MajorAntiepileptics. Carboxamide derivatives×Calcium channel blocker, non-DHP (benzothiazepine derivative)
Updated · Methodology
Mechanism
The interaction works both ways. Diltiazem inhibits CYP3A4, the main enzyme of carbamazepine metabolism, and blood carbamazepine levels rise by 40–72%, in some patients to toxic levels (diltiazem and carbamazepine labels). Carbamazepine, in turn, is a potent CYP3A4 inducer and can lower levels of drugs metabolized by this enzyme (carbamazepine label). Diltiazem is metabolized by CYP3A4, and CYP3A4 inducers can lower its blood levels (diltiazem label).
Symptoms
Ataxia, diplopia, nausea, drowsiness, tremor. Severe cases: cardiac conduction abnormalities and AV block.
Management
The FDA diltiazem labels advise avoiding diltiazem with any CYP3A4 inducer and considering other treatment, and carbamazepine is a potent CYP3A4 inducer (carbamazepine label). If the combination is still needed, measure the blood carbamazepine level after diltiazem is added and adjust the carbamazepine dose if needed (diltiazem and carbamazepine labels). The usual adult therapeutic range of carbamazepine is 4–12 mcg/mL (FDA carbamazepine label). Warn the patient about signs of carbamazepine excess: dizziness, drowsiness, unsteady gait and double vision (carbamazepine label). The effect of diltiazem may weaken on carbamazepine, and its dose may also need adjustment (FDA carbamazepine label).
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Sources
- FDA: Tegretol / Tegretol-XR (carbamazepine) prescribing information (2026)– FDA label, DailyMed setid 8d409411-aa9f-4f3a-a52c-fbcb0c3ec053, PRECAUTIONS, Drug Interactions
- AEMPS: Ficha técnica: Diltiazem (nº registro 62328), sección 4.5 (2023)– AEMPS, CIMA, nº registro 62328, revisión 06/2023, sección 4.5
- AEMPS: Ficha técnica: Diltiazem, Masdil Retard 120 mg (nº registro 58483), sección 4.5 (2025)– AEMPS, CIMA, nº registro 58483, revisión 03/2025, sección 4.5
- FDA: Cardizem CD (diltiazem) prescribing information (2025)– FDA label, DailyMed setid 1042fa13-e6af-46b9-8008-6c941f0978b1, revised 12/2025, PRECAUTIONS: Drug Interactions
- FDA: Cardizem (diltiazem) prescribing information (2025)– FDA label, Bausch Health US LLC, DailyMed setid f3e7ecef-f360-4987-a4f5-933214130ab2, revised 04/2025, Precautions: Drug Interactions (Digitalis, Carbamazepine, Rifampin, Statins)
- AEMPS: Ficha técnica: Carbamazepina (nº registro 39955), secciones 4.3 y 4.5 (2026)– AEMPS, CIMA, nº registro 39955, revisión 09/2026, secciones 4.3 y 4.5