LORAZEPAM
Clinical safety rating: avoid
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
Benzodiazepine that enhances GABA-A receptor activity by increasing frequency of chloride channel opening, leading to neuronal hyperpolarization and inhibition.
| Metabolism | Primarily hepatic via glucuronidation (UGT2B15, UGT1A4); inactive metabolites. |
| Excretion | Primarily renal excretion as glucuronide conjugates; less than 1% excreted unchanged. Approximately 60-80% eliminated in urine, with 15-20% in feces. |
| Half-life | Terminal elimination half-life is 12-18 hours. Clinically significant for once-daily dosing; may accumulate in elderly or hepatic impairment. |
| Protein binding | Approximately 85-90% bound to serum albumin. |
| Volume of Distribution | 1.0-1.3 L/kg, indicating extensive tissue distribution including central nervous system. |
| Bioavailability | Oral: 90-95% (well absorbed); Intramuscular: 90-100% (rapid and complete absorption). |
| Onset of Action | Oral: 1-2 hours; Intramuscular: 30-60 minutes; Intravenous: 2-5 minutes. |
| Duration of Action | Benzodiazepine: 6-12 hours for anxiolytic effect; sedative effects may last longer. Duration affected by redistribution and metabolic clearance. |
| Molecular Weight | 321.16 |
2-3 mg orally or IV, 3-4 times daily; maximum 10 mg/day. For anxiety, 0.5-2 mg orally 2-3 times daily. For procedural sedation, IV: 0.044 mg/kg or 2 mg total, may repeat.
| Dosage form | TABLET |
| Renal impairment | No specific GFR-based dose adjustment required; use caution in severe impairment (CrCl <10 mL/min) due to accumulation of inactive metabolites. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid or use with extreme caution; reduce dose by 75%. |
| Pediatric use | Child >12 years: 2-6 mg/day in 2-4 divided doses; 6-12 years: 1.5-3 mg/day in 2-4 divided doses; 2-5 years: 0.5-2 mg/day in 2-4 divided doses. IV for seizures: 0.05-0.1 mg/kg slow IV, max 4 mg. |
| Geriatric use | Initial dose 0.5-1 mg/day in divided doses; increase cautiously. Maximum 3-4 mg/day. Increased sensitivity to CNS depression; monitor for falls, confusion, and sedation. |
| 1st trimester | Avoid if possible; associated with increased risk of oral clefts (meta-analysis OR 1.79). Use only if benefit outweighs risk. |
| 2nd trimester | Use with caution; no consistent evidence of major malformations, but potential for fetal CNS depression. |
| 3rd trimester | Avoid; risk of neonatal withdrawal, hypotonia, 'floppy infant syndrome,' respiratory depression, and poor feeding. |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| FDA category | Positive |
| Placental transfer | Crosses placenta; cord-to-maternal ratio approx 1.0, indicating free passage. Accumulation in fetal circulation may occur due to immature hepatic metabolism. |
| Breastfeeding |
■ FDA Black Box Warning
Concomitant use of benzodiazepines with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate.
| Common Effects | insomnia |
| Serious Effects |
Severe respiratory insufficiency (e.g., acute COPD, sleep apnea)Myasthenia gravisHistory of hypersensitivity to lorazepam or any benzodiazepineAcute narrow-angle glaucoma
| Precautions | Risk of respiratory depression, especially with concomitant CNS depressants; tolerance, dependence, and withdrawal; abuse potential; paradoxical reactions; not recommended for primary psychotic disorders; use with caution in hepatic impairment, elderly, and debilitated patients. |
| Food/Dietary | No specific food interactions. Avoid grapefruit juice as it may potentiate effects. Limit caffeine intake as it may reduce anxiolytic effect. Alcohol is contraindicated due to additive CNS depression. |
Loading safety data…
| Lorazepam is excreted into breast milk in small amounts (estimated infant dose 2-6% of maternal weight-adjusted dose). Occasional use may be acceptable, but monitor infant for sedation, poor feeding, and respiratory depression. Avoid chronic high doses. Prefer shorter-acting benzodiazepines. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Possible increased risk of oral cleft (cleft lip/palate) from exposure in first trimester based on some epidemiological studies; absolute risk increase small (from 0.06% to 0.1-0.2%). Second and third trimesters: Risk of floppy infant syndrome (hypotonia, hypothermia, respiratory depression, poor feeding) with late third trimester or chronic use. Neonatal withdrawal (jitteriness, hypertonia, seizures) may occur after prolonged exposure. Avoid use in first trimester if possible; use only if benefit outweighs risk in later trimesters. |
| Fetal Monitoring | Maternal: Liver function tests (LFTs), renal function, and baseline CBC prior to initiation; periodic reassessment with prolonged use. Fetal/neonatal: Ultrasound for growth and anatomy if first trimester exposure; neonatal observation for signs of floppy infant syndrome or withdrawal after delivery, including respiratory rate, muscle tone, temperature, and feeding ability for at least 48 hours postnatally. |
| Fertility Effects | Animal studies: High doses may impair fertility (estrous cycle irregularities, decreased conception rates) in rats; no human data available. Human: Limited evidence; theoretical risk with chronic use due to hormonal influence on hypothalamic-pituitary-gonadal axis, but no established effect on fertility in humans. |
| Clinical Pearls | Lorazepam is preferred over diazepam for IM injection due to reliable absorption. Monitor for respiratory depression, especially when combined with opioids. Use with caution in elderly due to increased risk of falls and cognitive impairment. Onset of action is slower than midazolam; not ideal for procedural sedation. Tolerance develops to sedative effects but not anxiolytic effects. Avoid abrupt discontinuation to prevent withdrawal seizures. |
| Patient Advice | Do not drive or operate machinery until you know how this medication affects you. · Avoid alcohol and other central nervous system depressants. · Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not stop taking abruptly; withdrawal symptoms may occur including seizures. · May cause drowsiness, dizziness, or blurred vision. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Store at room temperature away from light and moisture. |