Rifampicin Ethinylestradiol

LeBel M, Masson E, Guilbert E, et al. Effects of rifabutin and rifampicin on the pharmacokinetics of ethinylestradiol and norethindrone. J Clin Pharmacol 1998 38(11) 1042-1050. 

In two studies rifabutin 300 mg daily for 10 or 14 days reduced the plasma levels of ethinylestradiol and norethisterone in women taking a combined oral contraceptive, but to a lesser extent than rifampicin. The AUC for ethinylestradiol decreased hy about 35% in both studies, and the AUC of norethisterone decreased by 17%. In one study, spotting occurred in 21.7% of women when they took rifabutin (compared with 3.7% in the control cycle and 36% with rifampicin). Ovulation did not occur with rifabutin or rifampicin in either study. - There appear to be no reports of contraceptive failure attributed to rifabutin. 

Rifampicin is a potent non-specific enzyme inducer, which has been shown to increase the hydroxylation of ethinylestradiol fourfold in an in vitro studyand twofold in an in vivo studyAnother study showed that the metabolism of ethinylestradiol derived from mestranol was similarly affected. As a result, the reduced steroid levels may be insufficient to prevent the re-establishment of a normal menstrual cycle with ovulation, which would explain the breakthrough bleeding and pregnancies that have occurred. Rifabutin similarly acts as an enzyme inducer, but it is less... 

The interactions of herbal medicines with P450 3A4 have already been mentioned and are one of the worst problems with these mixtures [1448]. One of the most studied issues is St. John s wort, which induces P450 3A4 as an agonist of the receptor PXR [1449, 1450]. The induction of P450 3A4 by St. John s wort has been responsible for the loss of the effectiveness of oral contraceptives [83, 1451]. The resulting pregnancies are the resirlt of more rapid ehmi-nation of 17a-ethinylestradiol, a phenomenon previously reported for P450 3A4 induction by rifampicin and barbiturates [26, 82, 90]. 

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