Rifampicin Coumarins

Fluconazole Fluconazole may increase the plasma concentration of phenytoin, sulfonylurea (hypoglycemic), cyclosporin, zidovudine, cisapride, and terfenadine. Coadministration of fluconazole with rifampicin results in the reduced plasma concentration of fluconazole. Griseofulvin may reduce the plasma concentration of salicylates, coumarin, anticoagulants, and oral contraceptives. 

Acceleration of hepatic coumarin metabolism enzyme induction, e.g., by carbamazepine, rifampicin ... 

A reduction in efficacy due to an interaction can sometimes be just as harmful as an increase patients taking warfarin who are given rifampicin need more warfarin to maintain adequate and protective anticoagulation (see Coumarins + Antibacterials Rifamycins , p.375), while patients taking tetracyclines , (p.347) or quinolones , (p.332) need to avoid antacids and milky foods (or separate their ingestion) because the effects of these antibacterials can be reduced or even abolished if admixture occurs in the gut. 

It makes sense to assume therefore, that an inhibitor of CYP2C9 (e.g. flueonazole , (p.387)) is likely to inerease the eoneentration of the cou-marin and enhanee the anticoagulant effect. Drugs that induce CYP2C9 (e.g. rifampicin , (p.375)) reduce plasma levels of the coumarins by increasing the clearance. 

Some of this resistance to warfarin was undoubtedly due to the rifampicin (a known and potent inducer of warfarin metabolism) but as the ESTRs remained depressed for a further 20 days after rifampicin was withdrawn the authors suggested that the teicoplanin had its own part to play. However, rifampicin has been shown is several cases to decrease the ef-feets of warfarin for 3 or more weeks after its withdrawal (see Coumarins + Antibaeterials Rifamyeins p.375), so an interaction with teicoplanin would seem doubtful. 

The first observation of a strongly antagonistic action of rifampicin on the coumarin effect has been confirmed in normal volunteers (45 -, 53 ) and in patients (46 ). In normal individuals rifampicin lowered the blood level of experimentally administered warfarin (45 ). 

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