A 26-year-old woman taking a combined oral contraceptive pill (COC) is prescribed rifampicin for tuberculosis. The pharmacokinetic interaction that reduces OCP efficacy involves:
- A Rifampicin is a potent inducer of CYP3A4 and P-glycoprotein, accelerating hepatic metabolism of ethinylestradiol and progestins, reducing plasma levels below effective contraceptive concentrations ✓
- B Rifampicin inhibits GnRH pulsatility, reducing FSH and LH, paradoxically improving contraceptive efficacy
- C Rifampicin inhibits intestinal absorption of ethinylestradiol by chelating the drug in the gut
- D Rifampicin activates SHBG synthesis, reducing free estradiol levels but not affecting synthetic progestins
Correct answer: A. Rifampicin is a potent inducer of CYP3A4 and P-glycoprotein, accelerating hepatic metabolism of ethinylestradiol and progestins, reducing plasma levels below effective contraceptive concentrations
Explanation
Rifampicin is one of the most potent inducers of CYP3A4, CYP2C9, and P-glycoprotein known. Induction of CYP3A4 dramatically increases first-pass and systemic metabolism of ethinylestradiol and most progestins, reducing their AUC by 40–80% and causing contraceptive failure. This interaction can persist for up to 4 weeks after stopping rifampicin while enzyme induction reverses. Women on rifampicin must use additional non-hormonal contraception; high-dose COCs are not reliably protective during rifampicin therapy.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.