Alprazolam × Fluoxetine

Fluoxetine slows the elimination of alprazolam. According to the FDA alprazolam label, co-administration raised alprazolam peak concentration by 46%, reduced its clearance by 21%, prolonged its half-life by 17% and worsened psychomotor performance. The FDA fluoxetine label describes the same: alprazolam levels rise and psychomotor function suffers more. The Spanish alprazolam SmPC lists fluoxetine among drugs that need special attention, because inhibitors of liver enzymes, mainly CYP3A4, raise alprazolam levels. Both drugs also act on the central nervous system, and the alprazolam SmPC warns that CNS depression can be enhanced when alprazolam is combined with antidepressants.

Drowsiness, slowed reactions and impaired psychomotor performance, as the FDA labels of both drugs describe for this combination. In older people, sedation and muscle weakness raise the risk of falls, often with serious consequences (alprazolam SmPC). Driving and operating machinery become riskier.

Use the combination with caution and with limits on dose and duration: the alprazolam SmPC requires limiting the dose and duration of alprazolam use with antidepressants and asks for special attention when it is combined with fluoxetine. The FDA fluoxetine label advises considering a lower starting dose of the co-administered drug, slow titration and monitoring of the patient's clinical state. Alprazolam itself is given for as short a time as possible, no longer than 2–4 weeks without reassessment, and older people start at a lower dose (alprazolam SmPC). The long half-life of fluoxetine and its metabolite norfluoxetine has to be taken into account when assessing interactions (fluoxetine SmPC).