A young woman on combined OCP (ethinylestradiol + levonorgestrel) for contraception is prescribed rifampicin for TB. She becomes pregnant despite continuing the OCP. The mechanism of OCP failure is:

• A Rifampicin inhibits intestinal UGT enzymes preventing glucuronide conjugation of estrogen
• B Rifampicin competitively binds progesterone receptors in the endometrium reducing hormonal effect
• C Rifampicin reduces gut flora that deconjugate estrogen enterohepatic recirculation
• D Rifampicin induces CYP3A4 and CYP2C9, markedly accelerating ethinylestradiol and progestin metabolism, reducing plasma concentrations below contraceptive threshold ✓

Explanation

Rifampicin is one of the most potent inducers of cytochrome P450 enzymes (CYP3A4, CYP2C9) and UDP-glucuronosyltransferases. Ethinylestradiol and progestins in combined OCPs are CYP3A4 substrates; rifampicin induction dramatically increases their first-pass and systemic metabolism, reducing plasma hormone levels by 50-80%. This falls below the threshold required for reliable ovulation suppression and cervical mucus effects, leading to contraceptive failure. Alternative non-hormonal contraception (condoms, copper IUD) is mandatory during and for 28 days after 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.