with Unknown HBsAg Status IM Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.Ref Give a dose of monovalent HepB vaccine within 12 hours of birth.Ref Determine HBsAg status of the mother as soon as possible.Ref If mother is found to be HBsAg-positive, give neonate a dose of HBIG (0.5 mL) as soon as possible (no later than 1 week of age).Ref If neonate was preterm and weighed <2 kg at birth, give neonate a dose of HBIG (0.5 mL) within 12 hours of birth if mother is found to be HBsAg-positive or if results are not available.Ref Complete the 3-dose HepB vaccine series using usually recommended doses and intervals.Ref (See Prevention of Hepatitis B Virus [HBV] Infection (Monovalent Vaccines) or Prevention of Hepatitis B Virus [HBV] Infection (Combination Vaccines) under Dosage and Administration.) If neonate was preterm and weighed <2 kg at birth, do not count initial (birth) dose of HepB vaccine as part of the 3-dose vaccine series.Ref In addition to the birth dose, give 3 vaccines doses beginning at 1 month of age (total of 4 doses).Ref Postexposure Prophylaxis of Hepatitis B Virus (HBV) Unvaccinated or Incompletely Vaccinated Infants <12 Months of Age Exposed to Acute HBV Infection IM Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.Ref If mother or other primary caregiver has acute HBV infection, give a dose of HBIG and initiate or complete primary immunization with HepB vaccine.Ref HBIG is not necessary if infant already received ≥2 doses of HepB vaccine.Ref Unvaccinated or Incompletely Vaccinated Sexual Assault Victims IM Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.Ref Initiate or complete HepB vaccine series.Ref(See Prevention of Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Give initial dose within 14 days of the assault (preferably within 24 hours).Ref Give second and third doses at 1-2 and 4-6 months, respectively, after initial dose.Ref If perpetrator is HBsAg-positive, also give victim a dose of HBIG (0.06 mL/kg) within 14 days of the assault (preferably within 24 hours).Ref Adults Prevention of Hepatitis B Virus (HBV) Infection (Monovalent Vaccines) Adults ≥20 Years of Age (Engerix-B®) IM Primary immunization consists of 3 doses.Ref Use adult formulation containing 20 mcg/mL.Ref Give initial dose of 20 mcg.Ref Give second and third 20-mcg doses at 1-2 and 4-6 months, respectively, after initial dose.Ref Alternatively, a 4-dose regimen can be used.Ref Give initial 20-mcg dose and give additional 20-mcg doses at 1, 2, and 12 months after initial dose.Ref Adults ≥20 Years of Age (Recombivax HB®) IM Primary immunization consists of 3 doses.Ref Use adult formulation containing 10 mcg/mL.Ref Give initial dose of 10 mcg.Ref Give second and third 10-mcg doses at 1-2 and 4-6 months, respectively, after initial dose.Ref Adults Undergoing Hemodialysis (Engerix-B®) IM Primary immunization consists of 4 doses.Ref Use adult formulation containing 20 mcg/mL.Ref Each dose consists of 40 mcg and may be given using 1 or 2 injections.Ref Give initial dose of 40 mcg.Ref Give additional 40-mcg doses at 1, 2, and 6 months after initial dose.Ref Adults Undergoing Hemodialysis (Recombivax HB®) IM Primary immunization in predialysis and dialysis patients consists of 3 doses.Ref Use dialysis formulation containing 40 mcg/mL.Ref Give initial dose of 40 mcg.Ref Give second and third 40-mcg doses at 1 and 6 months, respectively, after initial dose.Ref Prevention of Hepatitis B Virus (HBV) Infection (Combination Vaccines) Adults ≥18 Years of Age (HepA-HepB; Twinrix®) IM Primary immunization consists of a series of 3 doses.Ref Each 1-mL dose contains at least 720 units of HAV antigen and 20 mcg of hepatitis B surface antigen (HBsAg).Ref For primary immunization, give initial dose on a selected date and give second and third doses at 1 and 6 months, respectively, after initial dose.Ref Alternatively, if an accelerated dosing schedule is needed, give initial dose on a selected date and give second and third doses at 7 and 21-30 days, respectively, after initial dose; also give a booster dose at 12 months after initial dose.Ref Preexposure Vaccination Against Hepatitis B Virus (HBV) in High-risk Groups Primary immunization with the usually recommended HepB vaccine series before an expected exposure to HBV or HBsAg-positive materials (e.g., blood, plasma, serum) ensures the highest level of protection.Ref (See Prevention of Hepatitis B Virus [HBV] Infection (Monovalent Vaccines) or Prevention of Hepatitis B Virus [HBV] Infection (Combination Vaccines) under Dosage and Administration.) Travelers IM Individuals traveling to areas with intermediate or high levels of endemic HBV (see Preexposure Vaccination Against Hepatitis B Virus [HBV] Infection in High-risk Groups under Uses): Give initial dose on a selected date and give second and third doses 1 and 6 months, respectively, after initial dose.Ref To ensure completion of the 3-dose series and optimal protection against HBV, begin HepB vaccine series 6 months prior to travel.Ref Because a partial series offers some protection, initiate the series even if it cannot be completed before travel.Ref Alternatively, for travelers who will depart before the usual 3-dose series can be completed, CDC suggests an optional accelerated schedule† (initial dose given on a selected date and second and third doses given 7 and 21 days, respectively, after initial dose).Ref If the accelerated schedule is used, give a booster dose 1 year after start of the series to promote long-term immunity.Ref Alternatively, a 4-dose regimen can be used.Ref Give initial dose on a selected date and give other 3 doses at 1, 2, and 12 months after initial dose.Ref This regimen induces immunity more rapidly than the usual 3-dose regimen and may be useful when there are time constraints; first 3 doses should be administered before travel (i.e., at 0, 1, and 2 months).Ref Postexposure Prophylaxis of Hepatitis B Virus (HBV) Occupational Exposure in Susceptible Health-care Personnel IM Depending on exposure circumstances, combined active immunization with HepB vaccine and passive immunization with HBIG may be indicated.Ref(See Table 1 under Uses.) Initiate HepB vaccine series in unvaccinated individuals.Ref(See Prevention of Hepatitis B Virus [HBV] Infection under Dosage and Administration.) If vaccine series was initiated prior to exposure, give remaining doses as originally scheduled.Ref Give initial dose as soon as possible following exposure (preferably within 24 hours).Ref Give second and third doses at 1 and 6 months, respectively, after initial dose.Ref Unvaccinated or Incompletely Vaccinated Sexual Assault Victims IM Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.Ref Initiate or complete HepB vaccine series.Ref(See Prevention of Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Give initial dose at time of initial medical examination within 14 days of the assault (preferably within 24 hours).Ref Give second and third doses at 1-2 and 4-6 months, respectively, after initial dose.Ref If perpetrator is HBsAg-positive, also give victim a dose of HBIG (0.06 mL/kg) within 14 days of the assault (preferably within 24 hours).Ref Unvaccinated or Incompletely Vaccinated Contacts of Individuals with Acute HBV Infection IM Initiate HepB vaccine series in unvaccinated individuals.Ref(See Prevention of Hepatitis B Virus [HBV] Infection under Dosage and Administration.) If vaccine series was initiated prior to exposure, give remaining doses as originally scheduled.Ref Unvaccinated or Incompletely Vaccinated Individuals Wounded in Mass Casualty Settings IM Give a dose of HepB vaccine as soon as possible (preferably within 24 hours) and not later than 7 days after the event.Ref Complete primary vaccine series at the time of discharge or during follow-up health-care visits.Ref Special Populations Hepatic Impairment No specific dosage recommendations.Ref Renal Impairment For dosage recommendations for patients undergoing hemodialysis, see Adults Undergoing Hemodialysis under Dosage and Administration. Geriatric Patients No specific dosage recommendations.Ref HepB vaccine may be less immunogenic in geriatric individuals than in younger adults.Ref Cautions See the full AHFS monograph for more information. Contraindications Monovalent HepB Vaccine (HepB; Engerix-B®, Recombivax HB®) Hypersensitivity to any ingredient in the vaccine (including yeast).Ref Previous hypersensitivity to any HepB vaccine.Ref Fixed-combination Vaccine Containing Hib vaccine and HepB Vaccine (Hib-HepB; Comvax®) Hypersensitivity to any vaccine component (including yeast).Ref Fixed-combination Vaccine Containing DTaP, HepB, and IPV Vaccines (DTaP-Hib-HepB; Pediarix®) Hypersensitivity to any ingredient in the vaccine (e.g., yeast, neomycin, polymyxin B).Ref Serious allergic reaction (e.g., anaphylaxis) temporally associated with a previous dose of the vaccine or any vaccine component.Ref Encephalopathy (e.g., coma, decreased consciousness, prolonged seizures) within 7 days of a previous dose of vaccine containing pertussis antigens that is not attributed to another identifiable cause.Ref Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.Ref Fixed-combination Vaccine Containing HepA Vaccine and HepB Vaccine (HepA-HepB; Twinrix®) Hypersensitivity to any ingredient in the formulation, including the HepA vaccine component (Havrix®), the HepB vaccine component (Engerix-B®), yeast, or neomycin.Ref Previous hypersensitivity reaction to Twinrix® or monovalent HepA or HepB vaccines.Ref Warnings/Precautions Sensitivity Reactions Hypersensitivity Reactions Life-threatening hypersensitivity reactions reported rarely.Ref Anaphylaxis and symptoms of immediate hypersensitivity, including rash, pruritus, urticaria, edema, angioedema, dyspnea, chest discomfort, bronchospasm (including asthma-like symptoms), palpitation, or symptoms consistent with a hypotensive episode, reported within the first few hours after administration of HepB vaccine.Ref Take all known precautions to prevent adverse reactions, including a review of the patient's history with respect to possible hypersensitivity to the vaccine or similar vaccines.Ref Epinephrine and other appropriate agents should be readily available in case anaphylaxis or an anaphylactoid reaction occurs.Ref If hypersensitivity reaction occurs, immediately institute appropriate therapy as indicated.Ref Do not administer additional vaccine doses to individuals with symptoms of hypersensitivity after a previous dose.Ref Serum-sickness Reactions An apparent serum-sickness reaction with delayed onset reported days to weeks after administration of HepB vaccine.Ref Delayed reaction consists of arthralgia and/or arthritis (usually transient), fever, and dermatologic reactions such as urticaria, erythema multiforme (including Stevens-Johnson syndrome), ecchymoses, and erythema nodosum.Ref Yeast Allergy See the full AHFS monograph for more information. Manufacturing process for HepB vaccine involves baker's yeast (Saccharomyces cerevisiae).Ref Final products (monovalent and fixed-combination vaccines) contain ≤5% yeast protein.Ref Manufacturers state monovalent and fixed-combination vaccines containing HepB vaccine should not be used in individuals with yeast allergy.Ref A theoretical risk of allergic reaction in individuals allergic to yeast exists, but no evidence to date that such reactions have occurred when HepB vaccine used in such individuals.Ref Allergy to Neomycin or Other Anti-infectives See the full AHFS monograph for more information. Fixed-combination vaccine containing diphtheria, tetanus, pertussis, HBV, and poliovirus antigens (DTaP-HepB-IPV; Pediarix®) contains trace amounts of neomycin sulfate (≤0.05 ng) and polymyxin B (≤0.01 ng).Ref Fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix®) contains trace amounts of neomycin sulfate (≤20 ng).Ref Manufacturers state these vaccines contraindicated in individuals hypersensitive to these anti-infectives.Ref Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.Ref ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh the risks.Ref Latex Sensitivity Some packaging components (e.g., needle cover, syringe plunger) of the single-dose prefilled syringes of Engerix-B® or single-dose prefilled syringes of DTaP-HepB-IPV (Pediarix®) contain dry natural latex;Ref the stopper on the single-dose vial of Engerix-B® does not contain latex.Ref The stopper on vials of Comvax® contains natural rubber latex.Ref Some individuals may be hypersensitive to natural latex proteins found in a wide range of medical devices, including such packaging components, and the level of sensitivity may vary depending on the form of natural rubber present;Ref rarely hypersensitivity reactions to natural latex proteins have been fatal.Ref ACIP states that vaccines supplied in vials or syringes containing dry natural rubber or natural rubber latex may be administered to individuals with latex allergies other than anaphylactic allergies (e.g., history of contact allergy to latex gloves), but should not be used in those with a history of severe (anaphylactic) allergy to latex, unless the benefits of vaccination outweigh the risk of a potential allergic reaction.Ref General Precautions Use of Combination Vaccines See the full AHFS monograph for more information. Whenever a fixed-combination vaccine is used, consider the adverse effects, precautions, and contraindications related to each antigen.Ref Limitations of Vaccine Effectiveness See the full AHFS monograph for more information. May not protect all vaccine recipients against HBV infection,Ref especially individuals who have not achieved protective titers of anti-HBs (≥10 mIU/mL measured 1-2 months after completion of HepB vaccine series).Ref Consider possibility that unrecognized HBV infection may be present in some individuals at the time of vaccination (infection has an incubation period of 6 weeks to 6 months) and that the vaccine may not prevent infection in such individuals.Ref Monovalent HepB vaccine (Engerix-B®, Recombivax HB®) provides protection only against HBV.Ref Fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix®) provides protection only against HAV and HBV.Ref Monovalent and fixed-combination vaccines containing HepB vaccine generally will also prevent HDV infection by preventing HBV infection since HDV occurs only as a coinfection or superinfection in patients infected with HBV.Ref These vaccines do not provide protection against other hepatitis viruses (e.g., HCV, HEV).Ref Duration of Immunity Duration of protection from HBV infection following primary immunization with HepB vaccine and need for additional (booster) doses of the vaccine have not been fully determined.Ref Vaccine-induced levels of anti-HBs decline over time,Ref but immunologic memory may persist for at least 10-20 years and may confer protection.Ref Booster doses of vaccine may not be necessary in immunocompetent individuals, even if antibody titers decline after vaccination.Ref Subsequent exposure to HBV results in an anamnestic anti-HBs response that prevents clinically significant HBV infection.Ref Data are limited regarding the extent and duration of immunologic memory following HBV vaccination in immunocompromised individuals, including HIV-infected individuals, transplant recipients, hemodialysis patients, or those receiving chemotherapy or immunosuppressive therapy.Ref Routine booster doses not recommended for immunocompetent children, adolescents, or adults.Ref In hemodialysis patients and other immunocompromised individuals (e.g., HIV-infected individuals, hematopoietic stem-cell transplant recipients, individuals receiving chemotherapy or immunosuppressive therapy), assess anti-HBs levels annually (see Pre- and Postvaccination Serologic Testing under Cautions) to determine need for booster doses; give booster dose when anti-HBs level decreases to <10 mIU/mL.Ref Individuals with Altered Immunocompetence See the full AHFS monograph for more information. Recommendations regarding use of HepB vaccine in individuals with altered immunocompetence generally are the same as those for individuals who are not immunocompromised.Ref May be used in immunocompromised individuals, including those who are HIV-infected or immunocompromised because of congenital immunodeficiency, leukemia, lymphoma, generalized malignancy, or therapy with alkylating agents, antimetabolites, radiation, or corticosteroids.Ref Also may be used in solid organ or hematopoietic stem cell transplant recipients, patients with asplenia, renal failure, diabetes, alcoholism, or alcoholic cirrhosis.Ref Consider possibility that the immune response to the vaccine may be reduced in these individuals.Ref Recommendations regarding use in HIV-infected children, adolescents, or adults are the same as those for individuals who are not HIV-infected.Ref Some HIV-infected individuals may not have a satisfactory response to HepB vaccine, and anti-HBs may persist for shorter periods of time in HIV-infected individuals.Ref In HIV-infected adults, some experts recommend that HepB vaccine be administered before CD4+ T-cell count decreases to <350/mm3, but vaccination should not be deferred until T-cell count increases to >350/mm3.Ref Because HIV-infected individuals (especially children with CD4+ T-cell counts <200/mm3 or adults with CD4+ T-cell counts <350/mm3) may not have an adequate response, postvaccination serologic testing should be performed.Ref(See Pre- and Postvaccination Serologic Testing under Cautions.) Immunogenicity of higher or additional doses of HepB vaccine in HIV-infected individuals not fully evaluated; firm recommendations cannot be made regarding use of such doses in these individuals.Ref Anti-HBs response generally is lower and persists for shorter periods in hemodialysis patients than in healthy adults.Ref Only 50-86% of hemodialysis patients reportedly develop protective levels of anti-HBs after receiving a 3-dose series consisting of 40-mcg doses of HepB vaccine.Ref Larger vaccine doses (e.g., 2-4 times the usual adult dose) or an increased number of doses (4 doses) are required to induce protective antibody levels in a large proportion of patients undergoing hemodialysis.Ref Concomitant Illness See the full AHFS monograph for more information. Manufacturer of Recombivax HB® states use caution and exercise appropriate care in individuals with severely compromised cardiopulmonary status or in others in whom a febrile or systemic reaction could pose a significant risk.Ref A decision to administer or delay vaccination in an individual with a current or recent febrile illness depends on the severity of symptoms and etiology of the illness.Ref Some manufacturers state the vaccine may be given to individuals with acute infection or febrile illness if withholding the vaccine poses greater risk to the patient.Ref ACIP states that minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever), generally does not preclude vaccination, but defer vaccination in individuals with moderate or severe acute illness (with or without fever).Ref Individuals with Bleeding Disorders See the full AHFS monograph for more information. Because bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy, use caution in such individuals.Ref ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient's bleeding risk determines that the preparation can be administered with reasonable safety.Ref In these cases, use a fine needle (23 gauge) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.Ref If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.Ref Advise individual and/or their family about the risk of hematoma from IM injections.Ref The manufacturers of Engerix-B® and Recombivax HB® state the vaccines can be administered sub-Q in individuals at risk of hemorrhage following IM injection (e.g., hemophiliacs).Ref However, sub-Q administration of HepB vaccines has been associated with reduced antibody response.Ref Also consider that an increased incidence of local reactions (e.g., sub-Q nodules) has occurred following sub-Q administration of vaccines containing an aluminum adjuvant.Ref Exacerbation of Multiple Sclerosis Exacerbation of multiple sclerosis reported following administration of HepB vaccine or other vaccines; causal relationship not established.Ref Weigh benefit of HepB vaccine against risk of exacerbation of multiple sclerosis.Ref Pre- and Postvaccination Serologic Testing Need for prevaccination serologic testing to determine whether an individual was previously infected with HBV generally based on whether such testing is less costly than unnecessarily vaccinating an individual who is already immune.Ref For routine testing, use a single test (anti-hepatitis core antigen; anti-HBc) or a panel of tests (HBsAg and anti-HBs).Ref Anti-HBc identifies individuals with previous HBV infection, including those with chronic HBV infection.Ref Anti-HBc-negative individuals are susceptible and should be vaccinated against HBV.Ref Anti-HBc-positive individuals should be tested for HBsAg.Ref Prevaccination testing for serologic markers of HBV infection not usually necessary for groups with low prevalence of HBV serologic markers, including infants, children, or adolescents undergoing routine vaccination or health-care personnel undergoing vaccination during their training years.Ref Prevaccination serologic testing recommended for all foreign-born individuals (e.g., immigrants, refugees, asylum seekers, internationally adopted children) born in Africa, Asia, the Pacific Islands, or other regions with high HBV endemicity (i.e., prevalence of HB

Erythromycin (ointment)

