Week 2 - Part 2

Réussis tes devoirs et examens dès maintenant avec Quizwiz!

rosuvastatin: medication guide

• 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, dyspepsia, or arthralgia. Have patient report immediately to prescriber signs of pancreatitis, hematuria, urinary retention, oliguria, signs of severe muscle problems, or signs of hepatic impairment (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.

benazepril: pharmacology and PK = MOA

Competitive inhibition of angiotensin I being converted to angiotensin II, a potent vasoconstrictor, through the angiotensin I-converting enzyme (ACE) activity, with resultant lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion

benazepril: warnings/precaution

Concerns related to adverse effects: • Angioedema: Any time during treatment (especially following first dose) angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). African-Americans and patients with idiopathic or hereditary angioedema may be at an increased risk. Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Contraindicated in patients with history of angioedema with or without prior ACE inhibitor therapy. • Cholestatic jaundice: A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, which may progress to fulminant hepatic necrosis; discontinue if marked elevation of hepatic transaminases or jaundice occurs. • Cough: An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1-4 weeks after discontinuation of the ACE inhibitor. Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation. • Hyperkalemia: May occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium containing salts. Use cautiously, if at all, with these agents and monitor potassium periodically. • Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors. • Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation. • Neutropenia/agranulocytosis: Another ACE Inhibitor, captopril, has been associated with rare cases of agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia. Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Periodically monitor CBC with differential in these patients. • Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Disease-related concerns: • Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia. • Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs. • Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity. • Diabetes: Use with caution in patients with diabetes receiving insulin or oral antidiabetic agents; may be at increased risk for episodes of hypoglycemia. • 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. • Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. • Renal impairment: Use with caution in preexisting renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment. 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 populations: • Pregnancy: [U.S. Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. Other warnings/precautions: • Surgery: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis, 2011).

simvastatin: warnings/precaution

Concerns related to adverse effects: • Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy far outweigh the risk of dysglycemia. • Hepatotoxicity: Postmarketing reports of fatal and nonfatal hepatic failure are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy. If an alternate etiology is not identified, do not restart simvastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated; routine periodic monitoring of liver enzymes is not necessary. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption. • Immune-mediated necrotizing myopathy (IMNM): IMNM, an autoimmune-mediated myopathy, has been reported (rarely) with HMG-CoA reductase inhibitor therapy. IMNM presents as proximal muscle weakness with elevated CPK levels, which persists despite discontinuation of HMG-CoA reductase inhibitor therapy; additionally, muscle biopsy may show necrotizing myopathy with limited inflammation. Immunosuppressive therapy (eg, corticosteroids, azathioprine) may be used for treatment. • Myopathy/rhabdomyolysis: Patients receiving HMG-CoA reductase inhibitors have developed rhabdomyolysis with acute renal failure and/or myopathy; patients should be monitored closely. This risk is dose-related and is increased with high doses (80 mg), concurrent use of other lipid-lowering medications (fibric acid derivatives, or niacin at doses ≥1 g/day), other interacting drugs (eg, moderate-to-strong CYP3A4 inhibitors), age ≥65 years, female gender, uncontrolled hypothyroidism, and renal dysfunction. Use with caution in patients taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine. Disease-related concerns: • Hepatic impairment and/or ethanol use: Use with caution in patients who consume large amounts of ethanol or have a history of liver disease. Use is contraindicated with active liver disease and with unexplained transaminase elevations. • Renal impairment: Use with caution in patients with severe renal impairment (creatinine clearance not defined); initial dosage adjustment is necessary; monitor closely. Initial dosage adjustment is not necessary in mild-to-moderate impairment. Renal impairment may also increase risk for myopathy. Concurrent drug therapy issues: • High potential for interactions: Concomitant use of simvastatin with some drugs may require cautious use, may not be recommended, may require dosage adjustments, or may be contraindicated. If concurrent use of a contraindicated interacting medication is unavoidable, treatment with simvastatin should be suspended during use or consider the use of an alternative HMG-CoA reductase inhibitor void of CYP3A4 metabolism. Special Populations: • Chinese patients: Do not use high dose simvastatin (80 mg) if concurrently taking niacin ≥1 g/day; concomitant use may increase risk of myopathy in Chinese patients. • Elderly: Use with caution in patients ≥65 years of age; these patients are predisposed to myopathy. • Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure (eg, sepsis, hypotension, trauma, uncontrolled seizures). Based on current research and clinical guidelines (Fleisher, 2009), HMG-CoA reductase inhibitors should be continued in the perioperative period. Postoperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality. Other warnings/precautions: • Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.

rosuvastatin: warnings/precautions

Concerns related to adverse effects: • Diabetes mellitus: Small increases in HbA1c (mean: ~0.1%) and fasting blood glucose have been reported with rosuvastatin; however, the benefits of statin therapy far outweigh the risk of dysglycemia. • Hematuria/proteinuria: Hematuria (microscopic) and proteinuria have been observed; more commonly reported in adults receiving rosuvastatin 40 mg daily. Typically, transient and not associated with a decrease in renal function. Consider dosage reduction if unexplained hematuria and proteinuria persists. • Hepatotoxicity: Postmarketing reports of fatal and nonfatal hepatic failure are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy. If an alternate etiology is not identified, do not restart rosuvastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated; routine periodic monitoring of liver enzymes is not necessary. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption. • Immune-mediated necrotizing myopathy (IMNM): IMNM, an autoimmune-mediated myopathy, has been reported (rarely) with HMG-CoA reductase inhibitor therapy. IMNM presents as proximal muscle weakness with elevated CPK levels, which persists despite discontinuation of HMG-CoA reductase inhibitor therapy; additionally, muscle biopsy may show necrotizing myopathy with limited inflammation. Immunosuppressive therapy (eg, corticosteroids, azathioprine) may be used for treatment. • Myopathy/rhabdomyolysis: Patients receiving HMG-CoA reductase inhibitors have developed rhabdomyolysis with acute renal failure and/or myopathy; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of other lipid-lowering medications (fibric acid derivatives or niacin doses ≥1 g/day), other interacting drugs, other drugs associated with myopathy (eg, colchicine), age ≥65 years, female gender, uncontrolled hypothyroidism, and renal dysfunction. Use caution in patients with renal impairment, inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or dark urine. Disease-related concerns: • Hepatic impairment and/or ethanol use: Use with caution in patients who consume large amounts of ethanol or have a history of liver disease. Use is contraindicated with active liver disease or unexplained transaminase elevations. • Renal impairment: Dosage adjustment required in patients with a CrCl <30 mL/minute/1.73 m2 and not receiving hemodialysis (contraindicated in the Canadian labeling). 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 populations: • Asian population: Increased risk of rosuvastatin-associated myopathy in certain subgroups; dosage adjustment should be considered for patients of Asian descent. Use of rosuvastatin at a dose of 40 mg/day in Asian patients is contraindicated in the Canadian labeling. • Elderly: Use with caution in patients with advanced age; these patients are more predisposed to myopathy. • Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure (eg, sepsis, hypotension, trauma, uncontrolled seizures). Based on current research and clinical guidelines (Fleisher 2009), HMG-CoA reductase inhibitors should be continued in the perioperative period. Postoperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality. Other warnings/precautions: • Appropriate use: Secondary causes of hyperlipidemia should be ruled out prior to therapy. Rosuvastatin has not been studied when the primary lipid abnormality is chylomicron elevation (Fredrickson types I and V).

