Lorazepam

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:

Risk of dependence increases in patients with a history of alcohol or drug abuse and those with significant personality disorders; use with caution in these patients. Tolerance, psychological and physical dependence may also occur with higher dosages and prolonged use. The risk of dependence is decreased with short-term treatment (2 to 4 weeks); evaluate the need for continued treatment prior to extending therapy duration.

Use with caution in patients with hepatic impairment, insufficiency, and/or encephalopathy. Dose adjustment (lower doses) may be needed. May worsen hepatic encephalopathy. Parenteral use is not recommended in patients with hepatic failure.

Use with caution in patients with an impaired gag reflex.

Preexisting depression may emerge or worsen during therapy. Not recommended for use in primary depressive or psychotic disorders. Should not be used in patients at risk for suicide without adequate antidepressant treatment.

Use with caution in patients with renal impairment. Parenteral use is not recommended in patients with renal failure.

Use with caution in patients with respiratory disease, including COPD or sleep apnea. Benzodiazepines may cause significant respiratory depression. Concurrent drug therapy issues:

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. In patients already receiving an opioid analgesic, prescribe a lower initial dose of lorazepam than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking lorazepam, prescribe a lower initial dose of the opioid and titrate based upon clinical response.

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; initial doses should be at the lower end of dosing range.

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

In pediatric and neonatal patients FDA 2016). Dosage form specific issues:

Some dosage forms may contain 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 suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

Parenteral formulation may contain polyethylene glycol. May be associated with toxicity in high-dose and/or longer-term therapy.

Parenteral formulation may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling. May consider using enteral delivery of lorazepam tablets to decrease the risk of propylene glycol toxicity (Lugo 1999). Other warnings/precautions:

Does not have analgesic, antidepressant, or antipsychotic properties. Status epilepticus should not be treated with injectable benzodiazepines alone; requires close observation and management and possibly ventilatory support. When used as a component of preanesthesia, monitor for heavy sedation and airway obstruction; equipment necessary to maintain airway and ventilatory support should be available.

Appropriate use: As a hypnotic, should be used only after evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate psychiatric or medical illness. A worsening of insomnia or the emergence of new abnormalities of thought or behavior may represent unrecognized psychiatric or medical illness and requires immediate and careful evaluation.

Lorazepam is a short 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 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. Flumazenil may cause acute withdrawal in patients receiving long-term benzodiazepine therapy.