A woman taking a combined oral contraceptive containing ethinylestradiol and levonorgestrel starts rifampicin for latent TB prophylaxis. The contraceptive failure risk arises from:

• A Rifampicin inhibits hepatic SHBG synthesis, increasing free ethinylestradiol levels that down-regulate FSH receptors
• B Rifampicin enterohepatic circulation disruption reduces steroid reabsorption
• C Rifampicin chelates the progestin component in the gut, reducing absorption
• D Rifampicin potently induces CYP3A4 and also induces intestinal P-glycoprotein and UGT enzymes, dramatically increasing ethinylestradiol and progestin first-pass metabolism and reducing systemic bioavailability to sub-therapeutic levels ✓

Explanation

Rifampicin is one of the most potent CYP3A4 inducers known, increasing CYP3A4 activity by up to 10-fold within 2 weeks. Ethinylestradiol and most synthetic progestins are predominantly metabolised by CYP3A4 in intestinal wall and liver. Rifampicin also induces intestinal P-gp and UGT1A enzymes, further reducing bioavailability. The combined effect lowers EE plasma levels by 40-55%, rendering standard OCP doses insufficient for contraception. Women requiring rifampicin should use non-hormonal contraception during treatment and for 4 weeks after stopping rifampicin. This is a critically important drug interaction in clinical practice.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.