Moderate
Established
Description
Fluoxetine is a potent CYP2D6 inhibitor that significantly increases aripiprazole plasma concentrations, enhancing both efficacy and adverse effects.
Mechanism
Aripiprazole is metabolized by CYP2D6 to dehydro-aripiprazole (active); fluoxetine inhibition of CYP2D6 increases parent drug exposure significantly.
Clinical Significance
Aripiprazole AUC increases by approximately 112% with potent CYP2D6 inhibitors; akathisia, sedation, and weight gain may worsen.
Management
Reduce aripiprazole dose to half when combined with fluoxetine or other potent CYP2D6 inhibitors; per FDA label.