Warfarin

JANTOVEN ® is indicated for: Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (PE). Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (AF) and/or cardiac valve replacement. Reduction in the risk of death, recurrent myocardial infarction (MI), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Limitations of Use Warfarin Sodium has no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. Once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae.

Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors, which include Factors II, VII, IX, and X, and the anticoagulant proteins C and S. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K-dependent clotting factors. Vitamin K promotes the biosynthesis of γ-carboxyglutamic acid residues in the proteins that are essential for biological activity. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K 1 epoxide.

Individualize dosing regimen for each patient, and adjust based on INR response. Knowledge of genotype can inform initial dose selection. Monitoring: Obtain daily INR determinations upon initiation until stable in the therapeutic range. Obtain subsequent INR determinations every 1 to 4 weeks. Review conversion instructions from other anticoagulants.

JANTOVEN is contraindicated in: Pregnancy JANTOVEN is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism. JANTOVEN can cause fetal harm when administered to a pregnant woman. JANTOVEN exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. If JANTOVEN is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Boxed warning (bleeding risk): Warfarin Sodium can cause major or fatal bleeding. Perform regular monitoring of INR in all treated patients. Drugs, dietary changes, and other factors affect INR levels achieved with Warfarin Sodium therapy. Instruct patients about prevention measures to minimize risk of bleeding and to report signs and symptoms of bleeding. Tissue necrosis: Necrosis or gangrene of skin or other tissues can occur, with severe cases requiring debridement or amputation. Discontinue JANTOVEN and consider alternative anticoagulants if necessary. Calciphylaxis: Fatal and serious cases have occurred. Discontinue JANTOVEN and consider alternative anticoagulation therapy. Acute kidney injury may occur during episodes of excessive anticoagulation and hematuria. Systemic atheroemboli and cholesterol microemboli: Some cases have progressed to necrosis or death.

The following serious adverse reactions to JANTOVEN are discussed in greater detail in other sections of the labeling: Hemorrhage Tissue Necrosis Calciphylaxis Acute Kidney Injury Systemic Atheroemboli and Cholesterol Microemboli Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS Other Clinical Settings with Increased Risks Other adverse reactions to JANTOVEN include: Immune system disorders: hypersensitivity/allergic reactions (including urticaria and anaphylactic reactions) Vascular disorders: vasculitis Hepatobiliary disorders: hepatitis, elevated liver enzymes. Cholestatic hepatitis has been associated with concomitant administration of warfarin sodium and ticlopidine.

Concomitant use of drugs that increase bleeding risk, antibiotics, antifungals, botanical (herbal) products, and inhibitors and inducers of CYP2C9, 1A2, or 3A4. Consult labeling of all concurrently used drugs for complete information about interactions with JANTOVEN or increased risks for bleeding.

Store at 20° to 25°C (68° to 77°F). Excursions permitted to 15° to 30°C (59° to 86°F). Protect from light and moisture.