Warik Adverse Reactions

The major risk from Warfarin therapy is hemorrhage from almost any organ of the body with the consequent effects of hematomas as well as anemia. Skin necrosis and purple discoloration of the toes (due to cholesterol embolization) have been occasionally occurred. Hypersensitivity reactions are extremely rare. Other effects not necessarily associated with hemorrhage include alopecia, fever, nausea, vomiting, diarrhea, skin reactions, jaundice, hepatic dysfunction, and pancreatitis.
Effects on Pregnancy: Warfarin is a recognized teratogen. Given in the first trimester of pregnancy it can cause a fetal warfarin syndrome or warfarin embryopathy characterized by bone stippling (chondrodysplasia punctata) and nasal hypoplasia. CNS abnormalities may develop following use in any trimester but appear most likely after use in the second or third trimester. Use of Warfarin during pregnancy has been associated with an increased rate of abortion and still-birth, although this may, in part, be the consequence of an underlying maternal condition. Use in the late stages of pregnancy is associated with fetal hemorrhage.
Effects on the blood: The risk of bleeding was generally higher with more intense anticoagulation and in the presence of other risk factors but the relationship with age was less clear. Although cumulative risk of bleeding was related to duration of anticoagulation therapy, risk may be highest early in the course.
Withdrawal of Warfarin therapy may lead to rebound hypercoagulability and it has been suggested that Warfarin should be withdrawn gradually.
Effects on the bones: Vitamin K is involved in bone metabolism and vitamin K deficiency is associated with an increased risk of osteoporotic fractures. It has been suggested, therefore, that patients on long-term treatment with oral anticoagulants which are vitamin K antagonists, may be at increased risk of osteoporosis and fractures.
Effects on the skin and hair: Necrosis of skin and soft tissue associated with Warfarin anticoagulant therapy has been reviewed. Warfarin-induced necrosis occurs rarely and is characterized by a localized, painful skin lesion, initially erythematous or hemorrhagic in appearance that becomes bullous and eventually culminates in gangrenous necrosis. Fatalities have occurred. Areas of increased subcutaneous fat such as breast, thigh, and buttocks have most often been involved. Patients with protein C deficiency appear to be at highest risk. Treatment with Warfarin anticoagulants should be discontinued on appearance of skin lesions and vitamin K should be given to reverse their effect.
Treatment of Adverse Effects: The methods used to manage bleeding and/or excessive anticoagulation during Warfarin therapy, or following Warfarin overdosage, depend upon the degree of bleeding, the value of the International Normalized Ratio (INR), and the degree of thromboembolic risk. If the INR is greater than 5.0 but there is no bleeding or only minor bleeding, Warfarin should be temporarily withheld until the INR falls to below 5.0. In some cases where the INR is between 5.0 and 6.0 a reduction in Warfarin dose, rather than withdrawal, may be sufficient. For an INR greater than 8.0 administration of phytomenadione (vitamin K1) should also be considered if there are other factors for bleeding; typical doses of phytomenadione are 0.5 mg intravenously or up to 5 mg orally.
If there is any major bleeding Warfarin should be stopped and phytomenadione 5 mg by slow intravenous injection given together with a concentrate of factors II, VII, IX, and X. The dose of concentrate should be calculated based on 50 units of factor IX per kg body-weight. If no concentrate is available fresh frozen plasma should be infused (about one liter for an adult), but may not be as effective. Higher doses of phytomenadione have been used but it should be remembered that phytomenadione takes several hours to act and large doses may reduce the response to resumed therapy with anticoagulants for a week or more.
If bleeding occurs unexpectedly at therapeutic INR values, the possibility of an underlying cause such as renal or alimentary tract disease should be investigated.