Alprazolam is not recommended with concomitant intake of alcohol as it may enhance the sedative effect. This affects the ability to drive or use machines. Enhancement of the depressive effect may occur in cases of concomitant use with Antipsychotics, Hypnotics, Anxiolytics, Antidepressant agents, Anti-epileptic drugs, Anaesthetics and some sedative antihistamines.

Compounds that inhibit certain liver enzymes may increase the concentration of Alprazolam and enhance its activity. Administrating Alprazolam with ketoconazole, itraconazole, or other antifungals is not recommended. Caution is recommended when Alprazolam is administered with Fluoxetine, Propoxyphene, Oral contraceptives, Sertraline, Diltiazem, or Erythromycin. Low doses of Ritonavir can cause a larger impairment in Alprazolam clearance and thus prolongs its clinical effects.