Midazolam-Baxter

What it is

Midazolam-Baxter is a solution for injection or infusion. It is available in two strengths: 1 mg/mL (in ampoules of 5 mL or bottles of 50 mL or 100 mL) and 5 mg/mL (in ampoules of 1 mL or 10 mL). The solution is clear and colourless. Midazolam is a short-acting central nervous system depressant, which induces sedation, hypnosis, amnesia and anaesthesia. Benzodiazepines appear to intensify the physiological inhibitory mechanisms mediated by gamma-aminobutyric acid (GABA), the most common inhibitory neurotransmitter in the brain.

Approved indications

— Intravenous use as an agent for conscious sedation prior to short surgical, diagnostic, therapeutic or endoscopic procedures, such as bronchoscopy, gastroscopy, cystoscopy, coronary angiography and cardiac catheterisation, either alone or in conjunction with a narcotic. — Intravenous use for induction of anaesthesia, preliminary to administration of other anaesthetic agents. — Intravenous use for sedation in intensive care units; intermittent administration or continuous infusion. — Intramuscular use for preoperative sedation (induction of sleepiness or drowsiness and relief of apprehension) and to impair memory of perioperative events.

Dosing overview

Dosage should be individualised and the drug should be administered slowly. Lower doses may be required in elderly or debilitated patients or in patients with hepatic or renal insufficiency. For conscious sedation via intravenous injection: In healthy adults the initial dose is approximately 2.5 mg. Some patients may respond to as little as 1 mg. Further doses of 1 mg may be given if necessary. A total dose greater than 5 mg is not usually necessary to reach the desired end point. In cases of severe illness and in elderly patients, the initial dose must be reduced to 1 to 1.5 mg. Total doses greater than 3.5 mg are not usually necessary. For induction of anaesthesia via intravenous injection: Administration should be by slow intravenous injection until consciousness is lost using approximately 0.15–0.2 mg/kg (10–15 mg) administered at a rate of approximately 2.5 mg/10 sec. For sedation in intensive care units: The recommended infusion rate is 0.03–0.2 mg/kg/hour. For intramuscular preoperative sedation: The recommended premedication dose for low-risk adult patients below the age of 60 years is 0.07–0.08 mg/kg intramuscularly (approximately 5 mg intramuscularly) administered approximately 1 hour before surgery.

Key safety warnings

Serious and life-threatening cardio-respiratory adverse events have been reported; provision for monitoring, detection and correction of these reactions must be made for every patient to whom Midazolam-Baxter is administered, regardless of age or health status. Intravenous midazolam should only be used in settings with equipment and skilled personnel for continuous monitoring of cardio-respiratory function and resuscitation procedures. During intravenous application of midazolam, respiratory depression, apnoea, respiratory arrest and/or cardiac arrest have occurred. In some cases where this was not recognised promptly and treated, hypoxic encephalopathy or death has resulted. Particular care must be used in administering the drug, by the intravenous route, to the elderly, to very ill patients, high-risk surgical patients and to those with significant hepatic impairment, chronic renal insufficiency, congestive heart failure, or with limited pulmonary reserve because of the possibility that apnoea or respiratory depression may occur. These patients require lower doses whether premedicated or not. Patients with chronic obstructive pulmonary disease are unusually sensitive to the respiratory depressant effect of midazolam. After prolonged intravenous administration of midazolam, abrupt discontinuation of the product may be accompanied by withdrawal symptoms. Therefore, a gradual reduction of Midazolam-Baxter is recommended. The following withdrawal symptoms may occur: headaches, diarrhoea, muscle pain, extreme anxiety, tension, sleep disturbances, restlessness, confusion, irritability, mood changes, hallucinations and convulsions. As with other benzodiazepines, midazolam may have the potential to cause dependence. Benzodiazepines should be avoided in patients with a history of alcohol or drug abuse. The risk of dependence increases with the duration of treatment; it is also greater in patients with a medical history of alcohol and/or drug abuse.

Contraindications

Midazolam should not be used in patients with myasthenia gravis, or those with hypersensitivity to benzodiazepines or any of their formulation excipients. Midazolam should not be administered to patients in shock or coma, or in acute alcoholic intoxication with depression of vital signs. Benzodiazepines are contraindicated in patients with acute narrow angle glaucoma.

Regulatory history

Midazolam-Baxter was first listed on the Australian Register of Therapeutic Goods on 8 October 2014, with four registered variants including 5 mg/1 mL, 5 mg/5 mL, 15 mg/3 mL and 50 mg/10 mL ampoules. The sponsor received initial approval on 12 June 2015.