In a patient on rifampicin for TB who is also taking combined OCP for contraception, failure of contraception can occur. The molecular mechanism is:

• A Rifampicin competes with oestrogen for hepatic protein binding, reducing its plasma half-life
• B Rifampicin inhibits intestinal P-glycoprotein increasing OCP absorption but causing enterohepatic recirculation
• C Rifampicin directly displaces oestrogen from nuclear receptors reducing transcriptional activity
• D Rifampicin induces CYP3A4 and UGT enzymes, accelerating first-pass and systemic metabolism of OCP hormones ✓

Explanation

Rifampicin is one of the most potent inducers of hepatic CYP3A4 and UDP-glucuronosyltransferases (UGTs). Both ethinylestradiol (CYP3A4 substrate) and levonorgestrel/norethindrone (CYP3A4 and UGT substrates) undergo markedly increased first-pass and systemic metabolism. This reduces plasma hormone levels by 50–80%, abolishing reliable ovulation suppression. Barrier methods or non-hormonal alternatives are strongly recommended during rifampicin-based TB therapy. Rifampicin does not inhibit P-gp; it induces it.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.