Major
Clarithromycin × Quetiapine
Macrolide antibiotic×Atypical antipsychotics
Mechanism
Clarithromycin blocks CYP3A4 – the main quetiapine metabolic route. Quetiapine plasma levels rise 6-fold, with stronger sedation, orthostatic hypotension, and QT effect.
Symptoms
Marked sedation, drowsiness, orthostatic hypotension with syncope on standing. Tachycardia, QT prolongation. In older patients: fall and fracture risk.
Management
During clarithromycin therapy, reduce quetiapine 4- to 6-fold and monitor ECG (QT) and blood pressure. Alternative antibiotics: azithromycin or doxycycline (minimal CYP3A4 impact). Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole.