Major
Ketoconazole × Quetiapine
Systemic antimycotics. Imidazole derivatives×Atypical antipsychotics
Mechanism
Ketoconazole is a potent CYP3A4 inhibitor – the main quetiapine metabolic route. Quetiapine plasma levels rise 6- to 7-fold. Marked sedation, orthostatic hypotension, QT prolongation emerge.
Symptoms
Deep sedation, orthostatic hypotension with syncope, tachycardia, QT prolongation on ECG. Older patients: fall risk.
Management
During ketoconazole therapy, reduce quetiapine 4- to 6-fold and monitor ECG and blood pressure. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole.