Interactions of Clozapine
The cytochrome P450 system of enzymes in the liver inactivates and removes the toxic substances, including drugs, from the body. These enzymes include CYP 2D6, 2C9, 2C19, and 1 A2. But certain drugs can inhibit or induce these enzymes themselves. Some SSRIs are potent inhibitors of an individual or multiple hepatic cytochrome P450 (CYP) pathways and the magnitude of these effects is dose-related. Several clinically significant drug interactions can, therefore, be predicted. For example, fluvoxamine is a potent inhibitor of CYP1A2 which can result in increased theophylline serum levels, fluoxetine is a potent inhibitor of CYP2D6 which can cause increased seizure risk with clozapine, and paroxetine is a potent inhibitor of CYP2D6 which can cause treatment failure with tamoxifen (a prodrug), leading to increased mortality. Escitalopram has the least impact on these enzymes.