Erythromycin (Topical) (Pediatric and Neonatal Lexi-Drugs) Pronunciation (er ith roe MYE sin) Brand Names: USAkne-Mycin [DSC]; Ery; Erygel Brand Names: CanadaErysol Therapeutic CategoryAntibiotic, Macrolide; Antibiotic, Topical Dosing: UsualNote: Akne-Mycin ointment has been discontinued in the US for more than 1 year. Children and Adults: Apply 2% solution over the affected area twice daily after the skin has been thoroughly washed and patted dry UseTreatment of acne vulgaris AdministrationApply thin film to the cleansed, affected area. Storage/Stability Akne-Mycin: Store below 27°C (80°F). Ery: Store at 20°C to 25°C (68°F to 77°F). Erygel: Store at 20°C to 25°C (68°F to 77°F). Protect from heat and flame. Erysol [Canadian product]: Store at 15°C to 30°C (59°F to 86°F). Protect from heat and flame. Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience dry skin, itching, or peeling. Have patient report immediately to prescriber severe skin irritation, eye irritation, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Medication Safety Issues Sound-alike/look-alike issues: Contraindications Hypersensitivity to erythromycin or any component of the formulation Documentation of allergenic cross-reactivity for erythromycin is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty. Warnings/Precautions Concerns related to adverse effects: • Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Discontinue if significant diarrhea, abdominal cramps, or passage of blood and mucus occurs. Concurrent drug therapy issues: • Concurrent topical acne therapy: Use with caution especially with peeling, desquamating or abrasive agents; irritation may be cumulative. Discontinue use if irritation or dermatitis occurs. Dosage form specific issues: • Topical gel: May be flammable. Keep away from heat and flame. Other warnings/precautions: • Appropriate use: For topical use only; not for ophthalmic use. Avoid contact with eyes, nose, mouth, mucous membranes, or broken skin. Lack of improvement or worsening of acne may indicate microbial resistance. Alternative therapy may be required for severe acne (eg, nodular). Consider alternate therapy in patients with poor tolerance to macrolides or clindamycin. Warnings: Additional Pediatric ConsiderationsSome dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP, 1997; Shehab, 2009). Pregnancy Risk FactorB Pregnancy ConsiderationsAdverse events were not observed in animal reproduction studies. Erythromycin has been shown to cross the placenta following oral dosing. Refer to the Erythromycin (Systemic) monograph for details. The amount of erythromycin available systemically following topical application is considered to be very low (Akhavan, 2003). Systemic absorption would be required in order for erythromycin to cross the placenta and reach the fetus. Topical erythromycin may be used for the treatment of acne in pregnancy (Dréno, 2013; Eichenfield, 2013; Gollnick, 2003). Breast-Feeding ConsiderationsIt is not known if erythromycin is excreted into breast milk following topical application. The manufacturer recommends that caution be exercised when administering to nursing women. Erythromycin has been shown to enter breast milk following oral dosing. Refer to the Erythromycin (Systemic) monograph for details. The amount of erythromycin available systemically following topical application is considered to be very low (Akhavan, 2003). Systemic absorption would be required in order for erythromycin to enter breast milk and reach the nursing infant. Lexicomp Pregnancy & Lactation, In-Depth Erythromycin (Topical) Briggs' Drugs in Pregnancy & Lactation Erythromycin Adverse Reactions Frequency not defined. Dermatologic: Desquamation, erythema, exfoliation of skin, leathery skin, oily skin, pruritus, skin fissure (around mouth), skin tenderness, urticaria, xeroderma Local: Application site irritation (includes local dryness, localized burning, localized erythema, localized tenderness, stinging of the skin) Ophthalmic: Eye irritation Rare but important or life-threatening: Abdominal distress, abdominal pain, diarrhea, facial edema, hypersensitivity reaction, skin rash Allergy and Idiosyncratic Reactions Macrolide Allergy Drug Interactions: Metabolism/Transport EffectsNone known. Drug Interactions Open Interactions Clindamycin (Topical): Erythromycin (Topical) may diminish the therapeutic effect of Clindamycin (Topical). Risk X: Avoid combination Product AvailabilityAkne-Mycin ointment has been discontinued in the US for more than 1 year. Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product Gel, External: Erygel: 2% (30 g, 60 g) Generic: 2% (30 g, 60 g) Ointment, External: Akne-Mycin: 2% (25 g [DSC]) [contains cetostearyl alcohol] Pad, External: Ery: 2% (60 ea) [contains propylene glycol] Generic: 2% (60 ea) Solution, External: Generic: 2% (60 mL) Generic Availability (US)May be product dependent Mechanism of ActionAntibacterial activity is due to inhibition of RNA-dependent protein synthesis at the chain elongation step; binds to the 50S ribosomal subunit resulting in blockage of transpeptidation. Alcohol component induces skin drying and peeling.

Magnesium Sulfate (perinatal application)

Magnesium Sulfate (Lexi-Drugs) Drug ShortagesOne or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information: ASHP: http://www.ashp.org/menu/DrugShortages ASPEN: https://www.nutritioncare.org/Professional_Resources/Drug_Shortages_Update/ FDA: http://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Magnesium Sulfate Injection&st=c&tab=tabs-4 SCCM: http://www.learnicu.org/Lists/Web%20Contents/Attachments/11221/DrugShortage-3-6-14.pdf Pronunciation (mag NEE zhum SUL fate) Brand Names: USEpsom Salt [OTC]; GoodSense Epsom Salt [OTC] Pharmacologic CategoryAnticonvulsant, Miscellaneous; Electrolyte Supplement, Parenteral; Magnesium Salt Dosing: AdultDose represented as magnesium sulfate unless stated otherwise. Note: Serum magnesium is poor reflection of repletional status as the majority of magnesium is intracellular; serum concentrations may be transiently normal for a few hours after a dose is given, therefore, aim for consistently high normal serum concentrations in patients with normal renal function for most efficient repletion. Note: 1 g of magnesium sulfate = 98.6 mg elemental magnesium = 8.12 mEq elemental magnesium = magnesium 4.06 mmol Constipation (occasional): Oral: 2 to 4 level teaspoons of granules dissolved in 8 ounces of water; may repeat in 6 hours. Do not exceed 2 doses per day. Eclampsia/pre-eclampsia (severe): Manufacturer's labeling: IV: An initial total dose of 10 to 14 g administered as follows: 4 g infusion with simultaneous IM injections of 4 to 5 g in each buttock. After the initial IV/IM doses, may administer a 1 to 2 g/hour continuous infusion or may follow with IM doses of 4 to 5 g into alternate buttocks every 4 hours as necessary. Maximum: 40 g/24 hours. IV use for pre-eclampsia/eclampsia is contraindicated during the 2 hours prior to delivery. Alternate dosing (off-label): IV: 4 to 6 g loading dose followed by 1 to 2 g/hour continuous infusion for at least 24 hours (ACOG, 2013) Hypomagnesemia, treatment:Note: Treatment depends on severity and clinical status. In asymptomatic patients (when oral route is available), oral replacement therapy is a better replacement method than IV administration. Mild deficiency: IM: Manufacturer's labeling: 1 g every 6 hours for 4 doses, or as indicated by serum magnesium concentrations Mild-to-moderate (serum concentration 1 to 1.5 mg/dL): IV: 1 to 4 g (up to 0.125 g/kg), administer at ≤1 g/hour if asymptomatic; do not exceed 12 g over 12 hours (Kraft, 2005). Note: Additional supplementation may be required after the initial dose with replenishment occurring over several days. Severe deficiency: IM: Manufacturer's labeling: Up to 250 mg/kg within a 4-hour period IV: Severe (<1 mg/dL): 4 to 8 g (up to 0.1875 g/kg), administer at ≤1 g/hour if asymptomatic; in symptomatic patients, may administer ≤4 g over 4-5 minutes (Kraft, 2005) With polymorphic VT (including torsade de pointes): IV push: 1 to 2 g (ACLS, 2010) Obesity: Weight >130% of ideal body weight (IBW) or body mass index (BMI) ≥30 kg/m2: When determining maximum per kg dose for replacement, some clinicians suggest using adjusted body weight (AdjBW) (Kraft, 2005). AdjBW (men) = ([wt (kg) -IBW (kg)] x 0.3) + IBW AdjBW (women) = ([wt (kg) -IBW (kg)] x 0.25) + IBW Hypomagnesemia, prevention (parenteral nutrition supplementation): IV: 8 to 20 mEq elemental magnesium daily (ASPEN [Mirtallo, 2004]) Soaking aid: Topical: Dissolve 2 cupfuls of granules per gallon of warm water; may also soak a towel with the solution to apply as a wet dressing. Asthma (acute severe exacerbations) (off-label use): IV: 2 g as a single dose over 20 minutes (NAEPP, 2007; GINA, 2015); recommended as adjunctive therapy for severe life-threatening exacerbations and for exacerbations that remain severe after 1 hour of intensive conventional therapy (NAEPP, 2007) Torsade de pointes or VF/pulseless VT associated with torsade de pointes (off-label use): IV, I.O.: 1 to 2 g over 15 minutes (ACLS, 2010) RDA (IOM, 1997): Adults 19 to 30 years: Females: 310 mg elemental magnesium daily Pregnant females: 350 mg elemental magnesium daily Breast-feeding females: 310 mg elemental magnesium daily Males: 400 mg elemental magnesium daily Adults ≥31 years: Females: 320 mg elemental magnesium daily Pregnant females: 360 mg elemental magnesium daily Breast-feeding females: 320 mg elemental magnesium daily Males: 420 mg elemental magnesium daily * See Dosage and Administration in AHFS Essentials for additional information. Dosing: GeriatricRefer to adult dosing. Dosing: PediatricDose represented as magnesium sulfate unless stated otherwise. Note: Serum magnesium is poor reflection of repletional status as the majority of magnesium is intracellular; serum concentrations may be transiently normal for a few hours after a dose is given, therefore, aim for consistently high normal serum concentrations in patients with normal renal function for most efficient repletion. Note: 1 g of magnesium sulfate = 98.6 mg elemental magnesium = 8.12 mEq elemental magnesium = magnesium 4.06 mmol Constipation (occasional): Oral: Children 6 to <12 years: 1 to 2 level teaspoons of granules dissolved in water; may repeat in 4 to 6 hours (maximum: 2 doses/24 hours) Children ≥12 years and Adolescents: Refer to adult dosing. Hypomagnesemia, treatment:Note: Treatment depends on severity and clinical status: IV, I.O.: 25 to 50 mg/kg/dose over 10 to 20 minutes (over several minutes for torsade de pointes); maximum single dose: 2000 mg (PALS, 2010) Hypomagnesemia, prevention (parenteral nutrition supplementation) (ASPEN [Mirtallo, 2004]): IV: ≤50 kg: 0.3 to 0.5 mEq elemental magnesium/kg/day >50 kg: 10 to 30 mEq elemental magnesium daily Asthma (acute severe exacerbations) (off-label use): IV: Children and Adolescents: 25 to 75 mg/kg (maximum: 2000 mg) as a single dose over 20 to 60 minutes (GINA 2015; NAEPP, 2007); recommended as adjunctive therapy for severe life-threatening exacerbations and for exacerbations that remain severe after 1 hour of intensive conventional therapy (NAEPP, 2007) RDA (IOM, 1997): Children 1 to 3 years: 80 mg elemental magnesium daily 4 to 8 years: 130 mg elemental magnesium daily 9 to 13 years: 240 mg elemental magnesium daily 14 to 18 years: Females: 360 mg elemental magnesium daily Pregnant females: 400 mg elemental magnesium daily Breast-feeding females: 360 mg elemental magnesium daily Males: 410 mg elemental magnesium daily Dosing: Renal Impairment Hypomagnesemia: Renal dysfunction: Reduce dose by 50% (Kraft, 2005). Use with caution; monitor for hypermagnesemia; Close monitoring is required. Pre-eclampsia/eclampsia: Severe renal impairment: Per the manufacturer, do not exceed 20 grams during a 48 hour period. Dosing: Hepatic ImpairmentNo dosage adjustment necessary. Dosing: ObesityRefer to indication-specific dosing for obesity-related information (may not be available for all indications). Calculations Creatinine Clearance by Cockcroft-Gault Creatinine Clearance by Cockcroft-Gault (SI units) Creatinine Clearance by Cockcroft-Gault with IBW Creatinine Clearance by Cockcroft-Gault with IBW (SI units) Creatinine Clearance by Jelliffe Creatinine Clearance by Sanaka Glomerular Filtration Rate by Abbreviated MDRD Glomerular Filtration Rate by Abbreviated MDRD (SI units) Glomerular Filtration Rate by MDRD Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr) Glomerular Filtration Rate by MDRD (SI units) Glomerular Filtration Rate by Schwartz Magnesium Sulfate Use: Labeled Indications Oral: Laxative for the relief of occasional constipation (OTC labeling) Parenteral: Treatment and prevention of hypomagnesemia; prevention and treatment of seizures in severe pre-eclampsia or eclampsia, pediatric acute nephritis; treatment of cardiac arrhythmias (VT/VF) caused by hypomagnesemia Topical: Soaking aid for minor cuts and bruises (OTC labeling) * See Uses in AHFS Essentials for additional information. Use: Off-Label Asthma (acute exacerbations)Level of Evidence [G] Based on the National Asthma Education and Prevention Program Coordinating Committee (NAEPP) Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and Management of Asthma, magnesium sulfate given as adjunctive therapy for life-threatening asthma or for exacerbations that remain severe after 1 hour of intensive conventional treatment is effective and recommended in the management of this condition. The Global Initiative for Asthma (GINA): Global Strategy for Asthma Management and Prevention guidelines recommend magnesium sulfate be considered for patients with severe exacerbations not responding to initial treatment in an acute care setting, such as an emergency room. Magnesium sulfate is not recommended for routine use. Torsades de pointes or VF/pulseless VT associated with torsades de pointesLevel of Evidence [G] Based on the American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, magnesium sulfate given for torsades de pointes or VF/pulseless VT associated with torsades de pointes is effective and recommended in the management of this condition. Level of Evidence Definitions Level of Evidence Scale Clinical Practice Guidelines Advanced Cardiac Life Support (ACLS)/Emergency Cardiovascular Care (ECC): AHA, "2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care," October 2015. AHA, "2010 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care," November 2010. AHA, "Cardiac Arrest in Pregnancy," October 2015 Administration: IMMust be diluted prior to administration for children (Adults: 25% or 50% concentration; Children: ≤20% diluted solution) Administration: IVMust be diluted to a ≤20% solution for IV infusion and may be administered IV push, IVPB, or continuous IV infusion. When giving IV push, must dilute first and should generally not be given any faster than 150 mg/minute; may administer over 1 to 2 minutes in patients with persistent pulseless VT or VF with known hypomagnesemia (Dager, 2006). ACLS guidelines recommend administration over 15 minutes in patients with torsade de pointes (ACLS, 2010). In patients not in cardiac arrest, hypotension and asystole may occur with rapid administration. In patients with asthma (acute severe exacerbation) (off-label use), may administer single dose over 20 minutes to 60 minutes (GINA 2015; NAEPP 2007). Maximal rate of infusion: Up to 50% of an IV dose may be eliminated in the urine, therefore, slower administration may improve retention (maximum rate: 1 g/hour in asymptomatic patients). For doses <6 g, infuse over 8 to 12 hours and for larger doses infuse over 24 hours if patient is asymptomatic. If patient is severely symptomatic (or has conditions such as preeclampsia or eclampsia) more aggressive therapy (≤4 g over 4 to 5 minutes) may be required; patients should be closely monitored (Kraft, 2005). Administration: OralWhen used as a laxative, dissolve dose in 8 ounces of water prior to ingesting. Lemon juice may be added to the solution to improve the taste. Administration: TopicalMay dissolve granules to prepare a solution for use as a soaking aid or as a compress. To make a compress, use a towel to apply as a wet dressing. Dietary ConsiderationsWhole grains, legumes and dark-green leafy vegetables are dietary sources of magnesium (IOM, 1997). Storage/StabilityPrior to use, store at room temperature of 20°C to 25°C (68°F to 77°F). Do not freeze. Refrigeration of solution may result in precipitation or crystallization. Preparation for Administration IV: Dilute to a ≤20% solution for IV infusion. IM: A 25% or 50% concentration may be used for adults and dilution to a ≤20% solution is recommended for children. Oral: Dissolve granules in 8 ounces of water prior to administration. May add lemon juice to improve taste. Topical: Dissolve 2 cups of granules per gallon of warm water to use as a soaking aid. CompatibilityStable in D5W, D10W, D51/4NS, D5NS, LR, NS, R; incompatible with fat emulsion 10%. Y-site administration: Compatible: Acyclovir, aldesleukin, amifostine, amikacin, ampicillin, aztreonam, bivalirudin, caspofungin, cefazolin, cefotaxime, cefoxitin, chloramphenicol, cisatracurium, clindamycin, clonidine, dexmedetomidine, dobutamine, docetaxel, doripenem, doxorubicin liposome, doxycycline, enalaprilat, erythromycin lactobionate, esmolol, etoposide phosphate, famotidine, fenoldopam, fludarabine, furosemide, gallium nitrate, gentamicin, granisetron, heparin, hetastarch in lactate electrolyte injection (Hextend), hydrocortisone sodium succinate, hydromorphone, idarubicin, insulin (regular), kanamycin, labetalol, levofloxacin, linezolid, meperidine, metronidazole, micafungin, milrinone, minocycline, morphine, nafcillin, nicardipine, nitroprusside, ondansetron, oxacillin, oxaliplatin, paclitaxel, pancuronium, penicillin G potassium, piperacillin, piperacillin/tazobactam, potassium chloride, propofol, remifentanil, sargramostim, telavancin, thiotepa, tobramycin, trimethoprim/sulfamethoxazole, vancomycin, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, cefepime, drotrecogin alfa. Variable (consult detailed reference): Amiodarone, amphotericin B, ciprofloxacin, cyclosporine, pantoprazole. Compatibility in syringe: Compatible: Dimenhydrinate, metoclopramide. Incompatible: Calcium chloride, pantoprazole, phytonadione. Variable (consult detailed reference): Folic acid, hydrocortisone sodium succinate, potassium phosphate. Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience injection site irritation. Have patient report immediately to prescriber arrhythmia, severe dizziness; passing out; severe loss of strength and energy; sweating a lot; vision changes; confusion; severe flushing; severe edema; muscle weakness; difficulty moving; seizures; severe diarrhea; severe nausea; severe vomiting; black, tarry, or bloody stools; or cramps (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Medication Safety Issues Sound-alike/look-alike issues: High alert medication: ContraindicationsHypersensitivity to any component of the formulation; heart block; myocardial damage; IV use for pre-eclampsia/eclampsia during the 2 hours prior to delivery Warnings/Precautions Disease-related concerns: • Neuromuscular disease: Use with extreme caution in patients with myasthenia gravis or other neuromuscular disease. • Renal impairment: Use with caution in patients with renal impairment; accumulation of magnesium may lead to magnesium intoxication. Special populations: • Obstetrics: Vigilant monitoring and safe administration techniques (ISMP, 2005) recommended to avoid potential for errors resulting in toxicity. Monitor mother and fetus closely. Use longer than 5 to 7 days may cause adverse fetal events. Dosage form specific issues: • Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register, 2002). See manufacturer's labeling. Other warnings/precautions: • Appropriate use: Unlikely to effectively terminate irregular/polymorphic VT (with normal baseline QT interval) (AHA [Neumar 2010]). • Electrolyte abnormalities: Concurrent hypokalemia or hypocalcemia can accompany a magnesium deficit. Hypomagnesemia is frequently associated with hypokalemia and requires correction in order to normalize potassium. • Parenteral administration: Magnesium toxicity can lead to fatal cardiovascular arrest and/or respiratory paralysis. • Self-medication (OTC Use): When used as a soaking aid, patients should not use if there is evidence of infection or prompt relief is not obtained. When used as a laxative, patients should consult a healthcare provider prior to use if they have: kidney disease; are on a magnesium-restricted diet; have abdominal pain, nausea, or vomiting; change in bowel habits lasting >2 weeks; have already used a laxative for >1 week. * See Cautions in AHFS Essentials for additional information. Pregnancy Risk FactorD Pregnancy ConsiderationsMagnesium crosses the placenta; serum concentrations in the fetus are similar to those in the mother (Idama, 1998; Osada, 2002). Continuous maternal use for >5-7 days (in doses such as those used for preterm labor, an off-label use) may cause fetal hypocalcemia and bone abnormalities, as well as fractures in the neonate. Magnesium sulfate injection is used for the prevention and treatment of seizures in pregnant or postpartum women with severe pre-eclampsia or eclampsia (ACOG, 2013). Magnesium sulfate may also be used prior to early preterm delivery to reduce the risk of cerebral palsy (ACOG, 2010; Reeves, 2011). Tocolytics may be used for the short-term (48 hour) prolongation of pregnancy to allow for the administration of antenatal steroids and should not be used prior to fetal viability or when the risks of use to the fetus or mother are greater than the risk of preterm birth; maintenance therapy with tocolytics is ineffective and not recommended. Magnesium sulfate injection may be used in conjunction with tocolytics for neuroprotection (it is not preferred for use as a tocolytic); however, an increased risk of maternal complications may be observed when used in combination with some tocolytic agents (ACOG, 2012). Breast-Feeding ConsiderationsMagnesium is found in breast milk; concentrations remain constant during the first year of lactation and are not influenced by dietary intake under normal conditions. Magnesium requirements are the same in lactating and nonlactating females (IOM, 1997). When magnesium sulfate is used in the intrapartum management of eclampsia, breast milk concentrations are generally increased for only ~24 hours after the end of treatment (Idama, 1998). The manufacturer recommends that caution be used if administered to nursing women. Briggs' Drugs in Pregnancy & Lactation Magnesium Sulfate Adverse ReactionsAdverse effects on neuromuscular function may occur at lower concentrations in patients with neuromuscular disease (eg, myasthenia gravis). Frequency not defined: Cardiovascular: Flushing (IV; dose related), hypotension (IV; rate related), vasodilation (IV; rate related) Endocrine & metabolic: Hypermagnesemia * See Cautions in AHFS Essentials for additional information. Toxicology Magnesium Metabolism/Transport EffectsNone known. Drug Interactions Open Interactions Alfacalcidol: May increase the serum concentration of Magnesium Salts. Risk D: Consider therapy modification Alpha-Lipoic Acid: Magnesium Salts may decrease the absorption of Alpha-Lipoic Acid. Alpha-Lipoic Acid may decrease the absorption of Magnesium Salts. Risk D: Consider therapy modification Bisphosphonate Derivatives: Magnesium Salts may decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral magnesium salts within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Pamidronate; Zoledronic Acid. Risk D: Consider therapy modification Calcitriol (Systemic): May increase the serum concentration of Magnesium Salts. Management: Consider using a non-magnesium-containing antacid or phosphate-binding product in patients also receiving calcitriol. If magnesium-containing products must be used with calcitriol, serum magnesium concentrations should be monitored closely. Risk D: Consider therapy modification Calcium Channel Blockers: May enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy Calcium Polystyrene Sulfonate: Laxatives (Magnesium Containing) may enhance the adverse/toxic effect of Calcium Polystyrene Sulfonate. More specifically, concomitant use of calcium polystyrene sulfonate with magnesium-containing laxatives may result in metabolic alkalosis or with sorbitol may result in intestinal necrosis. Management: Avoid concomitant use of calcium polystyrene sulfonate (rectal or oral) and magnesium-containing laxatives. Risk X: Avoid combination CNS Depressants: Magnesium Sulfate may enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Deferiprone: Magnesium Salts may decrease the serum concentration of Deferiprone. Management: Separate administration of deferiprone and oral medications or supplements that contain polyvalent cations by at least 4 hours. Risk D: Consider therapy modification Dolutegravir: Magnesium Salts may decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral magnesium salts. Risk D: Consider therapy modification Doxercalciferol: May enhance the hypermagnesemic effect of Magnesium Salts. Management: Consider using a non-magnesium-containing antacid or phosphate-binding product in patients also receiving doxercalciferol. If magnesium-containing products must be used with doxercalciferol, serum magnesium concentrations should be monitored closely. Risk D: Consider therapy modification Eltrombopag: Magnesium Salts may decrease the serum concentration of Eltrombopag. Management: Administer eltrombopag at least 2 hours before or 4 hours after oral administration of any magnesium-containing product. Risk D: Consider therapy modification Gabapentin: Magnesium Salts may enhance the CNS depressant effect of Gabapentin. Specifically, high dose intravenous/epidural magnesium sulfate may enhance the CNS depressant effects of gabapentin. Magnesium Salts may decrease the serum concentration of Gabapentin. Management: Administer gabapentin at least 2 hours after oral magnesium salts administration. Monitor patients closely for evidence of reduced response to gabapentin therapy. Monitor for CNS depression if high dose IV/epidural magnesium sulfate is used. Risk D: Consider therapy modification Levothyroxine: Magnesium Salts may decrease the serum concentration of Levothyroxine. Management: Separate administration of oral levothyroxine and oral magnesium salts by at least 4 hours. Risk D: Consider therapy modification Multivitamins/Fluoride (with ADE): Magnesium Salts may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Specifically, magnesium salts may decrease fluoride absorption. Management: To avoid this potential interaction separate the administration of magnesium salts from administration of a fluoride-containing product by at least 1 hour. Risk D: Consider therapy modification Mycophenolate: Magnesium Salts may decrease the serum concentration of Mycophenolate. Management: Separate doses of mycophenolate and oral magnesium salts. Monitor for reduced effects of mycophenolate if taken concomitant with oral magnesium salts. Risk D: Consider therapy modification Neuromuscular-Blocking Agents: Magnesium Salts may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy Phosphate Supplements: Magnesium Salts may decrease the serum concentration of Phosphate Supplements. Management: This applies only to oral phosphate and magnesium administration. Administer oral phosphate supplements at least 1 hour before, or 2 hours after, oral magnesium salt administration. Exceptions: Sodium Glycerophosphate Pentahydrate. Risk D: Consider therapy modification Quinolone Antibiotics: Magnesium Salts may decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Exceptions: LevoFLOXacin (Oral Inhalation). Risk D: Consider therapy modification Raltegravir: Magnesium Salts may decrease the serum concentration of Raltegravir. Management: Avoid the use of oral / enteral magnesium salts with raltegravir. No dose separation schedule has been established that adequately reduces the magnitude of interaction. Risk X: Avoid combination Sodium Polystyrene Sulfonate: Laxatives (Magnesium Containing) may enhance the adverse/toxic effect of Sodium Polystyrene Sulfonate. More specifically, concomitant use of sodium polystyrene sulfonate with magnesium-containing laxatives may result in metabolic alkalosis or with sorbitol may result in intestinal necrosis. Management: Avoid concomitant use of sodium polystyrene sulfonate (rectal or oral) and magnesium-containing laxatives. Risk X: Avoid combination Tetracycline Derivatives: Magnesium Salts may decrease the absorption of Tetracycline Derivatives. Only applicable to oral preparations of each agent. Risk D: Consider therapy modification Trientine: May decrease the serum concentration of Magnesium Salts. Magnesium Salts may decrease the serum concentration of Trientine. Risk D: Consider therapy modification Food InteractionsIncreased alcohol intake can deplete magnesium stores (IOM, 1997). Monitoring Parameters IV: Rapid administration: ECG monitoring, vital signs, deep tendon reflexes; magnesium concentrations if frequent or prolonged dosing required particularly in patients with renal dysfunction, calcium, and potassium concentrations; renal function Obstetrics: Patient status including vital signs, oxygen saturation, deep tendon reflexes, level of consciousness, fetal heart rate, maternal uterine activity. Reference RangeSerum magnesium: 1.5-2.5 mg/dL; slightly different ranges are reported by different laboratories Nursing: Physical Assessment/MonitoringWhen administered parenterally, monitor serum magnesium, calcium and potassium concentration, vital signs, deep tendon reflex, and renal function. In obstetrics, monitor vital signs, oxygen saturation, deep tendon reflexes, level of consciousness, fetal heart rate, and maternal uterine activity. Dosage Forms Considerations 1 g of magnesium sulfate = elemental magnesium 98.6 mg = magnesium 8.12 mEq = magnesium 4.06 mmol Magnesium sulfate 1% [10 mg/mL] in Dextrose 5% injection is equivalent to elemental magnesium 0.081 mEq/mL. Magnesium sulfate 2% [20 mg/mL] in Dextrose 5% injection is equivalent to elemental magnesium 0.162 mEq/mL. Magnesium sulfate 4% [40 mg/mL] in Water injection is equivalent to elemental magnesium 0.325 mEq/mL. Magnesium sulfate 8% [80 mg/mL] in Water injection is equivalent to elemental magnesium 0.65 mEq/mL. Magnesium sulfate 50% injection is equivalent to elemental magnesium 4 mEq/mL. Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product Capsule, Oral: Generic: 70 mg Granules, Oral: Epsom Salt: (454 g, 1810 g, 1816 g) GoodSense Epsom Salt: (1810 g) Solution, Injection: Generic: 50% (2 mL, 10 mL, 20 mL, 50 mL [DSC]) Solution, Injection [preservative free]: Generic: 50% (20 mL, 50 mL) Solution, Intravenous: Generic: 1 g/100 mL (100 mL); 10 g/500 mL (500 mL); 2 g/50 mL (50 mL); 4 g/100 mL (100 mL); 4 g/50 mL (50 mL); 20 g/500 mL (500 mL); 40 g/1000 mL (1000 mL); 40 mg/mL (50 mL, 500 mL, 1000 mL); 80 mg/mL (50 mL) Anatomic Therapeutic Chemical (ATC) Classification A06AD04 A12CC02 B05XA05 D11AX05 V04CC02 Generic Available (US)Yes Pricing: US Solution (Magnesium Sulfate Injection) 50% (10 mL): $2.08 Solution (Magnesium Sulfate Intravenous) 2 gm/50 mL (50 mL): $17.50 4 g/100 mL (100 mL): $8.68 4 gm/50 mL (50 mL): $8.84 20 g/500 mL (500 mL): $6.72 40GM/1000ML (1000 mL): $9.96 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of ActionWhen taken orally, magnesium promotes bowel evacuation by causing osmotic retention of fluid which distends the colon with increased peristaltic activity; parenterally, magnesium decreases acetylcholine in motor nerve terminals and acts on myocardium by slowing rate of S-A node impulse formation and prolonging conduction time. Magnesium is necessary for the movement of calcium, sodium, and potassium in and out of cells, as well as stabilizing excitable membranes. Intravenous magnesium may improve pulmonary function in patients with asthma; causes relaxation of bronchial smooth muscle independent of serum magnesium concentration. Pharmacodynamics/Kinetics Onset of action: Anticonvulsant: IM: 1 hour; IV: Immediate; Laxative: Oral: 0.5 to 6 hours Duration of anticonvulsant activity: IM: 3-4 hours; IV: 30 minutes Absorption: Oral: Slow and poor (approximately one-third absorbed) Distribution: Bone (50% to 60%); extracellular fluid (1% to 2%) (IOM 1997) Protein binding: 30%, to albumin Excretion: Urine (as magnesium); feces (as unabsorbed drug) Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Effects on Dental TreatmentKey adverse event(s) related to dental treatment: Magnesium products may prevent GI absorption of tetracyclines by forming a large ionized chelated molecule with the tetracyclines in the stomach. Tetracyclines should be given at least 1 hour before magnesium. Effects on BleedingNo information available to require special precautions Related Information Beers Criteria − Potentially Inappropriate Medications for Geriatrics Laxatives, Classification and Properties Index TermsEpsom Salts; MgSO4 (error-prone abbreviation)

