Uses of MILAM 7.5: - Conscious sedation during diagnostic or therapeutic procedures Short-term treatment of insomnia. Sedation in premedication before surgical or diagnostic procedures. 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.

Benzodiazepine hypnotics, Benzodiazepine sedatives

Midazolam binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites w/in the CNS, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to Cl ions, which results in hyperpolarisation (a less excitable state) and stabilisation. Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors.

How to use Midazolam: Use this medicine in the dose and duration as advised by your doctor. Check the label for directions before use. Insert the bottle tip into one nostril and close the other nostril. Direct the spray towards the sides of your nostril, away from the cartilage dividing the two sides of your nose. As you spray, breath gently and keep the head upright. Repeat the same process for the other nostrils. Administration: May be taken with or without food. Midazolam IV should be administered very slowly. 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

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.

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.

Common - Nasal discomfort - Throat irritation >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

Insufficient data are available on Midazolam to assess its safety during pregnancy. But benzodiazepines adversely affect the human fetus. So their use should be avoided if there is safer alternative. Midazolam is excreted through breast milk. Therefore, Midazolam should not be used by the nursing mothers.

Precaution: 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

Extreme overdosage may lead to coma, areflexia, cardiorespiratory depression and apnea. The effects of overdosage can be controlled with benzodiazepine antagonist flumazenil.

Protect from light and moisture, store in cool and dry place. Keep out of the reach of children.

Benzodiazepine hypnotics, Benzodiazepine sedatives

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.

Midazolam should be avoided during pregnancy unless there is no safer alternative. Since Midazolam passes into breast milk, it should not be administered to breast-feeding mothers.