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Carbamazepine-Macrolide Interaction — RACP Adult Medicine MCQ

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ModerateClinical PharmacologyCarbamazepine-Macrolide InteractionRACP Adult Medicine

A 70-year-old woman with known temporal lobe epilepsy on carbamazepine presents with ataxia, diplopia, and nystagmus. Her carbamazepine level is 52 µmol/L (therapeutic range 20–50 µmol/L). She was recently commenced on erythromycin for a chest infection. What is the mechanism of toxicity?

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Correct answer: C — Erythromycin inhibits CYP3A4, reducing carbamazepine metabolism

Erythromycin (and clarithromycin) are potent CYP3A4 inhibitors. Carbamazepine is primarily metabolised by CYP3A4, so co-administration leads to reduced carbamazepine clearance and elevated levels causing dose-dependent toxicity (ataxia, diplopia, nystagmus, drowsiness). This is a predictable and clinically significant interaction. Azithromycin has minimal CYP3A4 inhibition and is a safer macrolide choice with carbamazepine.

Reference: AMH – 2025 – Drug Interactions; eTG – 2025 – Neurology