Clofibrate with warfarin

Drugs that may interact with dantrolene include clofibrate, estrogens, warfarin, and verapamil. 

The interactions of clofibrate with dicoumarol, warfarin and phenindione are established, clinically important and potentially serious. Severe bleeding (fatal in some instances) has been seen. The incidence of the interaction is reported to be between 20 and 100%, but it would be prudent to assume that all patients will be affected. Dosage reduetions of one-third to one-half may be needed to avoid the risk of bleeding. Monitor the INR and adjust the dose accordingly. Information about other eoumarins and indanediones is lacking but it would be prudent to assume that they will interact with clofibrate in a similar way. 

Solomon RB, Rosner F. Massive hemorrhage and death during treatment with clofibrate and warfarin. N Y State JMed (1973) 73, 2002. 

Bjomsson TD, Meffin PJ, Blaschke TF. Interaction of clofibrate with the optical enantio-morphs of warfarin. Pharmacologist (1976) 18,207. 

Synergism Increased anticoagulation of warfarin with clofibrate, corticosteroids, tetracycline, vitamin K and naloxone. 

Warfarin antagonists include vitamin K, barbiturates, glutethimide. rifampin, and cholestyramine. Warfarin potentiators include phenylbutazone. oxyphenbutazone, anabolic steroids, clofibrate, aspirin, hepatotoxins, disnlfirain, and metronidazole. In patients undergoing anticoagulation therapy with warfann, it has been found that cimetidine (used in therapy of duodenal ulcer) may increase anticoagulant blood levels and consequently prolong the prothrombin time. 

Warfarin + clofibrate Higher blood levels of warfarin with risk of haemorrhage Displacement from protein Warfarin dose may require a reduction of one-third to one-half according to coagulation test... 

Uncertain. Clofibrate can displace warfarin from its plasma protein binding sites, but this does not adequately explain the interaetion. Another suggestion is that the fibrates have an additive pharmacodynamic effect. Altered metabolism may also account for the interaetion with ciprofibrate, since this decreased the clearance of 5-warfarin. However, this did not occur with clofibrate or gemfibrozil. ... 

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