LORAZEPAM PRESERVATIVE FREE
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, increasing chloride ion conductance and producing sedative, anxiolytic, anticonvulsant, and muscle relaxant effects.
| Metabolism | Primarily hepatic via glucuronidation (UGT2B7 and UGT1A4); minor CYP3A4 involvement. No active metabolites. |
| Excretion | Renal: ~88% as glucuronide conjugates; <1% unchanged. Fecal: ~7%. Biliary: minor. |
| Half-life | Terminal elimination half-life: 12–14 hours (range 10–20 h). Clinically, no active metabolites; accumulation minimal at standard dosing intervals. |
| Protein binding | Approximately 85–90%, primarily to albumin. |
| Volume of Distribution | 1.3 L/kg (range 0.8–1.5 L/kg). Indicates extensive tissue distribution with slow equilibration. |
| Bioavailability | Oral: 90–100% (well absorbed). Intramuscular: 90–95% (complete and rapid absorption). |
| Onset of Action | Oral: 30–60 min. Intramuscular: 15–30 min. Intravenous: 1–5 min (rapid). |
| Duration of Action | Oral/IM: 6–8 hours. IV: 2–4 hours for acute effects (peak at 30 min). Effects may persist longer due to redistribution. |
| Molecular Weight | 321.2 |
0.5-2 mg orally every 6-8 hours as needed; maximum 4 mg/day. IV: 0.044 mg/kg (max 4 mg) every 6-8 hours for acute anxiety or sedation.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, increase dosing interval to every 12-24 hours to avoid excessive sedation. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50% and monitor. Child-Pugh C: Avoid use; if necessary, use 25% of usual dose with extreme caution. |
| Pediatric use | Neonates: 0.05 mg/kg IV/IM every 6-8 hours (max 2 mg/dose). Infants/Children: 0.1 mg/kg orally every 6-8 hours (max 4 mg/day) or 0.05-0.1 mg/kg IV/IM every 6-8 hours. |
| Geriatric use | Start with 0.5-1 mg/day orally in divided doses; increase cautiously. Avoid doses >2 mg/day due to increased risk of falls, cognitive impairment, and paradoxical reactions. |
| 1st trimester | Lorazepam is associated with a small risk of oral clefts if used in the first trimester; generally avoided unless clearly needed. |
| 2nd trimester | Avoid routine use; consider risk of fetal growth restriction and neurodevelopmental effects. |
| 3rd trimester | Use near term may cause neonatal withdrawal syndrome (hypotonia, respiratory depression, feeding difficulties). Avoid during labor. |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| FDA category | Positive |
| Placental transfer | Lorazepam crosses the placenta; fetal plasma levels are approximately 70-100% of maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve for patients without alternative treatment options.
| Common Effects | insomnia |
| Serious Effects |
Hypersensitivity to lorazepam or any benzodiazepineAcute narrow-angle glaucoma (due to potential anticholinergic effects)Severe respiratory insufficiency (e.g., sleep apnea, COPD without adequate ventilation)Myasthenia gravisSevere hepatic impairment
| Precautions | Respiratory depression, sedation, dependence/withdrawal, paradoxical reactions (especially in elderly), myasthenia gravis exacerbation, renal impairment, hepatic impairment, pregnancy (risk of neonatal withdrawal), lactation, IV administration requires monitoring for respiratory arrest. |
| Food/Dietary |
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| Lorazepam enters breast milk in low amounts; infant monitoring for sedation and feeding issues is recommended. Short-term, low-dose use is likely compatible with breastfeeding, but caution is advised with prolonged or high-dose therapy. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data, but benzodiazepines are associated with a small increased risk of oral clefts (odds ratio ~1.8) based on meta-analyses; absolute risk increase is low (<0.1%). Second/third trimester: Risk of floppy infant syndrome, neonatal withdrawal (irritability, tremors, hypertonia), and respiratory depression. Avoid chronic high doses near term. |
| Fetal Monitoring | Monitor maternal CNS depression (sedation, dizziness); fetal heart rate and uterine tone if used IV during labor; neonatal APGAR scores, respiratory effort, and feeding for 24-48 hours after delivery. For chronic use, assess neonatal withdrawal symptoms. |
| Fertility Effects | No well-controlled studies in humans. Animal studies show no significant impairment of fertility. High doses or chronic use may cause menstrual irregularities or anovulation due to hyperprolactinemia or hypothalamic-pituitary axis suppression. |
| No specific food interactions. However, grapefruit juice may theoretically increase lorazepam levels via CYP3A4 inhibition; monitor for excessive sedation. Avoid alcohol and CNS depressants. |
| Clinical Pearls | Lorazepam preservative-free formulation is indicated for intravenous use, especially in patients with benzyl alcohol sensitivity. Administer IV at a rate not exceeding 2 mg/min to minimize respiratory depression. Coadministration with other CNS depressants requires dose reduction by 30-50%. Avoid intra-arterial injection due to risk of arteriospasm. Have flumazenil available for reversal. |
| Patient Advice | Do not drink alcohol while taking lorazepam; it can cause severe drowsiness and respiratory depression. · This medication may be habit-forming; use exactly as prescribed. · Avoid driving or operating machinery until you know how lorazepam affects you. · Do not stop taking abruptly; withdrawal seizures may occur. · Inform your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. |