Alprazolam

Benzodiazepines have been associated with anterograde amnesia.

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients. Disease-related concerns:

Use caution in patients with depression, particularly if suicidal risk may be present; episodes of mania or hypomania have occurred in depressed patients treated with alprazolam.

Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use (generally >10 days).

Use with caution in patients with hepatic impairment.

Use with caution in patients with renal impairment or predisposition to urate nephropathy; has weak uricosuric properties.

Use with caution in patients with respiratory disease. Concurrent drug therapy issues:

Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 inducers and major CYP3A4 substrates (see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution in debilitated patients; use lower starting dose.

Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury.

Use with caution in obese patients; may have prolonged action when discontinued.

Cigarette smoking may decrease alprazolam concentrations up to 50%. Other warnings/precautions:

Does not have analgesic, antidepressant, or antipsychotic properties.

At the end of dosing interval, breakthrough anxiety may occur.

Alprazolam has a short half-life for a benzodiazepine and the duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance does not develop to the anxiolytic effects (Vinkers 2012). Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect.

Rebound or withdrawal symptoms, including seizures, may occur following abrupt discontinuation or large decreases in dose (more common in adult patients receiving >4 mg/day or prolonged treatment); the risk of seizures appears to be greatest 24 to 72 hours following discontinuation of therapy. Use caution when reducing dose or withdrawing therapy; decrease slowly (eg, ≤0.5 mg every 3 days in adults) and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.