Midazolam

Indications
 Oral
Short-term management of insomnia
Adult: 7.5-15 mg given at night.
Oral
Sedation for dental and minor surgical procedures
Child: ≥6 mth: Single dose of 250-500 mcg/kg, up to a max of 20 mg. Younger patients (6 mth-<6 yr) may require up to 1 mg/kg.
Oral
Premedication in surgery
Child: ≥6 mth: Single dose of 250-500 mcg/kg, up to a max of 20 mg. Younger patients (6 mth-<6 yr) may require up to 1 mg/kg.
Intramuscular
Premedication in surgery
Adult: 70-100 mcg/kg (usual dose: 5 mg) given 20-60 minutes before surgery by deep IM inj.
Child: ≥1 yr: 80-200 mcg/kg given 20-60 minutes before surgery by deep IM inj.
Elderly: 20-50 mcg/kg given 20-60 minutes before surgery by deep IM inj.
Parenteral
Sedation for dental and minor surgical procedures
Adult: IV admin: Initially, up to 2.5 mg given over at least 2-5 minutes, 5-10 minutes before procedure. Repeat after at least 2 minutes if necessary. Usual total: 3.5-5 mg. Max total: 7.5 mg.
Child: IV admin: 6 mth-5 yr: Initial: 50-100 mcg/kg given over 2 minutes, increase slowly at 2-minute intervals up to a total of 600 mcg/kg, max total dose: 6 mg. 6-12 yr: 25-50 mcg/kg given over 2 minutes and increase slowly at 2-minute intervals up to a total of 400 mcg/kg; max total dose: 10 mg. IM admin (used only in exceptional cases): 1-15 yr: 50-150 mcg/kg; max: 10 mg.
Elderly: Initially 1-1.5 mg given over 2 min, increased by increments of 0.5-1 mg at 2 min intervals as needed.
Intravenous
Induction of anaesthesia
Adult: 150-200 mcg/kg by slow inj in premedicated patients and at least 300 mcg/kg for those who have not received a premedicant. Additional doses may be required to complete induction, up to 600 mcg/kg in resistant cases.
Child: >7 yr: 150 mcg/kg. Max total: 500 mcg/kg (not >25 mg).
Elderly: 100-200 mcg/kg in divided doses at 2-minute intervals.
Intravenous
Sedation in critical care
Adult: Loading dose: 30-300 mcg/kg given as infusion over 5 minutes to induce sedation. Maintenance dose: 20-200 mcg/kg/hr. For patients with hypothermia, hypovolaemia or vasoconstriction: Reduce or omit loading dose, and reduce maintenance dose.
Child: Neonates with gestational age <32 wk: 30 mcg/kg/hr by continuous IV infusion. Neonates with gestational age >32 wk and who are <6 mth: 60 mcg/kg/hr. ≥6 mth: Initial loading dose of 50-200 mcg/kg given by slow IV inj; maintenance dose of 60-120 mcg/kg/hr given as IV infusion. In obese paediatric patients, calculate dose based on ideal wt.
Elderly: Dosage may need to be reduced.
Rectal
Sedation for dental and minor surgical procedures
Child: >6 mth: 300-500 mcg/kg as a single dose. May dilute with water for inj up to a total volume of 10 mL if the volume is too small.
Rectal
Premedication in surgery
Child: >6 mth: 300-500 mcg/kg as a single dose. May dilute with water for inj up to a total volume of 10 mL if the volume is too small.

Special Populations: If premedicated with opioids, debilitation and neonates, the dose should be adjusted appropriately.

