Aripiprazole

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

Aripiprazole is an atypical antipsychotic medication mainly used for the treatment of schizophrenia. It is also indicated for the acute and maintenance treatment of manic and mixed episodes associated with bipolar I disorder and for an adjunctive therapy treatment to antidepressants for the treatment of major depressive disorder. The mechanism of action is unknown, but aripiprazole shows partial agonist activity at DRD2 and HTR1A receptors and antagonist activity at HTR2A receptors.
Aripiprazole undergoes hepatic metabolization, primarily by the cytochrome P450 enzymes CYP3A4 and CYP2D6.

Excerpts from the Aripiprazole drug label:

"Approximately 8% of Caucasians lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PM), whereas the rest are extensive metabolizers (EM). PMs have about an 80% increase in aripiprazole exposure and about a 30% decrease in exposure to the active metabolite compared to EMs, resulting in about a 60% higher exposure to the total active moieties from a given dose of aripiprazole compared to EMs. Coadministration of ABILIFY with known inhibitors of CYP2D6, such as quinidine or fluoxetine in EMs, approximately doubles aripiprazole plasma exposure, and dose adjustment is needed (see DRUG INTERACTIONS (7.1)). The mean elimination half-lives are about 75 hours and 146 hours for aripiprazole in EMs and PMs, respectively."

"Inhibitors of CYP3A4 (eg, ketoconazole) or CYP2D6 (eg. quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels. Aripiprazole dose should be reduced to one-half of its normal dose when quinidine is given concomitantly with aripiprazole. Other significant inhibitors of CYP2D6, such as fluoxetine or paroxetine, would be expected to have similar effects and should lead to similar dose reductions. When the CYP2D6 inhibitor is withdrawn from the combination therapy, the aripiprazole dose should be increased. "

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