benazepril: dosing hepatic impairment

No dosage adjustment provided in manufacturer's labeling (has not been studied); use with caution.

benazepril: interactions - metabolism/transport

None known.

simvastatin: brand names

Zocor

simvastatin: adverse reactions

1% to 10%: Cardiovascular: Atrial fibrillation (6%; placebo 5%), edema (3%; placebo 2%) Central nervous system: Headache (3% to 7%), vertigo (5%) Dermatologic: Eczema (5%) Gastrointestinal: Abdominal pain (7%), constipation (2% to 7%), gastritis (5%), nausea (5%) Hepatic: Transaminases increased (>3 x ULN; 1%) Neuromuscular & skeletal: CPK increased (>3 x normal; 5%), myalgia (4%) Respiratory: Upper respiratory infections (9%), bronchitis (7%) <1%, postmarketing, and/or case reports: Alkaline phosphatase increased, alopecia, amnesia (reversible), anaphylaxis, anemia, angioedema, arthralgia, arthritis, blood glucose increased, chills, cognitive impairment (reversible), confusion (reversible), depression, dermatomyositis, diabetes mellitus (new onset), diarrhea, dizziness, dryness of skin/mucous membranes, dyspepsia, dyspnea, eosinophilia, erythema multiforme, ESR increased, fever, flatulence, flushing, glycosylated hemoglobin (Hb A1c) increased, GGT increased, hemolytic anemia, hepatic failure, hepatitis, hypersensitivity reaction, jaundice, leukopenia, malaise, memory disturbance (reversible), memory impairment (reversible), muscle cramps, nail changes, nodules, pancreatitis, paresthesia, peripheral neuropathy, photosensitivity, polymyalgia rheumatica, positive ANA, pruritus, purpura, rash, rhabdomyolysis, skin discoloration, Stevens-Johnson syndrome, systemic lupus erythematosus-like syndrome, thrombocytopenia, toxic epidermal necrolysis, urticaria, vasculitis, vomiting, weakness Additional class-related events or case reports (not necessarily reported with simvastatin therapy): Alteration in taste, anorexia, anxiety, bilirubin increased, cataracts, cholestatic jaundice, cirrhosis, decreased libido, depression, erectile dysfunction/impotence, facial paresis, fatty liver, fulminant hepatic necrosis, gynecomastia, hepatoma, hyperbilirubinemia, immune-mediated necrotizing myopathy (IMNM), impaired extraocular muscle movement, increased CPK (>10 x normal), interstitial lung disease, ophthalmoplegia, peripheral nerve palsy, psychic disturbance, renal failure (secondary to rhabdomyolysis), thyroid dysfunction, tremor, vertigo

benazepril: adverse reactions

1% to 10%: Central nervous system: Headache (6%), dizziness (4%), drowsiness (2%), orthostatic dizziness (2%) Renal: Increased serum creatinine (2%), renal insufficiency (may occur in patients with bilateral renal artery stenosis or hypovolemia) Respiratory: Cough (1% to 10%) <1%, postmarketing, and/or case reports (Limited to important or life-threatening): Agranulocytosis, alopecia, anaphylactoid reaction, angina pectoris, angioedema (includes head, neck, and intestinal angioedema), arthralgia, arthritis, asthma, dermatitis, dyspnea, ECG changes, eosinophilia, flushing, gastritis, hemolytic anemia, hyperbilirubinemia, hyperglycemia, hyperkalemia, hypersensitivity, hypertonia, hyponatremia, hypotension, impotence, increased blood urea nitrogen (transient), increased serum transaminases, increased uric acid, insomnia, leukopenia, myalgia, neutropenia, orthostatic hypotension, palpitations, pancreatitis, paresthesia, pemphigus, peripheral edema, proteinuria, pruritus, shock, skin photosensitivity, skin rash, Stevens-Johnson syndrome, syncope, thrombocytopenia, vomiting Eosinophilic pneumonitis, anaphylaxis, neutropenia, agranulocytosis, renal insufficiency, and renal failure have been reported with other ACE inhibitors. In addition, a syndrome including fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia, and elevated ESR has been reported to be associated with ACE inhibitors.

rosuvastatin: adverse reactions

>10%: Neuromuscular & skeletal: Myalgia (3% to 13%) 1% to 10%: Central nervous system: Headache (6%), dizziness (4%) Endocrine & metabolic: Diabetes mellitus (new onset: 3%) Gastrointestinal: Nausea (2% to 3%), abdominal pain (2%), constipation (2%) Hepatic: Increased serum ALT (2%; >3 times ULN) Neuromuscular & skeletal: Arthralgia (4% to 10%), increased creatine phosphokinase (3%; >10 x ULN: Children 3%), weakness (3%) <1%, postmarketing, and/or case reports: Abnormal thyroid function test, cognitive dysfunction (reversible; includes amnesia, confusion, memory impairment), depression, elevated glycosylated hemoglobin (HbA1c), gynecomastia, hematuria (microscopic), hepatic failure, hepatitis, hypersensitivity reaction (including angioedema, pruritus, skin rash, urticaria), immune-mediated necrotizing myopathy, increased gamma-glutamyl transferase, increased serum alkaline phosphatase, increased serum bilirubin, increased serum glucose, increased serum transamines, jaundice, myoglobinuria, myopathy, myositis, pancreatitis, peripheral neuropathy, proteinuria (dose related), renal failure, rhabdomyolysis, sleep disorder (including insomnia and nightmares), thrombocytopenia

