Potentiation of Warfarin Effect by Nabumetone
Potentiation of Warfarin Effect by Nabumetone
Concomitant therapy with warfarin and nonsteroidal antiinflammatory drugs (NSAIDs) is of concern due to the potential for increased bleeding. Nonsteroidal antiinflammatory drugs may alter patient response to warfarin by pharmacodynamic or pharmacokinetic interactions. A man receiving long-term, stable warfarin therapy experienced a significant increase in international normalized ratio 1 week after nabumetone was added to his regimen. Despite prompt reduction of the warfarin dosage, he experienced hemarthrosis of his right knee. Previous reports suggested lack of interaction between nabumetone and warfarin. Caution and close monitoring are advisable when the two agents are administered concomitantly.
Warfarin is an oral anticoagulant with a relatively predictable onset and duration of action, as well as favorable bioavailability. The most significant complication with oral anticoagulation is bleeding, the risk of which may depend on the intensity of anticoagulation, patient characteristics, and concomitant drugs that interfere with hemostasis or impair warfarin metabolism.
There is historical and continuing reluctance among many physicians regarding therapy with nonsteroidal antiinflammatory drugs (NSAIDs) for patients receiving oral anticoagulants due to safety concerns. Several mechanisms exist by which NSAIDs may interact with warfarin and increase the risk for, or severity of, bleeding. These interactions can be classified as pharmaco-dynamic or pharmacokinetic. Pharmacodynamic interactions include those with agents that alter hemostasis and therefore affect anticoagulation. The NSAIDs can inhibit normal platelet aggregation and cause gastrointestinal bleeding by mucosal erosion and/or ulceration. Pharmacokinetic interactions are due to drug-induced alterations in protein-binding or metabolism of warfarin.
Compared with other NSAIDs, nabumetone (Relafen; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) has been shown to cause comparatively less inhibition of platelet aggregation and minimal damage to the gastric mucosa, supporting a suggestion that it may be preferred when concomitant therapy with an oral anticoagulant is warranted.
Concomitant therapy with warfarin and nonsteroidal antiinflammatory drugs (NSAIDs) is of concern due to the potential for increased bleeding. Nonsteroidal antiinflammatory drugs may alter patient response to warfarin by pharmacodynamic or pharmacokinetic interactions. A man receiving long-term, stable warfarin therapy experienced a significant increase in international normalized ratio 1 week after nabumetone was added to his regimen. Despite prompt reduction of the warfarin dosage, he experienced hemarthrosis of his right knee. Previous reports suggested lack of interaction between nabumetone and warfarin. Caution and close monitoring are advisable when the two agents are administered concomitantly.
Warfarin is an oral anticoagulant with a relatively predictable onset and duration of action, as well as favorable bioavailability. The most significant complication with oral anticoagulation is bleeding, the risk of which may depend on the intensity of anticoagulation, patient characteristics, and concomitant drugs that interfere with hemostasis or impair warfarin metabolism.
There is historical and continuing reluctance among many physicians regarding therapy with nonsteroidal antiinflammatory drugs (NSAIDs) for patients receiving oral anticoagulants due to safety concerns. Several mechanisms exist by which NSAIDs may interact with warfarin and increase the risk for, or severity of, bleeding. These interactions can be classified as pharmaco-dynamic or pharmacokinetic. Pharmacodynamic interactions include those with agents that alter hemostasis and therefore affect anticoagulation. The NSAIDs can inhibit normal platelet aggregation and cause gastrointestinal bleeding by mucosal erosion and/or ulceration. Pharmacokinetic interactions are due to drug-induced alterations in protein-binding or metabolism of warfarin.
Compared with other NSAIDs, nabumetone (Relafen; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) has been shown to cause comparatively less inhibition of platelet aggregation and minimal damage to the gastric mucosa, supporting a suggestion that it may be preferred when concomitant therapy with an oral anticoagulant is warranted.
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