Alprazolam × Valproic acid

Both drugs depress the central nervous system (CNS), and their effects add up. The alprazolam SmPC warns that combining it with antiepileptics increases CNS depression and the risk of respiratory depression, coma and death (alprazolam SmPC). Valproate can also enhance the effect of benzodiazepines (valproic acid SmPC).

Drowsiness, slowed thinking and reactions, impaired coordination. With marked depression: slow, shallow breathing and confusion, up to coma (alprazolam SmPC). In older patients, sedation and muscle weakness increase the risk of falls (alprazolam SmPC).

The alprazolam SmPC requires limiting the dose and duration of co-administration with antiepileptics (alprazolam SmPC; alprazolam label of the US Food and Drug Administration, FDA). Use alprazolam at the lowest effective dose for the shortest time, no longer than 2–4 weeks; in older patients, start with 0.25 mg two or three times a day and use caution because of sedation, muscle weakness and the risk of falls (alprazolam SmPC). Valproate can enhance the effect of benzodiazepines, so monitor the patient clinically and adjust the dose when needed (valproic acid SmPC). Advise the patient not to drive or operate machinery while taking alprazolam (alprazolam FDA label).