Major
Established
Description
Diltiazem is a potent CYP3A4 inhibitor that significantly increases quetiapine plasma concentrations, raising risk of quetiapine toxicity and QT prolongation.
Mechanism
Diltiazem inhibits CYP3A4, the primary enzyme responsible for quetiapine metabolism, substantially increasing quetiapine AUC; both drugs also have modest QT-prolonging effects.
Clinical Significance
Quetiapine levels may increase 2- to 5-fold; sedation, metabolic adverse effects, and QTc prolongation are clinical risks.
Management
Reduce quetiapine dose substantially when adding diltiazem; monitor for excessive sedation, metabolic effects, and ECG changes.