LORAZEPAM INTENSOL
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 the frequency of chloride channel opening, leading to neuronal hyperpolarization and inhibition.
| Metabolism | Primarily hepatic via glucuronidation (UGT2B7, UGT2B15) to inactive metabolites. |
| Excretion | Renal excretion of glucuronide conjugates; <1% unchanged drug excreted renally. Fecal elimination accounts for approximately 10% of administered dose. |
| Half-life | Terminal elimination half-life is 12-15 hours in healthy adults; prolonged in elderly (15-20 hours) and patients with hepatic impairment (up to 30-40 hours). |
| Protein binding | Approximately 85-90% bound to albumin. |
| Volume of Distribution | 1.0-1.3 L/kg; distribution into tissues including brain. |
| Bioavailability | Oral (Intensol): approximately 90% (rapidly and completely absorbed). Intramuscular: 80-100%. |
| Onset of Action | Intensol (oral concentrate): 20-30 minutes. Intramuscular: 15-30 minutes. Intravenous: 2-5 minutes. |
| Duration of Action | Duration of clinical effect: 6-8 hours for anxiolysis; sedation may persist up to 12 hours. |
| Molecular Weight | 321.16 |
0.5-2 mg orally every 6-8 hours as needed. Maximum 4 mg/day.
| Dosage form | CONCENTRATE |
| Renal impairment | GFR 10-50 mL/min: no adjustment needed. GFR <10 mL/min: caution, risk of accumulation; use 50% of usual dose. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid or use with extreme caution. |
| Pediatric use | 0.05-0.1 mg/kg/dose orally every 4-8 hours as needed; maximum single dose 2 mg. |
| Geriatric use | Initial dose 0.5 mg orally once daily, titrate slowly; maximum 2 mg/day in divided doses. Avoid prolonged use due to fall risk and cognitive impairment. |
| 1st trimester | Lorazepam crosses the placenta. First trimester use associated with a slight increased risk of oral clefts (odds ratio ~1.2-1.4). |
| 2nd trimester | Risk of fetal growth restriction and neurobehavioral effects with chronic use. Avoid unless benefit outweighs risk. |
| 3rd trimester | Use near term may cause neonatal withdrawal, hypotonia, respiratory depression, and feeding difficulties. Avoid in late pregnancy. |
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 rapidly; cord blood levels are approximately 70-80% of maternal plasma levels. |
| Breastfeeding |
■ FDA Black Box Warning
Concomitant use of benzodiazepines and 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 |
Acute narrow-angle glaucomaSevere hepatic impairment (Child-Pugh Class C)Known hypersensitivity to benzodiazepinesMyasthenia gravisSevere respiratory insufficiency (e.g., sleep apnea)
| Precautions | Risk of respiratory depression, especially with other CNS depressants, Dependence and withdrawal reactions with prolonged use, Paradoxical reactions (e.g., hyperactivity, aggression), Use with caution in hepatic or renal impairment, Elderly patients more sensitive to effects (e.g., falls, cognitive impairment) |
| Food/Dietary |
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| Lorazepam is excreted into breastmilk in low amounts. Peak milk levels occur 2-4 hours after dose. Monitor infant for sedation, poor feeding, and weight gain. Limited data suggest no significant adverse effects with occasional low doses. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Benzodiazepine use is associated with a small increased risk of oral clefts (absolute risk increase ~0.1%). Second and third trimesters: Exposure may cause fetal CNS depression (hypotonia, respiratory depression, hypothermia, and poor feeding known as 'floppy infant syndrome'). Chronic use in late pregnancy can lead to neonatal withdrawal syndrome. |
| Fetal Monitoring | Monitor maternal vital signs, respiratory rate, sedation level, and signs of withdrawal. In third trimester, monitor fetal heart rate and uterine activity if used intravenously for seizure or anxiety. Neonatal monitoring for respiratory depression, hypotonia, and withdrawal symptoms if used near delivery. |
| Fertility Effects | Data on fertility in humans are lacking. Animal studies have shown no consistent impairment of fertility. Menstrual irregularities have been reported in some women, but no clear causal association. |
| Grapefruit juice may increase lorazepam levels; avoid concurrent intake. Take with food if gastrointestinal upset occurs, but avoid high-fat meals that may delay absorption. No other significant food interactions. |
| Clinical Pearls | Lorazepam Intensol is a concentrated oral solution (2 mg/mL) requiring careful measurement with the provided dropper. Onset is rapid (15-30 min). Use as a preanesthetic or for acute anxiety/status epilepticus. Avoid in narrow-angle glaucoma, respiratory insufficiency, or severe hepatic impairment. Taper to discontinue after prolonged use to prevent rebound anxiety or seizures. |
| Patient Advice | Measure dose only with the provided calibrated dropper; do not use household teaspoons. · Mix dose with liquid or semi-solid food (e.g., water, juice, applesauce) immediately before taking. · Avoid alcohol and other CNS depressants (e.g., opioids, sleep aids) due to additive sedation. · Do not drive or operate machinery until you know how this medication affects you. · Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not stop suddenly; dose must be tapered to avoid withdrawal symptoms like anxiety, insomnia, or seizures. · Store at room temperature, protect from light, and keep out of reach of children. |