Fluoxetine and Olanzapine

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

Combined fluoxetine and olanzapine is a drug mixture used for the treatment of bipolar disorder and major depressive disorder. Fluoxetine is a selective serotonin reuptake inhibitor and metabolized by several cytochrome P450 enzymes with CYP2D6 being a major contributor (see Fluoxetine Pathway and CYP2D6 VIP for more details). Olanzepine is an atypical antipsychotic. Olanzepine is metabolized via CYP1A2 and clearance is influences by smoking (see CYP1A2 VIP for additional information).

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Fluoxetine and Olanzapine.

Excerpt from the Fluoxetine and Olanzapine (Symbyax) drug label:
"A subset (about 7%) of the population has reduced activity of the drug metabolizing enzyme CYP2D6. Such individuals are referred to as "poor metabolizers" of drugs such as debrisoquin, dextromethorphan, and the tricyclic antidepressants (TCAs). In a study involving labeled and unlabeled enantiomers administered as a racemate, these individuals metabolized S-fluoxetine at a slower rate and thus achieved higher concentrations of S-fluoxetine. Consequently, concentrations of S-norfluoxetine at steady state were lower."

"Fluoxetine inhibits the activity of CYP2D6 and may make individuals with normal CYP2D6 metabolic activity resemble a poor metabolizer. Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6 ... should be approached with caution."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Fluoxetine and Olanzapine drug label PDF.