A 28-year-old woman with bipolar disorder is started on lamotrigine. Her dermatologist notes she also uses an oral contraceptive pill containing ethinyl estradiol and levonorgestrel. The pharmacokinetic consequence of this combination relevant to the psychiatrist is:

• A OCP inhibits lamotrigine glucuronidation, raising lamotrigine levels and increasing toxicity risk
• B Lamotrigine induces CYP3A4, reducing ethinyl estradiol levels and causing contraceptive failure
• C Both drugs compete for plasma protein binding, leading to increased free fractions of both
• D OCP induces lamotrigine glucuronidation, lowering lamotrigine levels and reducing seizure control ✓

Explanation

Ethinyl estradiol in combined OCPs is a potent inducer of UGT (UDP-glucuronosyltransferase) enzymes, particularly UGT1A4, which is the primary metabolic pathway for lamotrigine. This significantly increases lamotrigine clearance, reducing its plasma levels by up to 50%, potentially compromising seizure or mood control. During pill-free weeks, lamotrigine levels rebound, potentially causing toxicity. This is a clinically important interaction requiring lamotrigine dose adjustment. Valproate (not OCP) inhibits lamotrigine glucuronidation.

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

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Written and medically reviewed by the StethoPrep medical team.