From the Guidelines
Yes, Prozac (fluoxetine) can increase olanzapine concentrations.
Mechanism of Interaction
- The combination of olanzapine and fluoxetine is approved for bipolar depression in adults 1.
- Fluoxetine is a potent inhibitor of the CYP2D6 enzyme, which is involved in the metabolism of olanzapine 1.
- Inhibition of CYP2D6 by fluoxetine can lead to increased olanzapine concentrations, as olanzapine is a substrate of this enzyme.
Clinical Implications
- The increased olanzapine concentrations can lead to increased risk of adverse effects, such as sedation, dry mouth, and orthostatic hypotension.
- Clinicians should be aware of this potential interaction and monitor patients closely for adverse effects when co-prescribing fluoxetine and olanzapine.
- Dose adjustments may be necessary to minimize the risk of adverse effects 1.
From the FDA Drug Label
Inhibitors of CYP2D6 Fluoxetine: Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance
Yes, Prozac (fluoxetine) may increase olanzapine concentrations, with a reported small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance 2.
From the Research
Pharmacokinetic Interaction between Olanzapine and Fluoxetine
- The study 3 investigated the potential pharmacokinetic interaction between olanzapine and fluoxetine in 15 healthy nonsmoking volunteers.
- The results showed that olanzapine mean Cmax was slightly higher (by about 18%) and mean CL/F was slightly lower (by about 15%) when olanzapine was coadministered with fluoxetine in single or multiple doses.
- The mechanism of influence is consistent with an inhibition of CYP2D6, which is known to control a minor pathway of olanzapine metabolism.
Effect of Fluoxetine on Olanzapine Concentrations
- The study 3 found that the pharmacokinetic effects of fluoxetine on olanzapine were statistically significant, but the effects were small and are unlikely to modify olanzapine's safety profile.
- The increase in olanzapine concentrations due to fluoxetine is likely due to the inhibition of CYP2D6, which can lead to increased levels of olanzapine in the body.
Clinical Implications
- The studies 4, 5, 6, and 7 investigated the efficacy and safety of the olanzapine/fluoxetine combination in treating various conditions, including treatment-resistant depression and acute bipolar depression.
- While these studies did not directly investigate the effect of fluoxetine on olanzapine concentrations, they provide evidence for the safety and efficacy of the combination therapy.
- However, the study 3 is the only one that directly investigated the pharmacokinetic interaction between olanzapine and fluoxetine, and its findings suggest that fluoxetine can increase olanzapine concentrations, although the effect is small.