VERSED

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VERSED (VERSED).

How it works

Benzodiazepine that enhances GABA-A receptor activity, increasing chloride ion conductance and causing neuronal hyperpolarization.

What the body does with it

Metabolism	Hepatic via CYP3A4 isoenzymes; major metabolites include midazolam glucuronide (inactive) and alpha-hydroxymidazolam (active).
Excretion	Renal: ~1% unchanged; Hepatic metabolism to glucuronide conjugates and 1-hydroxymidazolam, with subsequent renal elimination of metabolites. Fecal excretion is minimal (<2%).
Half-life	Terminal elimination half-life: 1.8–2.5 hours in healthy adults; prolonged in elderly (up to 6 hours), obesity (up to 8 hours), hepatic cirrhosis (up to 20 hours), and critically ill patients.
Protein binding	97% bound primarily to albumin.
Volume of Distribution	1–1.5 L/kg (0.5–1.2 L/kg in adults); increased in obesity and hepatic disease, indicating extensive tissue distribution.
Bioavailability	IM: 90%±; Oral: 40–50% (range 30–70%); Intranasal: ~75%; Rectal: ~50%.
Onset of Action	IV: 1–2 minutes; IM: 15 minutes; Oral: 15–30 minutes; Intranasal: 10–15 minutes; Rectal: 10–20 minutes.
Duration of Action	IV: 20–30 minutes (amnesia persists up to 1–2 hours); IM: 30–60 minutes; Oral: 1–2 hours; effects may be prolonged in elderly and hepatic impairment.

Classification & Brands

Dosing & administration

IV: Initial 1-2.5 mg; titrate by 0.5-1 mg every 2-3 min; usual total 2.5-5 mg for sedation. IM: 0.07-0.08 mg/kg (max 5 mg) once. Oral: 7.5-15 mg once (preoperative).

Dosage form	INJECTABLE
Renal impairment	eGFR 10-50 mL/min: No dose adjustment needed but monitor for prolonged sedation. eGFR <10 mL/min: Consider 50% dose reduction and monitor closely.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use or reduce dose by 75%.
Pediatric use	Neonates: IV 0.05-0.1 mg/kg; max 0.15 mg/kg. Children: IV 0.025-0.05 mg/kg (max 2 mg); titrate. Oral 0.25-0.5 mg/kg (max 20 mg) for sedation. IM 0.07-0.08 mg/kg.
Geriatric use	IV: Initial 0.5-1 mg over 2 minutes; titrate slowly; max total dose 3.5 mg. Oral: 5 mg preoperatively. Reduced clearance necessitates careful titration.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for VERSED (VERSED).

Breastfeeding

Midazolam is excreted in human breast milk in low concentrations. The milk-to-plasma (M/P) ratio is approximately 0.05 to 0.15. Relative infant dose is estimated to be <1% of maternal weight-adjusted dose. Due to potential for accumulation and CNS effects in the neonate, caution is advised; alternative agents with shorter half-lives and no active metabolites are preferred. Use only if clearly needed and monitor infant for sedation, poor feeding, and respiratory depression.

Teratogenic Risk

Midazolam is classified as FDA Pregnancy Category D. There is evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans. First trimester exposure may be associated with an increased risk of congenital malformations (e.g., cleft palate). Second and third trimester exposure may cause fetal CNS depression, respiratory depression, and withdrawal symptoms (floppy infant syndrome). Use during labor may cause neonatal respiratory depression and hypotonia. Maternal hypotension and decreased uterine blood flow may occur.

Warnings & precautions

■ FDA Black Box Warning

Intravenous administration may cause respiratory depression and arrest, especially when used with opioids. Resuscitation equipment and skilled personnel must be available. Do not administer by rapid bolus injection.

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to benzodiazepines, acute narrow-angle glaucoma, severe respiratory insufficiency (COPD), pregnancy (labor and delivery), breastfeeding (caution).

Clinical Precautions

Precautions

Respiratory depression, hypotension, paradoxical reactions, dependence and withdrawal, use in elderly or debilitated patients, hepatic/renal impairment, myasthenia gravis, glaucoma, pregnancy (category D).

Clinical Tips & Counseling

Drug interactions

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VERSED

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VERSED (VERSED).

How it works

Benzodiazepine that enhances GABA-A receptor activity, increasing chloride ion conductance and causing neuronal hyperpolarization.

What the body does with it

Metabolism	Hepatic via CYP3A4 isoenzymes; major metabolites include midazolam glucuronide (inactive) and alpha-hydroxymidazolam (active).
Excretion	Renal: ~1% unchanged; Hepatic metabolism to glucuronide conjugates and 1-hydroxymidazolam, with subsequent renal elimination of metabolites. Fecal excretion is minimal (<2%).
Half-life	Terminal elimination half-life: 1.8–2.5 hours in healthy adults; prolonged in elderly (up to 6 hours), obesity (up to 8 hours), hepatic cirrhosis (up to 20 hours), and critically ill patients.
Protein binding	97% bound primarily to albumin.
Volume of Distribution	1–1.5 L/kg (0.5–1.2 L/kg in adults); increased in obesity and hepatic disease, indicating extensive tissue distribution.
Bioavailability	IM: 90%±; Oral: 40–50% (range 30–70%); Intranasal: ~75%; Rectal: ~50%.
Onset of Action	IV: 1–2 minutes; IM: 15 minutes; Oral: 15–30 minutes; Intranasal: 10–15 minutes; Rectal: 10–20 minutes.
Duration of Action	IV: 20–30 minutes (amnesia persists up to 1–2 hours); IM: 30–60 minutes; Oral: 1–2 hours; effects may be prolonged in elderly and hepatic impairment.

Classification & Brands

Dosing & administration

IV: Initial 1-2.5 mg; titrate by 0.5-1 mg every 2-3 min; usual total 2.5-5 mg for sedation. IM: 0.07-0.08 mg/kg (max 5 mg) once. Oral: 7.5-15 mg once (preoperative).

Dosage form	INJECTABLE
Renal impairment	eGFR 10-50 mL/min: No dose adjustment needed but monitor for prolonged sedation. eGFR <10 mL/min: Consider 50% dose reduction and monitor closely.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use or reduce dose by 75%.
Pediatric use	Neonates: IV 0.05-0.1 mg/kg; max 0.15 mg/kg. Children: IV 0.025-0.05 mg/kg (max 2 mg); titrate. Oral 0.25-0.5 mg/kg (max 20 mg) for sedation. IM 0.07-0.08 mg/kg.
Geriatric use	IV: Initial 0.5-1 mg over 2 minutes; titrate slowly; max total dose 3.5 mg. Oral: 5 mg preoperatively. Reduced clearance necessitates careful titration.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for VERSED (VERSED).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to benzodiazepines, acute narrow-angle glaucoma, severe respiratory insufficiency (COPD), pregnancy (labor and delivery), breastfeeding (caution).