Caution should be exercised when botanical medicines (botanicals) are taken concomitantly with warfarin. Few adequate, well-controlled studies exist evaluating the potential for metabolic and/or pharmacologic interactions between botanicals and warfarin. Due to a lack of manufacturing standardization with botanical medicinal preparations, the amount of active ingredients may vary. This could further confound the ability to assess potential interactions and effects on anticoagulation. It is good practice to monitor the patient’s response with additional PT/INR determinations when initiating or discontinuing botanicals.
Specific botanicals reported to affect warfarin therapy include the following:
- Bromelains, danshen, dong quai (Angelica sinensis), garlic, Ginkgo biloba, ginseng, and cranberry products are associated most often with an INCREASE in the effects of warfarin.
- Coenzyme Q10 (ubidecarenone) and St. John’s wort are associated most often with a DECREASE in the effects of warfarin.
Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the anticoagulant effects of warfarin. Conversely, other botanicals may have coagulant properties when taken alone or may decrease the effects of warfarin.
Some botanicals that may affect coagulation are listed below for reference; however, this list should not be considered all-inclusive. Many botanicals have several common names and scientific names. The most widely recognized common botanical names are listed.
|1 Contains coumarins, has antiplatelet properties, and may have coagulant properties due to possible Vitamin K content.2 Contains coumarins and salicylates.3 Contains coumarins and has fibrinolytic properties.4 Contains coumarins and has antiplatelet properties.5 Has antiplatelet and fibrinolytic properties.|
|Botanicals that contain coumarins with potential anticoagulant effects:|
|Agrimony1 AlfalfaAngelica (Dong Quai)AniseedArnicaAsafoetidaBogbean2 BoldoBuchuCapsicum3||Cassia4 CeleryChamomile (German and Roman)Dandelion4 FenugreekHorse ChestnutHorseradishLicorice4 Meadowsweet2 Nettle||ParsleyPassion FlowerPrickly Ash (Northern)QuassiaRed CloverSweet CloverSweet WoodruffTonka BeansWild CarrotWild Lettuce|
|Miscellaneous botanicals with anticoagulant properties:|
|Bladder Wrack (Fucus)||Pau d’arco|
|Botanicals that contain salicylate and/or have antiplatelet properties:|
|Agrimony1 Aloe GelAspenBlack CohoshBlack HawBogbean2 Cassia4 Clove||Dandelion4 FeverfewGarlic5 German SarsaparillaGingerGinkgo BilobaGinseng (Panax) 5 Licorice4||Meadowsweet2 Onion5 PolicosanolPoplarSenegaTamarindWillowWintergreen|
|Botanicals with fibrinolytic properties:|
|BromelainsCapsicum3||Garlic5 Ginseng (Panax) 5||Inositol NicotinateOnion5|
|Botanicals with coagulant properties:|
Coumarins may also affect the action of other drugs. Hypoglycemic agents (chlorpropamide and tolbutamide) and anticonvulsants (phenytoin and phenobarbital) may accumulate in the body as a result of interference with either their metabolism or excretion.
Warfarin sodium is a narrow therapeutic range (index) drug, and additional caution should be observed when warfarin sodium is administered to certain patients. Reported risk factors for bleeding include high intensity of anticoagulation (INR >4.0), age ≥65, highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, trauma, renal insufficiency, concomitant drugs (see PRECAUTIONS) and long duration of warfarin therapy. Identification of risk factors for bleeding and certain genetic variation in CYP2CP and VKORC1 in a patient may increase the need for more frequent INR monitoring and the use of lower warfarin doses (see CLINICAL PHARMACOLOGY: Metabolism and DOSAGE AND ADMINISTRATION). Bleeding is more likely to occur during the starting period and with a higher dose of warfarin sodium (resulting in a higher INR).
Intramuscular (I.M.) injections of concomitant medications should be confined to the upper extremities which permits easy access for manual compression, inspections for bleeding and use of pressure bandages.
Caution should be observed when warfarin is administered concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, to be certain that no change in anticoagulation dosage is required. In addition to specific drug interactions that might affect PT/INR, NSAIDs, including aspirin, can inhibit platelet aggregation, and can cause gastrointestinal bleeding, peptic ulceration and/or perforation.
The objective of anticoagulant therapy is to decrease the clotting ability of the blood so that thrombosis is prevented, while avoiding spontaneous bleeding. Effective therapeutic levels with minimal complications are in part dependent upon cooperative and well-instructed patients who communicate effectively with their physician. Patients should be advised: Strict adherence to prescribed dosage schedule is necessary. Do not take or discontinue any other medication, including salicylates (e.g., aspirin and topical analgesics), other over-the-counter medications and botanical (herbal) products except on advice of the physician. Avoid alcohol consumption. Do not take warfarin during pregnancy and do not become pregnant while taking it (see CONTRAINDICATIONS). Avoid any activity or sport that may result in traumatic injury. Prothrombin time tests and regular visits to physician or clinic are needed to monitor therapy. Carry identification stating that warfarin is being taken. If the prescribed dose of warfarin is forgotten, notify the physician immediately. Take the dose as soon as possible on the same day but do not take a double dose of warfarin the next day to make up for missed doses. The amount of vitamin K in food may affect therapy with warfarin. Eat a normal, balanced diet maintaining a consistent amount of vitamin K. Avoid drastic changes in dietary habits, such as eating large amounts of green leafy vegetables. You should also avoid intake of cranberry juice or any other cranberry products. Notify your health care provider if any of these products are part of your normal diet. Contact physician to report any illness, such as diarrhea, infection or fever. Notify physician immediately if any unusual bleeding or symptoms occur. Signs and symptoms of bleeding include: pain, swelling or 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. If therapy with warfarin is discontinued, patients should be cautioned that the anticoagulant effects of warfarin may persist for about 2 to 5 days. Patients should be informed that all warfarin sodium, USP, products represent the same medication, and should not be taken concomitantly, as overdosage may result. A Medication Guide14 should be available to patients when their prescriptions for warfarin sodium are issued
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