Carbamazepine × Lamotrigine

Carbamazepine induces the liver glucuronidation enzymes that clear lamotrigine, so lamotrigine leaves the blood faster (lamotrigine SmPC). According to the US Food and Drug Administration (FDA) label, carbamazepine lowers lamotrigine concentrations by about 40%. The effect also runs the other way: when lamotrigine is started in a patient on carbamazepine, central nervous system adverse effects can occur, and the FDA label notes that carbamazepine epoxide, the active metabolite, may rise.

If the lamotrigine dose is not adapted to carbamazepine, lamotrigine levels stay low and seizures may return. The lamotrigine SmPC notes a weaker response to lamotrigine when it is combined with enzyme inducers. After lamotrigine is started on top of carbamazepine, dizziness, ataxia, double vision, blurred vision and nausea can occur. When carbamazepine is stopped and the lamotrigine dose is not reduced, lamotrigine levels rise.

The labels do not ban the pair, but lamotrigine with carbamazepine follows a separate schedule for inducers, and neither the starting dose nor the rate of increase may be exceeded (lamotrigine SmPC). In epilepsy, adults and adolescents from 13 years without valproate: 50 mg/day in weeks 1 and 2, 100 mg/day in two doses in weeks 3 and 4, then increases of no more than 100 mg every 1–2 weeks to the usual maintenance dose of 200–400 mg/day (lamotrigine SmPC). If the patient also takes valproate, the lower-dose valproate schedule applies (lamotrigine SmPC). In bipolar disorder, when carbamazepine is added to a stable lamotrigine dose of 200 mg, the dose stays at 200 mg in week 1, then 300 mg in week 2 and 400 mg from week 3. When carbamazepine is stopped, the steps go back down: from 400 mg to 300 mg in week 2 and 200 mg from week 3 (lamotrigine SmPC). The US Food and Drug Administration (FDA) label asks for these schedules to be followed closely; there is no target lamotrigine blood level, and the dose is set by clinical response (lamotrigine FDA label). If dizziness, ataxia or double vision appear after lamotrigine is started, the carbamazepine dose is reduced (lamotrigine SmPC).