Adult: 0.025-0.03 mg/kg via IV inj or deep IM inj 6 hourly if needed. Dosage is individualised according to patient's clinical response and tolerability. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Reduce to half of the usual dose.
Intramuscular, Intravenous Premedication in surgery
Adult: 0.05 mg/kg given 30-45 minutes before surgery via slow IV inj or 60-90 minutes before surgery via IM inj. Dosage is individualised according to patient's clinical response and tolerability. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Reduce to half of the usual dose.
Intravenous Status epilepticus
Adult: 4 mg as a single dose via slow IV inj (Max rate: 2 mg/min); may repeat once after 10-15 minutes if seizure continues or recurs. Dosage is individualised according to patient's clinical response and tolerability. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Reduce to half of the usual dose. Child: 2 mg as a single dose via slow IV inj.
Oral Anxiety
Adult: 1-4 mg daily in divided doses; may increase dose up to 10 mg daily if needed. Dosage is individualised according to patient's clinical response and tolerability. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Reduce to half of the usual dose.
Oral Premedication in surgery
Adult: 2-3 mg given the night before the operation, then 2-4 mg 1-2 hours before the procedure. Dosage is individualised according to patient's clinical response and tolerability. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Reduce to half of the usual dose. Child: 5-13 years 0.5-2.5 mg at 0.05 mg/kg to the nearest 0.5 mg based on weight, given not less than 1 hour before the operation. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Oral Insomnia associated with anxiety
Adult: 1-2 mg as a single dose given at bedtime. Dosage is individualised according to patient's clinical response and tolerability. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Reduce to half of the usual dose.
Special Patient Group
Debilitated patients: Reduce to half of the usual dose, and adjust dose as needed and tolerated.
Renal Impairment
Dose reduction may be needed.
Hepatic Impairment
Mild to moderate: Dose reduction may be needed. Severe: Contraindicated.
Administration
May be taken with or without food.
Reconstitution
Adult and children: IV inj: Dilute with an equal volume of compatible diluent (e.g. NaCl 0.9%, dextrose 5% in water, sterile water for inj).
Contraindications
Myasthenia gravis, acute narrow-angle glaucoma; sleep apnoea, acute pulmonary insufficiency, respiratory depression; obsessional states. Severe hepatic impairment. Pregnancy.
Special Precautions
Patient with chronic respiratory insufficiency, COPD, history of alcoholism or drug abuse; significant personality disorders, fall risk. Debilitated patients. Not indicated for primary treatment of psychotic illness or depressive disorders. Not recommended for long-term use. Avoid abrupt withdrawal. Renal and mild to moderate hepatic impairment. Neonates, children, and elderly. Lactation.
Adverse Reactions
Significant: Transient anterograde amnesia, memory impairment, paradoxical reactions, physical and psychological dependence, blood dyscrasia, elevated liver enzymes. Rarely, hypotension. General disorders and administration site conditions: Asthenia, fatigue; inj site pain (IM or IV). Musculoskeletal and connective tissue disorders: Muscle weakness. Nervous system disorders: Daytime drowsiness, dizziness, sedation, ataxia. Psychiatric disorders: Confusion, depression, unmasking of depression, hallucinations. Potentially Fatal: Respiratory depression, anaphylactic reactions (e.g. angioedema of the tongue, glottis or larynx); acute withdrawal reactions (abrupt discontinuation or rapid dosage reduction after continued use); abuse, misuse and addiction.
This drug may cause dizziness, sedation, blurred vision, amnesia, impaired concentration and impaired muscular function; if affected, do not drive or operate machinery.
Monitoring Parameters
Confirm pregnancy status before initiation of treatment. Monitor respiratory and cardiovascular status; heart rate, blood pressure. Obtain CBC, LFTs, LDH for long-term treatment. Assess mental alertness and symptoms of anxiety; signs and symptoms of withdrawal, aggressive or hyperactive behaviour; physical and/or psychological dependence.
Overdosage
Symptoms: Drowsiness, somnolence, mental confusion, paradoxical reactions, lethargy and dysarthria. Severe cases: Hypotension, hypotonia, ataxia, circulatory and respiratory depression, hypnotic state, coma. Management: Supportive and symptomatic treatment. Administer activated charcoal to reduce absorption. May induce vomiting or perform gastric lavage in case of recent ingestion. Maintain adequate airway and use assisted respiration as necessary. Control hypotension with norepinephrine or plasma replacement fluid. May give flumazenil as an antidote.
Drug Interactions
Enhanced central depressive effects with other centrally acting drugs such as sedative antihistamines, anaesthetics, neuroleptics, antidepressants, antipsychotics, barbiturates (e.g. phenobarbital), sedatives and hypnotics. Increases effects of Na oxybate. Increased serum concentration with valproate. Prolonged effect with probenecid. Increases the clearance of zidovudine. Increased risk of prolonged sedation with HIV protease inhibitors. Concomitant use with clozapine may result in marked sedation, excessive salivation, hypotension, ataxia, delirium and respiratory arrest. Increased overall muscle-relaxing effect with muscle relaxants. Decreased sedative effect with aminophylline or theophylline. Decreased anxiolytic and sedative effects with caffeine. Decreased clearance with CYP450 inhibitors (e.g. cimetidine, isoniazid, erythromycin, omeprazole, ketoconazole). Increased clearance with CYP450 inducers (e.g. rifampicin). Increased hypotensive effect with antihypertensives (e.g. ACE inhibitors, α-blockers, ARBs, β-blockers, Ca channel blockers), vasodilators (e.g. hydralazine, nitrates) and diuretics. Antacids may delay the absorption of lorazepam. May antagonise the effect of levodopa. Potentially Fatal: Increased risk of sedation, respiratory depression and coma with opioids.
Food Interaction
Enhanced sedative effects with alcohol. Increased serum concentration with grapefruit juice.
Action
Description: Mechanism of Action: Lorazepam is a short-acting benzodiazepine which binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the CNS (including reticular formation, limbic system). Increased neuronal membrane permeability to chloride ions potentiates the inhibitory effect of GABA on neuronal excitability thereby resulting in hyperpolarisation and stabilisation. Onset: Anticonvulsant: Within 10 minutes (IV). Hypnosis: 20-30 minutes (IM). Sedation: 15-20 minutes (IV); 20-30 minutes (oral). Duration: Anaesthesia premedication: Approx 6-8 hours (IM or IV). Pharmacokinetics: Absorption: Readily absorbed from the gastrointestinal tract. Rapidly and completely absorbed (IM). Bioavailability: 90% (oral). Time to peak plasma concentration: Oral: 14 hours, with a range of 7-23 hours (extended-release); approx 2 hours (immediate release). IM: ≤3 hours. Distribution: Crosses the placenta and blood-brain barrier; enters breast milk (small amounts). Volume of distribution: 1.3 L/kg (IV); 117 L (extended-release cap). Plasma protein binding: Approx 85%. Metabolism: Metabolised in the liver and conjugated into lorazepam glucuronide (inactive). Excretion: Via urine (approx 88%; predominantly as inactive metabolites); faeces (approx 7%). Elimination half-life: Approx 10-20 hours.
Chemical Structure
Storage
Tab: Store below 25°C. Oral solution or concentrate, solution for inj: Store between 2-8°C. Protect from light.