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. |
| Molecular Weight | 325.77 |
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 | Limited human data; animal studies show increased risk of cleft palate and neurobehavioral alterations. Use only if clearly needed. |
| 2nd trimester | May cause fetal sedation and withdrawal; use only if benefit outweighs risk. |
| 3rd trimester | Risk of neonatal withdrawal, floppy infant syndrome, and respiratory depression. Avoid use near term. |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Can cause profound respiratory depression and hypotension.
| FDA category | Positive |
| Placental transfer | Readily crosses the placenta; fetal concentrations reach 60-90% of maternal levels. |
| Breastfeeding |
â– 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 glaucomaKnown hypersensitivity to benzodiazepinesSevere respiratory insufficiencyMyasthenia gravis
| Precautions | Respiratory depression, hypotension, paradoxical reactions, IV extravasation, risk of dependence, not for epidural/intrathecal use. |
| Food/Dietary | No direct food interactions. Grapefruit juice may increase midazolam levels; avoid concurrent consumption. Avoid alcohol for at least 24 hours after administration due to additive CNS depression. |
Loading safety data…
| Midazolam is excreted into breast milk in low concentrations. However, due to risk of sedation in the infant, caution is advised. The American Academy of Pediatrics considers use to be compatible with breastfeeding after a single dose, but monitor infant for sedation and feeding difficulties. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Midazolam hydrochloride preservative-free is used for intravenous or intramuscular sedation, anesthesia induction, and conscious sedation. It is 3-4 times more potent than diazepam. Onset of action is 1-2 minutes IV, 15 minutes IM. Respiratory depression and hypotension are dose-dependent; have resuscitation equipment available. Flumazenil is the reversal agent. Use lower doses in elderly, debilitated, or those with COPD. Avoid in acute narrow-angle glaucoma. Preservative-free formulation is preferred for epidural or intrathecal administration. |
| Patient Advice | You will feel very drowsy and may not remember the procedure. · Do not drive, operate machinery, or make important decisions for at least 24 hours after receiving this medication. · Avoid alcohol and other sedatives for at least 24 hours after use. · You may experience dizziness, blurred vision, or confusion; ask for assistance before standing. · Report any difficulty breathing, severe drowsiness, or allergic reaction (rash, swelling) to your healthcare provider immediately. |