simvastatin: interactions- drug interaction

Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy Amiodarone: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Dose of HMG-CoA reductase inhibitor may need to be reduced (limit simvastatin adult maximum dose to 20 mg/day, limit lovastatin adult maximum dose to 40 mg/day). Risk D: Consider therapy modification AmLODIPine: May increase the serum concentration of Simvastatin. Management: Avoid the concurrent use of amlodipine with simvastatin when possible. If used together, avoid doses of simvastatin greater than 20 mg/day (for adults). Risk D: Consider therapy modification Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy Azithromycin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Risk C: Monitor therapy Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Monitor patients closely for myopathy with concomitant use of bezafibrate and HMG-CoA reductase inhibitors. Concomitant use is contraindicated in patients predisposed to myopathy and alternative therapy should be considered. Risk D: Consider therapy modification Boceprevir: May increase the serum concentration of Simvastatin. Risk X: Avoid combination Bosentan: May increase the metabolism of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Ceritinib: May increase the serum concentration of CYP3A4 Substrates. Management: Use of ceritinib with a narrow therapeutic index CYP3A substrate (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) should be avoided when possible. Risk C: Monitor therapy Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Risk D: Consider therapy modification Clarithromycin: May increase the serum concentration of Simvastatin. Risk X: Avoid combination Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Risk D: Consider therapy modification Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination CycloSPORINE (Systemic): May increase the serum concentration of Simvastatin. 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 decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy CYP3A4 Inhibitors (Strong): May increase the serum concentration of Simvastatin. Risk X: Avoid combination Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Avoid use of statins metabolized by CYP3A4 (eg, simvastatin) and consider avoiding fluvastatin as well in patients receiving high dose cyproterone (300 mg/day). Consider use of pravastatin, rosuvastatin, or pitavastatin if statin therapy is needed. 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 Danazol: May increase the serum concentration of Simvastatin. Risk X: Avoid combination DAPTOmycin: HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Risk D: Consider therapy modification 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 Diltiazem: May increase the serum concentration of Simvastatin. Simvastatin may increase the serum concentration of Diltiazem. Management: Avoid concurrent use of diltiazem with simvastatin when possible. If used together, limit adult doses to simvastatin 10 mg/day and diltiazem 240 mg/day; avoid Simcor (simvastatin/niacin) because fixed simvastatin doses exceed the maximum. Risk D: Consider therapy modification Dronedarone: May increase the serum concentration of Simvastatin. Management: Limit simvastatin to a max of 10 mg/day (in adults). Increase monitoring for signs of simvastatin toxicity (e.g., myositis, rhabdomyolysis). Risk D: Consider therapy modification Efavirenz: May decrease the serum concentration of Simvastatin. Risk C: Monitor therapy Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Management: According to eltrombopag prescribing information, consideration of a preventive dose reduction may be warranted. Risk D: Consider therapy modification Erythromycin (Systemic): May increase the serum concentration of Simvastatin. Risk X: Avoid combination Eslicarbazepine: May decrease the serum concentration of Simvastatin. Risk C: Monitor therapy Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. This applies to atorvastatin, lovastatin and simvastatin. Conversely, levels of fluvastatin may be increased. Management: Dose adjustment of the HMG-CoA reductase inhibitor may be warranted. No interaction is expected with rosuvastatin, pravastatin, or pitavastatin. Risk C: Monitor therapy Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy Fluconazole: May increase the serum concentration of Simvastatin. Risk C: Monitor therapy Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Fosphenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Risk D: Consider therapy modification Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Risk X: Avoid combination Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Gemfibrozil may increase the serum concentration of Simvastatin. Concentrations of the active simvastatin acid metabolite may also be increased by gemfibrozil. Risk X: Avoid combination Grapefruit Juice: May increase the serum concentration of Simvastatin. Risk X: Avoid combination Green Tea: May increase the serum concentration of Simvastatin. Specifically, Simvastatin lactone concentrations may be increased. Risk C: Monitor therapy Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Imatinib: May decrease the metabolism of Simvastatin. Risk C: Monitor therapy Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification Lercanidipine: May increase the serum concentration of Simvastatin. Management: Administer lercanidipine in the morning and simvastatin in the evening in patients receiving these drugs in combination. Risk D: Consider therapy modification Lomitapide: May increase the serum concentration of Simvastatin. Management: Reduce the recommended simvastatin dose by 50%. Generally, limit the maximum adult simvastatin dose to 20 mg/day. A 40 mg/day dose can be considered in patients who previously received 80 mg/day for at least a year without evidence of muscle toxicity. Risk D: Consider therapy modification Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Mifepristone: May increase the serum concentration of Simvastatin. Management: Avoid simvastatin during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. Risk X: Avoid combination 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 Netupitant: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: Greatest concern with niacin 1 g/d or greater. Avoid simvastatin 80 mg with niacin 1 g or greater in Chinese patients. Do not exceed 40 mg/d of simva or lovastatin with Niaspan. Use of niacin with rosuvastatin 40 mg is contraindicated (Canadian label). Risk D: Consider therapy modification Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy PAZOPanib: HMG-CoA Reductase Inhibitors may enhance the hepatotoxic effect of PAZOPanib. Specifically, the risk for increased serum transaminase concentrations may be increased. Management: Simvastatin is specifically implicated in this interaction. There is a lack of data regarding the risk with other statins, but caution appears warranted with any statins. Risk C: Monitor therapy Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Risk D: Consider therapy modification Protease Inhibitors: May increase the serum concentration of Simvastatin. Risk X: Avoid combination QuiNINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider using a lower starting dose and lower maintenance/maximum doses of atorvastatin, simvastatin, or lovastatin when used together with quinine. Risk D: Consider therapy modification Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy Ranolazine: May increase the serum concentration of Simvastatin. Management: Avoid the concurrent use of ranolazine with simvastatin when possible. If used together, avoid doses of simvastatin greater than 20 mg/day. Risk D: Consider therapy modification Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Risk X: Avoid combination Rifamycin Derivatives: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Risk D: Consider therapy modification Sildenafil: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Risk D: Consider therapy modification Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Simeprevir: May increase the serum concentration of Simvastatin. Risk C: Monitor therapy St Johns Wort: May increase the metabolism of HMG-CoA Reductase Inhibitors. Management: Consider avoiding the concomitant administration of St Johns Wort with interacting HMG-CoA reductase inhibitors in order to avoid the potential for decreased antilipemic effects. Monitor for decreased effects during concomitant therapy. Risk D: Consider therapy modification St Johns Wort: May decrease the serum concentration 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 Telaprevir: May increase the serum concentration of Simvastatin. Risk X: Avoid combination Telithromycin: May increase the serum concentration of Simvastatin. Risk X: Avoid combination Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Risk C: Monitor therapy Ticagrelor: May increase the serum concentration of Simvastatin. Management: Avoid using doses of simvastatin greater than 40 mg/day with ticagrelor. This specific recommendation is found in the U.S. prescribing information but not in the Canadian product monograph. Risk D: Consider therapy modification Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy Verapamil: May increase the serum concentration of Simvastatin. Management: Avoid concurrent use of verapamil with simvastatin when possible. If used together, limit adult maximum simvastatin dose to 10 mg/day, and avoid Simcor (simvastatin/niacin) because fixed simvastatin doses in the product exceed this maximum. Risk D: Consider therapy modification Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

rosuvastatin: interactions drug interaction

diltiazem: administration and storage

Administration: Oral Immediate release tablet (Cardizem): Administer before meals and at bedtime. The manufacturer recommends to swallow the tablet whole; do not split, crush, or chew. Crushing immediate release tablets may alter pharmacokinetics; film coating is designed to slowly release diltiazem. However, an oral suspension has been made using the immediate release tablets (Allen 1996). Long acting dosage forms: Do not open, chew, or crush; swallow whole. Cardizem CD, Cardizem LA, Cartia XT, Matzim LA: May be administered without regards to meals. Dilacor XR, Dilt-XR, Diltia XT: Administer on an empty stomach. Taztia XT, Tiazac: Capsules may be opened and sprinkled on a spoonful of applesauce. Applesauce should not be hot and should be swallowed without chewing, followed by drinking a glass of water. Tiazac XC [Canadian product; not available in U.S.]: Administer at bedtime Storage/Stability Capsule, tablet: Store at room temperature. Protect from light. Solution for injection: Store in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze. May be stored at room temperature for up to 1 month. Following dilution to ≤1 mg/mL with D51/2NS, D5W, or NS, solution is stable for 24 hours at room temperature or under refrigeration.

rosuvastatin: administration and storage

Administration: Oral May be administered with or without food. May be taken at any time of the day. Storage/Stability Store between 20°C and 25°C (68°F to 77°F). Protect from moisture.

simvastatin: administration and storage

Administration: Oral May be administered without regard to meals. Administer in the evening for maximal efficacy. Storage/Stability Tablets should be stored in tightly-closed containers at temperatures between 5°C to 30°C (41°F to 86°F).

