Diazepam

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 that require mental alertness (eg, operating machinery, driving).

Paradoxical reactions, including hyperactive or aggressive behavior, hallucinations, and psychoses, have been reported with benzodiazepines, particularly in pediatric or elderly patients. Discontinue if such reactions occur. Disease-related concerns:

When used as an adjunct in treating convulsive disorders, an increase in frequency/severity of tonic-clonic seizures may occur and require dose adjustment of anticonvulsant. Abrupt withdrawal may result in a temporary increase in the frequency and/or severity of seizures.

Use caution in patients with depression or anxiety associated with depression, particularly if suicidal risk may be present.

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

May be used in patients with open-angle glaucoma who are receiving appropriate therapy; contraindicated in acute narrow-angle glaucoma and untreated open-angle glaucoma.

Use with caution in patients with hepatic impairment. Oral tablet is contraindicated in patients with severe hepatic impairment.

Use benzodiazepines with caution in patients with an impaired gag reflex.

Use with caution in patients with renal impairment.

Use with caution in patients with respiratory disease; a lower dose is recommended for chronic respiratory insufficiency. Oral tablet is contraindicated in patients with severe respiratory impairment or sleep apnea syndrome. Concurrent drug therapy issues:

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.

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, and limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. Special populations:

Use with caution; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects; limit dose to smallest effective amount and increase gradually and as tolerated to avoid adverse reactions.

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

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

Use of diazepam is not recommended in place of appropriate therapy. Dosage form specific issues:

Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Vesicant; ensure proper needle or catheter placement prior to and during administration; avoid extravasation. Acute hypotension, muscle weakness, apnea, and/or cardiac arrest have occurred with parenteral administration. Acute effects may be more prevalent in patients receiving concurrent barbiturates, opioids, or ethanol. Appropriate resuscitative equipment and qualified personnel should be available during administration and monitoring. Avoid use of the injection in patients in shock, coma, or in acute ethanol intoxication with depression of vital signs. Intra-arterial injection should be avoided. Tonic status epilepticus has been precipitated in patients treated with diazepam IV for absence status or absence variant status.

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP ["Inactive" 1997]; Wilson 2000; Wilson 2005; Zar 2007).

Administration of rectal gel should only be performed by individuals trained to recognize characteristic seizure activity for which the product is indicated, and capable of monitoring response to determine need for additional medical intervention. Not recommended for chronic, daily use. Use with caution in patients with neurologic damage. Other warnings/precautions:

Does not have analgesic, antidepressant, or antipsychotic properties.

Diazepam is a long half-life benzodiazepine. Duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance develops to the sedative, hypnotic, and anticonvulsant effects. It does not develop to the anxiolytic or skeletal muscle relaxing effects (Vinkers 2012). Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect.

Rebound or withdrawal symptoms may occur following abrupt discontinuation or large decreases in dose. Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. The benzodiazepine receptor antagonist flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.