Methergine

Methylergonovine (Lexi-Drugs) Pronunciation (meth il er goe NOE veen) Brand Names: USMethergine Brand Names: CanadaMethergine® Pharmacologic CategoryErgot Derivative Dosing: AdultPrevention of hemorrhage: Oral: 0.2 mg 3-4 times daily in the puerperium for up to 7 days (maximum duration: 1 week) IM, IV: 0.2 mg after delivery of anterior shoulder, after delivery of placenta, or during puerperium; may be repeated every 2-4 hours as needed. Note: IV administration should only be considered during life-threatening situations. * See Dosage and Administration in AHFS Essentials for additional information. Dosing: Renal ImpairmentNo dosage adjustment provided in manufacturer's labeling; use with caution. Dosing: Hepatic ImpairmentNo dosage adjustment provided in manufacturer's labeling; use with caution. Use: Labeled IndicationsManagement of uterine atony, hemorrhage and subinvolution of the uterus following delivery of the placenta; control of uterine hemorrhage following delivery of the anterior shoulder in the second stage of labor * See Uses in AHFS Essentials for additional information. Administration: IMMay be administered intramuscularly. Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Administration: IVAdminister over ≥60 seconds. Should not be routinely administered IV because of possibility of inducing sudden hypertension and cerebrovascular accident. IV administration should only be considered during life-threatening situations. Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Administration: Injectable DetailpH: 2.7-3.5 Administration: OralAvailable in tablets for oral administration. Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Storage/Stability Injection: Store under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light. The following stability information has also been reported: May be stored at room temperature for up to 14 days (Cohen, 2007). Tablet: Store below 25°C (77°F). CompatibilityStable in NS. Y-site administration: Compatible: Heparin, hydrocortisone sodium succinate, potassium chloride, vitamin B complex with C. Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience abdominal pain, nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), angina, arrhythmia, severe dizziness, passing out, shortness of breath, severe headache, vision changes, hematuria, seizures, hallucinations, leg cramps, tinnitus, or sweating a lot (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Medication Safety Issues Sound-alike/look-alike issues: Administration issues: ContraindicationsHypersensitivity to methylergonovine or any component of the formulation; hypertension; toxemia; pregnancy Warnings/Precautions Concerns related to adverse effects: • Coronary artery disease: Patients with coronary artery disease (CAD) or risk factors for CAD may be more likely to develop myocardial ischemia and infarction following methylergonovine-induced vasospasm. • Ergotism: Ergot alkaloid use may result in ergotism (intense vasoconstriction) resulting in peripheral vascular ischemia and possible gangrene. Ergotism is usually associated with overdosage or prolonged chronic use; do not exceed dosing guidelines and avoid prolonged administration. • Pleural/retroperitoneal fibrosis: Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily use of other ergot alkaloids. Disease-related concerns: • Hepatic impairment: Use with caution in patients with hepatic impairment. • Labor: Use with caution in the second stage of labor. • Renal impairment: Use with caution in patients with renal impairment. • Sepsis: Use with caution in patients with sepsis. • Vascular disease: Use with caution in patients with obliterative vascular disease. Concurrent drug therapy issues: • CYP3A4 inhibitors: Concomitant use with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics) and ergot alkaloids has been associated with acute ergot toxicity (ergotism); concurrent use of certain ergot alkaloids (eg, ergotamine and dihydroergotamine) are not recommended by the manufacturer. Special handling: • Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Other warnings/precautions: • IV administration: Not for routine IV administration due to risk of inducing sudden hypertensive and cerebrovascular accidents. IV administration should only be considered during life-threatening situations. • Medication errors: Inadvertent administration to newborns has been reported. * See Cautions in AHFS Essentials for additional information. Pregnancy Risk FactorC Pregnancy ConsiderationsAnimal reproduction studies have not been conducted. Methylergonovine is intended for use after delivery of the infant; use is contraindicated during pregnancy. Breast-Feeding ConsiderationsAt normal doses used to control postpartum uterine bleeding, small amounts are excreted in breast milk. In one study, ten women were given a single dose of methylergonovine 0.5 mg once lactation was established. Simultaneous maternal milk and plasma samples were taken 1 and 2 hours later. Maximum milk concentrations were 410-830 pg/mL, 2-3 hours after the dose and declined to 0.2 pg/mL (median) at 5 hours. The mean M/P ratios were 0.18 (at 1 hour) and 0.17 (at 2 hours) (Vogel, 2004). Methylergonovine may decrease breast milk production. Some manufacturers do not recommend breast-feeding during therapy or for 12 hours after the last dose due to adverse reactions reported in breast-feeding infants. Briggs' Drugs in Pregnancy & Lactation Methylergonovine Maleate Adverse ReactionsFrequency not defined. Cardiovascular: Angina pectoris, arterial spasm, atrioventricular block, bradycardia, cerebrovascular accident, chest pain, hypertension, hypotension, local thrombophlebitis, myocardial infarction, palpitations, paresthesia, tachycardia, vasospasm, ventricular fibrillation Central nervous system: Dizziness, hallucination, headache, seizure Dermatologic: Diaphoresis, skin rash Endocrine & metabolic: Water intoxication Gastrointestinal: Abdominal pain, diarrhea, nausea, unpleasant taste, vomiting Genitourinary: Hematuria Hypersensitivity: Anaphylaxis Neuromuscular & skeletal: Leg cramps Otic: Tinnitus Respiratory: Dyspnea, nasal congestion * See Cautions in AHFS Essentials for additional information. Allergy and Idiosyncratic Reactions Ergot Alkaloid Allergy Metabolism/Transport EffectsSubstrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential Drug Interactions Open Interactions Alpha-/Beta-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Risk X: Avoid combination Alpha1-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha1-Agonists. Risk X: Avoid combination Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy Antihepaciviral Combination Products: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination Anti-Parkinson Agents (Monoamine Oxidase Inhibitor): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity if selegiline or rasagiline is combined with a serotonin modulator. Use of transdermal selegiline with serotonin modulators is contraindicated. Risk D: Consider therapy modification Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Beta-Blockers: May enhance the vasoconstricting effect of Ergot Derivatives. Risk D: Consider therapy modification Boceprevir: May increase the serum concentration of Methylergonovine. Risk X: Avoid combination Cobicistat: May increase the serum concentration of Methylergonovine. Risk X: Avoid combination Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Risk X: Avoid combination Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Itraconazole: May increase the serum concentration of Methylergonovine. Risk X: Avoid combination Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Ketoconazole (Systemic): May increase the serum concentration of Methylergonovine. Risk X: Avoid combination Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Risk D: Consider therapy modification Lorcaserin: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Risk X: Avoid combination Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Macrolide Antibiotics: May increase the serum concentration of Ergot Derivatives. Cabergoline and Clarithromycin may interact, see specific monograph for full details. Exceptions: Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk X: Avoid combination Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Risk C: Monitor therapy MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification Netupitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Nitroglycerin: Ergot Derivatives may diminish the vasodilatory effect of Nitroglycerin. This is of particular concern in patients being treated for angina. Nitroglycerin may increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Posaconazole: May increase the serum concentration of Methylergonovine. Risk X: Avoid combination Protease Inhibitors: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination Reboxetine: May enhance the hypertensive effect of Ergot Derivatives. Risk C: Monitor therapy Roxithromycin: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination Serotonin 5-HT1D Receptor Agonists: Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Risk C: Monitor therapy Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy Telaprevir: May increase the serum concentration of Methylergonovine. Risk X: Avoid combination TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy Voriconazole: May increase the serum concentration of Methylergonovine. Risk X: Avoid combination Genes of Interest Cytochrome P450, Family 3, Subfamily A, Polypeptide 4 Monitoring ParametersBlood pressure Nursing: Physical Assessment/MonitoringBlood pressure, CNS status, and vaginal bleeding should be monitored on a regular basis. Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. Solution, Injection, as maleate: Generic: 0.2 mg/mL (1 mL) Solution, Injection, as maleate [preservative free]: Generic: 0.2 mg/mL (1 mL) Tablet, Oral, as maleate: Methergine: 0.2 mg [contains methylparaben, propylparaben] Generic: 0.2 mg Anatomic Therapeutic Chemical (ATC) Classification G02AB01 Generic Available (US)Yes Pricing: US Solution (Methylergonovine Maleate Injection) 0.2 mg/mL (1 mL): $8.58 Tablets (Methergine Oral) 0.2 mg (12): $676.80 Tablets (Methylergonovine Maleate Oral) 0.2 mg (28): $758.80 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of ActionIncreases the tone, rate and amplitude of contractions on the smooth muscles of the uterus, producing sustained contractions which shortens the third stage of labor and reduces blood loss. Pharmacodynamics/Kinetics Onset of action: Oxytocic: Oral: 5-10 minutes; IM: 2-5 minutes; IV: Immediately Duration: Oral: ~3 hours; IM: ~3 hours; IV: 45 minutes Absorption: Rapid Distribution: Vd: 39-73 L Metabolism: Hepatic Bioavailability: Oral: 60%; IM: 78% Half-life elimination: ~3 hours (range: 1.5-12.7 hours) Time to peak, serum: Oral: 0.3-2 hours; IM: 0.2-0.6 hours Excretion: Urine and feces Local Anesthetic/Vasoconstrictor PrecautionsUse vasoconstrictor with caution in patients taking methylergonovine; this ergot alkaloid derivative causes constriction of peripheral blood vessels Effects on Dental TreatmentNo significant effects or complications reported Effects on BleedingThrombosis has been reported; however, there are no special precautions associated with bleeding related to dental procedures. Related Information Safe Handling of Hazardous Drugs Index TermsMethylergometrine Maleate; Methylergonovine Maleate