diltiazem: interaction - drug interaction

Alfentanil: Diltiazem may increase the serum concentration of Alfentanil. Risk C: Monitor therapy Alfuzosin: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification Amiodarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk D: Consider therapy modification Anilidopiperidine Opioids: May enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Anilidopiperidine Opioids may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). 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 Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy Aprepitant: May increase the serum concentration of Diltiazem. Diltiazem may increase the serum concentration of Aprepitant. Risk C: Monitor therapy ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy AtorvaSTATin: May increase the serum concentration of Diltiazem. Diltiazem may increase the serum concentration of AtorvaSTATin. Management: Consider using lower atorvastatin doses when used together with diltiazem. Risk D: Consider therapy modification 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 Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects. Risk D: Consider therapy modification 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 Hypotensive Agents. Risk C: Monitor therapy Beta-Blockers: Calcium Channel Blockers (Nondihydropyridine) may enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Bosentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Risk C: Monitor therapy Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Risk X: Avoid combination Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Risk C: Monitor therapy Brimonidine (Topical): May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Risk D: Consider therapy modification BusPIRone: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification 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 Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy CarBAMazepine: May decrease the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of CarBAMazepine. Management: Consider empiric reductions in carbamazepine dose with initiation of nondihydropyridine calcium channel blockers. Monitor for increased toxic effects of carbamazepine and reduced therapeutic effects of the calcium channel blocker. Risk D: Consider therapy modification Cardiac Glycosides: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk X: Avoid combination Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP3A4. Risk D: Consider therapy modification 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 CloNIDine: May enhance the AV-blocking effect of Calcium Channel Blockers (Nondihydropyridine). Sinus node dysfunction may also be enhanced. Risk C: Monitor therapy Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification Colestipol: May decrease the absorption of Diltiazem. Risk C: Monitor therapy Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE (Systemic). Risk D: Consider therapy modification 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 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 CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy 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 Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers (Nondihydropyridine). Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers (Nondihydropyridine). Management: This interaction has only been described with intravenous dantrolene administration. Risk X: Avoid combination Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg/day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider therapy modification 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 Antihypertensives. Risk C: Monitor therapy Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Risk X: Avoid combination DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Risk D: Consider therapy modification Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Risk C: Monitor therapy Dronedarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Dronedarone. Other electrophysiologic effects of Dronedarone may also be increased. Dronedarone may increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Dronedarone. Management: Use lower starting doses of the nondihydropyridine calcium channel blockers (i.e., verapamil, diltiazem), and only consider increasing calcium channel blocker dose after obtaining ECG-based evidence that the combination is being well-tolerated. Risk D: Consider therapy modification DULoxetine: Hypotensive Agents may enhance the orthostatic hypotensive effect of DULoxetine. Risk C: Monitor therapy Efavirenz: May decrease the serum concentration of Diltiazem. Risk C: Monitor therapy Eletriptan: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Eletriptan. Risk C: Monitor therapy Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Risk D: Consider therapy modification Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations may vary depending on international labeling. Consult appropriate labeling for specific recommendations. Risk D: Consider therapy modification Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Risk D: Consider therapy modification Fingolimod: Diltiazem may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy Fosaprepitant: Diltiazem may increase the serum concentration of Fosaprepitant. Specifically, diltiazem may increase the concentration of the active metabolite aprepitant. Fosaprepitant may increase the serum concentration of Diltiazem. The active metabolite aprepitant is likely responsible for this effect. Risk C: Monitor therapy Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Grapefruit Juice: May increase the serum concentration of Diltiazem. Risk C: Monitor therapy Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Risk D: Consider therapy modification Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Hydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Hydrocodone. Risk C: Monitor therapy Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: If a moderate CYP3A inhibitor must be used, consider reducing the dose of ibrutinib to 140mg daily and monitor closely for signs of toxicity. Risk X: Avoid combination Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy Imatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib. Risk C: Monitor therapy Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Risk X: Avoid combination Ivabradine: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Ivabradine. Ivabradine may enhance the QTc-prolonging effect of Calcium Channel Blockers (Nondihydropyridine). Specifically, the QTc prolonging effects of bepridil may be enhanced. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Ivabradine. Specifically, verapamil or diltiazem may increase serum ivabradine concentrations. Risk X: Avoid combination Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult prescribing information for specific age- and weight-based recommendations. Risk D: Consider therapy modification Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy Levodopa: Hypotensive Agents may enhance the orthostatic hypotensive effect of Levodopa. Risk C: Monitor therapy Lithium: Calcium Channel Blockers (Nondihydropyridine) may enhance the neurotoxic effect of Lithium. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Lithium. Decreased or unaltered lithium concentrations have also been reported with this combination. Risk C: Monitor therapy Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Risk X: Avoid combination Lovastatin: Diltiazem may increase the serum concentration of Lovastatin. Lovastatin may increase the serum concentration of Diltiazem. Management: Initiate lovastatin at a maximum adult dose of 10 mg/day, and do not exceed 20 mg/day, in patients receiving diltiazem. Monitor closely for signs of HMG-CoA reductase inhibitor toxicity (e.g., myositis, rhabdomyolysis). Risk D: Consider therapy modification Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: U.S. labeling: start at 20 mg/day and limit to max of 80 mg/day with moderate CYP3A4 inhibitor. Canadian labeling: limit to max of 40 mg/day with moderate CYP3A4 inhibitor; avoid concomitant use of grapefruit products. Risk D: Consider therapy modification 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; 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 MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Exceptions: Linezolid; Tedizolid. Risk C: Monitor therapy Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Midodrine: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Midodrine. 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 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 Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Risk X: Avoid combination 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 Nicorandil: May enhance the hypotensive effect of Hypotensive Agents. Risk C: Monitor therapy Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy Obinutuzumab: Antihypertensives may enhance the hypotensive effect of Obinutuzumab. Management: Consider temporarily withholding antihypertensive medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 200 mg twice daily. Risk X: Avoid combination OxyCODONE: 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 D: Consider therapy modification Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk X: Avoid combination Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Management: Avoid concurrent use when possible. If used, monitor for CCB toxicity. The manufacturer of atazanavir recommends a 50% dose reduction for diltiazem be considered. Saquinavir, tipranavir, and darunavir/cobicistat use with bepridil is contraindicated. Risk D: Consider therapy modification QuiNIDine: Diltiazem may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy Ranolazine: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Ranolazine. Management: Limit ranolazine dose to a maximum of 500 mg twice daily when used with diltiazem or verapamil. Risk D: Consider therapy modification Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Risk D: Consider therapy modification Red Yeast Rice: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin (and possibly other related compounds) may be increased. Risk C: Monitor therapy Regorafenib: May enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor therapy Rifampin: May decrease the serum concentration of Diltiazem. Risk X: Avoid combination Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Risk D: Consider therapy modification RisperiDONE: Hypotensive Agents may enhance the hypotensive effect of RisperiDONE. Risk C: Monitor therapy RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Management: In patients with impaired renal function (i.e., CrCl 15-80 mL/min) the U.S. prescribing information warns that moderate inhibitors of P-glycoprotein and CYP3A4 should not be used unless the potential benefits outweigh the potential risks. Risk D: Consider therapy modification Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Risk C: Monitor therapy Salicylates: Calcium Channel Blockers (Nondihydropyridine) may enhance the anticoagulant effect of Salicylates. Risk C: Monitor therapy Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Risk X: Avoid combination Simvastatin: Diltiazem may increase the serum concentration of Simvastatin. Simvastatin may increase the serum concentration of Diltiazem. Management: Avoid concurrent use of diltiazem with simvastatin when possible. If used together, limit adult doses to simvastatin 10 mg/day and diltiazem 240 mg/day; avoid Simcor (simvastatin/niacin) because fixed simvastatin doses exceed the maximum. Risk D: Consider therapy modification St Johns Wort: May decrease the serum concentration 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 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 Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Risk D: Consider therapy modification Tacrolimus (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus (Systemic). Risk C: Monitor therapy Tacrolimus (Topical): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Risk X: Avoid combination Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Risk X: Avoid combination Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The initial starting dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Risk D: Consider therapy modification Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy

