Carbamazepine × Quetiapine

Carbamazepine strongly induces CYP3A4, the liver enzyme that is the main route of quetiapine breakdown. In a study in patients, quetiapine exposure (area under the concentration-time curve) on carbamazepine fell on average to 13% of the baseline value, and even lower in some patients (quetiapine SmPC). The effect also runs the other way: quetiapine can raise the active carbamazepine metabolite, carbamazepine-10,11-epoxide (carbamazepine SmPC).

Quetiapine loses its effect: hallucinations, delusions and agitation return, and in bipolar disorder the risk of a new manic or depressive episode rises. Excess carbamazepine epoxide causes dizziness, somnolence, ataxia and double vision. If carbamazepine is stopped but the raised quetiapine dose is kept, quetiapine levels rise: somnolence, dizziness, orthostatic hypotension.

Quetiapine may be started in a patient on carbamazepine only if its benefit outweighs the risk of withdrawing the inducer; the inducer is changed gradually and, if needed, replaced with a non-inducer such as sodium valproate (quetiapine SmPC). If the combination is needed for longer than 7–14 days, the quetiapine dose is increased up to 5-fold of the original dose, titrated to clinical response and tolerability (US Food and Drug Administration (FDA) quetiapine label). The Spanish SmPC caps the daily quetiapine dose at 750 mg in schizophrenia and 800 mg in bipolar disorder (quetiapine SmPC). After carbamazepine is stopped, the quetiapine dose is brought back to the original level within 7–14 days (quetiapine FDA label). Because of the epoxide rise, the carbamazepine dose is adjusted or its blood levels are monitored (carbamazepine SmPC).