Sunday, February 18, 2007
Warfarin
January 17, 2007 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise about the need for individualization of warfarin sodium therapy to minimize the risk of bleeding and to advise about the risks of worsening depression and emergence of suicidality in patients receiving quetiapine fumarate for the treatment of depression and other conditions.
Warfarin Sodium (Coumadin) Requires Individualized Dosing to Minimize Bleeding Risk
On October 4, 2006, the FDA approved safety labeling revisions for warfarin sodium tablets and injection (Coumadin, made by Bristol-Myers Squibb) to warn about the risk for major or fatal bleeding associated with their use.
The most serious risks for anticoagulant therapy with warfarin are hemorrhage in any tissue/organ and less frequently (incidence, < 0.1%) necrosis and/or gangrene of skin and other tissues. In some cases, hemorrhage and necroses have resulted in death or permanent disability.
The risk of bleeding is highest during treatment initiation and with higher doses. Risk factors include a high intensity of anticoagulation (international normalized ratio [INR], > 4.0); age, 65 years or older; highly variable INRs; a history of gastrointestinal bleeding; hypertension; cerebrovascular disease; serious heart disease; anemia; malignancy; trauma; renal insufficiency; concomitant drugs; and long duration of warfarin therapy.
The FDA emphasizes the need for individualized treatment with warfarin because of its low therapeutic index and potential effects from other drugs and dietary vitamin K intake. Pharmacokinetic mechanisms for drug interactions include synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and altered physiologic control loop for vitamin K metabolism (hereditary resistance). Pharmacodynamic interactions are based on enzyme induction/inhibition and reduced plasma protein binding.
Regular monitoring of INR is recommended for all patients. Those at high risk of bleeding can benefit from more frequent monitoring, careful dose adjustments to achieve desired INR, and a shorter duration of therapy.
To minimize the risk of bleeding, patients should be advised to avoid initiating or discontinuing other medications, including salicylates (eg, aspirin and topical analgesics), other over-the-counter medications, and herbal products. Maintenance of a balanced diet with a consistent amount of vitamin K is advised; drastic changes in diet (eg, eating large amounts of green leafy vegetables) and consumption of cranberry juice/products should be avoided.
According to the FDA, bromelains, danshen, dong quai (Angelica sinensis), garlic, Ginkgo biloba, ginseng, and cranberry products are associated most often with an increased effect of warfarin. Coenzyme Q10 (ubidecarenone) and St. John's Wort are associated most often with a decrease in the effects of warfarin.
Some botanicals can cause bleeding events when taken alone (eg, garlic and Ginkgo biloba) because of anticoagulant, antiplatelet, and/or fibrinolytic properties, which would be expected to provide an additive effect when taken with warfarin. Conversely, other botanicals (eg, mistletoe, agrimony, goldenseal, and yarrow) can have coagulant properties when taken alone or might decrease the effects of warfarin.
Patients should be advised to contact their healthcare professional immediately if unusual bleeding or related symptoms occur, such as pain, swelling/discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness.
Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension and pulmonary embolism and thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. It can also be used to reduce the risk for death, recurrent myocardial infarction, and thromboembolic events (such as stroke or systemic embolization) after myocardial infarction.
Warfarin Sodium (Coumadin) Requires Individualized Dosing to Minimize Bleeding Risk
On October 4, 2006, the FDA approved safety labeling revisions for warfarin sodium tablets and injection (Coumadin, made by Bristol-Myers Squibb) to warn about the risk for major or fatal bleeding associated with their use.
The most serious risks for anticoagulant therapy with warfarin are hemorrhage in any tissue/organ and less frequently (incidence, < 0.1%) necrosis and/or gangrene of skin and other tissues. In some cases, hemorrhage and necroses have resulted in death or permanent disability.
The risk of bleeding is highest during treatment initiation and with higher doses. Risk factors include a high intensity of anticoagulation (international normalized ratio [INR], > 4.0); age, 65 years or older; highly variable INRs; a history of gastrointestinal bleeding; hypertension; cerebrovascular disease; serious heart disease; anemia; malignancy; trauma; renal insufficiency; concomitant drugs; and long duration of warfarin therapy.
The FDA emphasizes the need for individualized treatment with warfarin because of its low therapeutic index and potential effects from other drugs and dietary vitamin K intake. Pharmacokinetic mechanisms for drug interactions include synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and altered physiologic control loop for vitamin K metabolism (hereditary resistance). Pharmacodynamic interactions are based on enzyme induction/inhibition and reduced plasma protein binding.
Regular monitoring of INR is recommended for all patients. Those at high risk of bleeding can benefit from more frequent monitoring, careful dose adjustments to achieve desired INR, and a shorter duration of therapy.
To minimize the risk of bleeding, patients should be advised to avoid initiating or discontinuing other medications, including salicylates (eg, aspirin and topical analgesics), other over-the-counter medications, and herbal products. Maintenance of a balanced diet with a consistent amount of vitamin K is advised; drastic changes in diet (eg, eating large amounts of green leafy vegetables) and consumption of cranberry juice/products should be avoided.
According to the FDA, bromelains, danshen, dong quai (Angelica sinensis), garlic, Ginkgo biloba, ginseng, and cranberry products are associated most often with an increased effect of warfarin. Coenzyme Q10 (ubidecarenone) and St. John's Wort are associated most often with a decrease in the effects of warfarin.
Some botanicals can cause bleeding events when taken alone (eg, garlic and Ginkgo biloba) because of anticoagulant, antiplatelet, and/or fibrinolytic properties, which would be expected to provide an additive effect when taken with warfarin. Conversely, other botanicals (eg, mistletoe, agrimony, goldenseal, and yarrow) can have coagulant properties when taken alone or might decrease the effects of warfarin.
Patients should be advised to contact their healthcare professional immediately if unusual bleeding or related symptoms occur, such as pain, swelling/discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness.
Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension and pulmonary embolism and thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. It can also be used to reduce the risk for death, recurrent myocardial infarction, and thromboembolic events (such as stroke or systemic embolization) after myocardial infarction.
# posted by roodbont @ 6:14 AM 