benazepril: interaction - drug interaction

Alfuzosin: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Aliskiren: May enhance the hyperkalemic effect of ACE Inhibitors. Aliskiren may enhance the hypotensive effect of ACE Inhibitors. Aliskiren may enhance the nephrotoxic effect of ACE Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification Allopurinol: ACE Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of ACE Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of ACE Inhibitors. Management: Concurrent use of telmisartan and ramipril is specifically not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives to the combination when possible. Risk D: Consider therapy modification Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy Aprotinin: May diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy AzaTHIOprine: ACE Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy Barbiturates: May enhance the hypotensive effect of Hypotensive Agents. Risk C: Monitor therapy Brimonidine (Topical): May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Canagliflozin: May enhance the hyperkalemic effect of ACE Inhibitors. Canagliflozin may enhance the hypotensive effect of ACE Inhibitors. Risk C: Monitor therapy Ciprofloxacin (Systemic): ACE Inhibitors may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Risk C: Monitor therapy Dapoxetine: May enhance the orthostatic hypotensive effect of ACE Inhibitors. Risk C: Monitor therapy Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy DPP-IV Inhibitors: May enhance the adverse/toxic effect of ACE Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy DULoxetine: Hypotensive Agents may enhance the orthostatic hypotensive effect of DULoxetine. Risk C: Monitor therapy Eplerenone: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy Everolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy Ferric Gluconate: ACE Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy Gold Sodium Thiomalate: ACE Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. An increased risk of nitritoid reactions has been appreciated. Risk C: Monitor therapy Grass Pollen Allergen Extract (5 Grass Extract): ACE Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk D: Consider therapy modification Heparin: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Hydrochlorothiazide: May enhance the hypotensive effect of Benazepril. Hydrochlorothiazide may enhance the nephrotoxic effect of Benazepril. Benazepril may decrease the serum concentration of Hydrochlorothiazide. Risk C: Monitor therapy Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy Icatibant: May diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy Iron Dextran Complex: ACE Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Management: Follow iron dextran recommendations closely regarding both having resuscitation equipment and trained personnel on-hand prior to iron dextran administration and the use of a test dose prior to the first therapeutic dose. Risk D: Consider therapy modification Lanthanum: May decrease the serum concentration of ACE Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification Levodopa: Hypotensive Agents may enhance the orthostatic hypotensive effect of Levodopa. Risk C: Monitor therapy Lithium: ACE Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor patient response to lithium closely following addition or discontinuation of concurrent ACE inhibitor treatment. Risk D: Consider therapy modification Loop Diuretics: May enhance the hypotensive effect of ACE Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Exceptions: Linezolid; Tedizolid. Risk C: Monitor therapy MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Exceptions: Linezolid; Tedizolid. Risk C: Monitor therapy Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Nicorandil: May enhance the hypotensive effect of Hypotensive Agents. Risk C: Monitor therapy Nicorandil: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy Nonsteroidal Anti-Inflammatory Agents: ACE Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy Obinutuzumab: Antihypertensives may enhance the hypotensive effect of Obinutuzumab. Management: Consider temporarily withholding antihypertensive medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Potassium Salts: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy Pregabalin: ACE Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy RisperiDONE: Hypotensive Agents may enhance the hypotensive effect of RisperiDONE. Risk C: Monitor therapy RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification Salicylates: May diminish the antihypertensive effect of ACE Inhibitors. They may also diminish other beneficial pharmacodynamic effects desired for the treatment of CHF. The effects are likely dose-related. 100 mg doses aspirin appear to cause no problems, whereas 300 mg doses appear to significantly affect ACE Inhibitor efficacy. Risk C: Monitor therapy Sirolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Risk C: Monitor therapy Sodium Phosphates: ACE Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ACEIs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification Temsirolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Risk C: Monitor therapy Thiazide Diuretics: May enhance the hypotensive effect of ACE Inhibitors. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy TiZANidine: May enhance the hypotensive effect of ACE Inhibitors. Risk C: Monitor therapy Tolvaptan: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy Trimethoprim: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

diltiazem: dosing adult

Angina: Oral: Capsule, extended release: Dilacor XR, Dilt-XR, Diltia XT: Initial: 120 mg once daily; titrate over 7-14 days; usual dose range: 120-320 mg daily: maximum: 480 mg daily Cardizem CD, Cartia XT: Initial: 120-180 mg once daily; titrate over 7-14 days; usual dose range: 120-320 mg daily; maximum: 480 mg daily Tiazac, Taztia XT: Initial: 120-180 mg once daily; titrate over 7-14 days; usual dose range: 120-320 mg daily; maximum: 540 mg daily Tablet, extended release (Cardizem LA, Matzim LA, Tiazac XC [CAN; not available in U.S.]): 180 mg once daily; may increase at 7- to 14-day intervals; usual dose range: 120-320 mg/day; maximum: 360 mg daily Tablet, immediate release (Cardizem): Usual starting dose: 30 mg 4 times daily; titrate dose gradually at 1- to 2-day intervals; usual dose range: 120-320 mg daily Hypertension: Oral: Capsule, extended release (once-daily dosing): Cardizem CD, Cartia XT: Initial: 180-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (ASH/ISH [Weber, 2014]): 240-360 mg daily; maximum: 480 mg daily Dilacor XR, Diltia XT, Dilt-XR: Initial: 180-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (ASH/ISH [Weber, 2014]): 240-360 mg daily; maximum: 540 mg daily Tiazac, Taztia XT: Initial: 120-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (ASH/ISH [Weber, 2014]): 240-360 mg daily; maximum: 540 mg daily Capsule, extended release (twice-daily dosing): Initial: 60-120 mg twice daily; dose adjustment may be made after 14 days; usual range: 240-360 mg daily Note: Diltiazem is available as a generic intended for either once- or twice-daily dosing, depending on the formulation; verify appropriate extended release capsule formulation is administered. Tablet, extended release (Cardizem LA, Matzim LA, Tiazac XC [CAN; not available in U.S.]): Initial: 180-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (ASH/ISH [Weber, 2014]): 240-360 mg daily Atrial fibrillation, atrial flutter, PSVT: IV: Initial bolus dose: 0.25 mg/kg actual body weight over 2 minutes (average adult dose: 20 mg); ACLS guideline recommends 15-20 mg Repeat bolus dose (may be administered after 15 minutes if the response is inadequate): 0.35 mg/kg actual body weight over 2 minutes (average adult dose: 25 mg); ACLS guideline recommends 20-25 mg Continuous infusion (infusions >24 hours or infusion rates >15 mg/hour are not recommended): Initial infusion rate of 10 mg/hour; rate may be increased in 5 mg/hour increments up to 15 mg/hour as needed; some patients may respond to an initial rate of 5 mg/hour. If diltiazem injection is administered by continuous infusion for >24 hours, the possibility of decreased diltiazem clearance, prolonged elimination half-life, and increased diltiazem and/or diltiazem metabolite plasma concentrations should be considered. Atrial fibrillation (rate control) (off-label use): Oral: Extended release (capsule or tablet): Usual maintenance dose: 120 to 360 mg once daily (AHA/ACC/HRS [January, 2014]) Conversion from IV diltiazem to oral diltiazem: Oral dose (mg daily) is approximately equal to [rate (mg/hour) x 3 + 3] x 10. 3 mg/hour = 120 mg daily 5 mg/hour = 180 mg daily 7 mg/hour = 240 mg daily 11 mg/hour = 360 mg daily

