Generic Name

Midazolam Hydrochloride

---

Classification

FDA Approved Indications

• Preoperative sedation, anxiolysis, and amnesia
• Induction of anesthesia
• Sedation of mechanically ventilated patients
• Status epilepticus (injectable form)

Mechanism of Action

Midazolam enhances the effects of gamma-aminobutyric acid (GABA) at the GABA-A receptor, resulting in sedative, anxiolytic, muscle relaxant, and anticonvulsant properties.

Dosage and Administration

Adult: Dosage varies based on indication and route; for preoperative sedation, 1-2.5 mg IV over 2 minutes, repeated as needed; for status epilepticus, 5 mg IV every 10-15 minutes up to 30 mg total.

Pediatric: Typically, 0.05-0.1 mg/kg IV; oral doses are 0.25-0.5 mg/kg.

Geriatric: Lower initial doses recommended; e.g., 0.5-1 mg IV slow administration.

Renal Impairment: Use caution; dosage may need adjustment based on response.

Hepatic Impairment: Reduce dosage; clearance may be decreased.

Pharmacokinetics

Absorption: Rapid IV absorption with quick onset of action, peaks in 1-5 minutes.

Distribution: Widely distributed; high affinity for brain tissue. Protein binding approximately 94%.

Metabolism: Extensively metabolized in the liver via CYP3A4 to inactive metabolites.

Excretion: Primarily excreted in urine; minimal in feces.

Half Life: Approx. 1.5-2.5 hours in healthy adults.

Contraindications

• Hypersensitivity to benzodiazepines or any component of the formulation.
• Acute narrow-angle glaucoma.

Precautions

• Use with caution in patients with respiratory insufficiency, sleep apnea, hepatic impairment, or myasthenia gravis.
• Risk of respiratory depression; closely monitor airway and respiration.
• Use in pregnancy only if clearly needed; category D.
• Lactation: can be excreted in breast milk; caution advised.

Adverse Reactions - Common

• Respiratory depression (Common)
• Hypotension (Common)
• Amnesia (Common)
• Drowsiness (Common)

Adverse Reactions - Serious

• Cardiorespiratory depression (Serious)
• Anaphylaxis (Rare)
• Seizures (paradoxical reaction in some cases) (Rare)

Drug-Drug Interactions

• CNS depressants (opioids, alcohol)
• Cimetidine and other CYP3A4 inhibitors increasing midazolam levels.
• Rifampin decreases midazolam levels.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Do not operate heavy machinery or drive after use.
• Inform about potential side effects such as drowsiness, dizziness.
• Caution about alcohol and other CNS depressants.
• Report any respiratory issues or severe side effects.

Special Considerations

Black Box Warnings:

• Respiratory depression leading to hypoxia, respiratory arrest, or death—use only where resuscitation equipment and trained personnel are available.

Genetic Factors: CYP3A4 genetic variants may affect metabolism.

Lab Test Interference: None known.

Overdose Management

Signs/Symptoms: Excessive sedation, respiratory depression, hypotension.

Treatment: Supportive care, airway management, intravenous flumazenil as an antidote (if appropriate), caution due to risk of seizures from flumazenil in benzodiazepine-dependent seizures.

Storage and Handling

Storage: Store at room temperature, away from moisture, heat, and light.

Stability: Stable for the duration of the shelf life specified by the manufacturer.