Warfarin - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Tissue necrosis: Necrosis or gangrene of skin or other tissues can occur, with severe cases requiring debridement or amputation.

Discontinue warfarin sodium and consider alternative anticoagulants if necessary.

Calciphylaxis: Fatal and serious cases have occurred.

Discontinue warfarin sodium 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.

Discontinue warfarin sodium if such emboli occur.

Heparin-induced thrombocytopenia (HIT): Initial therapy with warfarin sodium in HIT has resulted in cases of amputation and death.

Warfarin sodium may be considered after platelet count has normalized.

Pregnant women with mechanical heart valves: Warfarin sodium may cause fetal harm; however, the benefits may outweigh the risks.

5.1 Hemorrhage Warfarin sodium can cause major or fatal bleeding.

Bleeding is more likely to occur within the first month.

Risk factors for bleeding include high intensity of anticoagulation (INR >4.0), age greater than or equal to 65, history of highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, anemia, malignancy, trauma, renal impairment, certain genetic factors [see Clinical Pharmacology ], certain concomitant drugs [see Drug Interactions ], and long duration of warfarin therapy.

Perform regular monitoring of INR in all treated patients.

Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shortest duration of therapy appropriate for the clinical condition.

However, maintenance of INR in the therapeutic range does not eliminate the risk of bleeding.

Drugs, dietary changes, and other factors affect INR levels achieved with warfarin sodium therapy.

Perform more frequent INR monitoring when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs [see Drug Interactions ].

Instruct patients about prevention measures to minimize risk of bleeding and to report signs and symptoms of bleeding [see Patient Counseling Information ].

5.2 Tissue Necrosis Warfarin sodium can cause necrosis and/or gangrene of skin and other tissues, which is an uncommon but serious risk (<0.1%).

Necrosis may be associated with local thrombosis and usually appears within a few days of the start of warfarin sodium therapy.

In severe cases of necrosis, treatment through debridement or amputation of the affected tissue, limb, breast, or penis has been reported.

Careful clinical evaluation is required to determine whether necrosis is caused by an underlying disease.

Although various treatments have been attempted, no treatment for necrosis has been considered uniformly effective.

Discontinue warfarin sodium therapy if necrosis occurs.