benazepril: pharmacologic category

Angiotensin-Converting Enzyme (ACE) Inhibitor; Antihypertensive

diltiazem: pharmacologic category

Antianginal Agent; Antiarrhythmic Agent, Class IV; Antihypertensive; Calcium Channel Blocker; Calcium Channel Blocker, Nondihydropyridine

rosuvastatin: pharmacologic category

Antilipemic Agent, HMG-CoA Reductase Inhibitor

simvastatin: pharmacologic category

Antilipemic Agent, HMG-CoA Reductase Inhibitor

diltiazem: brand names

Cardizem; Cardizem CD; Cardizem LA; Cartia XT; Dilacor XR [DSC]; Dilt-CD [DSC]; Dilt-XR; Diltiazem CD; Diltiazem HCl CD [DSC]; Diltzac [DSC]; Matzim LA; Taztia XT; Tiazac

diltiazem: warnings/precaution

Concerns related to adverse effects: • Conduction abnormalities: May cause first-, second-, and third-degree AV block or sinus bradycardia; risk increases with agents known to slow cardiac conduction. • Dermatologic reactions: Transient dermatologic reactions have been observed with use; if reaction persists, discontinue. May (rarely) progress to erythema multiforme or exfoliative dermatitis. • Hepatic effects: Rarely, significant elevations in hepatic transaminases have been observed with use. • 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. Ethanol may increase risk of hypotension or vasodilation. Advise patients to avoid ethanol. • Peripheral edema: The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy. Disease-related concerns: • Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose. • Hypertrophic obstructive cardiomyopathy (HOCM): Use with caution in patients with HOCM; routine use is currently not recommended due to insufficient evidence (Maron, 2003). • Left ventricular dysfunction: Use with caution in left ventricular dysfunction; due to negative inotropic effects, may exacerbate condition. 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 (ACCF/AHA [Yancy, 2013]). • Renal impairment: Use with caution in patients with renal impairment. Concurrent drug therapy: • Agents with SA/AV nodal-blocking properties: Use caution when using diltiazem together with a beta-blocker; may result in conduction disturbances, hypotension, and worsened LV function. Simultaneous administration of IV diltiazem and an IV beta-blocker or administration within a few hours of each other may result in asystole and is contraindicated. Use with other agents known to either reduce SA node function and/or AV nodal conduction (eg, digoxin) or reduce sympathetic outflow (eg, clonidine) may increase the risk of serious bradycardia.

benazepril: dosing renal impairment

CrCl <30 mL/minute: Children: Use is not recommended. Adults: Administer 5 mg daily initially; maximum daily dose: 40 mg. Hemodialysis: Moderately dialyzable (20% to 50%); administer dose postdialysis or administer 25% to 35% supplemental dose. Peritoneal dialysis: Supplemental dose is not necessary.

rosuvastatin: dosing renal impairment

CrCl ≥30 mL/minute/1.73 m2: No dosage adjustment necessary. CrCl <30 mL/minute/1.73 m2: Initial: 5 mg once daily; maximum: 10 mg once daily

rosuvastatin: brand name

Crestor

diltiazem: interaction - food

Diltiazem serum levels may be elevated if taken with food. Serum concentrations were not altered by grapefruit juice in small clinical trials.

simvastatin: medication guide

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, dyspepsia, constipation, rhinitis, rhinorrhea, or pharyngitis. Have patient report immediately to prescriber arrhythmia, urinary retention, oliguria, signs of severe muscle problems, or signs of hepatic impairment (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.

benazepril: medication guide

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. Have patient report immediately to prescriber signs of renal impairment, signs of hyperkalemia, severe dizziness, syncope, dyspnea, excessive weight gain, edema of extremities, significant dyspepsia, considerable nausea, or signs of hepatic impairment (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.

rosuvastatin: use labeled indications

Heterozygous familial hypercholesterolemia in children: Adjunct to diet to reduce total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apo B) levels in adolescent males and females who are at least 1 year postmenarche and are 10-17 years of age with heterozygous familial hypercholesteremia if after an adequate trial of diet therapy the following findings are present: LDL-C more than 190 mg/dL or more than 160 mg/dL and there is a positive family history of premature cardiovascular (CV) disease or 2 or more other CV disease risk factors. Homozygous familial hypercholesterolemia: To reduce LDL-C, total cholesterol, and apo B in adults with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or alone if such treatments are unavailable. Hyperlipidemia and mixed dyslipidemia: Adjunctive therapy to diet to reduce elevated total cholesterol, LDL-C, apo B, non-high-density lipoprotein cholesterol (non-HDL-C), and triglyceride levels, and to increase HDL-C in patients with primary hyperlipidemia or mixed dyslipidemia. Hypertriglyceridemia: Adjunct to diet for the treatment of adults with hypertriglyceridemia. Primary dysbetalipoproteinemia (type III hyperlipoproteinemia): Adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (type III hyperlipoproteinemia). Prevention of cardiovascular disease: Primary prevention: To reduce the risk of stroke, myocardial infarction, or arterial revascularization procedures in patients without clinically evident coronary heart disease or lipid abnormalities but with all of the following: 1) an increased risk of cardiovascular disease based on age ≥50 years old in men and ≥60 years old in women, 2) hsCRP ≥2 mg/L, and 3) the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease. Secondary prevention: Adjunctive therapy to diet to slow the progression of atherosclerosis in adults as part of a treatment strategy to lower total cholesterol and LDL-C to target levels. Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) according to the American College of Cardiology/American Heart Association: To reduce the risk of ASCVD in patients with clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin); in patients without clinical ASCVD if LDL-C is 190 mg/dL or greater; in patients without clinical ASCVD who have type 1 or type 2 diabetes and are between 40 and 75 years of age; in patients with an estimated 10-year ASCVD risk 7.5% or greater and who are between 40 and 75 years of age (Stone 2013). The American Heart Association (AHA) recommends statin therapy (unless contraindicated) for all coronary artery bypass graft (CABG) surgery patients to help maintain long-term graft patency and help obtain the highest level of physical health and quality of life (AHA [Kulik 2015]). Specific recommendations from the Kidney Disease: Improving Global Outcomes (KDIGO) organization have also been released for patients with chronic kidney disease (KDIGO [Tonelli 2013]).

benazepril: dosing adult

Hypertension: Oral: Initial: 10 mg/day in patients not receiving a diuretic; 20 to 80 mg/day as a single dose or 2 divided doses; the need for twice-daily dosing should be assessed by monitoring peak (2 to 6 hours after dosing) and trough responses. Usual dosage (ASH/ISH [Weber, 2014]): 10 to 40 mg daily. Note: Patients taking diuretics should have them discontinued 2 to 3 days prior to starting benazepril. If they cannot be discontinued, then initial dose should be 5 mg; restart after blood pressure is stabilized if needed.

