Rifamycins Warfarin

Hydrolysis reactions are illustrated by the deacylation of colchicine (10) (amide hydrolysis), olivomycin A (29), Rifamycin B (46) or thymoxamine (52) (ester hydrolysis). The reduction of pentoxyfylline (32), zearalenone (56) or warfarin (65) are examples of the common reduction of keto groups, generally affording, with a high stereospecificity, one of the alcohol stereoisomers. 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

Drugs that may be affected by nevirapine include rifamycins, clarithromycin, oral contraceptives, efavirenz, ketoconazole, methadone, protease inhibitors, warfarin, zidovudine. 

St. John s wort, rifamycins, and ritonavir. Drugs that may be affected by efavirenz include phenytoin, phenobarbital, carbamazepine, itraconazole, ketoconazole, methadone, ritonavir, amprenavir, benzodiazepines, clarithromycin, ethinyl estradiol, indinavir, nelfinavir, saquinavir, and warfarin. 

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. 

Reduced or increased metabolism. Sulfamethoxazole clearly inhibits the metabolism of warfarin by the cytochrome P450 isoenzyme CYP2C9, so enhancing its effect. Some macrolides such as erythromycin inhibit CYP3A4, and therefore have a minor inhibitory effect on warfarin, which would, on its own, be unlikely to be of any clinical relevance. Conversely, rifamycins , (p.375) are well established inducers of drug metabolism, and clearly reduce the effect of warfarin. Most other antibacterial classes have no effect on warfarin pharmacokinetics. 

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