Clozapine

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

Clozapine is an atypical antipsychotic drug. It is approved for the treatment of severely ill patients with schizophrenia who fail to show an acceptable response to standard antipsychotic drug treatment. Clozapine is a substrate for many CYP450 isozymes, in particular 1A2, 2D6, and 3A4.

Excerpts from the Clozapine drug label:

"A subset (3%-10%) of the population has reduced activity of certain drug metabolizing enzymes such as the cytochrome P450 isozyme P450 2D6. Such individuals are referred to as "poor metabolizers" of drugs such as debrisoquin, dextromethorphan, the tricyclic antidepressants, and clozapine. These individuals may develop higher than expected plasma concentrations of clozapine when given usual doses. In addition, certain drugs that are metabolized by this isozyme, including many antidepressants (clozapine, selective serotonin reuptake inhibitors, and others), may inhibit the activity of this isozyme, and thus may make normal metabolizers resemble poor metabolizers with regard to concomitant therapy with other drugs metabolized by this enzyme system, leading to drug interaction.
Concomitant use of clozapine with other drugs metabolized by cytochrome P450 2D6 may require lower doses than usually prescribed for either clozapine or the other drug. Therefore, coadministration of clozapine with other drugs that are metabolized by this isozyme, including antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide and encainide), or that inhibit this enzyme (e.g., quinidine), should be approached with caution."

(For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Clozapine drug label PDF.)