Misoprostol

MiSOPROStol (Lexi-Drugs) ALERT: US Boxed Warning Women of childbearing potential: Pronunciation (mye soe PROST ole) Brand Names: USCytotec Brand Names: CanadaNovo-Misoprostol; PMS-Misoprostol Pharmacologic CategoryProstaglandin Dosing: Adult NSAID-induced gastric ulcers, prevention: Oral: 200 mcg 4 times daily with food; if not tolerated, may decrease dose to 100 mcg 4 times daily with food; last dose of the day should be taken at bedtime Termination of intrauterine pregnancy: Oral: Refer to Mifepristone monograph. Early pregnancy loss (off-label use): Intravaginal (off-label route): Initial dose: 800 mcg. May repeat with one dose if needed, ≥3 hours after the first dose and typically within 7 days if no response to the initial dose is observed (ACOG 150, 2015). Incomplete abortion (treatment) (off-label use): Oral: 600 mcg as a single dose (ACOG 427, 2009) Labor induction or cervical ripening (off-label uses): Intravaginal (off-label route): 25 mcg (1/4of 100 mcg tablet); may repeat at intervals no more frequent than every 3 to 6 hours (ACOG 107, 2009). Missed abortion (treatment) (off-label use): Intravaginal (off-label route): 800 mcg; may repeat every 3 hours for 2 additional doses if needed (ACOG 427, 2009). Sublingual (off-label route): 600 mcg; may repeat every 3 hours for 2 additional doses if needed (ACOG 427, 2009). Postpartum hemorrhage (prevention) (off-label use): Oral: 600 mcg as a single dose administered immediately after delivery (FIGO, 2012a). Postpartum hemorrhage (treatment) (off-label use): Rectal (off-label route): 800 to 1000 mcg (ACOG 76, 2006). Sublingual (off-label route): 800 mcg as a single dose. Use caution if a prophylactic dose was already given, especially if adverse events were observed (FIGO, 2012b). * See Dosage and Administration in AHFS Essentials for additional information. Dosing: GeriatricNSAID-induced gastric ulcers, prevention: Refer to adult dosing. Dosing: PediatricTermination of intrauterine pregnancy: Oral: Refer to adult dosing. Dosing: Renal ImpairmentDose adjustment is not routinely needed; however, the dose may be reduced if the recommended dose is not tolerated. It is not known if misoprostol is removed by dialysis. Dosing: Hepatic ImpairmentNo dosage adjustment provided in manufacturer's labeling. Use: Labeled Indications NSAID-induced gastric ulcers: Prevention of NSAID-induced gastric ulcers Termination of intrauterine pregnancy: Medical termination of intrauterine pregnancy through 70 days' gestation in combination with mifepristone (Mifeprex prescribing information March 2016) * See Uses in AHFS Essentials for additional information. Use: Off-Label Cervical ripening and labor inductionLevel of Evidence [G] Based on the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 107: Induction of Labor, misoprostol given for cervical ripening and labor induction is effective and recommended in the management of this condition (ACOG 107, 2009). Early pregnancy lossLevel of Evidence [G] Based on the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 150: Early Pregnancy Loss, misoprostol given for early pregnancy loss is effective and recommended for patients who desire to shorten the time to complete expulsion and prefer to avoid surgical evacuation (ACOG 150, 2015). Incomplete or missed abortion (treatment)Level of Evidence [G] Based on the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 427: Misoprostol for Postabortion Care, misoprostol given for treatment of incomplete or missed abortion in women <12 weeks gestation is effective and recommended in the management of this condition (ACOG 427, 2009). Postpartum hemorrhage (prevention/treatment)Level of Evidence [G] Based on the International Federation of Gynecology and Obstetrics (FIGO) Prevention of Postpartum Hemorrhage With Misoprostol guidelines and the FIGO Treatment of Postpartum Hemorrhage With Misoprostol guidelines, misoprostol given for the prevention and treatment of postpartum hemorrhage is effective and recommended in the management of this condition (FIGO, 2012a; FIGO, 2012b). Level of Evidence Definitions Level of Evidence Scale Administration: Oral Incidence of diarrhea may be lessened by having patient take dose right after meals and avoiding magnesium-containing antacids. When used for the prevention of NSAID-induced ulcers, therapy is usually begun on the second or third day of the next normal menstrual period in women of childbearing potential. Termination of intrauterine pregnancy: Refer to Mifepristone monograph. Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Dietary ConsiderationsWhen used for the prevention of NSAID-induced ulcers, take with food. Storage/StabilityStore at or below 25°C (77°F). Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience abdominal cramps. Have patient report immediately to prescriber severe nausea, vomiting, severe abdominal pain, or severe diarrhea (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Medication Safety Issues Sound-alike/look-alike issues: Contraindications Hypersensitivity to misoprostol, other prostaglandins, or any component of the formulation When used for NSAID-induced gastric ulcer prevention (additional contraindications): Pregnancy When used for termination of intrauterine pregnancy (additional contraindications): Refer to Mifepristone monograph. Warnings/Precautions Concerns related to adverse effects: • Abortifacient: [US Boxed Warning]: Due to the abortifacient property of this medication, patients must be warned not to give this drug to others. Disease-related concerns: • Cardiovascular disease: Use with caution in patients with cardiovascular disease. • Renal impairment: Use with caution in patients with renal impairment. Special populations: • Elderly: Use with caution in the elderly. • Pregnancy: Adverse events have been reported when used outside of current product labeling (cervical ripening, induction of labor, postpartum hemorrhage). Uterine tachysystole may occur and progress to uterine tetany; uteroplacental blood flow may be impaired and uterine rupture or amniotic fluid embolism may occur. The risk of uterine rupture may be increased with advanced gestational age, grand multiparity, or prior uterine surgery. Uterine activity and fetal status should be monitored in a hospital setting. Misoprostol should not be used in situations where uterotonic drugs are otherwise contraindicated or inappropriate. • Women of childbearing potential: [US Boxed Warning]: Use of misoprostol during pregnancy may cause abortion, birth defects, or premature birth. Uterine rupture has been reported when used to induce labor after the eighth week of pregnancy. Misoprostol is not to be used to reduce NSAID-induced ulcers in a woman of childbearing potential unless she is capable of complying with effective contraceptive measures and is at high risk of developing gastric ulcers and/or their complications. If needed, the patient must have a negative pregnancy test within 2 weeks of starting therapy, she must use effective contraception during treatment, and therapy should begin on the second or third day of next normal menstrual period. Written and verbal warnings concerning the hazards of misoprostol should be provided. Concurrent drug therapy issues: • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special handling: • Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Other warnings/precautions: • Appropriate use: Termination of pregnancy: Misoprostol is approved for use with mifepristone for termination of pregnancy. Refer to mifepristone warnings, precautions, and contraindications for appropriate use of misoprostol for this indication. • Appropriate use: Ulcers: For use only in patients at high risk of complications from gastric ulcers (eg, elderly patients, patients with concomitant diseases) or patients at high risk for developing gastric ulcers (eg, those with a history of ulcers) taking NSAIDs. Misoprostol must be taken during the duration of NSAID therapy. It is not effective in preventing duodenal ulcers in patients taking NSAIDs. * See Cautions in AHFS Essentials for additional information. Geriatric ConsiderationsElderly, due to extensive use of NSAIDs and the high percentage of asymptomatic hemorrhage and perforation from NSAIDs, are at risk for NSAID-induced ulcers and may be candidates for misoprostol use. However, routine use for prophylaxis is not justified. Patients must be selected upon demonstration that they are at risk for NSAID-induced lesions. Misoprostol should not be used as a first-line therapy for gastric or duodenal ulcers. Pregnancy Risk FactorX Pregnancy ConsiderationsUse for the prevention of NSAID-induced gastric ulcers is contraindicated in pregnant women. [US Boxed Warning]: Use of misoprostol during pregnancy may cause abortion, birth defects, or premature birth. Uterine rupture has been reported when used to induce labor after the eighth week of pregnancy. Misoprostol is not to be used to reduce NSAID-induced ulcers in a woman of childbearing potential unless she is capable of complying with effective contraceptive measures and is at high risk of developing gastric ulcers and/or their complications. If needed, the patient must have a negative pregnancy test within 2 weeks of starting therapy, she must use effective contraception during treatment, and therapy should begin on the second or third day of next normal menstrual period. Written and verbal warnings concerning the hazards of misoprostol should be provided. Due to the abortifacient property of this medication, patients must be warned not to give this drug to others. Congenital anomalies following first trimester exposure have been reported, including skull defects, cranial nerve palsies, facial malformations, and limb defects. Misoprostol may produce uterine contractions; fetal death, uterine perforation, and abortion may occur. Misoprostol is FDA approved for the medical termination of pregnancy of ≤70 days in conjunction with mifepristone. Because misoprostol may induce or augment uterine contractions, it has been used off-label as a cervical-ripening agent for induction of labor. Misoprostol should not be used for this purpose during the third trimester in women who have had a prior cesarean delivery or major uterine surgery because the risk of uterine rupture is increased (ACOG 107, 2009; ACOG 115, 2010). It has also been used for the treatment of incomplete or missed abortion (ACOG 427, 2009), early pregnancy loss (ACOG 150, 2015), or severe postpartum hemorrhage (ACOG 76, 2006; FIGO, 2012a; FIGO, 2012b). Some guidelines recommend misoprostol for postpartum hemorrhage only secondary to oxytocin in situations where oxytocin is not available (Leduc, 2000; FIGO, 2012a; FIGO, 2012b). Various routes of administration have been used for postpartum hemorrhage. Sublingual administration has the most rapid onset, the oral route produces the most pronounced initial increase in tonus, and rectal and vaginal routes exhibit longer durations of action as compared to oral and sublingual routes (Leduc, 2009). Adverse events associated with off-label obstetric uses include uterine tachysystole (may impair placental blood flow), uterine rupture, amniotic fluid embolism, or adverse fetal heart changes. Breast-Feeding ConsiderationsMisoprostol acid (the active metabolite of misoprostol) has been detected in breast milk. Concentrations following a single oral dose were 7.6 to 20.9 pg/mL after 1 hour and decreased to <1 pg/mL by 5 hours. Adverse events have not been reported in nursing infants (FIGO, 2012a; FIGO, 2012b). The manufacturer recommends that caution be used if administered to a nursing woman. Briggs' Drugs in Pregnancy & Lactation Misoprostol Adverse Reactions >10%: Gastrointestinal: Diarrhea, abdominal pain 1% to 10%: Central nervous system: Headache Gastrointestinal: Constipation, dyspepsia, flatulence, nausea, vomiting <1%: Gynecological disorders (cramps, dysmenorrhea, hypermenorrhea, spotting, postmenopausal vaginal bleeding, and other menstrual disorders) Postmarketing and/or case reports: Abnormal taste, abnormal vision, alkaline phosphatase increased, alopecia, anaphylaxis, anemia, amylase increase, anxiety, appetite changes, arrhythmia, arterial thrombosis, arthralgia, back pain, breast pain, bronchitis, bronchospasm, cardiac enzymes increased, chest pain, chills, confusion, conjunctivitis, CVA, deafness, depression, dermatitis, diaphoresis, dizziness, drowsiness, dysphagia, dyspnea, dysuria, earache, edema, epistaxis, ESR increased, fatigue, fetal or infant death (when used during pregnancy), fever, GI bleeding, GI inflammation, gingivitis, glycosuria, gout, hematuria, hepatobiliary function abnormal, hyper-/hypotension, impotence, loss of libido, MI, muscle cramps, myalgia, neuropathy, neurosis, nitrogen increased, pallor, phlebitis, pneumonia, polyuria, pulmonary embolism, purpura, rash, reflux, rigors, stiffness, syncope, thirst, thrombocytopenia, tinnitus, upper respiratory tract infection, urinary tract infection, uterine rupture, weakness, weight changes * See Cautions in AHFS Essentials for additional information. Metabolism/Transport EffectsNone known. Drug Interactions Open Interactions Antacids: May enhance the adverse/toxic effect of MiSOPROStol. More specifically, concomitant use with magnesium-containing antacids may increase the risk of diarrhea. Management: Avoid concomitant use of misoprostol and magnesium-containing antacids. In patients requiring antacid therapy, employ magnesium-free preparations. Monitor for increased adverse effects (e.g., diarrhea, dehydration). Exceptions: Aluminum Hydroxide; Calcium Carbonate; Sodium Bicarbonate. Risk X: Avoid combination Carbetocin: MiSOPROStol may enhance the adverse/toxic effect of Carbetocin. Specifically, Carbetocin oxytocic effects may be enhanced. Risk X: Avoid combination Oxytocin: MiSOPROStol may enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: The manufacturer of misoprostol recommends avoiding concomitant use with oxytocin. Misoprostol may augment effects of oxytocin, particularly when given within 4 hours of oxytocin initiation. Risk D: Consider therapy modification Food InteractionsMisoprostol peak serum concentrations may be decreased if taken with food (not clinically significant). Monitoring Parameters Prevention of NSAID-induced gastric ulcers: Pregnancy test in women of reproductive potential prior to therapy; adequate diagnostic measures in all cases of undiagnosed abnormal vaginal bleeding Off-label pregnancy-related uses: Uterine activity and fetal status. When used for incomplete or missed abortion, reevaluate 1 to 2 weeks after dosing (ACOG 427, 2009). When used for termination of pregnancy: Prior to procedure, confirm pregnancy and Rh status; assess hemoglobin and hematocrit if anemia is suspected (ACOG 2014). Following procedure: Clinical exam, human Chorionic Gonadotropin (hCG) testing, and/or ultrasound to confirm complete termination of pregnancy; hemoglobin, hematocrit, and red blood cell count in cases of heavy bleeding. Consider CBC in any patient who reports nausea, vomiting, or diarrhea and weakness with or without abdominal pain, and without fever or other signs of infection more than 24 hours after administration of misoprostol (Mifeprex prescribing information March 2016). Nursing: Physical Assessment/MonitoringTeach appropriate diet and lifestyle if being used to prevent ulcers. Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. Tablet, Oral: Cytotec: 100 mcg Cytotec: 200 mcg [scored] Generic: 100 mcg, 200 mcg Anatomic Therapeutic Chemical (ATC) Classification A02BB01 G02AD06 Generic Available (US)Yes Pricing: US Tablets (Cytotec Oral) 100 mcg (100): $363.54 200 mcg (100): $504.72 Tablets (MiSOPROStol Oral) 100 mcg (60): $49.45 200 mcg (100): $119.95 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of ActionMisoprostol is a synthetic prostaglandin E1 analog that replaces the protective prostaglandins consumed with prostaglandin-inhibiting therapies (eg, NSAIDs); has been shown to induce uterine contractions Pharmacodynamics/Kinetics Onset of action: Inhibition of gastric acid secretion: 30 minutes; peak effect: 60 to 90 minutes Duration of action: Inhibition of gastric acid secretion: 3 hours Absorption: Rapid and extensive Protein binding: Misoprostol acid: 80% to 90% Metabolism: Hepatic; rapidly de-esterified to misoprostol acid (active) Bioavailability: 88% Half-life elimination: Misoprostol acid: 20 to 40 minutes Time to peak, serum: Misoprostol acid: Fasting: 14 ± 8 minutes Excretion: Urine (80%) Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Effects on Dental TreatmentNo significant effects or complications reported Effects on BleedingNo information available to require special precautions Related Information Safe Handling of Hazardous Drugs

