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Drug Reference

midazolam

benzodiazepine· Brands: Dormicum, Hypnovel, Versed, Buccolam, Ozolam, EpistatusIMIVPOPR

Mechanism of action
Midazolam is a short-acting benzodiazepine that binds to the benzodiazepine site on the gamma-aminobutyric acid type A (GABA-A) receptor. This enhances the inhibitory effect of GABA, increasing chloride ion influx and hyperpolarising the neuronal membrane. The result is central nervous system depression, producing sedation, anxiolysis, anterograde amnesia, muscle relaxation and anticonvulsant effects.
Pharmacokinetics
Midazolam is rapidly absorbed after oral, intramuscular and rectal administration, but undergoes extensive first-pass metabolism, so oral bioavailability is around 40-50%. It is highly lipophilic, ensuring rapid brain penetration. Metabolism is predominantly hepatic via CYP3A4 to the active metabolite 1-hydroxymidazolam, which is then conjugated and excreted renally. The elimination half-life is approximately 1.5-2.5 hours in healthy adults, but may be prolonged in the elderly, in hepatic impairment, and with co-administration of CYP3A4 inhibitors. Onset of action is 1-5 minutes IV, 15-30 minutes IM, and about 15-20 minutes orally.
Indications & dosing

Premedication

Given 30-60 min before procedure.

  • adult · PO: 7.5–15 mg Once · Given 30-60 min before procedure.

Procedural sedation

Titrate to effect; monitor respiratory function.

  • adult · IV: 1–2.5 mg Slow IV, titrate · Titrate to effect; monitor respiratory function.

Induction of anaesthesia

Given slowly over 1-2 min.

  • adult · IV: 0.15–0.3 mg/kg Once · Given slowly over 1-2 min.

Status epilepticus

May repeat once after 5 min if needed.

  • adult · IV: 10 mg Once, repeat PRN · May repeat once after 5 min if needed.

Status epilepticus

If IV access unavailable.

  • adult · IM: 10 mg Once · If IV access unavailable.

ICU sedation

Loading dose may be given; titrate to sedation score.

  • adult · IV: 0.02–0.1 mg/kg/h Continuous infusion · Loading dose may be given; titrate to sedation score.

Procedural sedation

Titrate to effect; monitor respiratory function.

  • pediatric · IV: 0.1–0.2 mg/kg Slow IV, titrate · Titrate to effect; monitor respiratory function.
Contraindications & precautions
  • Hypersensitivity to benzodiazepines or any component of the formulation · Cross-sensitivity may occur with other benzodiazepines.
  • Myasthenia gravis · Muscle relaxant effects may worsen symptoms.
  • Severe respiratory insufficiency · Risk of respiratory depression and failure.
  • Sleep apnoea syndrome · May exacerbate apnoeic episodes.
  • Severe hepatic impairment · Benzodiazepines can precipitate hepatic encephalopathy.
  • Shock or coma · Vital signs may be masked.
  • Monitor respiratory and cardiac function closely, especially during IV administration; resuscitative equipment and flumazenil should be immediately available.
  • Reduce the dose in the elderly, debilitated patients, and those with hepatic impairment or chronic respiratory disease.
  • Avoid abrupt withdrawal after prolonged use to prevent rebound insomnia, anxiety, and seizures.
  • Warn the patient not to drive or operate machinery after administration.
  • Caution with concurrent CNS depressants, including alcohol and opioids, as they potentiate sedative and respiratory depressant effects.
  • Use with extreme caution in patients with a history of drug or alcohol dependence.
Adverse effects
  • Drowsiness and sedation
  • Amnesia (anterograde)
  • Ataxia and impaired coordination
  • Dizziness
  • Respiratory depressionserious
  • Hypotensionserious
  • Paradoxical agitation or restlessness
  • Laryngospasm or bronchospasm (with IV use)serious
  • Cardiac arrest (especially with rapid IV administration)serious
Renal & hepatic adjustment
  • eGFR 0–30: Use with caution, reduce dose and monitor for prolonged sedation due to accumulation of active metabolite.
  • Hepatic impairment (mild): No specific dose adjustment required, but caution is advised; use lower doses.
  • Hepatic impairment (moderate): Reduce dose by 30-50% or use with caution; monitor for prolonged sedation.
  • Hepatic impairment (severe): Avoid use if possible; use with extreme caution, reduce dose significantly, and consider alternative. (avoid)
Monitoring, pregnancy & toxicity
  • Respiratory rate · During and after sedation
  • Blood pressure · Continuously during IV administration
  • Heart rate · Continuously during IV administration
  • Oxygen saturation · Continuously during sedation
  • Level of consciousness/sedation depth · Regularly during and after sedation
  • Pregnancy: Avoid in pregnancy unless clearly necessary. Use lowest effective dose for shortest duration; if used in late pregnancy, be prepared for neonatal sedation and respiratory depression.
  • Toxicity: CNS depression (e.g., excessive sedation, ataxia, confusion, coma) · Supportive care: monitor and maintain airway, breathing, and circulation. Consider flumazenil (benzodiazepine antagonist) in severe cases, but use with caution if co-ingestants or chronic benzodiazepine use suspected.
  • Toxicity: Respiratory depression (hypoventilation, apnoea) · Provide respiratory support, supplemental oxygen, and mechanical ventilation if needed. Flumazenil may reverse respiratory depression, but only if no contraindications.
  • Toxicity: Hypotension · Administer IV fluids and, if refractory, vasopressors. Monitor blood pressure continuously.
Antidotes & reversal
  • Flumazenil · Short duration of action of midazolam often means supportive care suffices.
Clinical notes
Midazolam is used for procedural sedation, premedication, induction of anaesthesia, sedation in intensive care, and the management of acute seizures (buccal or intranasal). It causes dose-dependent respiratory depression and hypotension, particularly when given intravenously, and should be used with caution in the elderly, those with respiratory compromise, and in patients with hepatic impairment. Paradoxical reactions such as agitation and restlessness can occur, especially in children and the elderly. Tolerance and dependence can develop with prolonged use; abrupt withdrawal should be avoided. Flumazenil is a specific antidote. Prescribing practices vary; local guidelines and formularies should be consulted.

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BNF; local formulary