LORAZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LORAZ (LORAZ).
Binds to gamma-aminobutyric acid (GABA) type A receptors at the benzodiazepine binding site, potentiating the effect of GABA, leading to increased chloride ion influx, neuronal hyperpolarization, and inhibition of neurotransmission.
| Metabolism | Primarily hepatic via glucuronidation (UGT2B7, UGT2B15, and UGT1A4); minor oxidation by CYP3A4. |
| Excretion | Renal: ~85% as glucuronide conjugates and ~10% as unchanged drug. Biliary/fecal: ~5%. |
| Half-life | Terminal elimination half-life: 12–15 hours in healthy adults. Extended in elderly (15–20 hours), hepatic impairment (up to 50 hours), and obesity. |
| Protein binding | 85–90% bound to albumin. |
| Volume of Distribution | 0.7–1.2 L/kg; larger Vd in obesity due to lipophilicity. |
| Bioavailability | Oral: 90–95%; Intramuscular: 82–88%; Intravenous: 100%. |
| Onset of Action | Oral: 1–2 hours; Intramuscular: 15–30 minutes; Intravenous: 5–15 minutes. |
| Duration of Action | Oral: 6–8 hours; Intramuscular/Intravenous: 6–8 hours. Prolonged in elderly or hepatic impairment due to reduced clearance. |
| Molecular Weight | 321.16 |
| Action Class | Benzodiazepines |
| Brand Substitutes | Zepnap 2mg Tablet, Lorel 2mg Tablet, Texina 2mg Tablet, Larpose 2mg Tablet, Zelor 2mg Tablet, Lzepam 1mg Tablet, Lopam 1mg Tablet, Zepnap 1mg Tablet, Lorel 1mg Tablet, Larpose 1mg Tablet, Calmese 2mg Injection, Zeepam 2mg Injection, Lorawel Injection, Axitan 2mg Injection, Lorazen Injection |
2-6 mg orally or intravenously daily in divided doses; usual range 2-10 mg/day
| Dosage form | TABLET |
| Renal impairment | No specific adjustment required; use caution in severe impairment (CrCl <10 mL/min) due to accumulation of metabolites |
| Liver impairment | Child-Pugh Class A: caution with increased sedation; Child-Pugh B or C: reduce dose by 50% or avoid use |
| Pediatric use | 0.05-0.1 mg/kg/dose orally or intravenously per dose; maximum 2 mg/dose; frequency based on indication |
| Geriatric use | Start with 1-2 mg/day orally in divided doses; titrate slowly; reduce total daily dose by 50% compared to younger adults |
| 1st trimester | Avoid in first trimester unless benefit outweighs risk; associated with oral clefts and other congenital anomalies. |
| 2nd trimester | Use only if clearly needed; may cause fetal harm including CNS depression and withdrawal. |
| 3rd trimester | Avoid near term; risk of neonatal floppy infant syndrome, withdrawal, and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for LORAZ (LORAZ).
| Placental transfer | Crosses placenta readily with fetal concentrations similar to maternal; accumulates in fetal tissues. |
| Breastfeeding | LORAZ (lorazepam) is excreted into breast milk in small amounts; potential for infant sedation and poor feeding. Use with caution, especially with prolonged or high doses. |
| Lactation Rating |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use for patients without alternative treatment options.
| Serious Effects |
Hypersensitivity to lorazepam or any componentAcute narrow-angle glaucomaSevere respiratory insufficiency (e.g., sleep apnea, COPD with CO2 retention)Myasthenia gravisSevere hepatic impairmentConcurrent use of opioid analgesics (risk of profound sedation)
| Precautions | Risk of sedation, respiratory depression, and dependence, May cause drowsiness, impair cognitive and motor function, Avoid abrupt discontinuation to prevent withdrawal symptoms, Use with caution in patients with hepatic impairment, Elderly patients more sensitive to effects |
| Food/Dietary | Avoid grapefruit and grapefruit juice; may increase lorazepam levels. Limit caffeine intake as it may reduce sedative effects. No specific food restrictions, but avoid heavy meals that may alter absorption. |
Loading safety data…
| L3 (Moderately Safe) or 'Avoid if possible' |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: Increased risk of oral clefts (odds ratio 2.5). Second/third trimester: Risk of floppy infant syndrome, neonatal withdrawal, and hypotonia. Avoid in third trimester if possible. |
| Fetal Monitoring | Monitor maternal sedation, respiratory rate, and withdrawal symptoms (tachyphylaxis/tolerance). Fetal monitoring: Consider fetal growth ultrasound if used chronically; assess for neonatal withdrawal at birth using Finnegan scoring if used near term. |
| Fertility Effects | No specific human studies. Animal studies show high doses may impair fertility; clinical significance unknown. Evaluate individual case. |
| Clinical Pearls | Lorazepam is a benzodiazepine with intermediate onset and duration. It is metabolized by glucuronidation, not CYP450, so it is safer in hepatic impairment. Use with caution in elderly due to increased fall risk and cognitive impairment. Avoid IM injection due to erratic absorption; IV administration requires slow push (≤2 mg/min) to avoid respiratory depression. For status epilepticus, IV lorazepam is first-line; repeat dose after 5-10 minutes if seizures persist. |
| Patient Advice | Do not drive or operate heavy machinery until you know how lorazepam affects you. · Avoid alcohol and other CNS depressants; this can cause severe drowsiness or breathing problems. · Take exactly as prescribed; do not increase dose or stop suddenly, as withdrawal can be dangerous. · May cause dizziness, drowsiness, or memory problems; rise slowly from sitting or lying down. · Report any suicidal thoughts, mood changes, or unusual behaviors to your healthcare provider immediately. · If you are pregnant, plan to become pregnant, or breastfeeding, discuss this medication with your doctor. |