d liver enzymes, hypotension, vasculitis, edema, anemia, pallor, fever, rash, dermatitis, including bullous eruptions, urticaria, angina syndrome, chest pain, abdominal pain including cramping, flatulence/bloating, fatigue, lethargy, malaise, asthenia, nausea, vomiting, diarrhea, pain, headache, dizziness, loss of consciousness, syncope, coma, taste perversion, pruritus, alopecia, cold intolerance, and paresthesia including feeling cold and chills.
Rare events of tracheal or tracheobronchial calcification have been reported in association with long-term warfarin therapy. The clinical significance of this event is unknown.
Priapism has been associated with anticoagulant administration; however, a causal relationship has not been established.
OVERDOSAGE
Signs and Symptoms
Suspected or overt abnormal bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries) are early manifestations of anticoagulation beyond a safe and satisfactory level.
Treatment
Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing warfarin sodium therapy and if necessary, by administration of oral or parenteral vitamin K1. (Please see recommendations accompanying vitamin K1 preparations prior to use.)15,16
Such use of vitamin K1 reduces response to subsequent warfarin sodium therapy. Patients may return to a pretreatment thrombotic status following the rapid reversal of a prolonged PT/INR. Resumption of warfarin sodium administration reverses the effect of vitamin K, and a therapeutic PT/INR can again be obtained by careful dosage adjustment. If rapid anticoagulation is indicated, heparin may be preferable for initial therapy.
If minor bleeding progresses to major bleeding, give 5 mg to 25 mg (rarely up to 50 mg) parenteral vitamin K1. In emergency situations of severe hemorrhage, clotting factors can be returned to normal by administering 200 to 500 mL of fresh whole blood or fresh frozen plasma, or by giving commercial Factor IX complex.
A risk of hepatitis and other viral diseases is associated with the use of these blood products; Factor IX complex is also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in exceptional or life threatening bleeding episodes secondary to warfarin sodium overdosage.
Purified Factor IX preparations should not be used because they cannot increase the levels of prothrombin, Factor VII and Factor X which are also depressed along with the levels of Factor IX as a result of warfarin sodium treatment. Packed red blood cells may also be given if significant blood loss has occurred. Infusions of blood or plasma should be monitored carefully to avoid precipitating pulmonary edema in elderly patients or patients with heart disease.
DOSAGE AND ADMINISTRATION
The dosage and administration of warfarin sodium tablets must be individualized for each patient according to the particular patient’s PT/INR response to the drug. The dosage should be adjusted based upon the patient’s PT/INR.15,16,17,18,19 The best available information supports the following recommendations for dosing of warfarin sodium tablets.
Venous Thromboembolism (including deep venous thrombosis [DVT] and pulmonary embolism [PE])
For patients with a first episode of DVT or PE secondary to a t
