Major
Established
Description
Phenytoin drastically reduces quetiapine plasma levels through potent CYP3A4 induction, risking complete loss of antipsychotic effect.
Mechanism
Phenytoin is a potent CYP3A4 inducer; quetiapine is primarily cleared by CYP3A4, and co-administration reduces quetiapine AUC by approximately 84%.
Clinical Significance
Quetiapine levels fall to sub-therapeutic concentrations; psychiatric relapse is a significant clinical risk.
Management
Avoid combination if possible; if both are required, expect a 5-fold or greater quetiapine dose requirement and monitor response closely.