Midazolam

Indications

Midazolam is used for: Short-term treatment of insomnia. Sedation in premedication before surgical or diagnostic procedures.

Adult Dose

Adult Oral Short-term management of insomnia Adult: 7.5-15 mg at bedtime. Elderly: 7.5 mg at bedtime. Hepatic impairment: Mild to moderate: Dosage reduction needed. Severe: Contraindicated. Parenteral Preoperative Sedation IM Adult: 0.07-0.1 mg/kg bodyweight i. m. Usual dose is about 5 mg. Elderly and debilitated patients: 0.025-0.05 mg/kg IV Endoscopic or Cardiovascular Procedures In healthy adults the initial dose is approximately 2.5 mg. In cases of severe illness and in elderly patients, the initial dose must be reduced to 1 to 1.5 mg. Induction of Anesthesia The dose is 10-15 mg I. V.

Child Dose

Oral Seizures Child: 3-6 mth Hospital setting: 2.5 mg; >6 mth to <1 yr 2.5 mg; 1-<5 yr 5 mg; 5-<10 yr 7.5 mg; 10-<18 yr 10 mg. Doses are given as single dose. Sedation 500-750 mcg/kg PO once diluted by juice 20-30 minutes prior to procedure; not to exceed 20 mg Rectal administration in children: For preoperative sedation, rectal administration of the ampoule solution (0.35-0.45 mg/kg) 20-30 min before induction of general anesthesia. Parenteral Sedation IM 100-150 mcg/kg IM; up to 500 mcg/kg used; not to exceed 10 mg IV <6 months: Initial, 50 mcg/kg IV over 2-3 minutes; titrate with small increments to clinical effect; monitor closely 6 months-6 years: Initial, 50-100 mcg/kg IV over 2-3 minutes; repeat q2-3min PRN; may require up to 600 mcg/kg total dose; not to exceed 6 mg total dose 6-12 years: Initial, 25-50 mcg/kg IV over 2-3 minutes; repeat q2-3min PRN; may require up to 400 mcg/kg; not to exceed 10 mg total dose Anesthesia (Non-neonatal) Loading dose: 50-150 mcg/kg IV over 2-3 minutes PRN to achieve desired effect Continuous infusion: 1-2 mcg/kg/min IV infusion Anesthesia (Neonatal) IV loading dose should not be used in neonates Continuous infusion: 0.5 mcg/kg/min IV infusion

Renal Dose

Administration

May be taken with or without food. Midazolam IV should be administered very slowly.

Contra Indications

Severe resp failure or acute resp depression, acute narrow-angle glaucoma, myasthenia gravis, sleep apnoea syndrome; severe hepatic impairment (oral). Concomitant use w/ potent CYP3A4 inhibitors.

Precautions

Patients w/ heart failure, impaired gag reflex, resp disease, history of alcohol or drug abuse. Patient at risk of falls. Hepatic and renal impairment. Childn, elderly and debilitated patient. Pregnancy and lactation. Avoid abrupt withdrawal after prolonged use. Avoid rapid inj in neonates. Patient Counselling May impair ability to drive or operate machinery. Monitoring Parameters Monitor resp and CV status, BP. Lactation: Distributed in breast milk, use caution

Pregnancy-Lactation

Pregnancy There are no adequate and well-controlled studies of midazolam intranasal in pregnant women Available data suggest benzodiazepines are not associated with marked increases in risk for congenital anomalies Clinical considerations Exposure to benzodiazepines during the second and third trimesters of pregnancy or immediately prior to or during childbirth may increase risk for decreased fetal movement and/or fetal heart rate variability, floppy infant syndrome, dependence, and withdrawal Clinical manifestations of withdrawal or neonatal abstinence syndrome may include hypertonia, hyperreflexia, hypoventilation, irritability, tremors, diarrhea, and vomiting Animal studies Administration of midazolam to rats and rabbits during the period of organogenesis or to rats during late pregnancy and throughout lactation at doses greater than those used clinically did not result in any apparent adverse effects on development However, published data for benzodiazepines suggest potential of neuronal cell death and long-term effects on neurobehavioral and immunological function in animals following prenatal or early postnatal exposure at clinically relevant doses Lactation Midazolam is excreted in human milk Studies assessing effects in the breastfed infant or on milk production/excretion have not been performed Postmarketing experience suggests that breastfed infants of mothers taking benzodiazepines may experience lethargy, somnolence, and poor sucking

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.

Adverse Effects

Side effects of Midazolam : >10% Decreased respiratory rate (23%), Apnea (15%) 1-10% Drowsiness (1-5%), Seizure-like activity (1%), Nausea/vomiting (3%), Cough (1%), Pain at injection site (4-5%) Frequency Not Defined Headache, Sedation, Hiccoughs, Delirium, Euphoria Pediatric Desaturation, Hypotension, Seizurelike activity, Nystagmus, Paradoxical reactions, Hiccoughs, Apnea

Mechanism of Action

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.