MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Clinical safety rating: avoid
CNS depressants including alcohol and opioids increase sedation risk Can cause profound respiratory depression and hypotension.
Benzodiazepine that enhances GABA-A receptor activity, increasing chloride ion conductance and neuronal hyperpolarization.
| Metabolism | Hepatic via CYP3A4 |
| Excretion | Primarily renal elimination of hydroxylated metabolites (midazolam 1-hydroxymidazolam and 4-hydroxymidazolam) as glucuronide conjugates. Only 0.03% of unchanged drug is excreted renally. Fecal excretion accounts for <2%. |
| Half-life | Terminal elimination half-life is 1.8-2.5 hours in healthy adults. In critically ill patients or those with hepatic impairment, half-life may extend to 2-6 hours. Obesity may prolong half-life due to increased volume of distribution. |
| Protein binding | Approximately 97% bound to albumin. |
| Volume of Distribution | Vd: 1.1-1.7 L/kg (healthy adults). In obesity, Vd increases to 2.5-3.5 L/kg. In critically ill or elderly, Vd may be larger due to altered tissue binding. |
| Bioavailability | Oral: 40-50% (first-pass metabolism). IM: >90%. Intranasal: 55-60% (with wide interindividual variation). Rectal: 50-80%. |
| Onset of Action | IV: 1-2 minutes; IM: 5-15 minutes (sedation typically within 15 minutes); Oral: 15-30 minutes; Intranasal: 10-15 minutes. |
| Duration of Action | Duration of sedative/anxiolytic effects: IV/IM: 1-2 hours, but clinical effects may be prolonged (2-6 hours) due to redistribution and active metabolites. Amnestic effects may persist up to 2-4 hours. |
0.5-2 mg slow IV over 2 minutes, may repeat q2-3min; typical total dose 2.5-5 mg. IM: 0.07-0.08 mg/kg (usual 5 mg).
| Dosage form | INJECTABLE |
| Renal impairment | CrCl <30 mL/min: consider dose reduction by 50% due to prolonged sedation risk. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B/C: reduce dose by 50% or more; titrate carefully. |
| Pediatric use | IV: 0.05-0.15 mg/kg (max 6 mg) over 2-3 min; repeat q2-3min as needed. IM: 0.1-0.15 mg/kg (max 10 mg). Oral premed: 0.25-0.5 mg/kg (max 20 mg). Intranasal: 0.2-0.3 mg/kg. |
| Geriatric use | Reduce dose by 30-50%; typical initial IV dose ≤0.5-1 mg slow IV; titrate slowly to avoid excessive sedation and respiratory depression. |
| 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 | Small amounts excreted in breast milk; theoretical risk of infant sedation. M/P ratio not established. Use with caution; monitor infant for drowsiness and feeding difficulties. Consider alternative agents if prolonged exposure. |
| Teratogenic Risk | First trimester: Not teratogenic in animal studies; human data insufficient. Second and third trimesters: Use only if clearly needed; may cause fetal respiratory depression, hypotonia, and withdrawal symptoms. Avoid prolonged or high-dose use near term. |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve for patients with inadequate alternatives.
| Common Effects | anesthesia |
| Serious Effects |
Acute narrow-angle glaucoma, severe respiratory insufficiency, known hypersensitivity to benzodiazepines.
| Precautions | Respiratory depression, hypotension, paradoxical reactions, IV extravasation, risk of dependence, not for epidural/intrathecal use. |
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| Fetal Monitoring | Maternal: respiratory rate, oxygen saturation, blood pressure, heart rate, sedation level. Fetal: heart rate monitoring (especially if used for procedures). Neonatal: observe for respiratory depression, hypotonia, and withdrawal if used near delivery. |
| Fertility Effects | No adverse effects on fertility reported in animal or human studies. |