LORAZEPAM PRESERVATIVE FREE

Clinical safety rating: avoid

CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.

How it works

Benzodiazepine that enhances GABA-A receptor activity, increasing chloride ion conductance and producing sedative, anxiolytic, anticonvulsant, and muscle relaxant effects.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.

FDA category	Positive
Breastfeeding	Lorazepam excreted into breast milk; M/P ratio ~0.2. Relative infant dose ~2-5% of maternal weight-adjusted dose. Use with caution; monitor infant for sedation, poor feeding, and weight gain. Short-term, low-dose use likely compatible.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	insomnia
Serious Effects

Absolute Contraindications

Hypersensitivity to benzodiazepines, acute narrow-angle glaucoma, severe respiratory insufficiency (e.g., COPD, sleep apnea), severe hepatic impairment, myasthenia gravis, concurrent use with opioids (except in specific monitored settings).

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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LORAZEPAM PRESERVATIVE FREE

Clinical safety rating: avoid

CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.

How it works

Benzodiazepine that enhances GABA-A receptor activity, increasing chloride ion conductance and producing sedative, anxiolytic, anticonvulsant, and muscle relaxant effects.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.

FDA category	Positive
Breastfeeding	Lorazepam excreted into breast milk; M/P ratio ~0.2. Relative infant dose ~2-5% of maternal weight-adjusted dose. Use with caution; monitor infant for sedation, poor feeding, and weight gain. Short-term, low-dose use likely compatible.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	insomnia
Serious Effects