Fluoxetine

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

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). Fluoxetine is indicated for the treatment of major depressive disorder, obsessive compulsive disorder, bulimia nervosa, and panic disorder. Fluoxetine is metabolized by several cytochrome P450 enzymes with CYP2D6 being a major contributor. At the same time, fluoxetine is an inhibitor of CYP2D6 mediated reactions.

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

Excerpts from the Fluoxetine drug label:
"Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway (7.9)"

"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, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. Therapy with medications that are predominantly metabolized by the CYP2D6 system and that have a relatively narrow therapeutic index (see list below) should be initiated at the low end of the dose range if a patient is receiving fluoxetine concurrently or has taken it in the previous 5 weeks. Thus, his/her dosing requirements resemble those of poor metabolizers. If fluoxetine is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need for decreased dose of the original medication should be considered. Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs). Due to the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued."

"Because fluoxetine's metabolism, like that of a number of other compounds including TCAs and other selective serotonin reuptake inhibitors (SSRIs), involves the CYP2D6 system, concomitant therapy with drugs also metabolized by this enzyme system (such as the TCAs) may lead to drug interactions."

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