MIDAZOLAM-AFT SOLUTION FOR INJECTION 5 MG/ML FOR INTRAVENOUS, INTRAMUSCULAR, RECTAL USE

Product Information

Registration Status: Active

MIDAZOLAM-AFT SOLUTION FOR INJECTION 5 MG/ML is approved to be sold in Singapore with effective from 2018-02-08. It is marketed by BAXTER HEALTHCARE (ASIA) PTE LTD, with the registration number of SIN15419P.

This product contains Midazolam 5 mg/mL in the form of INJECTION, SOLUTION. It is approved for INTRAVENOUS, INTRAMUSCULAR, RECTAL use.

This product is manufactured by Claris Injectables Limited in INDIA.

It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Description

A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. [PubChem] Midazolam is a schedule IV drug in the United States.

Indication

The midazolam injection is indicated for preoperative sedation/anziolysis/amnesia. It is also an agent for sedation/anziolysis/amnesia prior to or during diagnostic, therapeutic, or endoscopic procedures. Midazolam can also be given intravenously for induction of general anaesthesia.

Mechanism of Action

It is thought that the actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the brain. Benzodiazepines increase the activity of GABA, thereby producing a calming effect, relaxing skeletal muscles, and inducing sleep. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening.

Pharmacokinetics

Absorption: Rapidly absorbed after oral administration. The absolute bioavailability of the midazolam syrup in pediatric patients is about 36%. The absolute bioavailability, if given intramuscularly (IM), is greater than 90%. Cmax, IM = 90 ng/mL; Tmax, IM = 0.5 hours. Following IM administered, Cmax for midazolam and its 1-hydroxy metabolite were approxiately one-half of those achieved after intravenous injection.
Distribution: * 1.24 to 2.02 L/kg [pediatric patients (6 months to <16 years) receiving 0.15 mg/kg IV midazolam,] * 1 to 3.1 L/kg [intravenously administered, healthy adults] Female gender, old age, and obesity may increase the volume of distribution. Midazolam may also cross the placenta and has been detected in human milk and cerebrospinal fluid.
Metabolism: Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, (alpha)-hydroxymidazolam (also known as 1-hydroxy-midazolam), and 4-hydroxymidazolam (makes up 5% or less of the biotransformation products). 1-hydroxy-midazolam is at least as potent as the parent compound and may contributed to the overall activity of midazolam. In vitro studies have demonstrated that the affinities of 1- and 4-hydroxy-midazolam for the benzodiazepine receptor are approximately 20% and 7%, respectively, relative to midazolam. It also undergoes N-glucuronidation via UGT1A4.
Elimination

Clearance

* 9.3 to 11 mL/min/kg [pediatric patients (6 months to <16 years old)] * 0.25 to 0.54 L/hr/kg [intravenous, healthy adults]

Toxicity

LD₅₀=825 mg/kg (Orally in rats). Signs of overdose include sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma, and deleterious effects on vital signs.

Active Ingredient/Synonyms

Source of information: Drugbank (External Link). Last updated on: 3^rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.