warfarin (Coumadin)

(Adverse Reactions/Side Effects )

(CAPITALS indicate life-threatening) GI: cramps, nausea. Derm: dermal necrosis. Hemat: BLEEDING.

(Contraindications/Precautions)

Contraindicated in: Uncontrolled bleeding; Open wounds; Active ulcer disease; Recent brain, eye, or spinal cord injury or surgery; Severe liver or kidney disease; Uncontrolled hypertension; OB: Crosses placenta and may cause fatal hemorrhage in the fetus. May also cause congenital malformation. Use Cautiously in: Malignancy; Patients with history of ulcer or liver disease; History of poor compliance; Women with childbearing potential; Asian patients or those who carry the CYP2C9*2 allele and/or the CYP2C9*3 allele, or with the VKORC1 AA genotype (↑ risk of bleeding with standard dosing; lower initial doses should be considered); Pedi: Has been used safely but may require more frequent PT/INR assessments; Geri: Due to greater than expected anticoagulant response, initiate and maintain at lower doses.

(Interactions)

Drug-Drug: Abciximab, androgens, capecitabine, cefotetan, chloral hydrate,chloramphenicol, clopidogrel, disulfiram, fluconazole, fluoroquinolones,itraconazole, metronidazole (including vaginal use), thrombolytics, eptifibatide,tirofiban, ticlopidine, sulfonamides, quinidine, quinine, NSAIDs, valproates, andaspirin may ↑ the response to warfarin and ↑ the risk of bleeding. Chronic use ofacetaminophen may ↑ the risk of bleeding. Chronic alcohol ingestion may ↓ action of warfarin; if chronic alcohol abuse results in significant liver damage, action of warfarin may be ↑ due to ↓ production of clotting factor. Acute alcohol ingestion may ↑ action of warfarin. Barbiturates, carbamazepine, rifampin, and hormonal contraceptives containing estrogen may ↓ the anticoagulant response to warfarin. Many other drugs may affect the activity of warfarin. Drug-Natural: St. John's wort ↓ effect. ↑ bleeding risk with anise, arnica, chamomile,clove, dong quai, fenugreek, feverfew, garlic, ginger, ginkgo, Panax ginseng,licorice, and others. Drug-Food: Ingestion of large quantities of foods high in vitamin K content (see list in Appendix M) may antagonize the anticoagulant effect of warfarin

(Action)

Interferes with hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X). Therapeutic Effects: Prevention of thromboembolic events.

(Route/Dosage)

PO, IV (Adults): 2-5 mg/day for 2-4 days; then adjust daily dose by results of INR. Initiate therapy with lower doses in geriatric or debilitated patients or in Asian patients or those with CYP2C9*2 and/or CYP2C9*3 alleles or VKORC1 AA genotype. PO, IV (Children> 1 mo): Initial loading dose—0.2 mg/kg (maximum dose: 10 mg) for 2-4 days then adjust daily dose by results of INR, use 0.1 mg/kg if liver dysfunction is present. Maintenance dose range—0.05-0.34 mg/kg/day.

(Classification)

Therapeutic: anticoagulants Pharmacologic: coumarins Pregnancy Category X

Assessment

• Assess for signs of bleeding and hemorrhage (bleeding gums; nosebleed; unusual bruising; tarry, black stools; hematuria; fall in hematocrit or blood pressure; guaiac-positive stools, urine, or nasogastric aspirate). • Assess for evidence of additional or increased thrombosis. Symptoms depend on area of involvement. • Geri: Patients over 60 yr exhibit greater than expected PT/INR response. Monitor for side effects at lower therapeutic ranges. • Pedi: Achieving and maintaining therapeutic PT/INR ranges may be more difficult in the pediatric patient. Assess PT/INR levels more frequently. • Lab Test Considerations: Monitor PT, INR and other clotting factors frequently during therapy. Therapeutic PT ranges 1.3-1.5 times greater than control; however, the INR, a standardized system that provides a common basis for communicating and interpreting PT results, is usually referenced. Normal INR (not on anticoagulants) is 0.8-1.2. An INR of 2.5-3.5 is recommended for patients at very high risk of embolization (for example, patients with mitral valve replacement and ventricular hypertrophy). Lower levels are acceptable when risk is lower. Heparin may affect the PT/INR; draw blood for PT/INR in patients receiving both heparin and warfarin at least 5 hrs after the IV bolus dose, 4 hrs after cessation of IV infusion, or 24 hrs after subcut heparin injection. Asian patients and those who carry the CYP2C9*2 allele and/or the CYP2C9*3 allele, or those with VKORC1 AA genotype may require more frequent monitoring and lower doses. • Monitor hepatic function and CBC before and periodically throughout therapy. • Monitor stool and urine for occult blood before and periodically during therapy. • Toxicity and Overdose: Withholding 1 or more doses of warfarin is usually sufficient if INR is excessively elevated or if minor bleeding occurs. If overdose occurs or anticoagulation needs to be immediately reversed, the antidote is vitamin K (phytonadione, AquaMEPHYTON). Administration of whole blood or plasma also may be required in severe bleeding because of the delayed onset of vitamin K.

IV Administration

• Direct IV: Reconstitute each 5-mg vial with 2.7 mL of sterile water for injection. Reconstituted solution is stable for 4 hr at room temperature. Diluent: No further dilution needed before administration. Concentration: 2 mg/mL. Rate: Administer over 1-2 min.

Implementation

• High Alert: Medication errors involving anticoagulants have resulted in serious harm or death from internal or intracranial bleeding. Before administering, evaluate recent INR or PT results and have second practitioner independently check original order. • Because of the large number of medications capable of significantly altering warfarin's effects, careful monitoring is recommended when new agents are started or other agents are discontinued. Interactive potential should be evaluated for all new medications (Rx, OTC, and natural products). • Administer medication at same time each day. • PO: Medication requires 3-5 days to reach effective levels; usually begun while patient is still on heparin. • Do not interchange brands; potencies may not be equivalent.