MIDAZOLAM HYDROCHLORIDE
Clinical safety rating: avoid
CNS depressants including alcohol and opioids increase sedation risk Can cause profound respiratory depression and hypotension.
Benzodiazepine agonist at GABA-A receptors, enhancing chloride influx and neuronal hyperpolarization, leading to anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant effects.
| Metabolism | Hepatic via CYP3A4 and CYP3A5; major metabolite is 1-hydroxymidazolam (active). |
| Excretion | Renal: <1% unchanged; hepatic metabolism to 1-hydroxymidazolam (active) and other metabolites, excreted primarily in urine (60-80%) as glucuronide conjugates, and about 2-10% in feces. |
| Half-life | Terminal elimination half-life: 1.5-3.5 hours (range 1-12 hours) in healthy adults; prolonged in elderly (5-6 hours), obese, hepatic impairment (up to 20 hours), and critical illness (up to 12 hours). Context: short-acting benzodiazepine; half-life supports use for procedural sedation and ICU sedation, but accumulation can occur with prolonged infusions. |
| Protein binding | Approximately 94-97% bound to serum albumin, primarily to albumin; also binds to alpha1-acid glycoprotein. |
| Volume of Distribution | 1-2.5 L/kg; increases with age (elderly: 2-4 L/kg), obesity (up to 5 L/kg), and critical illness (up to 7 L/kg). Clinical meaning: high Vd indicates extensive tissue distribution; loading doses required for rapid effect. |
| Bioavailability | Oral: ~36-44% (first-pass effect); IM: >90%; Intranasal: ~50-83% with wide interindividual variability; Rectal: ~25-50%. |
| Onset of Action | IV: 1-2 minutes; IM: 5-15 minutes; Intranasal: 10-15 minutes; Oral: 15-30 minutes; Rectal: 10-20 minutes. |
| Duration of Action | IV: 20-30 minutes (sedation) with recovery in 1-2 hours; IM: 1-1.5 hours; Oral: peak effect 1 hour, duration 2-6 hours (dose-dependent); Intranasal: 20-30 minutes sedation, recovery 30-60 minutes. Note: duration may be shorter in children due to faster clearance. |
Adults: IV: 0.5-2 mg slow IV over 2 minutes, may repeat q2-3min; IM: 0.07-0.08 mg/kg (usual total 2-3 mg); oral: 7.5-15 mg once. For sedation, titrate to effect.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild-moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), consider dose reduction by 50% and monitor for prolonged sedation. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Contraindicated or use with extreme caution; consider alternative. |
| Pediatric use | IV sedation: 0.05-0.1 mg/kg (max 6 mg) slow IV over 2-3 minutes; titrate. Oral: 0.25-0.5 mg/kg (max 20 mg) 30-60 min before procedure. Intranasal: 0.2-0.3 mg/kg. For neonates, use lower doses and monitor. |
| Geriatric use | Reduce initial dose by 50% (e.g., IV: 0.25-0.5 mg; oral: 3.75-7.5 mg). Titrate slowly to avoid hypotension, respiratory depression, and prolonged sedation. Avoid doses > 5 mg IV in elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Can cause profound respiratory depression and hypotension.
| FDA category | Positive |
| Breastfeeding | Midazolam is excreted into breast milk in low amounts (M/P ratio approximately 0.1). Limited data suggests low risk at single doses; however, monitor infant for sedation and respiratory depression with repeated use. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show increased risk of cleft palate at high doses. Second and third trimesters: Risk of fetal sedation and withdrawal symptoms; use near term may cause neonatal respiratory depression and hypotonia. |
■ FDA Black Box Warning
Concurrent 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 | anesthesia |
| Serious Effects |
Hypersensitivity to benzodiazepines, narrow-angle glaucoma (unless receiving appropriate therapy), severe respiratory insufficiency, myasthenia gravis, and concurrent use with ketoconazole or itraconazole.
| Precautions | Respiratory depression, risk of hypotension particularly in children, paradoxical reactions (restlessness, agitation), dependence risk, withdrawal symptoms upon abrupt discontinuation, caution in hepatic impairment, renal impairment, myasthenia gravis, and COPD. |
Loading safety data…
| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, sedation level, and blood pressure. Fetal heart rate monitoring recommended during prolonged or high-dose use, especially near term. |
| Fertility Effects | No significant adverse effects on fertility reported in animal studies; human data lacking. |