benazepril: use labeled indication

Hypertension: Treatment of hypertension, either alone or in combination with other antihypertensive agents The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients: • 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 is ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg. • Patients ≥18 years of age with diabetes and 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) and 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 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.

rosuvastatin: pharmacology and PK = MOA

Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA); this then results in a compensatory increase in the expression of LDL receptors on hepatocyte membranes and a stimulation of LDL catabolism. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).

benazepril: brand names

Lotensin

simvastatin: dosing renal impairment

Manufacturer's recommendations: Mild to moderate renal impairment: No dosage adjustment necessary; simvastatin does not undergo significant renal excretion. Severe renal impairment: CrCl <30 mL/minute: Initial: 5 mg/day with close monitoring.

diltiazem: pharmacology and PK - MOA

Nondihydropyridine calcium channel blocker which inhibits 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

rosuvastatin: dosing adult

Note: Doses should be individualized according to the baseline LDL-cholesterol levels, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 4 weeks or more. Hyperlipidemia, mixed dyslipidemia, hypertriglyceridemia, primary dysbetalipoproteinemia, slowing progression of atherosclerosis, primary prevention of cardiovascular disease: Oral: Initial dose: General dosing: 10-20 mg once daily; 20 mg once daily may be used in patients with severe hyperlipidemia (LDL >190 mg/dL) and aggressive lipid targets (McKenney 2009) Conservative dosing: Patients requiring less aggressive treatment or predisposed to myopathy (including patients of Asian descent): 5 mg once daily Titration: After initiation or upon titration, analyze lipid levels within 2-4 weeks (peak, steady-state lowering effects usually seen between 4-6 weeks [McKenney 2009]) and adjust dose accordingly; dosing range: 5-40 mg daily (maximum dose: 40 mg once daily) Note: The 40 mg dose should be reserved for patients who have not achieved goal cholesterol levels on a dose of 20 mg daily, including patients switched from another HMG-CoA reductase inhibitor. Homozygous familial hypercholesterolemia (FH): Oral: Initial: 20 mg once daily (maximum dose: 40 mg daily) Prevention of cardiovascular disease: ACC/AHA Blood Cholesterol Guideline recommendations to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) (Stone 2013): Adults ≥21 years: Oral: Primary prevention: LDL-C ≥190 mg/dL: High-intensity therapy: 20-40 mg once daily. Type 1 or 2 diabetes and age 40-75 years: Moderate-intensity therapy: 5-10 mg once daily. Type 1 or 2 diabetes, age 40-75 years, and an estimated 10-year ASCVD risk ≥7.5%: High intensity therapy: 20-40 mg once daily Age 40-75 years and an estimated 10-year ASCVD risk ≥7.5%: Moderate- to high-intensity therapy: 5-40 mg once daily Secondary prevention: Patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG (AHA [Kulik 2015]) and: Age ≤75 years: High-intensity therapy: 20-40 mg once daily. Age >75 years or not a candidate for high-intensity therapy: Moderate-intensity therapy: 5-10 mg once daily. Dosage adjustment for rosuvastatin with concomitant medications: Oral: US labeling: Cyclosporine: Rosuvastatin dose should not exceed 5 mg once daily Gemfibrozil: Avoid concurrent use; if unable to avoid concurrent use, initiate rosuvastatin at 5 mg once daily; dose should not exceed 10 mg once daily Atazanavir/ritonavir or lopinavir/ritonavir: Initiate rosuvastatin at 5 mg once daily; dose should not exceed 10 mg once daily Canadian labeling: Cyclosporine: Concomitant use is contraindicated Gemfibrozil: Rosuvastatin dose should not exceed 20 mg daily Dosage adjustment for hematuria and/or persistent, unexplained proteinuria while on 40 mg daily: Reduce dose and evaluate causes.

simvastatin: dosing adult

Note: Doses should be individualized according to the baseline LDL-cholesterol levels, the recommended goal of therapy, and the patient's response; adjustments should be made at intervals of 4 weeks or more; doses may need adjusted based on concomitant medications Note: Dosing limitation: Simvastatin 80 mg is limited to patients that have been taking this dose for >12 consecutive months without evidence of myopathy and are not currently taking or beginning to take a simvastatin dose-limiting or contraindicated interacting medication. If patient is unable to achieve low-density lipoprotein-cholesterol (LDL-C) goal using the 40 mg dose of simvastatin, increasing to 80 mg dose is not recommended. Instead, switch patient to an alternative LDL-C-lowering treatment providing greater LDL-C reduction. Homozygous familial hypercholesterolemia: Oral: 40 mg once daily in the evening Prevention of cardiovascular events (also see ACC/AHA Blood Cholesterol Guideline recommendations), hyperlipidemias: Oral: 10 to 20 mg once daily in the evening; range: 5 to 40 mg/day Patients requiring only moderate reduction of LDL-C: May be started at 5 to 10 mg once daily in the evening; adjust to achieve recommended LDL-C goal. Patients requiring reduction of >40% of LDL-C: May be started at 40 mg once daily in the evening; adjust to achieve recommended LDL-C goal. Patients with CHD or at high risk for cardiovascular events (patients with diabetes, PVD, history of stroke or other cerebrovascular disease): Dosing should be started at 40 mg once daily in the evening; start simultaneously with diet therapy. Prevention of cardiovascular disease: ACC/AHA Blood Cholesterol Guideline recommendations to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) (Stone, 2013): Adults ≥21 years: Oral: Primary prevention: LDL-C ≥190 mg/dL: High intensity therapy necessary; use alternate statin therapy (eg, atorvastatin or rosuvastatin) Type 1 or 2 diabetes and age 40 to 75 years: Moderate intensity therapy: 20 to 40 mg once daily Type 1 or 2 diabetes, age 40 to 75 years, and an estimated 10-year ASCVD risk ≥7.5%: High intensity therapy necessary; use alternate statin therapy (eg, atorvastatin or rosuvastatin) Age 40 to 75 years and an estimated 10-year ASCVD risk ≥7.5%: Moderate to high intensity therapy: 20 to 40 mg once daily or consider using high intensity statin therapy (eg, atorvastatin or rosuvastatin) Secondary prevention: Patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG (AHA [Kulik, 2015]) and: Age ≤75 years: High intensity therapy necessary; use alternate statin therapy (eg, atorvastatin or rosuvastatin) Age >75 years or not a candidate for high intensity therapy: Moderate intensity therapy: 20 to 40 mg once daily Dosage adjustment for simvastatin with concomitant medications: Note: Patients currently tolerating and requiring a dose of simvastatin 80 mg who require initiation of an interacting drug with a dose cap for simvastatin should be switched to an alternative statin with less potential for drug-drug interaction. Amiodarone, amlodipine, or ranolazine: Simvastatin dose should not exceed 20 mg/day Diltiazem, dronedarone, or verapamil: Simvastatin dose should not exceed 10 mg/day Lomitapide: Reduce simvastatin dose by 50% when initiating lomitapide. Simvastatin dose should not exceed 20 mg/day (or 40 mg daily for those who previously tolerated simvastatin 80 mg daily for ≥1 year without evidence of muscle toxicity) Dosage adjustment in Chinese patients on niacin doses ≥1 g/day: US labeling: Use caution with simvastatin doses exceeding 20 mg/day; because of an increased risk of myopathy, do not administer simvastatin 80 mg concurrently. Canadian labeling: Concomitant use is not recommended in Chinese and other Asian patients.

