• Prophylaxis and treatment of:
  • Venous thrombosis,
  • Pulmonary embolism,
  • Atrial fibrillation with embolization.
• Management of MI
• Prevention of thrombus formation and embolization after prosthetic valve placement.

Contraindicated in:

• Uncontrolled bleeding
• Open wounds
• Active ulcer disease
• Recent brain, eye, or spinal cord injury or surgery
• Severe hepatic impairment
• Uncontrolled hypertension
• OB: Pregnancy.

Use Cautiously in:

• Malignancy
• History of ulcer, liver disease, or acute kidney injury
• History of poor compliance
• 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)
• Women of reproductive potential
• Pedi: Has been used safely in children, but may require more frequent PT/INR assessments
• Geri: Appears on Beers list. ↑ risk of major bleeding when compared to direct acting oral anticoagulants (DOACs) in older adults. Avoid starting as initial therapy for treatment of nonvalvular atrial fibrillation or venous thromboembolism unless alternative options (DOACs) are contraindicated or there are significant barriers to their use. If already using warfarin, it may be reasonable to continue treatment, especially if INR is well controlled (i.e., >70% time in therapeutic range) and no adverse effects.

Derm: dermal necrosis.

GI: cramps, nausea.

GU: CALCIPHYLAXIS.

Hemat: BLEEDING.
Misc: fever.

Drug-Drug:

• Androgens, capecitabine, cefotetan, chloramphenicol, clopidogrel, disulfiram, fluconazole, fluoroquinolones, itraconazole, metronidazole (including vaginal use), thrombolytics, eptifibatide, tirofiban, sulfonamides, quinidine, quinine, NSAIDs, valproates, and aspirin may ↑ the response to warfarin and ↑ the risk of bleeding.
• Chronic use of acetaminophen 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 Products:

• 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.

(Generic available)

• Tablets: 1 mg; 2 mg; 2.5 mg; 3 mg; 4 mg; 5 mg; 6 mg; 7.5 mg; 10 mg;

• PO (Adults): 2–5 mg/day for 2–4 days; then adjust daily dose by results of INR. Initiate therapy with lower doses in older adults or in Asian patients or those with CYP2C9*2 and/or CYP2C9*3 alleles or VKORC1 AA genotype.
• PO (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 hepatic impairment is present. Maintenance dose range: 0.05–0.34 mg/kg/day.

Coumadin, Jantoven

• Interferes with hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X).

• Prevention of thromboembolic events.

Therapeutic Classification: anticoagulants

Pharmacologic Classification: coumarins

Absorption: Well absorbed from the GI tract after oral administration.

Distribution: Minimally distributed to tissues.

Protein Binding: 99%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2C9 isoenzyme, with some metabolism via the CYP3A4 isoenzyme; the CYP2C9 isoenzyme exhibits genetic polymorphism (intermediate or poor metabolizers may have significantly ↑ (S)-warfarin concentrations and an ↑ risk of adverse reactions).

Half-life: 42 hr.

(effects on coagulation tests)

†At a constant dose‡After discontinuation

• Instruct patient to take medication as directed. Take missed doses as soon as remembered that day; do not double doses. Inform health care professional of missed doses at time of checkup or lab tests. Inform patients that anticoagulant effect may persist for 2–5 days following discontinuation. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• Review foods high in vitamin K (see Appendix M). Patient should have consistent limited intake of these foods, as vitamin K is the antidote for warfarin, and alternating intake of these foods will cause PT levels to fluctuate. Advise patient to avoid cranberry juice or products during therapy.
• Caution patient to avoid IM injections and activities leading to injury. Instruct patient to use a soft toothbrush, not to floss, and to shave with an electric razor during warfarin therapy. Advise patient that venipunctures and injection sites require application of pressure to prevent bleeding or hematoma formation.
• Advise patient to report any symptoms of unusual bleeding or bruising (bleeding gums; nosebleed; black, tarry stools; hematuria; excessive menstrual flow) and pain, color, or temperature change to any area of your body to health care professional immediately.Patients with a deficiency in protein C and/or S mediated anticoagulant response may be at greater risk for tissue necrosis.
• Instruct patient not to drink alcohol or take other Rx, OTC, or herbal products, especially those containing aspirin or NSAIDs, or to start or stop any new medications during warfarin therapy without advice of health care professional.
• May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 1 month after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Instruct patient to carry identification describing medication regimen at all times and to inform all health care personnel caring for patient on anticoagulant therapy before lab tests, treatment, or surgery.
• Emphasize the importance of frequent lab tests to monitor coagulation factors.

WAR-fa-rin