Alprazolam × Pregabalin

Alprazolam and pregabalin depress the central nervous system (CNS) by different pathways, 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). Pregabalin enhances the effect of lorazepam, another benzodiazepine, and post-marketing reports describe respiratory failure, coma and death when pregabalin was taken with CNS depressants (pregabalin SmPC of the European Medicines Agency, EMA).

Drowsiness, dizziness, slowed thinking, impaired coordination. With marked depression: slow, shallow breathing, confusion and loss of consciousness (alprazolam and pregabalin SmPCs). In older patients, drowsiness and dizziness increase the risk of falls (alprazolam and pregabalin SmPCs).

The alprazolam SmPC requires limiting the dose and duration of co-administration with antiepileptics, which include pregabalin (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). The risk of severe respiratory depression is higher when pregabalin is taken with central nervous system depressants, in older patients and in those with lung disease, neurological disease or renal impairment; these patients may need a pregabalin dose adjustment (pregabalin SmPC of the European Medicines Agency, EMA). Advise the patient not to drive or operate machinery while taking alprazolam (alprazolam FDA label).