Coumadin - Warnings & Precautions

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Miscellaneous:

polycythemia vera, vasculitis, and severe diabetes. Minor and severe allergic/ hypersensitivity reactions and anaphylactic reactions have been reported.

In patients with acquired or inherited warfarin resistance, decreased therapeutic responses to COUMADIN have been reported. Exaggerated therapeutic responses have been reported in other patients.

Patients with congestive heart failure may exhibit greater than expected PT/ INR response to COUMADIN, thereby requiring more frequent laboratory monitoring, and reduced doses of COUMADIN (Warfarin Sodium).

Concomitant use of anticoagulants with streptokinase or urokinase is not recommended and may be hazardous. (Please note recommendations accompanying these preparations.)

PRECAUTIONS

Periodic determination of PT/ INR or other suitable coagulation test is essential.

Numerous factors, alone or in combination, including travel, changes in diet, environment, physical state and medications, including botanicals, may influence response of the patient to anticoagulants. It is generally good practice to monitor the patient's response with additional PT/ INR determinations in the period immediately after discharge from the hospital, and whenever other medications, including botanicals, are initiated, discon-tinued or taken irregularly. The following factors are listed for reference; however, other factors may also affect the anticoagulant response.

Drugs may interact with COUMADIN through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with COUMADIN are synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and altered physiologic control loop for vitamin K metabolism (hereditary resistance). Pharmacokinetic mechanisms for drug interactions with COUMADIN are mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. It is important to note that some drugs may interact by more than one mechanism.

The following factors, alone or in combination, may be responsible for INCREASED PT/ INR response: