A 28-year-old woman taking a combined oral contraceptive containing ethinyl estradiol is started on rifampicin for pulmonary tuberculosis. Three months later she presents pregnant despite consistent pill use. Which pharmacokinetic mechanism best explains this contraceptive failure?

• A Rifampicin inhibits intestinal P-glycoprotein, blocking contraceptive absorption
• B Rifampicin saturates biliary excretion, raising estrogen levels
• C Rifampicin competes with ethinyl estradiol for albumin binding sites
• D Rifampicin induces hepatic cytochrome enzymes, accelerating estrogen metabolism ✓

Explanation

Rifampicin is a classic inducer of hepatic microsomal cytochrome enzymes including CYP3A4. Induction increases the metabolism of ethinyl estradiol and progestins, lowering hormone levels enough to cause ovulation and contraceptive failure. Option A describes inhibition rather than induction, and option C is wrong because displacement from plasma protein transiently raises free drug rather than causing failure.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.