Coumarin anticoagulants cytochrome P450

Carbamazepine reduces the effects of coumarin anticoagulants (SED-14, 1185) (91,92), including phenpro-coumon (SEDA-22, 86), by inducing cytochrome P450 enzymes, and another case has been reported (93). 

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). 

Chemistry and pharmacokinetics The coumarin anticoagulants (eg, warfarin) are small, Upid-soluble molecules that are readily absorbed after oral administration. They cross the placental barrier readily and are potentially dangerous to the fetus. Warfarin is highly bound to plasma proteins (> 99%), and its elimination depends upon metabolism by hepatic cytochrome P450. 

Voriconazole is a known inhibitor of the cytochrome P450 isoenzymes CYP2C9 and CYP3A4, by which the coumarins (phenprocoumon, acenocoumarol and warfarin) are metabolised. The manufacturers advise close monitoring of the prothrombin time in any patient on a coumarin anticoagulant who is given voriconazole. Dose adjustments of the coumarin should be made accordingly. ... 

Although in one early report, chlorpromazine 40 to 100 mg daily was said to have slightly sensitised 2 out of 8 patients to the effects of acenocoumarol and in another was reported to increase its anticoagulant effects in animals, there appears to be nothing else published to suggest that an interaction occurs. In vitro study in human liver microsomes found that chlorpromazine did not inhibit CYP2C9, the cytochrome P450 isoenzyme predominantly involved in the metabolism of warfarin , (p.358) and other coumarins. No eoumarin dose adjustments would therefore be anticipated to be needed on eoneurrent use. 

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