New Formulation of Lorazepam

Lorazepam is now available as a solution for injection. Lorazepam is a medium-acting benzodiazepine with an elimination half-life of around 12-16 hours.

Lorazepam injection is for acute use only for the following indications:

• As a pre-operative medication;
• Premedication for prolonged investigations;
• Treatment of acute anxiety states and acute agitation; and
• Control of status epilepticus in adults, adolescents and children.

Like all benzodiazepines, careful consideration of dose and duration of therapy is essential. However, additional care is required for lorazepam injection due to the presence of the excipients, benzyl alcohol and propylene glycol.

Each lorazepam ampoule contains 21mg of benzyl alcohol. Benzyl alcohol is normally oxidised in the liver to produce benzoic acid, which is then conjugated with glycine and excreted in the urine as hippuric acid. However, this metabolic pathway may not be well developed in neonates, leading to the accumulation of benzoic acid. Intravenous administration of benzyl alcohol has been associated with serious adverse effects and death in neonates, and lorazepam injection should not be used in this population. Accumulation can also occur in adults which may present as metabolic acidosis. The manufacturer advises caution with high doses, particularly in pregnant or breastfeeding women and patients with renal or hepatic impairment.

A lorazepam ampoule also contains 840mg of propylene glycol. This solvent is typically well tolerated, although toxic effects can occur. Adverse events associated with propylene glycol include hyperosmolality, lactic acidosis, renal dysfunction, liver dysfunction, cardiotoxicity, respiratory depression, and seizures. Prolonged repeat injections or infusions of lorazepam are not recommended due to the potential for propylene glycol toxicity.

Other benzodiazepines available in injectable formulations are midazolam and diazepam. Diazepam injection also contains propylene glycol, while midazolam contains neither benzyl alcohol nor propylene glycol. Midazolam has a much shorter duration of action compared to lorazepam, although repeat doses or an infusion may be used.