A patient on rifampicin for TB develops sub-therapeutic levels of oral contraceptive pills and becomes pregnant. The mechanism of this drug interaction is:

• A Rifampicin increases hepatic CYP3A4 and P-glycoprotein via Pregnane X Receptor (PXR) activation, reducing bioavailability and increasing clearance of ethinylestradiol and progestins ✓
• B Rifampicin inhibits intestinal absorption of estradiol by binding in the GIT
• C Rifampicin reduces enterohepatic circulation of estrogen by inhibiting intestinal beta-glucuronidase
• D Rifampicin induces renal glucuronyl transferase, increasing renal clearance of ethinylestradiol

Explanation

Rifampicin is one of the most potent inducers of CYP3A4, CYP2C9, and P-glycoprotein (P-gp) expression. It acts as a ligand for the nuclear receptor PXR (pregnane X receptor), which binds to gene promoter elements and upregulates transcription of CYP3A4, CYP2B6, UGTs, and P-gp. Ethinylestradiol and progestins are primary CYP3A4 and P-gp substrates; induction accelerates their first-pass and systemic metabolism, reducing plasma levels by up to 70% and effectively rendering oral contraceptives unreliable. Women must use barrier contraception throughout rifampicin therapy and for 4–8 weeks after stopping.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.