Lorazepam

Lorazepam is an intermediate-acting benzodiazepine used for short-term anxiety, insomnia, acute agitation, catatonia, alcohol withdrawal, status epilepticus and pre-procedure sedation. It is conjugated directly by the liver without active metabolites, so it is preferred over diazepam in liver disease and older adults, and it is available as an injection.

Classification. Benzodiazepine, intermediate-acting.

Mechanism. Positive allosteric modulation of GABA-A receptors, which increases chloride channel opening and neuronal inhibition.

Pharmacokinetics. Well absorbed orally, peak in about 2 hours; intramuscular absorption is reliable and peak is in 60 to 90 minutes. Glucuronidated to an inactive metabolite. Half-life about 12 hours (longer in older adults and kidney failure). Approximate equivalence for switching: lorazepam 1 mg is about diazepam 10 mg.

Anxiety, adults (oral). 0.5 to 1 mg two or three times daily; maximum 4 mg daily in divided doses (up to 6 mg in some labels). Use for no longer than 2 to 4 weeks.

Insomnia, adults. 0.5 to 2 mg at night for no more than 2 to 4 weeks.

Acute agitation or severe anxiety. 0.5 to 2 mg orally, or 1 to 2 mg intramuscularly into a large muscle; repeat after 2 hours if needed. Maximum 4 mg in 24 hours in unmonitored settings.

Status epilepticus, adults (intravenous). 4 mg (0.1 mg/kg) at a rate not over 2 mg/min; repeat once after 10 to 15 minutes. Maximum 8 mg. Children: 0.1 mg/kg (maximum 4 mg), repeat once after 10 minutes.

Alcohol withdrawal, particularly with liver disease. 1 to 2 mg orally four times daily, reducing over 5 to 7 days; give thiamine to all patients.

Catatonia (specialist use). Challenge dose 1 to 2 mg intravenously or intramuscularly; if effective, 1 to 2 mg three times daily and adjust to response.

Pre-procedure sedation. Intramuscular 0.05 mg/kg (maximum 4 mg) 2 hours before the procedure, or intravenous 0.044 mg/kg (maximum 2 mg).

Dose limits. Older adults: start 0.5 mg (half the adult dose). Liver impairment: no adjustment but use lower doses in severe disease. Kidney impairment: start low; propylene glycol accumulates with prolonged high-dose infusion.

Contraindications. Respiratory depression, severe sleep apnoea, acute pulmonary insufficiency, myasthenia gravis, severe liver impairment, acute narrow-angle glaucoma, hypersensitivity. Major warning of profound sedation and death with opioids; abuse and misuse; dependence and withdrawal.

Serious adverse effects. Respiratory depression, hypotension (rapid intravenous), paradoxical agitation, dependence and withdrawal seizures, delirium in older adults, falls and fractures, anterograde amnesia, propylene glycol toxicity (metabolic acidosis, kidney injury) with high-dose infusion.

Common adverse effects. Drowsiness, dizziness, ataxia, confusion, weakness, memory impairment.

Interactions. Opioids, alcohol, gabapentinoids and other sedatives add respiratory depression. Valproate raises lorazepam levels; probenecid raises them; oral contraceptives lower them. Clozapine with lorazepam can cause collapse. Few cytochrome interactions.

Common prescribing errors. Long-term prescribing; giving the injection undiluted by the intravenous route; combining with opioids; high doses in older adults; not tapering after prolonged use.

Special groups.

• Pregnancy: avoid regular use; floppy infant syndrome and neonatal withdrawal with late exposure; use for seizures if needed.
• Breastfeeding: single doses acceptable; avoid repeated dosing because of infant sedation.
• Children: used for seizures and sedation; not for routine anxiety; avoid in neonates (benzyl alcohol content).
• Older adults: half the dose; high risk of falls and delirium; avoid where possible.
• Kidney impairment: start low.
• Liver impairment: preferred benzodiazepine; use lower doses in severe disease.

Formulations. Tablets 0.5 mg, 1 mg and 2.5 mg; sublingual tablets in some regions; injection 2 mg/mL and 4 mg/mL. For intravenous use dilute with an equal volume of sodium chloride 0.9% or water for injection and inject slowly into a large vein. Give intramuscular doses undiluted, deep into muscle. Store injection refrigerated.

Baseline. Respiratory status, alcohol and sedative use, kidney and liver function, pregnancy status, history of dependence, medicines list.

Monitoring. After intravenous or intramuscular dosing, monitor respiratory rate, oxygen saturation, blood pressure and level of consciousness until recovered; have airway equipment and oxygen ready. Review anxiety or insomnia treatment at 2 weeks. In alcohol withdrawal, assess withdrawal severity every 1 to 4 hours and withhold the dose if the patient is drowsy.

Stopping. After more than 2 to 4 weeks of use, reduce the dose by 5 to 10% every 1 to 2 weeks, more slowly at the lowest doses. Abrupt stopping can cause seizures and delirium.

Referral and escalation. Refer to addiction or psychiatric services for dependence or withdrawal. A seizure lasting more than 5 minutes, respiratory depression, or oxygen saturation under 92% needs emergency care.