Rifampicin causes a harmless red-orange discolouration of urine, tears, and saliva. More importantly, it is a potent enzyme inducer. Which enzyme system does it primarily induce, and what is the clinical consequence for oral contraceptive users?

• A Inhibits CYP3A4, raising oestrogen levels and causing break-through bleeding
• B Induces MAO, accelerating serotonin breakdown
• C Inhibits P-glycoprotein, increasing ethinyl oestradiol absorption
• D Induces CYP3A4 and glucuronosyltransferases, markedly accelerating oestrogen and progestogen metabolism and reducing OCP efficacy ✓

Explanation

Rifampicin powerfully induces CYP3A4 (and also CYP2C9, CYP2C19, UGTs, and P-glycoprotein) by activating the pregnane X receptor (PXR). This dramatically accelerates metabolism of ethinyl oestradiol and progestogens in combined oral contraceptive pills, reducing plasma hormone levels by 50–70% and producing contraceptive failure. Women on rifampicin must use additional non-hormonal contraception. The red-orange discolouration occurs because rifampicin and its metabolites are excreted in secretions.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.