Nifedipine

NIFEdipine (Lexi-Drugs) Pronunciation (nye FED i peen) Brand Names: USAdalat CC; Afeditab CR; Nifediac CC [DSC]; Nifedical XL; Procardia; Procardia XL Brand Names: CanadaAdalat XL; Apo-Nifed PA; Mylan-Nifedipine Extended Release; Nifedipine ER; PMS-Nifedipine; PMS-Nifedipine ER Pharmacologic CategoryAntianginal Agent; Antihypertensive; Calcium Channel Blocker; Calcium Channel Blocker, Dihydropyridine Dosing: AdultDosage adjustments should occur at 7- to 14-day intervals to allow for adequate assessment of new dose; however, if clinically indicated, titration may be done more rapidly with appropriate monitoring; when switching from immediate-release to sustained-release formulations, use same total daily dose. Chronic stable or vasospastic angina: Oral: Immediate release: Initial: 10 mg 3 times daily; usual dose: 10 to 20 mg 3 times daily; coronary artery spasm may require up to 20 to 30 mg 3 to 4 times daily; single doses >30 mg and total daily doses >120 mg are rarely needed; maximum: 180 mg daily (U.S. labeling) or 120 mg daily (Canadian labeling); Note: Do not use for acute anginal episodes; may precipitate myocardial infarction Extended release: US labeling: Initial: 30 or 60 mg once daily; titrate as clinically indicated. Doses >90 mg daily should be used with caution and only if necessary (maximum: 120 mg daily) Canadian labeling: Initial: 30 mg once daily; titrate as clinically indicated (maximum dose: 90 mg daily) Hypertension: Oral: Extended release: U.S. labeling: Initial: 30 or 60 mg once daily; usual dosage range (ASH/ISH [Weber, 2014]): 30 to 90 mg daily; maximum: 90 to 120 mg daily Canadian labeling: Initial: 20 or 30 mg once daily; usual maintenance: 30 to 60 mg once daily (maximum: 90 mg daily) Hypertension emergency in pregnancy (systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) (off-label dose): Oral: Immediate release: 10 mg; may repeat with a 20 mg dose in 20 minutes if needed. Also refer to administration protocols developed by the American College of Obstetricians and Gynecologists (ACOG, 2015). High altitude pulmonary edema (off-label use; Luks, 2010): Oral: Prevention: Extended release: 30 mg every 12 hours starting the day before ascent and may be discontinued after staying at the same elevation for 5 days or if descent initiated Treatment: Extended release: 30 mg every 12 hours Pulmonary hypertension (off-label use; Galie, 2004): Oral: Extended release: Initial: 30 mg twice daily; may increase cautiously to 120 to 240 mg daily Raynaud's phenomenon (off-label use; Wigley, 2002): Oral: Extended release: Dosage range: 30 to 120 mg once daily * See Dosage and Administration in AHFS Essentials for additional information. Dosing: GeriatricRefer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Aronow, 2011). Dosing: Pediatric High altitude pulmonary edema (off-label use; Pollard, 2001): Oral: Note: Treatment with NIFEdipine is only necessary if response to oxygen and/or descent is unsatisfactory; extended release preparation is preferred, but with proper dose and frequency adjustment: Immediate release: 0.5 mg/kg/dose (maximum: 20 mg/dose) every 8 hours Hypertension (off-label use): Oral: Children 1 to 17 years: Extended release tablet: Initial: 0.2 to 0.5 mg/kg/day once daily or in 2 divided doses; maximum: 3 mg/kg/day up to 120 mg daily Dosing: Renal ImpairmentThere are no dosage adjustments provided in manufacturer's labeling (has not been studied); the pharmacokinetics of nifedipine are not significantly influenced by the degree of renal impairment (only trace amounts of unchanged drug are found in urine). Hemodialysis: Supplemental dose is not necessary. Peritoneal dialysis effects: Supplemental dose is not necessary. Dosing: Hepatic ImpairmentThere are no dosage adjustments provided in manufacturer's labeling (has not been studied); use with caution. Clearance of nifedipine is reduced in cirrhotic patients, which may lead to increased systemic exposure; monitor closely for adverse effects/toxicity and consider dose adjustments. Use: Labeled Indications Management of chronic stable or vasospastic angina; treatment of hypertension (sustained release products only) The 2014 guideline for the management of high blood pressure in adults (JNC 8) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients (JNC 8 [James, 2013]): • Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg. • Patients <60 years of age with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg. • Patients ≥18 years of age with diabetes with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg. • Patients ≥18 years of age with chronic kidney disease (CKD) with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg. In patients with chronic kidney disease (CKD), regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB. * See Uses in AHFS Essentials for additional information. Use: Off-Label Hypertensive emergency in pregnancy Level of Evidence [G] Based on the American College of Obstetricians and Gynecologists (ACOG) guidelines on the management of hypertension in pregnancy, the use of nifedipine is effective and recommended as a treatment option in pregnant and postpartum patients who are experiencing acute onset, severe hypertension with preeclampsia or eclampsia (ACOG, 2015). Preterm laborLevel of Evidence [G] Based on the American College of Obstetricians and Gynecologists (ACOG) guidelines for the management of preterm labor, nifedipine is an effective and recommended treatment option for the management of preterm labor to prolong pregnancy and allow for the administration of antenatal steroids (ACOG, 2012). Raynaud phenomenonLevel of Evidence [A] Data from a randomized, double-blind, controlled clinical trial in patients with primary Raynaud phenomenon supports the use of nifedipine for the treatment of this condition (Raynaud's Treatment Study Investigators, 2000). Clinical experience also suggests the utility of nifedipine for the treatment of this condition (Wigley, 2002; Goundry, 2012). For women who are breast-feeding experiencing Raynaud's phenomenon of the nipple, data from a limited number of patients studied (case report and case series) suggest that nifedipine may also be used to treat Raynaud's phenomenon of the nipple (Barrett, 2013; Wu 2012). Ureteral calculi (distal)Level of Evidence [A, G] Use of nifedipine for treating distal ureteral calculi (less than 10 mm) is supported by US and European guidelines and by data from controlled trials. Nifedipine has been shown to improve stone expulsion when compared with patients not receiving medical expulsion therapy; however, it is not as effective as tamsulosin when measured by expulsion rates, mean time to expulsion, or use of adjunctive analgesics. Access Full Off-Label Monograph Additional Off-Label Uses High altitude pulmonary edema (prevention and treatment); Pulmonary hypertension Level of Evidence Definitions Level of Evidence Scale Clinical Practice Guidelines Altitude Illness: International Society for Mountain Medicine (ISMM), "Children at High Altitude: An International Consensus Statement by an Ad Hoc Committee of the International Society for Mountain Medicine," March 12, 2001 Wilderness Medical Society (WMS), "Wilderness Medical Society Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness," June 2010 Heart Failure: ACCF/AHA, "2013 ACCF/AHA Guideline for the Management of Heart Failure," June 2013 Hypertension: "ACCF/AHA Expert Consensus Document on Hypertension in the Elderly," 2011 AHA/ACC/CDC, "AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control" November 2013 ASH/ISH "Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension," January 2014 Eighth Joint National Committee (JNC 8), "2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults," December 2013 "Medical Therapy for Pulmonary Hypertension: Updated ACCP Evidence-Based Clinical Practice Guidelines," June 2007 "National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents," May 2005 Ischemic Heart Disease: ACC/AHA/AATS/PCNA/SCAI/STS, "2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease," July 2014 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS, "2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease," November 2012 Valvular Heart Disease: AHA/ACC, "2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease," March 2014 Administration: Oral Immediate release: In general, may be administered with or without food. Extended release: Tablets should be swallowed whole; do not crush, split, or chew. Adalat CC, Afeditab CR, Nifediac CC: Administer on an empty stomach (per manufacturer). Other extended release products may not have this recommendation; consult product labeling. Dietary ConsiderationsAvoid grapefruit juice with all products. Immediate release: Capsule is rapidly absorbed orally if it is administered without food, but may result in vasodilator side effects; if flushing is problematic, administration with low-fat meals may decrease. In general, can take with or without food. Extended release: Adalat CC, Afeditab CR, Nifediac CC: Take on an empty stomach (manufacturer's labeling). Other extended release products may not have this recommendation; consult product labeling. Storage/Stability Adalat CC, Afeditab CR, Procardia XL: Store below 30°C (86°F); protect from light and moisture. Nifediac CC, Nifedical XL: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); protect from light and moisture. Immediate release capsules (Procardia): Store at 15°C to 25°C (59°F to 77°F); prevent capsules from freezing; protect from light and moisture. Extemporaneously PreparedA 4 mg/mL oral suspension may be made with liquid capsules (Note: Concentration inside capsule may vary depending on manufacturer. Procardia: 10 mg capsule contains a concentration of 10 mg/0.34 mL [29.4 mg/mL]). Puncture the top of twelve 10 mg liquid capsules with one needle to create a vent. Insert a second needle attached to a syringe and extract the liquid; transfer to a calibrated bottle and add sufficient quantity of a 1:1 mixture of Ora-Sweet and Ora-Plus to make 30 mL. Label "shake well". Stable 90 days under refrigeration or at room temperature. Nahata MC, Morosco RS, and Willhite EA, "Stability of Nifedipine in Two Oral Suspensions Stored at Two Temperatures," J Am Pharm Assoc, 2002, 42(6):865-7. Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand? • Patient may experience headache, flushing, heartburn, nausea, loss of strength and energy, anxiety, or tablet shell in stool. Have patient report immediately to prescriber severe dizziness; passing out; arrhythmia; mood changes; shortness of breath; excessive weight gain; swelling of arms or legs; muscle pain; muscle cramps; tremors; severe abdominal pain; black, tarry, or bloody stools; or vomiting blood (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Medication Safety Issues Sound-alike/look-alike issues: Geriatric Patients: High-Risk Medication: International issues: Contraindications Hypersensitivity to nifedipine or any component of the formulation; concomitant use with strong CYP3A4 inducers (eg, rifampin); cardiogenic shock Note: Considered contraindicated in patients with ST-elevation myocardial infarction (STEMI) (ACCF/AHA [O'Gara, 2013]). Canadian labeling: Additional contraindications (not in U.S. labeling): Severe hypotension; patients with a Kock pouch (ileostomy after proctocolectomy; extended release tablets only); breast-feeding; pregnancy or women of childbearing potential. Note: SOGC and ACOG guidelines recommend nifedipine as a preferred agent for maternal hypertension (ACOG, 2013; SOGC [Magee, 2014]). Warnings/Precautions Concerns related to adverse effects: • Angina/MI: Increased angina and/or MI have occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade. In patients with unstable angina/non-STEMI, the use of immediate-release nifedipine is not recommended except with concomitant beta-blockade (ACCF/AHA [Anderson, 2013]). • Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. The use of immediate release nifedipine (sublingually or orally) in hypertensive emergencies and urgencies is neither safe nor effective. Serious adverse events (eg, death, cerebrovascular ischemia, syncope, stroke, acute myocardial infarction, and fetal distress) have been reported. Immediate release nifedipine should not be used for acute blood pressure reduction. • Peripheral edema: The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy. Disease-related concerns: • Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in myocardial ischemia. • Gastrointestinal strictures: Alterations in gastrointestinal anatomy (eg, severe gastrointestinal narrowing, history of GI cancer, obstruction, bowel resection, gastric bypass, vertical banded gastroplasty) and underlying hypomotility disorders have led to bezoar formation with extended release forms. • Heart failure (HF): The ACCF/AHA heart failure guidelines recommend to avoid use in patients with heart failure due to lack of benefit and/or worse outcomes with calcium channel blockers in general (Yancy, 2013). • Hepatic impairment: Use with caution in patients with hepatic impairment. Clearance of nifedipine is reduced in cirrhotic patients leading to increased systemic exposure; monitor closely for adverse effects/toxicity and consider dose adjustments. • Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition. Concurrent drug therapy issues: • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues: • Extended release formulation: Consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract (eg, severe gastrointestinal narrowing, colon cancer, obstruction, bowel resection, gastric bypass, vertical banded gastroplasty) has been associated with symptoms of obstruction (pharmacobezoar). • Immediate release formulation: Immediate release formulations should not be used to manage primary hypertension, adequate studies to evaluate outcomes have not been conducted. • Lactose: Adalat CC tablets contain lactose; do not use with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndromes. Other warnings/precautions: • Surgery: Use with caution before major surgery. Cardiopulmonary bypass, intraoperative blood loss or vasodilating anesthesia may result in severe hypotension and/or increased fluid requirements. Consider withdrawing nifedipine (>36 hours) before surgery if possible. • Withdrawal: Abrupt withdrawal may cause rebound angina in patients with CAD. * See Cautions in AHFS Essentials for additional information. Geriatric ConsiderationsElderly may experience a greater hypotensive response. Theoretically, constipation may be more of a problem in elderly patients. The half-life of nifedipine is extended in elderly patients (6.7 hours) as compared to younger subjects (3.8 hours). Pregnancy Risk FactorC Pregnancy ConsiderationsAdverse events were observed in animal reproduction studies. Nifedipine crosses the placenta and small amounts can be detected in the urine of newborn infants (Manninen, 1991; Silberschmidt, 2008). An increase in perinatal asphyxia, cesarean delivery, prematurity, and intrauterine growth retardation have been reported following maternal use. Untreated chronic maternal hypertension is also associated with adverse events in the fetus, infant, and mother. If treatment for chronic hypertension during pregnancy is needed, nifedipine is one of the preferred agents (ACOG, 2013; SOGC [Magee, 2014]). Nifedipine is also recommended for the management of acute onset, severe hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) with preeclampsia or eclampsia in pregnant and postpartum women (ACOG, 2015; Magee, 2014). Nifedipine has also been evaluated for the treatment of preterm labor. Tocolytics may be used for the short-term (48 hour) prolongation of pregnancy to allow for the administration of antenatal steroids and should not be used prior to fetal viability or when the risks of use to the fetus or mother are greater than the risk of preterm birth (ACOG, 2012). Nifedipine is ineffective for maintenance tocolytic therapy (ACOG, 2012; Roos, 2013). Breast-Feeding ConsiderationsNifedipine is excreted into breast milk. Reported concentrations are low and similar to those in the maternal serum (Ehrenkranz, 1989; Manninen, 1991; Penny, 1989). Breast-feeding is not recommended by the U.S. manufacturer (Canadian labeling contraindicates use). Nifedipine has been used for the treatment of Raynaud's phenomenon of the nipple in breast-feeding mothers (Barrett, 2013; Wu, 2012). Briggs' Drugs in Pregnancy & Lactation Nifedipine Adverse Reactions >10%: Cardiovascular: Flushing (10% to 25%; extended release products 3% to 4%), peripheral edema (dose related 7% to 30%) Central nervous system: Dizziness/lightheadedness/giddiness (10% to 27%), headache (10% to 23%) Gastrointestinal: Nausea/heartburn (10% to 11%) ≥1% to 10%: Cardiovascular: Palpitation (≤2% to 7%), transient hypotension (dose related 5%), CHF (2%) Central nervous system: Nervousness/mood changes (≤2% to 7%), fatigue (6%), shakiness (≤2%), jitteriness (≤2%), sleep disturbances (≤2%), difficulties in balance (≤2%), fever (≤2%), chills (≤2%) Dermatologic: Dermatitis (≤2%), pruritus (≤2%), urticaria (≤2%) Endocrine & metabolic: Sexual difficulties (≤2%) Gastrointestinal: Diarrhea (≤2%), constipation (≤2%), cramps (≤2%), flatulence (≤2%), gingival hyperplasia (≤10%) Neuromuscular & skeletal: Muscle cramps/tremor (≤2% to 8%), weakness (<3%), inflammation (≤2%), joint stiffness (≤2%) Ocular: Blurred vision (≤2%) Respiratory: Cough/wheezing (6%), nasal congestion/sore throat (≤2% to 6%), chest congestion (≤2%), dyspnea (≤2%) Miscellaneous: Diaphoresis (≤2%) <1%, postmarketing, and/or case reports: Agranulocytosis, allergic hepatitis, alopecia, anemia, aplastic anemia, angina, angioedema, arrhythmia, arthritis with positive ANA, bezoars (Procardia XL®), cerebral ischemia, depression, dysosmia, epistaxis, EPS, erectile dysfunction, erythema multiforme, erythromelalgia, exanthematous pustulosis, exfoliative dermatitis, facial edema, gastroesophageal reflux, gastrointestinal obstruction (Procardia XL®), gastrointestinal ulceration (Procardia XL®), gynecomastia, hematuria, ischemia, leukopenia, lip cancer (Friedman, 2012), memory dysfunction, migraine, myalgia, myoclonus, nocturia, paranoid syndrome, parotitis, periorbital edema, photosensitivity, polyuria, purpura, Stevens-Johnson syndrome, syncope, tachycardia, taste perversion, thrombocytopenia, tinnitus, toxic epidermal necrolysis, transient blindness, ventricular arrhythmia Reported with use of sublingual short-acting nifedipine: Cerebrovascular ischemia, syncope, heart block, stroke, sinus arrest, severe hypotension, acute MI, ECG changes, and fetal distress * See Cautions in AHFS Essentials for additional information. Allergy and Idiosyncratic Reactions Aniline Dye Allergy Calcium Channel Blocker, Dihydropyridine Allergy Toxicology Calcium Channel Blockers Metabolism/Transport EffectsSubstrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP, CYP1A2 (weak), CYP2C9 (weak) Drug Interactions Open Interactions Alcohol (Ethyl): May increase the serum concentration of NIFEdipine. Risk C: Monitor therapy Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. Risk D: Consider therapy modification Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Risk C: Monitor therapy Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Beta-Blockers: NIFEdipine may enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Risk C: Monitor therapy Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Risk D: Consider therapy modification Cisapride: May increase the serum concentration of NIFEdipine. Reported with sustained release nifedipine product. Risk C: Monitor therapy Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy CYP3A4 Inducers (Strong): May decrease the serum concentration of NIFEdipine. Risk X: Avoid combination CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Digoxin: NIFEdipine may increase the serum concentration of Digoxin. Risk C: Monitor therapy DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy FLUoxetine: May enhance the adverse/toxic effect of NIFEdipine. Risk C: Monitor therapy Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Grapefruit Juice: May increase the serum concentration of NIFEdipine. Risk X: Avoid combination Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Risk C: Monitor therapy Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Risk D: Consider therapy modification Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Netupitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Phenytoin: NIFEdipine may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of NIFEdipine. Risk X: Avoid combination Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy St John's Wort: May decrease the serum concentration of NIFEdipine. Risk X: Avoid combination Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy VinCRIStine: NIFEdipine may increase the serum concentration of VinCRIStine. Risk C: Monitor therapy VinCRIStine (Liposomal): NIFEdipine may increase the serum concentration of VinCRIStine (Liposomal). Risk C: Monitor therapy Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy Food InteractionsNifedipine serum levels may be decreased if taken with food. Food may decrease the rate but not the extent of absorption of Procardia XL®. Increased nifedipine concentrations resulting in therapeutic and vasodilator side effects, including severe hypotension and myocardial ischemia, may occur if nifedipine is taken by patients ingesting grapefruit. Management: Avoid grapefruit/grapefruit juice. Genes of Interest ATP-Binding Cassette, Sub-Family B (MDR/TAP), Member 1 Cytochrome P450, Family 3, Subfamily A, Polypeptide 4 Monitoring ParametersHeart rate, blood pressure, signs and symptoms of CHF, peripheral edema Nursing: Physical Assessment/MonitoringUse caution in presence of obstructive coronary disease (aortic stenosis), severe hepatic impairment, or heart failure. Monitor for hypotension, peripheral edema, and constipation when starting, adjusting dose, or discontinuing. Teach patient orthostatic precautions. Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product Capsule, Oral: Procardia: 10 mg Generic: 10 mg, 20 mg Tablet Extended Release 24 Hour, Oral: Adalat CC: 30 mg, 60 mg, 90 mg Afeditab CR: 30 mg, 60 mg Nifediac CC: 30 mg [DSC], 60 mg [DSC] Nifediac CC: 90 mg [DSC] [contains tartrazine (fd&c yellow #5)] Nifedical XL: 30 mg, 60 mg Procardia XL: 30 mg, 60 mg, 90 mg Generic: 30 mg, 60 mg, 90 mg Anatomic Therapeutic Chemical (ATC) Classification C08CA05 Generic Available (US)Yes Pricing: US Capsules (NIFEdipine Oral) 10 mg (100): $106.84 20 mg (100): $230.26 Capsules (Procardia Oral) 10 mg (100): $251.41 Tablet, 24-hour (Adalat CC Oral) 30 mg (100): $179.57 60 mg (100): $319.94 90 mg (100): $374.90 Tablet, 24-hour (Afeditab CR Oral) 30 mg (100): $125.79 60 mg (100): $224.07 Tablet, 24-hour (Nifedical XL Oral) 30 mg (100): $136.46 60 mg (100): $236.17 Tablet, 24-hour (NIFEdipine ER Oral) 30 mg (100): $139.40 60 mg (100): $248.32 90 mg (100): $302.81 Tablet, 24-hour (NIFEdipine ER Osmotic Release Oral) 30 mg (100): $132.45 60 mg (100): $229.15 90 mg (100): $256.15 Tablet, 24-hour (Procardia XL Oral) 30 mg (100): $554.35 60 mg (100): $959.30 90 mg (100): $1106.82 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of ActionInhibits calcium ion from entering the "slow channels" or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina; also reduces peripheral vascular resistance, producing a reduction in arterial blood pressure. Pharmacodynamics/Kinetics Onset of action: Immediate release: ~20 minutes Protein binding (concentration dependent): 92% to 98%; Note: Protein-binding may be significantly decreased in patients with renal or hepatic impairment Metabolism: Hepatic via CYP3A4 to inactive metabolites Bioavailability: Capsule: 40% to 77%; Sustained release: 65% to 89% relative to immediate release capsules; bioavailability increased with significant hepatic disease Half-life elimination: Adults: Healthy: 2 to 5 hours; Cirrhosis: 7 hours; Elderly: 7 hours (extended release tablet) Excretion: Urine (60% to 80% as inactive metabolites); feces Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Effects on Dental TreatmentNifedipine has been reported to cause 10% incidence of gingival hyperplasia; effects from 30-100 mg/day have appeared after 1-9 months. Discontinuance results in complete disappearance or marked regression of symptoms; symptoms will reappear upon remedication. Marked regression occurs after 1 week and complete disappearance of symptoms has occurred within 15 days. If a gingivectomy is performed and use of the drug is continued or resumed, hyperplasia usually will recur. The success of the gingivectomy usually requires that the medication be discontinued or that a switch to a noncalcium channel blocker be made. If for some reason nifedipine cannot be discontinued, hyperplasia has not recurred after gingivectomy when extensive plaque control was performed. If nifedipine is changed to another class of cardiovascular agent, the gingival hyperplasia will probably regress and resolve. Switching to another calcium channel blocker may result in continued hyperplasia. Effects on BleedingNo information available to require special precautions Related Information Beers Criteria − Potentially Inappropriate Medications for Geriatrics Calcium Channel Blockers − Comparative Pharmacokinetics Hyperglycemia- or Hypoglycemia-Causing Drugs Hypertension Oral Medications That Should Not Be Crushed or Altered Pharmacotherapy PearlsWhen measuring smaller doses from the liquid-filled capsules, consider the following concentrations (for Procardia) 10 mg capsule = 10 mg/0.34 mL; 20 mg capsule = 20 mg/0.45 mL; may be used preoperative to treat hypertensive urgency. Considerable attention has been directed to potential increases in mortality and morbidity when short-acting nifedipine is used in treating hypertension. The rapid reduction in blood pressure may precipitate adverse cardiovascular events. Short-acting nifedipine should not be used for acute anginal episodes since this may precipitate myocardial infarction. Extended-release formulations are preferred for the management of chronic or vasospastic angina (Poole-Wilson, 2004). Equivalency of extended release formulation (Adalat CC): The manufacturer states that it is acceptable to interchange two 30 mg tablets with one 60 mg tablet to effectively deliver a 60 mg dose. However, it is not recommended to substitute one 90 mg tablet with three 30 mg tablets, since the resulting Cmax is 29% higher compared to giving the single 90 mg tablet.

