Risperidone

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

Risperidone is an atypical antipsychotic used in the treatment of schizophrenia, bipolar I disorder, and autism. CYP2D6 is important in its metabolism.

Excerpts from the risperidone drug label:

"Risperidone is metabolized to 9-hydroxyrisperidone by CYP2D6, an enzyme that is polymorphic in the population and that
can be inhibited by a variety of psychotropic and other drugs (see Clinical Pharmacology (12.3)). Drug interactions that reduce
the metabolism of risperidone to 9-hydroxyrisperidone would increase the plasma concentrations of risperidone and lower the
concentrations of 9-hydroxyrisperidone. Analysis of clinical studies involving a modest number of poor metabolizers (n#70) does not
suggest that poor and extensive metabolizers have different rates of adverse effects. No comparison of effectiveness in the two groups
has been made."

"CYP2D6 is subject to genetic polymorphism (about 6% to 8% of Caucasians, and a very low percentage of Asians, have little or no activity and are "poor metabolizers") and to inhibition by a variety of substrates and some non-substrates, notably quinidine. Extensive CYP2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor CYP2D6 metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9- hydroxyrisperidone concentrations than poor metabolizers, the pharmacokinetics of risperidone and 9-hydroxyrisperidone combined, after single and multiple doses, are similar in extensive and poor metabolizers."

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