Annotation of U.S. Food and Drug Administration (FDA) label information
for clozapine
and CYP2D6
Summary
Clozapine is a substrate of CYP1A2, CYP3A4, and CYP2D6. The drug label notes to use caution when administering it concomitantly with drugs that are inducers or inhibitors of these enzymes. Additionally, it may be necessary to reduce the clozapine dose in patients with significant renal or hepatic impairment, or in CYP2D6 poor metabolizers.
Annotation
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:
Dose reduction may be necessary in patients who are CYP2D6 poor metabolizers. Clozapine concentrations may be increased in these patients, because clozapine is almost completely metabolized and then excreted.
A subset (3%–10%) of the population has reduced activity of CYP2D6 (CYP2D6 poor metabolizers). These individuals may develop higher than expected plasma concentrations of clozapine when given usual doses.
Concomitant use of CLOZARIL with other drugs metabolized by CYP2D6 can increase levels of these CYPD26 substrates. Use caution when coadministering CLOZARIL with other drugs that are metabolized by CYP2D6. It may be necessary to use lower doses of such drugs than usually prescribed. Such drugs include specific antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide).
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Clozapine drug label.
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