Percocet

Oxycodone and Acetaminophen (Lexi-Drugs) ALERT: US Boxed Warning Addiction, abuse, and misuse: Life-threatening respiratory depression: Accidental exposure: Neonatal opioid withdrawal syndrome: Hepatotoxicity: Special Alerts Benzodiazepines and Opioid Medicines Safety AlertAugust 2016 Opioid Pain Medicine Safety AlertMarch 2016 Drug ShortagesOne or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information: ASHP: http://www.ashp.org/menu/DrugShortages Pronunciation (oks i KOE done & a seet a MIN oh fen) Brand Names: USEndocet; Percocet; Primlev; Roxicet; Xartemis XR; Xolox [DSC] Brand Names: CanadaApo-Oxycodone/Acet; Endocet; Percocet; Percocet-Demi; PMS-Oxycodone-Acetaminophen; Ratio-Oxycocet; Rivacocet; Sandoz-Oxycodone/Acetaminophen Pharmacologic CategoryAnalgesic Combination (Opioid); Analgesic, Opioid Dosing: AdultNote: Initial dose is based on the oxycodone content; however, the maximum daily dose is based on the acetaminophen content. Extended-release: Acute pain: Oral: Usual dose: 2 tablets every 12 hours; the second initial dose may be administered as early as 8 hours after the first initial dose if needed; subsequent doses are to be administered 2 tablets every 12 hours. Do not exceed acetaminophen 4 g daily. NOTE: Oxycodone/acetaminophen ER is not interchangeable with other oxycodone/acetaminophen products because of differing pharmacokinetic profiles that affect the frequency of administration. Discontinuation: Do not stop abruptly in patients who may be physically dependent gradually decrease the dose by 50% every 2 to 4 days to prevent signs and symptoms of withdrawal. Immediate release: Management of pain: Oral: Doses should be titrated to appropriate analgesic effects. Manufacturer's labeling: Moderate to moderately severe pain: Initial dose, based on oxycodone content: 2.5-10 mg every 6 hours as needed. Titrate according to pain severity and individual response. Do not exceed acetaminophen 4 g daily. Alternate recommendations (APS, 2008): Moderate pain (off-label): Initial dose, based on oxycodone content: 5 mg. Doses typically given every 4-6 hours as needed; manufacturer's labeling recommends every 6 hours as needed. Do not exceed acetaminophen 4 g daily. Severe pain (off-label): Initial dose, based on oxycodone content: 10-20 mg. Doses typically given every 4-6 hours as needed; manufacturer's labeling recommends every 6 hours as needed. Do not exceed acetaminophen 4 g daily. Dosing: GeriatricManagement of pain: Oral: No dosage adjustment provided in manufacturer's labeling; however, use with caution and consider decreasing the initial dose and/or increasing the frequency. Severe pain (off-label dosing): Immediate release: Elderly >70 years: Consider decreasing the initial dose (based on oxycodone content) by 25% to 50%, then titrating the dose upward or downward as needed; monitor frequently during titration. Do not exceed acetaminophen 4 g daily (APS, 2008). Dosing: Pediatric Note: Initial dose is based on the oxycodone content; however, the maximum daily dose is based on the acetaminophen content. Management of pain: Children and Adolescents (off-label; American Pain Society [APS], 2008): Oral: Immediate-release: Doses should be titrated to appropriate analgesic effects: Moderate pain: Initial dose,based on oxycodone content: 0.1-0.2 mg/kg/dose. Doses typically given every 4-6 hours as needed; manufacturer's labeling recommends every 6 hours as needed; maxi mum initial oxycodone dose: 5 mg/dose. Do not exceed maximum daily acetaminophen dose: Children <45 kg: 90 mg/kg/day; Children ≥45 kg: 4000 mg daily Severe pain: Initial dose, based on oxycodone content: 0.2 mg/kg/dose. Doses typically given every 4-6 hours as needed; manufacturer's labeling recommends every 6 hours as needed; maximum initial oxycodone dose: 10 mg. Do not exceed maximum daily acetaminophen dose: Children <45 kg: 90 mg/kg/day; Children ≥45 kg: 4000 mg daily Dosing: Renal Impairment Extended-release: Initial dose: One tablet every 12 hours; adjust dose as needed. Immediate-release: There are no dosage adjustments provided in manufacturer's labeling. Use with caution; reduced clearance in severe impairment may require dosage adjustment. Dosing: Hepatic Impairment Extended-release: Initial dose: One tablet every 12 hours; adjust dose as needed. Immediate-release: There are no dosage adjustments provided in manufacturer's labeling. Use with caution; reduced clearance in severe impairment may require dosage adjustment. Use: Labeled Indications Acute pain (extended-release): Management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate. Limitations of use: Because of the risks of addiction, abuse, misuse, overdose, and death with opioids, even at recommended doses, reserve extended-release (ER) for use in patients for whom alternative treatment options (eg, nonopioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate. Moderate to moderately severe pain (immediate release): Management of moderate to moderately-severe pain Clinical Practice Guidelines Patient Safety: "CDC Guideline for Prescribing Opioids for Chronic Pain," 2016 Administration: OralAdminister without regards to food. Swallow ER tablets whole one tablet at a time; do not break, crush, cut, chew, dissolve, or split. Breaking, chewing, crushing, cutting, dissolving or splitting ER tablets will result in uncontrolled delivery of oxycodone and can lead to overdose or death. Storage/Stability Extended-release: Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Immediate-release: Store at 20°C to 25°C (68°F to 77°F). Protect from moisture. Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience fatigue, vomiting, or nausea. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe dizziness, passing out, difficulty breathing, slow breathing, shallow breathing, illogical thinking, severe constipation, loss of strength and energy, burning or numbness feeling, urinary retention, change in amount of urine passed, tachycardia, bradycardia, arrhythmia, chills, pharyngitis, hallucinations, mood changes, hearing loss, seizures, severe headache, severe abdominal pain, tremors, bruising, bleeding, vision changes, angina, memory impairment, abnormal gait, difficulty speaking, swelling of arms or legs, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Medication Safety Issues Sound-alike/look-alike issues: High alert medication: Other safety concerns: Medication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication: Xartemis XR: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM389284.pdf Contraindications Hypersensitivity to oxycodone, acetaminophen, or any component of the formulation; severe respiratory depression (in absence of resuscitative equipment or ventilatory support); bronchial asthma (acute or severe) or hypercarbia; paralytic ileus (suspected or known) Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty. Warnings/Precautions Concerns related to adverse effects: • CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). • Constipation: Oxycodone may cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation. • Hepatotoxicity: [US Boxed Warning]: Acetaminophen may cause severe hepatotoxicity, potentially requiring liver transplant or resulting in death; hepatotoxicity is usually associated with excessive acetaminophen intake (>4 g/day in adults). Risk is increased with alcohol use, preexisting liver disease, and intake of more than one source of acetaminophen-containing medications. Chronic daily dosing in adults has also resulted in liver damage in some patients. • Hypersensitivity/anaphylactic reactions: Hypersensitivity and anaphylactic reactions have been reported with acetaminophen use; discontinue immediately if symptoms of allergic or hypersensitivity reactions occur. Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydromorphone, levorphanol, oxycodone, oxymorphone). • Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). May produce orthostatic hypotension in ambulatory patients. Use with caution to patients in circulatory shock. • Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone/acetaminophen ER. Monitor for respiratory depression, especially during initiation of therapy or following a dose increase. To reduce the risk of respiratory depression, proper dosing and titration is essential. Overestimating the oxycodone/acetaminophen ER dose when converting patients from another opioid product can result in fatal overdose with the first dose. • Skin reactions: Serious and potentially fatal skin reactions, including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have occurred rarely with acetaminophen use. Discontinue therapy at the first appearance of skin rash. Disease-related concerns: • Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions. • Abuse potential: [US Boxed Warning]: Oxycodone/acetaminophen ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing oxycodone/acetaminophen ER, and monitor all patients regularly for the development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk for misuse include younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]). Abuse or misuse of XR tablets by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the oxycodone and can result in overdose and death • Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013). • Biliary tract impairment: Use oxycodone with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi. • CNS depression/coma: Avoid use in patients with CNS depression or coma as these patients are susceptible to intracranial effects of CO2 retention. • G6PD deficiency: Use with caution in patients with known G6PD deficiency. • GI disorders: Due to characteristics of the ER formulation that cause the tablets to swell and become sticky when wet, consider use of an alternative analgesic in patients who have difficulty swallowing and patients at risk for underlying GI disorders resulting in a small GI lumen. • Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. • Hepatic impairment: Use with caution in patients with hepatic impairment. Use with caution in patients with alcoholic liver disease; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage. • Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]). • Obesity: Use with caution in patients who are morbidly obese. • Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. • Psychosis: Use with caution in patients with toxic psychosis. • Renal impairment: Use with caution in patients with renal impairment. • Respiratory disease: Use oxycodone with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), cor pulmonale, COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages. • Seizures: Use with caution in patients with a history of seizure disorders. • Sleep-disordered breathing: Use opioids with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing, including HF and obesity. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]). • Thyroid dysfunction: Use with caution in patients with thyroid dysfunction. Concurrent drug therapy issues: • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. • Sedatives: Effects may be potentiated when used with other CNS depressants (eg, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). In the setting of chronic pain, avoid prescribing opioids and benzodiazepines concurrently whenever possible; epidemiologic studies suggest there is an increased risk for potentially fatal overdose with concurrent use (Dowell [CDC 2016]). Special populations: • Debilitated patients: Use with caution in debilitated patients; there is a greater potential for respiratory depression. • Elderly: Use with caution in the elderly; may be more sensitive to adverse effects, such as respiratory depression. Oxycodone clearance may also be slightly reduced in the elderly. Dosage adjustments may be necessary. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation (Dowell [CDC 2016]). • Neonates: Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged use of oxycodone/acetaminophen during pregnancy can cause neonatal withdrawal syndrome in the newborn which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If prolonged opioid therapy is required in a pregnant woman, ensure treatment is available and warn of risk to the neonate. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn. • Surgery: Opioids decrease bowel motility; monitor for decrease bowel motility in postop patients receiving opioids. Dosage form specific issues: • Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling. • Extended-release tablets: Do not to presoak, lick or otherwise wet ER tablets prior to placing in the mouth; take one tablet at a time with enough water to ensure complete swallowing. Do not break, chew, crush, cut, dissolve or split the ER tablets; breaking, chewing, crushing, cutting, dissolving or splitting will result in uncontrolled delivery of oxycodone and can lead to overdose or death. • Interchangeability: Oxycodone/acetaminophen ER is not interchangeable with other oxycodone/acetaminophen products because of differing pharmacokinetic profiles that affect the frequency of administration. • Sulfites: Some preparations contain sulfites which may cause allergic reactions. Other warnings/precautions: • Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, NSAIDs, acetaminophen, certain anticonvulsants and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and non-opioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using immediate-release opioids (instead of extended-release/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 morphine milligram equivalents (MME)/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]). • Dosage limit: Limit acetaminophen dose from all sources (prescription and OTC) to <4 g/day in adults. Do not use oxycodone/acetaminophen concomitantly with other acetaminophen-containing products. • Overdose: [US Boxed Warning]: Accidental ingestion of oxycodone/acetaminophen ER, especially in children, can result in a fatal overdose of oxycodone. • Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms. Do not abruptly stop ER tablets in patients who may be physically dependent; gradually decrease dose by 50% every 2 to 4 days to prevent signs and symptoms of withdrawal. Geriatric ConsiderationsThe elderly may be particularly susceptible to the CNS depressant and constipating effects of opioids. Prophylactic use of a laxative should be considered. Pregnancy Risk FactorC Pregnancy Considerations Animal reproduction studies have not been conducted with this combination. Refer to individual monographs for additional information. [U.S. Boxed Warning]: Prolonged use of oxycodone/acetaminophen during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome. Breast-Feeding ConsiderationsOxycodone and acetaminophen are both excreted into breast milk. Somnolence and lethargy have been reported in nursing infants following maternal use of this combination. Breast-feeding is not recommended by the manufacturer. Refer to individual monographs for additional information. Briggs' Drugs in Pregnancy & Lactation Acetaminophen Oxycodone Adverse ReactionsAlso see individual agents. Frequency not always defined. >10%: Central nervous system: Dizziness (13%) Gastrointestinal: Nausea (31%) 1% to 10%: Cardiovascular: Peripheral edema (1%), circulatory depression, hypotension, shock Central nervous system: Headache (10%), drowsiness (4%), fatigue (≥1%), insomnia (≥1%), dysphoria Dermatologic: Skin rash (2%) erythema (1%), excoriation (1%), pruritus (1%), skin blister (1%) , erythematous dermatitis Endocrine & metabolic: Hot flash (1%) Gastrointestinal: Vomiting (9%), constipation (4%), diarrhea (≥1%), dyspepsia (≥1%), xerostomia (≥1%) Genitourinary: Dysuria (1%) Hematologic & oncologic: Hemolytic anemia, neutropenia, pancytopenia, thrombocytopenia Hepatic: Increased liver enzymes (≥1%) Respiratory: Cough (≥1%), apnea, respiratory arrest, respiratory depression <1%, postmarketing, and/or case reports: Abdominal distress, abdominal pain, abnormal hepatic function tests, acidosis, agitation, alkalosis, altered mental status, anaphylactoid reaction, anaphylaxis (acute), angioedema, anxiety, arthralgia, aspiration, asthma, blurred vision, bradycardia, bronchospasm, bruise, cardiac arrhythmia, cerebral edema, chest discomfort, chest pain, chills, cognitive dysfunction, confusion, decreased appetite, dehydration, depression, dermatitis, diaphoresis, disorientation, drug abuse, drug dependence, drug overdose (accidental and nonaccidental), dysgeusia, dyspnea, ecchymoses, emotional lability, esophageal spasm, euphoria, eye redness, falling, fever, flatulence, flushing, hallucination, hearing loss, hepatic disease, hepatic failure, hepatitis, hepatotoxicity, hiccups, hyperglycemia, hyperhidrosis, hyperkalemia, hypersensitivity, hypersensitivity reaction, hypertension, hypoesthesia, hypoglycemia, hypothermia, hypoventilation, impaired consciousness, increased blood pressure, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, increased serum bilirubin, increased thirst, interstitial nephritis, intestinal obstruction, jaundice, jitteriness, laryngeal edema, lethargy, malaise, memory impairment, metabolic acidosis, migraine, miosis, musculoskeletal stiffness, myalgia, myoclonus, nervousness, noncardiac chest pain, obstructive sleep apnea hypopnea syndrome, oropharyngeal pain, orthostatic hypotension, palpitations, pancreatitis, paresthesia, proteinuria, pulmonary edema, renal failure, renal insufficiency, renal papillary necrosis, respiratory alkalosis, reduced urine flow, rhabdomyolysis, sedation, seizure, sleep disorder, stupor, suicide, tachycardia, tachypnea, throat irritation, tinnitus, tremor, urinary retention, urticaria, visual disturbance, weakness, withdrawal syndrome Allergy and Idiosyncratic Reactions Acetaminophen Allergy/Hypersensitivity Opioid Allergy/Hypersensitivity Toxicology Acetaminophen Opioids Metabolism/Transport EffectsRefer to individual components. Drug Interactions Open Interactions Alcohol (Ethyl): May enhance the hepatotoxic effect of Acetaminophen. Risk C: Monitor therapy Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy Anticholinergic Agents: May enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Busulfan: Acetaminophen may increase the serum concentration of Busulfan. Risk C: Monitor therapy Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification CNS Depressants: May enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Risk D: Consider therapy modification Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification CYP3A4 Inhibitors (Moderate): May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy CYP3A4 Inhibitors (Strong): May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk D: Consider therapy modification Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy Dasatinib: Acetaminophen may enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Diuretics: Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Risk D: Consider therapy modification Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Imatinib: Acetaminophen may enhance the hepatotoxic effect of Imatinib. Risk C: Monitor therapy Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy MAO Inhibitors: OxyCODONE may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Management: Seek alternatives when possible. Avoid use of oxycodone/naltrexone during and within 14 days of stopping monoamine oxidase inhibitor treatment. Non-US labeling for some oxycodone products states that such use is contraindicated. Risk D: Consider therapy modification Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification MetyraPONE: May increase the serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Risk C: Monitor therapy MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Mipomersen: Acetaminophen may enhance the hepatotoxic effect of Mipomersen. Risk C: Monitor therapy Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk X: Avoid combination Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Nalmefene: May diminish the therapeutic effect of Analgesics (Opioid). Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Risk D: Consider therapy modification Naltrexone: May diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk D: Consider therapy modification Netupitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Risk C: Monitor therapy Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification Phenylephrine (Systemic): Acetaminophen may increase the serum concentration of Phenylephrine (Systemic). Risk C: Monitor therapy Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Risk C: Monitor therapy Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy Probenecid: May increase the serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Risk D: Consider therapy modification Ramosetron: Analgesics (Opioid) may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy RifAMPin: May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Risk C: Monitor therapy Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification SORAfenib: Acetaminophen may enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification St John's Wort: May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Risk D: Consider therapy modification Tetracaine (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. This appears most likely with daily acetaminophen doses exceeding 1.3 or 2 g/day for multiple consecutive days. Risk C: Monitor therapy Voriconazole: May enhance the adverse/toxic effect of OxyCODONE. Voriconazole may increase the serum concentration of OxyCODONE. Management: A reduced oxycodone dose may be necessary with concurrent voriconazole. Increased frequency and duration of monitoring for oxycodone-related adverse effects is recommended. Risk D: Consider therapy modification Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification Test InteractionsSee individual agents. Genes of Interest Catechol-O-Methyltransferase Monitoring Parameters Monitor for pain relief, respiratory and mental status, blood pressure, constipation; signs or symptoms of hypogonadism or hypoadrenalism (Brennan, 2013) Alternate recommendations: Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and re-checking should be considered at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (Dowell [CDC 2016]). Nursing: Physical Assessment/MonitoringSee individual agents. Controlled SubstanceC-II Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product Capsule, Oral: 5/500: Oxycodone hydrochloride 5 mg and acetaminophen 500 mg [DSC] Solution, Oral: Roxicet: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg per 5 mL (5 mL, 500 mL) [contains ethanol <0.5%; mint flavor] Tablet, Oral: 2.5/325: Oxycodone hydrochloride 2.5 mg and acetaminophen 325 mg; 5/325: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg; 7.5/325: Oxycodone hydrochloride 7.5 mg and acetaminophen 325 mg; 7.5/500: Oxycodone hydrochloride 7.5 mg and acetaminophen 500 mg [DSC]; 10/325: Oxycodone hydrochloride 10 mg and acetaminophen 325 mg; 10/650: Oxycodone hydrochloride 10 mg and acetaminophen 650 mg [DSC] Endocet 2.5/325: Oxycodone hydrochloride 2.5 mg and acetaminophen 325 mg Endocet 5/325 [scored]: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg Endocet 7.5/325: Oxycodone hydrochloride 7.5 mg and acetaminophen 325 mg Endocet 7.5/500: Oxycodone hydrochloride 7.5 mg and acetaminophen 500 mg [DSC] Endocet 10/325: Oxycodone hydrochloride 10 mg and acetaminophen 325 mg Endocet 10/650: Oxycodone hydrochloride 10 mg and acetaminophen 650 mg [DSC] Magnacet 5/400: Oxycodone hydrochloride 5 mg and acetaminophen 400 mg [DSC] Magnacet 7.5/400: Oxycodone hydrochloride 7.5 mg and acetaminophen 400 mg [DSC] Magnacet 10/400: Oxycodone hydrochloride 10 mg and acetaminophen 400 mg [DSC] Percocet 2.5/325: Oxycodone hydrochloride 2.5 mg and acetaminophen 325 mg Percocet 5/325 [scored]: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg Percocet 7.5/325: Oxycodone hydrochloride 7.5 mg and acetaminophen 325 mg Percocet 7.5/500: Oxycodone hydrochloride 7.5 mg and acetaminophen 500 mg [DSC] Percocet 10/325: Oxycodone hydrochloride 10 mg and acetaminophen 325 mg Percocet 10/650: Oxycodone hydrochloride 10 mg and acetaminophen 650 mg [DSC] Primlev 5/300: Oxycodone hydrochloride 5 mg and acetaminophen 300 mg Primlev 7.5/300: Oxycodone hydrochloride 7.5 mg and acetaminophen 300 mg Primlev 10/300: Oxycodone hydrochloride 10 mg and acetaminophen 300 mg Roxicet 5/325 [scored]: Oxycodone hydrochloride 5 mg and acetaminophen 325 mg Tablet, Extended Release, Oral: Xartemis XR: Oxycodone hydrochloride 7.5 mg and acetaminophen 325 mg Generic Available (US)Yes: Excludes solution Pricing: US Solution (Oxycodone-Acetaminophen Oral) 5-325 mg/5 mL (500 mL): $142.50 Solution (Roxicet Oral) 5-325 mg/5 mL (5 mL): $1.83 Tablet, controlled release (Xartemis XR Oral) 7.5-325 mg (100): $276.00 Tablets (Endocet Oral) 2.5-325 mg (100): $266.40 5-325 mg (100): $136.87 7.5-325 mg (100): $271.54 10-325 mg (100): $355.08 Tablets (Oxycodone-Acetaminophen Oral) 2.5-325 mg (100): $204.91 5-325 mg (100): $136.87 7.5-325 mg (100): $271.54 10-325 mg (100): $355.08 Tablets (Percocet Oral) 2.5-325 mg (100): $975.84 5-325 mg (100): $1365.76 7.5-325 mg (100): $1475.53 10-325 mg (100): $1929.38 Tablets (Primlev Oral) 5-300 mg (30): $602.84 7.5-300 mg (30): $602.84 10-300 mg (30): $602.84 Tablets (Roxicet Oral) 5-325 mg (100): $136.87 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of Action Oxycodone, as with other opioid analgesics, blocks pain perception in the cerebral cortex by binding to specific receptor molecules (opiate receptors) within the neuronal membranes of synapses. This binding results in a decreased synaptic chemical transmission throughout the CNS thus inhibiting the flow of pain sensations into the higher centers. Mu and kappa are the two subtypes of the opiate receptor to which oxycodone binds to cause analgesia. Acetaminophen inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center. Pharmacodynamics/Kinetics Also see individual agents. Onset of action: Within 10 to 15 minutes Peak effect: Within 1 hour Duration: 3 to 6 hours Dental UseTreatment of moderate to moderately-severe postoperative dental pain Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Dental Health Professional ConsiderationsAlthough the OTC product labeling for acetaminophen products state to limit the maximum dose to 3,000 mg daily (for extra strength) or 3,250 mg (for regular strength) (see this site for details: http://www.tylenolprofessional.com/extra-strength-tylenol-dosage-faq.html), it is still appropriate for patients to take up to 4,000 mg daily "under the direction of a healthcare provider" (http://www.tylenolprofessional.com/assets/v4/faqs-new-dosing.pdf). Oxycodone, as with other opioid analgesics, is recommended only for limited acute dosing (ie, 3 days or less). Oxycodone has an addictive liability, especially when given long-term. The acetaminophen component requires use with caution in patients who use alcohol, with preexisting liver disease, and those receiving more than one source of acetaminophen-containing medication. Hepatotoxicity caused by acetaminophen is potentiated by chronic alcohol consumption. People who are taking acetaminophen, even at therapeutic doses, and consume alcohol are at risk of developing hepatotoxicity. Acetaminophen may increase the levels and enhance the anticoagulant effects of vitamin K antagonists acenocoumarol and warfarin (Coumadin). Studies have reported that acetaminophen has increased the INR in warfarin treated patients with daily acetaminophen doses as low as 2 g, particularly when taking acetaminophen for >1 week (Antlitz, 1968; Boeijinga, 1982; Gebauer, 2003; Hylek, 1998; Rubin, 1984). In addition, case reports of bleeding as a result of increased INR have been published (Bagheri, 1999; Bartle, 1991). There is no known mechanism of the interaction; furthermore, some studies have failed to demonstrate this interaction (Gadisseur, 2003; Kwan, 1995; van den Bemt, 2002). In terms of risk, the data suggest that acetaminophen and warfarin could interact in some clinically significant manner but that the benefits of concomitant use of acetaminophen for pain control in dental patients taking warfarin usually outweigh the risks. An appropriate monitoring plan should be in place to identify potential negative effects and dosage adjustments may be necessary in a minority of patients. The interaction may be more likely to occur with daily acetaminophen doses of >1.3 g for >1 week. There are no reports of acetaminophen interacting with antiplatelet drugs such as aspirin, clopidogrel (Plavix), or prasugrel (Effient). Also, there are no reports of acetaminophen in combination with hydrocodone, codeine, or oxycodone interacting with warfarin (Coumadin). Effects on Dental TreatmentKey adverse event(s) related to dental treatment: Nausea, sedation, constipation, and xerostomia (normal salivary flow resumes upon discontinuation) (see Dental Health Professional Considerations). Effects on BleedingAs a single agent, acetaminophen does not appear to affect bleeding or platelet aggregation. Acetaminophen may prolong the INR and increase bleeding in patients taking warfarin (Coumadin). For patients taking warfarin, single acetaminophen doses or acetaminophen therapy of short duration should be safe, but if large (>1.3 g/day) doses are administered for longer than 10-14 days, then the INR should be monitored (see Dental Health Professional Considerations). Dental Usual Dosing Note: Initial dose is based on the oxycodone content; however, the maximum daily dose is based on the acetaminophen content. Management of pain: Doses should be given every 4-6 hours as needed and titrated to appropriate analgesic effects. Mild-to-moderate pain: Children: Initial dose, based on oxycodone content: 0.05-0.1 mg/kg/dose Maximum acetaminophen dose: Children <45 kg: 90 mg/kg/day; children >45 kg: 4 g/day Adults: Initial dose, based on oxycodone content: 2.5-5 mg Severe pain: Children: Initial dose, based on oxycodone content: 0.3 mg/kg/dose Adults: Initial dose, based on oxycodone content: 10-30 mg. Do not exceed acetaminophen 4 g/day. Elderly: Doses should be titrated to appropriate analgesic effects: Initial dose, based on oxycodone content: 2.5-5 mg every 6 hours. Do not exceed acetaminophen 4 g/day. Dosage adjustment in hepatic impairment: Dose should be reduced in patients with severe liver disease. Related Information Acetaminophen Beers Criteria − Potentially Inappropriate Medications for Geriatrics OxyCODONE Index TermsAcetaminophen and Oxycodone; Oxycodone HCl/Acetaminophen; Oxycodone/Acetominophen; Tylox

