Combined oral contraceptive pills (COCPs) failure rate in women taking rifampicin is due to which specific drug interaction?
- A Rifampicin inhibits intestinal P-glycoprotein, reducing OCP absorption
- B Rifampicin binds directly to estrogen receptors, competing with ethinylestradiol
- C Rifampicin induces CYP3A4 (and CYP2C9), accelerating hepatic metabolism of ethinylestradiol and progestogens — reducing plasma hormone levels below contraceptive efficacy threshold ✓
- D Rifampicin reduces gut flora responsible for estrogen enterohepatic recycling only, not hepatic metabolism
Explanation
Rifampicin is one of the most potent known inducers of cytochrome P450 enzymes, particularly CYP3A4 (and CYP1A2, 2C9, 2C19). Ethinylestradiol and progestogens are CYP3A4 substrates. With rifampicin co-administration, accelerated oxidative metabolism dramatically reduces peak plasma levels and AUC of both hormone components, dropping them below the threshold needed for reliable ovulation suppression. This is a well-established enzyme induction interaction — women on rifampicin-containing TB therapy must use barrier contraception or high-dose OCPs (though reliability remains uncertain). Induction persists for 4–8 weeks after rifampicin is stopped.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.