Reconstitution: Midazolam solution for injection may be administered rectally. The inj solution may be diluted with Water for Injections up to a total volume of 10 ml if the volume is too small.
Contraindications
 Acute narrow-angle glaucoma; coma or patients in shock; acute alcohol intoxication; intrathecal and epidural admin. Acute pulmonary insufficiency or marked neuromuscular respiratory weakness including unstable myasthenia gravis; severe respiratory depression.
Warnings / Precautions
 Paediatric patients with cardiovascular instability; chronic renal failure; open-angle glaucoma; cardiac disease; respiratory disease; myasthenia gravis; neonates; history of drug or alcohol abuse; elderly and debilitated (reduce dose); avoid prolonged use or abrupt withdrawal; hepatic impairment; severe fluid or electrolyte disturbances. May impair ability to drive or operate machinery; titrate dose carefully; monitor for early signs of hypoventilation, airway obstruction, or apnea. Pregnancy, lactation
Adverse Reactions
 Physical and psychological dependence with withdrawal symptoms; decreased tidal volume and respiration rate; apnoea; headache; hiccup; nausea, increased appetite, vomiting; cough; oversedation; seizure-like activity (paediatrics); paradoxical reactions; kernicterus; nystagmus; skin rash, pruritus; reduced alertness, confusion, euphoria, hallucinations, fatigue, dizziness, ataxia, post-operative sedation, anterograde amnesia; jaundice; cardiac arrest, heart rate changes, thrombosis; anaphylaxis; laryngospasm, bronchospasm.
Potentially Fatal: Respiratory depression, respiratory arrest; hypotension.
Overdose Reactions
 Symptoms of overdose include sedation, confusion, impaired coordination, muscle relaxation or paradoxical excitation. More serious symptoms would be areflexia, hypotension, cardiorespiratory depression, apnoea and coma. Treatment is generally supportive and symptomatic. The benzodiazepine antagonist flumazenil is indicated in cases of severe intoxication accompanied with coma or respiratory depression. Caution should be observed in the use of flumazenil in case of mixed drug overdosage and in patients with epilepsy already treated with benzodiazepines.
Drug Interactions
 Increased CNS depression with alcohol, opioids, barbiturates, other sedatives and anaesthetics. Increased respiratory depression with opiates, phenobarbital, other benzodiazepines. Plasma concentrations increased by CYP3A4 inhibitors such as cimetidine, erythromycin, clarithromycin, diltiazem, verapamil, ketoconazole and itraconazole, antiretroviral agents, quinupristin with dalfopristin. Midazolam concentration decreased by phenytoin, carbamazepine, phenobarbital, rifampicin. Halothane, thiopental requirements may be reduced during concurrent use.
See Below for More midazolam Drug Interactions
Food Interactions
 Bioavailability of oral midazolam increased by grapefuit juice. Avoid concomittant use.
Mechanism of Actions
 Midazolam is a short-acting benzodiazepine. It exerts sedative and hypnotic, muscle relaxant, anxiolytic and anticonvulsant actions. While the probable anxiolytic action might be as a result of the drug's ability to increase glycine inhibitory neurotransmitter level, the hypnotic/anaesthetic action may be due to the occupation of the benzodiazepine and GABA receptors leading to membrane hyperpolarisation and neuronal inhibition, and further interfering with the re-uptake of GABA at the synapses.
Absorption: Rapidly absorbed (any route); peak plasma concentrations after 20-60 min (depending on route).
Distribution: Crosses the placenta; enters breast milk. Protein-binding: 96%
Metabolism: Extensively hepatic via CYP3A4 isoenzyme; converted to hydroxymethylmidazolam.
Excretion: Urine (as glucuronide conjugates); 2 hr (elimination half-life), prolonged in neonates, elderly and hepatic impairment.
Administration
 May be taken with or without food.
Storage Conditions
 Intramuscular: Store at 20-25°C. At a final concentration of 0.5 mg/ml, midazolam is stable for up to 24 hr when diluted with 0.9% sodium chloride or 5% dextrose in water. Intravenous: Store at 20-25°C. At a final concentration of 0.5 mg/ml, midazolam is stable for up to 24 hr when diluted with 0.9% sodium chloride or 5% dextrose in water. Parenteral: Store at 20-25°C. At a final concentration of 0.5 mg/ml, midazolam is stable for up to 24 hr when diluted with 0.9% sodium chloride or 5% dextrose in water. Rectal: Store at 20-25°C.
ATC Classification
 N05CD08 - midazolam ; Belongs to the class of benzodiazepine derivatives. Used as hypnotics and sedatives.
Storage
 Intramuscular: Store at 20-25°C. At a final concentration of 0.5 mg/ml, midazolam is stable for up to 24 hr when diluted with 0.9% sodium chloride or 5% dextrose in water. Intravenous: Store at 20-25°C. At a final concentration of 0.5 mg/ml, midazolam is stable for up to 24 hr when diluted with 0.9% sodium chloride or 5% dextrose in water. Parenteral: Store at 20-25°C. At a final concentration of 0.5 mg/ml, midazolam is stable for up to 24 hr when diluted with 0.9% sodium chloride or 5% dextrose in water. Rectal: Store at 20-25°C.
Available As
  • Midazolam 1 mg
  • Midazolam 10 mg
  • Midazolam 15 mg
  • Midazolam 2 mg
  • Midazolam 5 mg
  • Midazolam 7.5 mg

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