ATIVAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATIVAN (ATIVAN).
Benzodiazepine that potentiates GABA-A receptor activity by increasing the frequency of chloride channel opening, leading to neuronal hyperpolarization and inhibition.
| Metabolism | Hepatic via glucuronidation (UGT2B15, UGT2B7); major metabolite is lorazepam glucuronide (inactive). |
| Excretion | Renal: lorazepam is primarily excreted as inactive glucuronide conjugates; <1% is excreted unchanged. Total: ~95% excreted in urine, ~5% in feces. |
| Half-life | Terminal elimination half-life is 12–18 hours (mean ~14 h). In elderly, hepatic impairment, or obesity, half-life may be prolonged up to 30 hours. |
| Protein binding | 91% ± 2% bound to albumin. Binding is linear over therapeutic concentrations and not saturable. |
| Volume of Distribution | 1.3 ± 0.2 L/kg. Vd increases with obesity, hepatic cirrhosis, and in elderly patients, indicating extensive tissue distribution. |
| Bioavailability | Oral: 90% (range 80–100%) with first-pass metabolism negligible; Sublingual: ~90%; Intramuscular: 100% (absolute bioavailability). |
| Onset of Action | Oral: 1–2 hours; Sublingual: 20–30 minutes; Intramuscular: 15–30 minutes; Intravenous: 1–5 minutes (peak CNS effect at 15–20 min). |
| Duration of Action | Oral: 6–8 hours (effects may last up to 12 h with high doses). IV: 6–8 hours. IM: 6–8 hours. Clinical duration is sufficient for anxiety and seizure control, but may require repeat dosing for prolonged sedation. |
| Molecular Weight | 321.16 Da |
| 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 |
2-3 mg orally divided 2-3 times daily; up to 10 mg/day. IV: 2 mg slow IV push, may repeat in 1-2 hours; max 10 mg/day. IM: 0.05 mg/kg (max 4 mg) 2-4 hours before procedure.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: reduce dose by 50% or increase interval; CrCl <10 mL/min: avoid or reduce dose by 50-75% with caution. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid or reduce dose by 50-75% with monitoring. |
| Pediatric use | Children ≥6 months: 0.02-0.05 mg/kg/dose IV/IM (max 2 mg) for status epilepticus; PO: 0.05-0.1 mg/kg/dose (max 2 mg) 2-4 times daily. |
| Geriatric use | Initiate at 0.5-1 mg orally daily in divided doses; increase slowly; max 2 mg/day. IV/IM: 0.5-1 mg initial; avoid doses >2 mg due to increased sedation risk. |
| 1st trimester | Avoid unless benefit outweighs risk. Teratogenic risk in early pregnancy; risk of congenital malformations, particularly cleft palate, based on animal studies and limited human data. |
| 2nd trimester | Avoid unless benefit outweighs risk. Use may expose fetus to benzodiazepine effects; risk of floppy infant syndrome if used near term. |
| 3rd trimester | Avoid unless benefit outweighs risk. Use near term may cause neonatal respiratory depression, hypotonia, withdrawal symptoms (e.g., irritability, tremors, poor feeding). |
Clinical note
Comprehensive clinical and safety monograph for ATIVAN (ATIVAN).
| Placental transfer | Lorazepam crosses the placenta rapidly and can achieve fetal serum concentrations similar to maternal levels. Placental transfer is confirmed and significant. |
| Breastfeeding | Ativan (lorazepam) is excreted into breast milk in small amounts. Levels are generally low, but the infant may be exposed to a significant dose relative to body weight. Use with caution, especially in neonates or preterm infants, as they may be more sensitive to drug effects (e.g., sedation, lethargy). Alternative agents (e.g., oxazepam) have lower milk levels if treatment is necessary. |
■ FDA Black Box Warning
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
| Serious Effects |
Severe respiratory insufficiencySevere hepatic impairment (e.g., acute or chronic liver failure)Sleep apnea syndromeMyasthenia gravisKnown hypersensitivity to benzodiazepines or any component of the formulation
| Precautions | Respiratory depression risk, Dependence and withdrawal syndrome, Abuse potential, Paradoxical reactions (hyperactivity, aggression), Use with caution in hepatic impairment, Elderly at increased risk for sedation and falls |
| Food/Dietary | No specific food interactions. However, grapefruit juice may increase lorazepam levels (minor interaction). Avoid excessive caffeine as it may reduce sedative effects. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Increased risk of oral clefts (odds ratio 1.5–2.0); second and third trimesters: Risk of hypotonia, respiratory depression, and withdrawal symptoms in neonate; avoid in first trimester if possible; use lowest effective dose. |
| Fetal Monitoring | Monitor maternal sedation and respiratory status; fetal heart rate monitoring during third trimester; neonatal assessment for hypotonia, poor feeding, and withdrawal signs after delivery. |
| Fertility Effects | No known adverse effects on fertility; animal studies show no impairment; clinical data limited. |
| Clinical Pearls | ATIVAN (lorazepam) is a benzodiazepine with intermediate onset and duration; useful for status epilepticus (IV) and preoperative anxiolysis. Monitor for respiratory depression, especially when combined with opioids. Not ideal for long-term anxiety due to tolerance and dependence risk. Use with caution in elderly (increased fall risk). |
| Patient Advice | Do not drive or operate machinery until you know how this medication affects you. · Avoid alcohol and other CNS depressants while taking ATIVAN. · Take exactly as prescribed; do not increase dose or stop abruptly without consulting your doctor. · May cause drowsiness, dizziness, or blurred vision. · Report any unusual mood changes, confusion, or respiratory difficulty. · This medication can be habit-forming; prolonged use may lead to dependence. · Notify your doctor if you are pregnant, planning to become pregnant, or breastfeeding. |