CriticalSystemic antimycotics. Imidazole derivatives×Atypical antipsychotics
Updated · Methodology
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
The AEMPS label for quetiapine lists the combination with ketoconazole as contraindicated: quetiapine exposure rises 5 to 8 times. The FDA label reduces the quetiapine dose sixfold with ECG monitoring instead. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole.
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Sources
- FDA: Seroquel (quetiapine) label section 7 (2013)– ; DailyMed setid 8ae62aaf-f8c5-417f-baac-0098369ca322
- AEMPS: Ficha técnica: Quetiapina (nº registro 72882), sección 4.5 (2024)– AEMPS, CIMA, nº registro 72882, sección 4.5