Oxytocin

Oxytocin (Lexi-Drugs) ALERT: US Boxed Warning Appropriate use: Drug ShortagesOne or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information: ASHP: http://www.ashp.org/menu/DrugShortages Pronunciation (oks i TOE sin) Brand Names: USPitocin Brand Names: CanadaOxytocin for injection Pharmacologic CategoryOxytocic Agent Dosing: AdultNote: IV administration requires the use of an infusion pump. Induction or stimulation of labor: IV: Initial: 0.5 to 1 milliunits/minute; gradually increase dose in increments of 1 to 2 milliunits/minute every 30 to 60 minutes until desired contraction pattern is established; dose may be decreased by similar increments after desired frequency of contractions is reached and labor has progressed to 5 to 6 cm dilation. Infusion rates up to 6 milliunits/minute provide oxytocin levels similar to those with spontaneous labor; rates >9 to 10 milliunits/minute are rarely required. Higher dose regimens (eg, initial dose 2 to 6 milliunits/minute) with larger incremental dose increases (eg, 1 to 6 milliunits/minute) have also been proposed; decrease or discontinue dose for abnormal or excessive uterine contractions (ACOG, 2009). Note: Discontinue the oxytocin infusion immediately in the event of uterine hyperactivity and/or fetal distress. If uterine contractions become too powerful, the infusion can be stopped abruptly. Postpartum uterine bleeding: IM: 10 units after delivery of the placenta IV: 10 to 40 units added to a running infusion solution depending on amount of infusion fluid remaining (maximum: 40 units in 1,000 mL of IV fluid); adjust infusion rate to sustain uterine contraction and control uterine atony Adjunctive treatment of abortion: IV: Incomplete, inevitable, or elective abortion: 10 units as an IV infusion after suction or a sharp curettage (used to help contract the uterus) Midtrimester elective abortion: 10 to 20 milliunits/minute; maximum total dose: 30 units/12 hours (may decrease injection to abortion time) * See Dosage and Administration in AHFS Essentials for additional information. Dosing: Renal ImpairmentThere are no dosage adjustments provided in the manufacturer's labeling. Dosing: Hepatic ImpairmentThere are no dosage adjustments provided in the manufacturer's labeling. Use: Labeled Indications Antepartum: Induction of labor in patients with a medical indication (eg, Rh problems, maternal diabetes, preeclampsia, at or near term); stimulation or reinforcement of labor (as in selected cases of uterine inertia); adjunctive therapy in management of incomplete or inevitable abortion Postpartum: To produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. * See Uses in AHFS Essentials for additional information. Administration: IMPostpartum uterine bleeding: Administer by IV infusion or IM. Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Administration: IV Induction or stimulation of labor: Administer as an IV infusion (drip method) by use of an infusion pump; accurate control of the rate of infusion flow is essential. Incomplete or inevitable abortion: Administer by IV infusion Postpartum uterine bleeding: Administer by IV infusion or IM. Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Storage/StabilityStore at 20°C to 25°C (68°F to 77°F). Preparation for AdministrationHazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). IV: Induction or stimulation of labor: Add oxytocin 10 units to NS or LR 1,000 mL to yield a solution containing oxytocin 10 milliunits/mL. Rotate solution to mix. Postpartum uterine bleeding: Add oxytocin 10 to 40 units to running IV infusion; maximum: 40 units to 1,000 mL. Adjunctive management of abortion: Add oxytocin 10 units to 500 mL of a physiologic saline solution or D5W. CompatibilityStable in D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, 1/2NS, NS. Y-site administration: Compatible: Amikacin, ampicillin, cefazolin, cefotaxime, cefoxitin, clindamycin, doxycycline, erythromycin lactobionate, gentamicin, heparin, hydrocortisone sodium succinate, insulin (regular), meperidine, metronidazole, minocycline, morphine, nafcillin, oxacillin, piperacillin, potassium chloride, tobramycin, trimethoprim/sulfamethoxazole, vancomycin, vitamin B complex with C, warfarin, zidovudine. Incompatible: Pantoprazole. Compatibility in syringe: Incompatible: Dimenhydrinate, hydrocortisone sodium succinate, pantoprazole. Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience injection site irritation, vomiting, or nausea. Have patient report immediately to prescriber bleeding (soaking one pad an hour), arrhythmia, difficult urination, severe headache, severe abdominal pain, or signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight) (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Medication Safety Issues High alert medication: ContraindicationsHypersensitivity to oxytocin or any component of the formulation; significant cephalopelvic disproportion; unfavorable fetal positions or presentations (such as transverse lies); fetal distress when delivery is not imminent; hypertonic or hyperactive uterus; contraindicated vaginal delivery (invasive cervical cancer, active genital herpes, prolapse of the cord, cord presentation, total placenta previa, or vasa previa); obstetrical emergencies where surgical intervention is favored; where adequate uterine activity fails to achieve satisfactory progress Warnings/Precautions Concerns related to adverse effects: • Antidiuretic effect: May produce intrinsic antidiuretic effect (ie, water intoxication). Severe water intoxication with convulsions, coma, and death may occur, particularly with large doses (40 to 50 milliunits/minute) or when given as a slow infusion over 24 hours and if the patient is receiving fluids by mouth. • Maternal deaths: Maternal deaths caused by hypertensive episodes, subarachnoid hemorrhage, or rupture of the uterus and fetal deaths have occurred with oxytocic medications when used for induction of labor or for augmentation in the first and second stages of labor. • Uterine effects: High doses or hypersensitivity to oxytocin may cause uterine hypertonicity, spasm, tetanic contraction, or rupture of the uterus. Special handling: • Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]). Other warnings/precautions: • Appropriate use: [U.S. Boxed Warning]: To be used for medical rather than elective induction of labor. Oxytocin is used to initiate or improve uterine contractions in order to achieve a vaginal delivery; it should only be used when medically needed for fetal or maternal reasons. Medical indications for labor induction may include Rh problems, maternal diabetes, preeclampsia at or near term, when delivery is in the best interest of mother or fetus, or premature rupture of membranes when delivery is indicated. Use is generally not recommended in the following conditions: Fetal distress, hydramnios, partial placenta previa, prematurity, borderline cephalopelvic disproportion, or conditions where there is a predisposition for uterine rupture (eg, previous major surgery on cervix or uterus, cesarean section, overdistention of the uterus, grand multiparity, past history of uterine sepsis or traumatic delivery). • Trained personnel: Intravenous preparations should be administered by adequately trained individuals familiar with its use and able to identify complications; continuous observation is necessary for all patients. * See Cautions in AHFS Essentials for additional information. Pregnancy Risk FactorC (manufacturer specific) Pregnancy Considerations[U.S. Boxed Warning]: To be used for medical rather than elective induction of labor. Animal reproduction studies have not been conducted. When used as indicated, teratogenic effects would not be expected. Nonteratogenic adverse reactions are reported in the neonate as well as the mother. Breast-Feeding ConsiderationsEndogenous levels of oxytocin naturally increase during breast-feeding. Adverse ReactionsFrequency not defined. Fetus or neonate: Cardiovascular: Arrhythmias (including premature ventricular contractions), bradycardia Central nervous system: Brain or CNS damage (permanent), neonatal seizure Hepatic: Neonatal jaundice Ocular: Neonatal retinal hemorrhage Miscellaneous: Fetal death, low Apgar score (5 minute) Mother: Cardiovascular: Arrhythmias (including premature ventricular contractions), hypertensive episodes Gastrointestinal: Nausea, vomiting Genitourinary: Pelvic hematoma, postpartum hemorrhage, uterine hypertonicity, tetanic contraction of the uterus, uterine rupture, uterine spasm Hematologic: Afibrinogenemia (fatal) Miscellaneous: Anaphylactic reaction, subarachnoid hemorrhage; severe water intoxication with convulsions, coma, and death is associated with a slow oxytocin infusion over 24 hours * See Cautions in AHFS Essentials for additional information. Metabolism/Transport EffectsNone known. Drug Interactions Open Interactions Carboprost Tromethamine: May enhance the adverse/toxic effect of Oxytocic Agents. Specifically, oxytocic effects may be enhanced. Risk X: Avoid combination Dinoprostone: May enhance the adverse/toxic effect of Oxytocin. Specifically,oxytocic effects may be enhanced. Risk D: Consider therapy modification EPHEDrine (Systemic): Oxytocin may enhance the hypertensive effect of EPHEDrine (Systemic). Risk C: Monitor therapy Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Risk D: Consider therapy modification MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Risk D: Consider therapy modification MiSOPROStol: May enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: The manufacturer of misoprostol recommends avoiding concomitant use with oxytocin. Misoprostol may augment effects of oxytocin, particularly when given within 4 hours of oxytocin initiation. Risk D: Consider therapy modification Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Risk C: Monitor therapy Monitoring ParametersFluid intake and output during administration, uterine activity, blood pressure; electronic fetal monitoring Nursing: Physical Assessment/MonitoringMonitor blood pressure, fluid intake and output, and labor closely if using oxytocin for induction; fetal monitoring is strongly recommended. Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. Solution, Injection: Pitocin: 10 units/mL (1 mL, 10 mL, 50 mL) [contains chlorobutanol (chlorobutol)] Generic: 10 units/mL (1 mL, 10 mL, 30 mL) Anatomic Therapeutic Chemical (ATC) Classification H01BB02 Generic Available (US)Yes Pricing: US Solution (Oxytocin Injection) 10 units/mL (1 mL): $0.91 Solution (Pitocin Injection) 10 units/mL (10 mL): $12.66 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of ActionOxytocin stimulates uterine contraction by activating G-protein-coupled receptors that trigger increases in intracellular calcium levels in uterine myofibrils. Oxytocin also increases local prostaglandin production, further stimulating uterine contraction. Pharmacodynamics/Kinetics Onset of action: Uterine contractions: IM: 3 to 5 minutes; IV: ~1 minute Duration: IM: 2 to 3 hours; IV: 1 hour Half-life elimination: 1 to 6 minutes; decreased in late pregnancy and during lactation Excretion: Urine (small amount unchanged) Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Effects on Dental TreatmentNo significant effects or complications reported Effects on BleedingNo information available to require special precautions Related Information Drug-Induced Prolongation of the QT Interval and Torsades de Pointes Safe Handling of Hazardous Drugs

Vitamin K

Phytonadione (Lexi-Drugs) ALERT: US Boxed Warning Hypersensitivity/anaphylactoid reactions (injection): Pronunciation (fye toe na DYE one) Brand Names: USMephyton Brand Names: CanadaAquaMEPHYTON; Konakion; Mephyton Pharmacologic CategoryVitamin, Fat Soluble Dosing: AdultNote: According to the manufacturer, SubQ is the preferred parenteral route; IM route should be avoided due to the risk of hematoma formation; IV route should be restricted for emergency use only. The American College of Chest Physicians (ACCP) recommends the IV route in patients with major bleeding secondary to use of vitamin K antagonists (VKAs). Adequate intake (AI): Oral: Males: 120 mcg/day; Females: 90 mcg/day Hypoprothrombinemia due to drugs (other than coumarin derivatives) or factors limiting absorption or synthesis: Oral, SubQ, IM, IV: Initial: 2.5-25 mg (rarely up to 50 mg) Vitamin K deficiency (supratherapeutic INR) secondary to VKAs (eg, warfarin) (off-label dose): If INR above therapeutic range to <4.5 (no evidence of bleeding): Lower or hold next VKA dose and monitor frequently; when INR approaches desired range, resume VKA dosing with a lower dose (Patriquin, 2011). If INR 4.5-10 (no evidence of bleeding): The 2012 ACCP guidelines recommend against routine phytonadione (aka, vitamin K) administration in this setting (Guyatt, 2012). Previously, the 2008 ACCP guidelines recommended if no risk factors for bleeding exist, to omit next 1 or 2 VKA doses, monitor INR more frequently, and resume with an appropriately adjusted VKA dose when INR in desired range; may consider administering vitamin K orally 1-2.5 mg if other risk factors for bleeding exist (Hirsh, 2008). Others have recommended consideration of vitamin K 1 mg orally or 0.5 mg IV (Patriquin, 2011). If INR >10 (no evidence of bleeding): The 2012 ACCP guidelines recommend administration of oral vitamin K (dose not specified) in this setting (Guyatt, 2012). Previously, the 2008 ACCP guidelines recommended to hold warfarin, administer vitamin K orally 2.5-5 mg, expect INR to be reduced within 24-48 hours, monitor INR more frequently and give additional vitamin K at an appropriate dose if necessary; resume warfarin at an appropriately adjusted dose when INR is in desired range (Hirsh, 2008). Others have recommended consideration of vitamin K 2-2.5 mg orally or 0.5-1 mg IV (Patriquin, 2011). If minor bleeding at any INR elevation: Hold warfarin, may administer vitamin K orally 2.5-5 mg, monitor INR more frequently, may repeat dose after 24 hours if INR correction incomplete; resume warfarin at an appropriately adjusted dose when INR is in desired range (Patriquin, 2011). If major bleeding at any INR elevation: The 2012 ACCP guidelines recommend administration of four-factor prothrombin complex concentrate (PCC) and IV vitamin K 5-10 mg in this setting (Guyatt, 2012). The only available four-factor PCC in the U.S. is Kcentra. Other four-factor PCCs not available in the U.S. include Beriplex P/N, Cofact, and Octaplex. Bebulin VH and Profilnine SD do not contain adequate levels of factor VII and are considered three-factor PCCs. Previously, the 2008 ACCP guidelines recommended to hold warfarin, administer vitamin K 10 mg by slow IV infusion and supplement with PCC depending on the urgency of the situation; IV vitamin K may be repeated every 12 hours (Hirsh, 2008). Note: Use of high doses of vitamin K (eg, 10-15 mg) may cause warfarin resistance for ≥1 week. During this period of resistance, heparin or low-molecular-weight heparin (LMWH) may be given until INR responds (Ansell, 2008). Preprocedural/surgical INR normalization in patients receiving warfarin (routine use): Oral: 1-2.5 mg once administered on the day before surgery; recheck INR on day of procedure/surgery (Douketis, 2012). Others have recommended the use of vitamin K 1 mg orally for mild INR elevations (ie, INR 3.0-4.5) (Patriquin, 2011). * See Dosage and Administration in AHFS Essentials for additional information. Dosing: GeriatricRefer to adult dosing. Dosing: PediatricNote: According to the manufacturer, SubQ is the preferred parenteral route; IM route should be avoided due to the risk of hematoma formation; IV route should be restricted for emergency use only. The American College of Chest Physicians (ACCP) recommends the IV route in patients with major bleeding secondary to use of vitamin K antagonists (VKAs). Adequate intake (AI): Oral: Infants: 0-6 months: 2 mcg/day 7-12 months: 2.5 mcg/day Children: 1-3 years: 30 mcg/day 4-8 years: 55 mcg/day 9-13 years: 60 mcg/day 14-18 years: 75 mcg/day Hemorrhagic disease of the newborn: Prophylaxis: IM: 0.5-1 mg within 1 hour of birth Treatment: IM, SubQ: 1 mg/dose/day; higher doses may be necessary if mother has been receiving oral anticoagulants Vitamin K deficiency (supratherapeutic INR) secondary to vitamin K antagonists (VKAs) (eg, warfarin) (off-label use): Infants and Children: Excessively prolonged INR (usually INR >8; no significant bleeding): Note: Limited data available: IV: 0.03 mg/kg/dose; maximum dose: 1 mg (Bolton-Maggs, 2002); if significant bleeding, consider use of fresh frozen plasma, prothrombin complex concentrates, or recombinant factor VIIa (Monagle, 2012). Dosing: Renal ImpairmentNo dosage adjustment provided in manufacturer's labeling. Dosing: Hepatic ImpairmentNo dosage adjustment provided in manufacturer's labeling. Use: Labeled IndicationsPrevention and treatment of hypoprothrombinemia caused by vitamin K antagonist (VKA)-induced (eg, warfarin-induced) or other drug-induced vitamin K deficiency, altered activity, or altered metabolism; hypoprothrombinemia caused by malabsorption or inability to synthesize vitamin K; prophylaxis and treatment of hemorrhagic disease of the newborn * See Uses in AHFS Essentials for additional information. Use: Off-Label Hypoprothrombinemia due to long-acting anticoagulant rodenticides (LAARs)Level of Evidence [C] Data from a few case reports suggest that phytonadione may be beneficial in the treatment of hypoprothrombinemia caused by long-acting anticoagulant rodenticides (brodifacoum) (Bruno, 2000; Gunja, 2011; Olmos, 2007). Data from a limited number of patients (case series) also suggest that phytonadione may be beneficial in this setting (Chua, 1998). Additional data may be necessary to further define the role of phytonadione in the treatment of this condition. Level of Evidence Definitions Level of Evidence Scale Clinical Practice Guidelines Stroke: "Guidelines for the Management of Spontaneous Intracerebral Hemorrhage in Adults," July 2010 Valvular Heart Disease: AHA/ACC, "2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease," March 2014 Other: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition), February 2012 Administration: IVInfuse slowly; rate of infusion should not exceed 1 mg/minute. Alternatively, dilute dose in a minimum of 50 mL of compatible solution and administer using an infusion pump over at least 20 minutes (Ageno, 2012). The injectable route should be used only if the oral route is not feasible or there is a greater urgency to reverse anticoagulation. Administration: Injectable DetailpH: 3.5 to 7 Administration: OralThe parenteral formulation may also be used for small oral doses (eg, 1 mg) or situations in which tablets cannot be swallowed (Crowther, 2000; O'Connor, 1986); may administer undiluted or diluted in a beverage (eg, orange juice) (Vanier 2006). Storage/Stability Injection: Store at 15°C to 30°C (59°F to 86°F). Protect from light. Note: Store Hospira product at 20°C to 25°C (68°F to 77°F). Oral: Store tablets at 15°C to 30°C (59°F to 86°F). Protect from light. Preparation for AdministrationDilute injection solution in preservative-free NS, D5W, or D5NS. To reduce the incidence of anaphylactoid reaction upon IV administration, dilute dose in a minimum of 50 mL of compatible solution and administer using an infusion pump over at least 20 minutes (Ageno, 2012). Extemporaneously PreparedA 1 mg/mL oral suspension may be made with tablets. Crush six 5 mg tablets in a mortar and reduce to a fine powder. Add 5 mL each of water and methylcellulose 1% and mix to a uniform paste. Mix while adding sorbitol in incremental proportions to almost 30 mL; transfer to a calibrated bottle, rinse mortar with sorbitol, and add quantity of sorbitol sufficient to make 30 mL. Label "shake well" and "refrigerate". Stable for 3 days. Nahata MC and Hipple TF, Pediatric Drug Formulations, 3rd ed, Cincinnati, OH: Harvey Whitney Books Co, 1997. Note: The parenteral formulation may also be used for small oral doses (eg, 1 mg) or situations in which tablets cannot be swallowed (Crowther, 2000; O'Connor, 1986); may administer undiluted or diluted in a beverage (eg, orange juice) (Vanier 2006). Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience injection site pain or irritation, change in taste, or flushing. Have patient report immediately to prescriber tachycardia, arrhythmia, severe dizziness, passing out, shortness of breath, sweating a lot, or skin discoloration (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients. Medication Safety Issues Sound-alike/look-alike issues: ContraindicationsHypersensitivity to phytonadione or any component of the formulation Warnings/Precautions Concerns related to adverse effects: • Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]: Severe reactions resembling hypersensitivity reactions (eg, anaphylaxis) have occurred rarely during or immediately after IV administration (even with proper dilution and rate of administration); some patients had no previous exposure to phytonadione. Anaphylactoid reactions typically occurred when patients received large IV doses administered rapidly with formulations containing polyethoxylated castor oil (also called polyoxyethylated castor oil); proper dosing, dilution, and administration will minimize risk (Ageno, 2012; Riegert-Johnson, 2002). Limit IV administration to situations where an alternative route of administration is not feasible and the benefit of therapy outweighs the risk of hypersensitivity reactions. Allergic reactions have also occurred with IM and SubQ injections, albeit less frequently. Disease-related concerns: • Anticoagulant-induced hypoprothrombinemia: In patients receiving a therapeutic vitamin K antagonist (VKA) (eg, warfarin), administer a dose of phytonadione that will quickly lower the INR into a safe range without causing resistance to warfarin. High phytonadione doses may lead to warfarin resistance for at least one week. • Liver disease induced hypoprothrombinemia: If initial doses do not reverse coagulopathy, then higher doses are unlikely to have any effect. Note: Ineffective in hereditary hypoprothrombinemia. • Long-acting anticoagulant rodenticide (LAAR) ingestion: Patients with LAAR-induced coagulopathy require much larger doses and longer treatment durations (up to months) after exposure compared to that needed to reverse VKA-induced coagulopathy. Special populations: • Neonates: Use with caution in neonates, especially premature infants; severe hemolytic anemia, jaundice, and hyperbilirubinemia have been reported with larger than recommended doses (10 to 20 mg). Dosage form specific issues: • Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register, 2002). See manufacturer's labeling. • Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling. • Polyoxyethylated castor oil: Some injectable dosage forms contain polyoxyethylated castor oil (Cremophor EL) which is associated with hypersensitivity reactions. • Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer's labeling. Other warnings/precautions: • Appropriate route: Oral administration is the safest and requires the presence of bile salts for absorption. In obstructive jaundice or with biliary fistulas, concurrent administration of bile salts would be necessary for proper absorption. Manufacturers recommend the SubQ route over other parenteral routes, however, SubQ is less predictable when compared to the oral route, and efficacy may be delayed. The American College of Chest Physicians recommends the IV route in patients with major bleeding secondary to use of VKAs such as warfarin. The IV route should be restricted to emergency situations only where oral phytonadione cannot be used. Efficacy (eg, control of bleeding, decrease in INR) is delayed regardless of route of administration; patient management may require other treatments in the interim. * See Cautions in AHFS Essentials for additional information. Geriatric ConsiderationsNo special recommendation for use or dosing in elderly. Pregnancy Risk FactorC Pregnancy ConsiderationsAnimal reproduction studies have not been conducted. Phytonadione crosses the placenta in limited concentrations (Kazzi, 1990). The dietary requirements of vitamin K are the same in pregnant and nonpregnant women (IOM, 2000). In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey, 2003). Breast-Feeding ConsiderationsSmall amounts of dietary vitamin K can be detected in breast milk and the dietary requirements of vitamin K are the same in nursing and non-nursing women (IOM, 2000). Information following the use of phytonadione has not been located. The manufacturer recommends caution be used if phytonadione is administered to a nursing woman. Briggs' Drugs in Pregnancy & Lactation Phytonadione Adverse Reactions Frequency not defined. Cardiovascular: Flushing, hypertension, hypotension Central nervous system: Dizziness Dermatologic: Diaphoresis, erythematous rash, pruritus Gastrointestinal: Dysgeusia, nausea Hypersensitivity: Anaphylactoid reaction (non-immunologic anaphylaxis), hypersensitivity reaction Local: Fibrosis at injection site, injection site reaction Respiratory: Cyanosis, dyspnea * See Cautions in AHFS Essentials for additional information. Metabolism/Transport EffectsNone known. Drug Interactions Open Interactions Mineral Oil: May decrease the serum concentration of Phytonadione. Specifically, mineral oil may decrease the absorption of phytonadione. Risk C: Monitor therapy Orlistat: May decrease the serum concentration of Vitamins (Fat Soluble). Management: Administer oral fat soluble vitamins at least 2 hours before or after the administration of orlistat. Similar precautions do not apply to parenterally administered fat soluble vitamins. Risk D: Consider therapy modification Vitamin K Antagonists (eg, warfarin): Phytonadione may diminish the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification Genes of Interest Vitamin K Epoxide Reductase Complex, Subunit 1 Monitoring ParametersPT, INR; monitor for hypersensitivity reactions if administering IV. Nursing: Physical Assessment/MonitoringNote dosing specifics according to use. Assess degree of bleeding. Dosage Forms Considerations Injectable products may contain alcohol, benzyl alcohol, polysorbate 80, propylene glycol, or polyoxyethylated/polyethoxylated castor oil (Cremophor EL). Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. Injection, aqueous colloidal: 1 mg/0.5 mL (0.5 mL); 10 mg/mL (1 mL) Injection, aqueous colloidal [preservative free]: 1 mg/0.5 mL (0.5 mL) Tablet, oral: 100 mcg Mephyton®: 5 mg [scored] Anatomic Therapeutic Chemical (ATC) Classification B02BA01 Generic Available (US)Yes Pricing: US Solution (Phytonadione Injection) 1 mg/0.5 mL (0.5 mL): $5.32 Tablets (Mephyton Oral) 5 mg (100): $7051.21 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Mechanism of ActionPromotes liver synthesis of clotting factors (II, VII, IX, X); however, the exact mechanism as to this stimulation is unknown. Menadiol is a water soluble form of vitamin K; phytonadione has a more rapid and prolonged effect than menadione; menadiol sodium diphosphate (K4) is half as potent as menadione (K3). Pharmacodynamics/Kinetics Onset of action: Increased coagulation factors: Oral: 6-10 hours; IV: 1-2 hours Peak effect: INR values return to normal: Oral: 24-48 hours; IV: 12-14 hours Absorption: Oral: From intestines in presence of bile; SubQ: Variable; IM: Readily Metabolism: Rapidly hepatic Excretion: Urine and feces Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Effects on Dental TreatmentKey adverse event(s) related to dental treatment: Abnormal taste. Effects on BleedingPhytonadione is a synthetic form of vitamin K and has been used as an antidote to reverse warfarin-induced bleeding complications or endogenous vitamin K deficiencies. Related Information Reversal of Oral Anticoagulants

Rubella (vaccine, pregnancy and postpartum)

Rubella Vaccine Printed on 2016-09-13 You must carefully read the "Consumer Information Use and Disclaimer" below in order to understand and correctly use this information Why is this procedure done? You can pass a rubella infection from one person to another with close contact. You can spread it through sneezing or coughing. Getting a vaccine is a way to stop the spread of this infection. Rubella vaccine is most often included in the shot for measles, mumps, or varicella. Your child needs two doses of this vaccine. The first dose should be when your child is 12 to 15 months old. The second dose should be when your child is 4 to 6 years old. Get this shot now if you did not have it as a child. What will the results be? The shots will protect you from rubella. What happens before the procedure? Your doctor will take your history. Do not get this shot if you: Are allergic to the vaccines Are pregnant Have HIV/AIDS or low immune system Have cancer Have low blood counts What happens during the procedure? The staff will clean your skin area with an alcohol wipe. The staff will give you a shot to inject the drug. You will feel a pinch to your skin when the needle goes into your skin. The staff will inject the drug into your muscle and then take out the needle. A bandage will cover the site. What happens after the procedure? You may go home right away and back to your activities. What care is needed at home? You may put a cold pad on the shot site if it is sore or painful. What follow-up care is needed? Your doctor may ask you to make visits to the office for your next shot. Be sure to keep these visits. What problems could happen? Fever Mild rash Where can I learn more? Centers for Disease Control and Prevention http://www.cdc.gov/features/rubella/ Immunization Action Coalition http://www.immunize.org/catg.d/p4218.pdf

Prenatal Vitamins

Vitamins (Multiple/Prenatal) (Lexi-Drugs) Pronunciation (VYE ta mins, MUL ti pul/pree NAY tal) Brand Names: USA-Free Prenatal [OTC]; CitraNatal 90 DHA; CitraNatal Assure; CitraNatal B-Calm; CitraNatal DHA; CitraNatal Harmony; CitraNatal Rx; Concept DHA; Concept OB; Duet; Duet DHA Balanced; Femecal OB; Focalgin-B; Folcaps Care One; Folet DHA; Folet One; Foltabs Prenatal; Foltabs Prenatal Plus DHA; Gesticare DHA; Infanate Balance; Infanate Plus [DSC]; KPN Prenatal [OTC]; Mini-Prenatal [OTC]; Multi-Nate 30; NataFort [OTC] [DSC]; Natal-V RX [DSC]; Nestabs ABC; Nexa Plus; Niva-Plus; Néevo DHA; Néevo [DSC]; OB Complete Gold; OB Complete One; OB Complete Petite; OB Complete Premier; One A Day Women's Prenatal [OTC]; OptiNate; Paire OB Plus DHA; PreCare; PreferaOB; PreferaOB + DHA; PreferaOB One; PreFol-DHA; Prena1; Prena1 True [OTC]; Prenaissance 90 DHA [DSC]; Prenaissance DHA [DSC]; Prenaissance Promise [DSC]; Prenatabs FA; Prenatabs Rx; Prenatal 19; Prenatal One Daily [OTC]; Prenatal Rx 1; Prenate AM; Prenate DHA; Prenate Elite; Prenate Essential [DSC]; Prenate Mini; Prenate Pixie; Prenate Star; PreNexa Premier; PrimaCare One; Provida DHA; Select-OB; Stuart Prenatal [OTC] [DSC]; TriCare Prenatal; TriCare Prenatal DHA One; TriStart DHA; Triveen-PRx RNF; Vinacal B [DSC]; Vinate Care; Virt Nate; Virt-Advance; Virt-C DHA; Virt-PN; Virt-PN DHA; Virt-Vite GT; VirtPrex; Vitafol Ultra; Vitafol-Nano; Vitafol-OB [OTC]; Vitafol-OB+DHA [OTC]; Vitafol-PN [DSC]; VitaPhil + DHA; Vol-Tab Rx; VP-CH-PNV; VP-Heme OB; VP-Heme OB + DHA; VP-PNV-DHA Pharmacologic CategoryVitamin Dosing: AdultDietary supplement: Oral: Capsule, tablet: One daily Dosing: GeriatricRefer to adult dosing. Use: Labeled IndicationsNutritional supplement for use prior to conception, during pregnancy, and postnatal (in lactating and nonlactating women) Administration: OralMay administer with food to decrease stomach upset. Dietary ConsiderationsMay be taken with food to decrease stomach upset. Some products may contain phenylalanine. Medication Patient Education with HCAHPS Considerations • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) • Patient may experience constipation, stool discoloration, or diarrhea. Have caregiver report immediately to prescriber black, tarry, or bloody stools, severe nausea, severe vomiting, severe abdominal pain, vomiting blood, or abdominal cramps (HCAHPS). • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients. Medication Safety Issues Sound-alike/look-alike issues: ContraindicationsHypersensitivity to any component of the formulation. Additional contraindications may be product-dependent; refer to manufacturer's labeling. Warnings/Precautions Concerns related to adverse effects: • Iron toxicity: Severe iron toxicity may occur in overdose, particularly when ingested by children; iron is a leading cause of fatal poisoning in children; store out of children's reach and in child-resistant containers. Adult preparations may contain amounts of iron which should not be used in children. Disease-related concerns: • Hemochromatosis/hemosiderosis: Iron supplementation should not be used with hemochromatosis and hemosiderosis. • Hepatic impairment: Use with caution in patients with severe hepatic impairment. • Kidney stones: Use with caution in patients with kidney stones due to calcium content. • Renal impairment: Use with caution in patients with severe renal impairment. Pregnancy ConsiderationsRefer to individual vitamin monographs for requirements during pregnancy. Breast-Feeding Considerations Refer to individual vitamin monographs for requirements while breast-feeding. Briggs' Drugs in Pregnancy & Lactation Vitamins, Multiple Adverse ReactionsFrequency not defined. Gastrointestinal: Abdominal pain, constipation, dark stools, diarrhea, nausea, vomiting Miscellaneous: Allergic reaction Toxicology Iron Niacin Pyridoxine Vitamin A Vitamin D Vitamin E (Systemic) Food InteractionsIron absorption is inhibited by eggs and milk. Dosage FormsExcipient information presented when available (limited, particularly for generics); consult specific product labeling. Content varies depending on product used. For more detailed information on ingredients in these and other multivitamins, please refer to specific product labeling. Generic Available (US)Yes Pricing: US Capsule Therapy Pack (Vitafol FE+ Oral) 90-1-200 & 50 mg (60): $124.99 Capsule, controlled release (VitaPearl Oral) 30-1.4-200 mg (30): $119.60 Capsules (CitraNatal Harmony Oral) 27-1-260 mg (30): $111.19 Capsules (Concept DHA Oral) 53.5-38-1 mg (30): $35.72 Capsules (Concept OB Oral) 130-92.4-1 mg (30): $33.07 Capsules (Folcaps Omega 3 Oral) 27-1 mg (30): $42.98 Capsules (Folet One Oral) 38-1-225 mg (30): $131.25 Capsules (Folivane-OB Oral) 130-92.4-1 mg (30): $26.70 Capsules (Macnatal CN DHA Oral) 28-1-250 mg (30): $59.29 Capsules (Marnatal-F Oral) 60-1 mg (30): $71.99 Capsules (Natelle ONE Oral) 28-1-250 mg (30): $192.81 Capsules (Neevo DHA Oral) 27-1.13 mg (90): $398.99 Capsules (Nexa Plus Oral) 29-1.25-350 mg (30): $139.56 Capsules (OB Complete Gold Oral) 27.5-1-200 mg (30): $150.00 Capsules (OB Complete One Oral) 50-1-476 mg (30): $155.74 Capsules (OB Complete Petite Oral) 35-5-1-200 mg (30): $150.97 Capsules (OB Complete/DHA Oral) 30-10-1-200 mg (60): $152.99 Capsules (Perry Prenatal Oral) 13.5-0.4 mg (200): $12.00 Capsules (PreferaOB One Oral) 22-6-1-200 mg (30): $140.45 Capsules (Prenatal-U Oral) 106.5-1 mg (100): $86.75 Capsules (Prenate DHA Oral) 18-0.6-0.4-300 mg (30): $182.58 28-0.6-0.4-300 mg (30): $130.19 Capsules (Prenate Enhance Oral) 28-0.6-0.4-400 mg (30): $182.58 Capsules (Prenate Essential Oral) 18-0.6-0.4-300 mg (30): $182.58 29-0.6-0.4-340 mg (30): $138.88 Capsules (Prenate Mini Oral) 18-0.6-0.4-350 mg (30): $182.58 29-0.6-0.4-350 mg (30): $142.70 Capsules (Prenate Pixie Oral) 10-0.6-0.4-200 mg (30): $182.58 Capsules (Prenate Restore Oral) 27-0.6-0.4-400 mg (30): $182.58 Capsules (Provida DHA Oral) 16-16-1.25-110 mg (30): $59.94 Capsules (Provida OB Oral) 20-20-1.25 mg (30): $31.50 Capsules (R-Natal OB Oral) 20-1-320 mg (30): $115.20 Capsules (Taron-C DHA Oral) 53.5-38-1 mg (30): $31.72 Capsules (Taron-Prex Oral) 30-1.2-265 mg (30): $51.28 Capsules (TriCare Prenatal DHA ONE Oral) 27-1-500 mg (30): $83.88 Capsules (Triveen-PRx RNF Oral) 26-1.2-300 mg (60): $104.78 Capsules (VemaVite-PRx 2 Oral) 27-1.25-300 mg (30): $56.68 Capsules (Vinate DHA RF Oral) 27-1.13 mg (90): $332.36 Capsules (Vinate IC Oral) 162-115.2-1 mg (90): $46.59 Capsules (Vitafol Ultra Oral) 29-0.6-0.4-200 mg (30): $124.20 Capsules (Vitafol-One Oral) 29-1-200 mg (30): $122.40 Capsules (VitaMedMD One Rx/Quatrefolic Oral) 30-0.6-0.4-200 mg (30): $119.60 Capsules (Viva DHA Oral) 28-1-200 mg (30): $119.99 Capsules (Zatean-CH Oral) 27-1-250 mg (30): $48.29 Capsules (Zatean-Pn DHA Oral) 27-0.6-0.4-300 mg (30): $67.98 Capsules (Zatean-Pn Plus Oral) 28-0.6-0.4-340 mg (30): $72.29 Chewable (NataChew Oral) 28-1 mg (90): $414.00 Chewable (PreNata Oral) 29-1 mg (90): $44.24 Chewable (Prenate Oral) 0.6-0.4 mg (30): $182.58 Chewable (Select-OB Oral) 29-0.6-0.4 mg (90): $352.08 29-1 mg (90): $179.56 Chewable (Vinate Care Oral) 40-1 mg (30): $34.75 Chewable (Vitafol Gummies Oral) 3.33-0.333-34.8 mg (90): $124.99 Chewable (VitaMedMD RediChew Rx Oral) 1.4 mg (30): $119.60 Misc (CitraNatal 90 DHA Oral) 90-1 & 300 mg (60): $114.82 Misc (CitraNatal Assure Oral) 35-1 & 300 mg (60): $110.83 Misc (CitraNatal DHA Oral) 27-1 & 250 mg (60): $105.76 Misc (Duet DHA 400 Oral) 25-1 & 400 mg (60): $193.20 Misc (Duet DHA Balanced Oral) 25-1 & 267 mg (60): $193.20 Misc (Focalgin 90 DHA Oral) 90-1 & 300 mg (60): $93.94 Misc (Focalgin CA Oral) 35-1 & 300 mg (60): $90.67 Misc (Nestabs ABC Oral) 32-1-200 mg (60): $113.26 Misc (PreferaOB +DHA Oral) 28-6-1 & 200 mg (60): $105.25 Misc (Vinacal B Oral) 20-1 & 25 (2) mg (90): $64.56 Misc (VitaTrue Oral) 30-1.4 & 300 mg (60): $119.60 Tablets (CitraNatal Rx Oral) 27-1 mg (90): $229.90 Tablets (Elite-OB Oral) 50-1.25 mg (100): $150.18 Tablets (Mynatal Oral) 90-1 mg (100): $12.78 Tablets (Nestabs Oral) 32-1 mg (90): $161.51 Tablets (Newgen Oral) 32-1 mg (90): $122.22 Tablets (Niva-Plus Oral) 27-1 mg (100): $18.88 Tablets (O-Cal FA Oral) 27-1 mg (100): $28.34 Tablets (OB Complete Oral) 50-1.25 mg (100): $194.60 Tablets (OB Complete Premier Oral) 30-20-1 mg (30): $109.14 Tablets (Obstetrix EC Oral) 29-1 mg (60): $23.13 Tablets (Prefera OB Oral) 34-1 mg (90): $420.08 Tablets (Prenatabs Rx Oral) 29-1 mg (90): $61.54 Tablets (Prenate AM Oral) 1 mg (30): $182.58 Tablets (Prenate Elite Oral) 20-0.6-0.4 mg (30): $182.58 26-0.6-0.4 mg (30): $126.59 Tablets (Prenate Star Oral) 20-1 mg (30): $182.58 Tablets (PreQue 10 Oral) 15-25-0.5-50 mg (60): $107.22 Tablets (Right Step Prenatal Oral) 27-0.8 mg (100): $16.59 Tablets (Vinate AZ Extra Oral) 29-1 mg (90): $55.07 Tablets (Vinate C Oral) 30-1 mg (30): $34.75 Tablets (Vinate Calcium Oral) 27-1 mg (100): $42.26 Tablets (Vinate II Oral) 29-1 mg (100): $36.67 Tablets (Vinate M Oral) 27-1 mg (100): $25.95 Tablets (Vinate One Oral) 60-1 mg (100): $28.78 Tablets (Vitafol-Nano Oral) 18-0.6-0.4 mg (30): $122.40 Therapy Pack (Folet DHA Oral) 38-1 & 350 mg (60): $137.50 Therapy Pack (TriCare Prenatal Oral) 4.5-1 & 150 mg (120): $126.39 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly. Local Anesthetic/Vasoconstrictor PrecautionsNo information available to require special precautions Effects on Dental TreatmentNo significant effects or complications reported Effects on BleedingNo information available to require special precautions Related Information Multivitamin Product Table Index TermsPrenatal Vitamins