Coumarin anticoagulants prothrombin time, increased

Potentiation of the effects of vitamin K antagonists by high-dose intravenous methylprednisolone has been prospectively studied in 10 consecutive patients and 5 controls after the observation of a sharp increase in the International Normalized Ratio (INR) in a patient taking oral anticoagulation after concomitant administration of methylprednisolone (1 g/day for 3 days) (262). The mean INR was 2.8 (range 2.0-3.8) at baseline and increased to 8.0 (5.3-20). The maximum increase in INR occurred after a mean of 93 (29-156) hours. The coumarins taken by these patients were fluindione in eight and acenocoumarol in two. The prothrombin time in the controls... 

Griseofulvin is a potent inducer of cytochrome P450 and has a significant effect on P450 expression in hepatocytes (SEDA-12, 236). It therefore increases the rate of metabolism of coumarin anticoagulants (50). However, both increases and decreases in prothrombin time have been reported (SED-12, 676) (18). 

Isolated cases suggest that doxycycline and tetracycline can increase the effects of coumarins. Similarly, some small studies (none controlled) suggest that chlortetracycline (alone or with oxytetracycline), doxycycline, or the tetracyclines as a class may increase the risks of over-anticoagulation, but there appear to be no studies of the effect of tetracyclines on the pharmacokinetics of coumarins. However, the related antibacterial, tigecycline, increased the AUC of warfarin, and has been shown to increase the prothrombin time when given alone. 

The combination of dipyridamole and coumarin anticoagulants does not alter the prothrombin time, but might cause an increased risk of serious bleeding when compared with anticoagulants alone. There is some evidence that the risk of bleeding may be lower, without a reduction in efficacy, if the INR is maintained within a lower range. 

Information seems to be limited to these three cases, but it would be prudent to monitor prothrombin times and INRs in any patient if warfarin and nevirapine are used concurrently, being alert for the need to increase the warfarin dosage (possibly twofold). Information about other oral anticoagulants seems to be lacking, but if the suggested mechanism is correct, all coumarins would be expected to interact to some extent. 

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