diltiazem: adverse reaction

Note: Frequencies represent ranges for various dosage forms. Patients with impaired ventricular function and/or conduction abnormalities may have higher incidence of adverse reactions. >10%: Cardiovascular: Edema (2% to 15%) Central nervous system: Headache (5% to 12%) 2% to 10%: Cardiovascular: Atrioventricular block (2% to 8%; first degree), edema (2% to 8%; lower limb), bradycardia (2% to 6%), hypotension (<2% to 4%), vasodilatation (2% to 3%), extrasystoles (2%), flushing (1% to 2%), palpitations (1% to 2%) Central nervous system: Dizziness (3% to 10%), pain (6%), nervousness (2%) Dermatologic: Skin rash (1% to 4%) Endocrine & metabolic: Gout (1% to 2%) Gastrointestinal: Dyspepsia (1% to 6%), constipation (<2% to 4%), vomiting (2%), diarrhea (1% to 2%) Local: Injection site reaction (4%; itching, burning) Neuromuscular & skeletal: Weakness (1% to 4%), myalgia (2%) Respiratory: Rhinitis (<2% to 10%), pharyngitis (2% to 6%), dyspnea (1% to 6%), bronchitis (1% to 4%), cough (≤3), sinus congestion (1% to 2%) <2%, postmarketing, and/or case reports: Abnormal dreams, abnormal gait, albuminuria, alopecia, amblyopia, amnesia, angina pectoris, angioedema, anorexia, asystole, atrioventricular block (second or third degree), bruise, bundle branch block, cardiac arrhythmia, cardiac failure, crystalluria, depression, drowsiness, dysgeusia, ECG abnormality, epistaxis, erythema multiforme, exfoliative dermatitis, extrapyramidal reaction, gingival hyperplasia, gynecomastia, hallucination, hemolytic anemia, hyperglycemia, hypersensitivity angiitis, hypersensitivity reaction, hyperuricemia, impotence, increased creatine phosphokinase, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum bilirubin, increased thirst, insomnia, leukopenia, muscle cramps, myopathy, nausea, neck stiffness, nocturia, pain, paresthesia, personality changes, petechia, polyuria, prolonged bleeding time, pruritus, purpura, retinopathy, skin photosensitivity, Stevens-Johnson syndrome, syncope, tachycardia, thrombocytopenia, tinnitus, toxic epidermal necrolysis, tremor, urticaria, ventricular premature contractions, weight gain, xerostomia

diltiazem: use labeled indications

Oral: Primary hypertension; chronic stable angina or angina from coronary artery spasm 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 (JNC8 [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. Injection: Control of rapid ventricular rate in patients with atrial fibrillation or atrial flutter; conversion of paroxysmal supraventricular tachycardia (PSVT)

diltiazem: pregnancy & lactation

Pregnancy Risk Factor = C Lactation = Enters breast milk/not recommended

benazepril: pregnancy & lactation

Pregnancy Risk Factor = D Lactation = Enters breast milk

rosuvastatin: pregnancy & lactation

Pregnancy Risk Factor = X Lactation = Excretion in breast milk unknown/contraindicated

simvastatin: pregnancy & lactation

Pregnancy Risk Factor = X Lactation = Excretion in breast milk unknown/contraindicated

simvastatin: pharmacology and PK = MOA

Simvastatin is a methylated derivative of lovastatin that acts by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus, 2002; Ray, 2005).

benazepril: administration and storage

Storage/Stability Store at ≤30°C (86°F). Protect from moisture.

diltiazem: interaction - metabolism/transport

Substrate of CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C9 (weak), CYP2D6 (weak), CYP3A4 (moderate)

rosuvastatin: interactions metabolism/transport

Substrate of CYP2C9 (minor), CYP3A4 (minor), SLCO1B1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

simvastatin: interactions- metabolism/transport

Substrate of CYP3A4 (major), SLCO1B1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (weak), CYP2C9 (weak), CYP2D6 (weak)

rosuvastatin: dosing hepatic impairment

US labeling: Manufacturer labeling does not provide specific dosing recommendations; however, systemic exposure may be increased in patients with liver disease (increased AUC and Cmax); use is contraindicated in active liver disease or unexplained transaminase elevations. Canadian labeling: Active hepatic disease or unexplained persistent transaminase >3 x ULN: Use is contraindicated. Mild-to-moderate impairment: No dosage adjustment necessary. Severe impairment: Initial: 5 mg daily. Maximum: 20 mg once daily.

simvastatin: dosing hepatic impairment

Use is contraindicated in the setting of active liver disease.

diltiazem: dosing renal impairment

Use with caution; no dosing adjustments recommended. Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.

diltiazem: dosing hepatic impairment

Use with caution; no specific dosing recommendations available; extensively metabolized by the liver; half-life is increased in patients with cirrhosis.

simvastatin: use labeled indications

Used with dietary therapy for the following: Secondary prevention of cardiovascular events in hypercholesterolemic patients with established coronary heart disease (CHD) or at high risk for CHD: To reduce cardiovascular morbidity (myocardial infarction, coronary/noncoronary revascularization procedures) and mortality; to reduce the risk of stroke Hyperlipidemias: To reduce elevations in total cholesterol (total-C), LDL-C, apolipoprotein B, triglycerides, and VLDL-C, and to increase HDL-C in patients with primary hypercholesterolemia (elevations of 1 or more components are present in Fredrickson type IIa, IIb, III, and IV hyperlipidemias); treatment of homozygous familial hypercholesterolemia Heterozygous familial hypercholesterolemia (HeFH): In adolescent patients (10-17 years of age, females >1 year postmenarche) with HeFH having LDL-C ≥190 mg/dL or LDL-C ≥160 mg/dL with positive family history of premature cardiovascular disease (CVD), or 2 or more CVD risk factors in the adolescent patient Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) according to the American College of Cardiology/American Heart Association: To reduce the risk of ASCVD in patients with clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) who are greater than 75 years of age or not a candidate for high-intensity statin therapy; in patients without clinical ASCVD if LDL-C is 190 mg/dL or greater and not a candidate for high-intensity statin therapy; in patients without clinical ASCVD who have type 1 or type 2 diabetes and are between 40 and 75 years of age; in patients with an estimated 10-year ASCVD risk 7.5% or greater and who are between 40 and 75 years of age (Stone, 2013). The American Heart Association (AHA) recommends statin therapy (unless contraindicated) for all coronary artery bypass graft (CABG) surgery patients to help maintain long-term graft patency and help obtain the highest level of physical health and quality of life (AHA [Kulik, 2015]). Specific recommendations from the Kidney Disease: Improving Global Outcomes (KDIGO) organization have also been released for patients with chronic kidney disease (KDIGO [Tonelli, 2013]).

diltiazem: medication guide

• 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 flushing, headache, dyspepsia, asthenia, rhinorrhea, pharyngitis, or injection site irritation. Have patient report immediately to prescriber signs of hepatic impairment, severe dizziness, syncope, bradycardia, arrhythmia, dyspnea, excessive weight gain, edema of extremities, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (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.

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