Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Mercury Pharmaceuticals Ltd, Capital House, 85 King William Street, London EC4N 7BL, UK
As intravenous sedative cover before and during minor medical, dental and surgical procedures such as gastroscopy, endoscopy, cystoscopy, bronchoscopy and cardiac catheterisation.
For sedation by continuous infusion in patients in intensive care.
As an intramuscular premedication for patients with physical status ASA I-IV who are to undergo surgical procedures.
As an alternative intravenous agent for the induction of anaesthesia in high risk and elderly patients, especially where cardiovascular stability is of particular importance. Induction is more reliable when heavy opiate premedication has been administered or when midazolam is given with a narcotic analgesic such as fentanyl.
One or more intravenous administrations over a single operating session.
In most circumstances, the 2mg/ml formulation is more convenient for titration purposes.
An assessment should be made of the degree of sedation necessary for the planned procedure.
The dose should be titrated against the response of the patient. The desired titration end point will depend upon the procedure. Full sedation will be evident by drowsiness, slurred speech but response to commands will be maintained.
As a guide, it is recommended that 0.4ml of Midazolam 5mg/ml solution (equivalent to 2mg midazolam) be administered intravenously over 30 seconds. If after 2 minutes, sedation is not adequate, incremental doses of 0.1ml to 0.2ml of Midazolam 5mg/ml solution (0.5 to 1mg midazolam) should be given.
Usual dose range 2.5mg – 7.5mg total dose (equivalent to around 0.07mg/kg body weight).
Dosages greater than 5.0mg are not usually necessary.
OLDER PATIENTS ARE MORE SENSITIVE TO THE EFFECTS OF BENZODIAZEPINES. IN THESE PATIENTS DOSES GREATER THAN 3.5MG ARE NOT USUALLY NECESSARY AND LOW DOSES AS LITTLE AS 1MG – 2MG (0.2 – 0.4ML) MAY BE ADEQUATE. THE INITIAL DOSE SHOULD NOT EXCEED 1 – 1.5MG (0.2 – 0.3ML).
Midazolam Injection has not been evaluated for use as an intravenous sedative in children.
For sedation in the intensive care unit, dosages vary considerably and the dosage of Midazolam Injection should be individualised and titrated to the desired state of sedation according to the clinical need, physical status, age and concomitant medication.
Patients receiving Midazolam Injection for sedation by continuous infusion in the intensive care situation should receive ventilatory support.
Safety of continuous infusion of midazolam injection for periods of over fourteen days in duration has not been established in clinical trials.
Loading dose: For patients already sedated, a loading dose of midazolam is not required. To induce sedation, a loading dose of 0.03 – 0.3mg/kg is recommended, depending on the level of sedation required. This should be administered over a five minute period.
Maintenance dose: The dosage varies considerably. A dose between 0.03 – 0.2mg/kg per hour is recommended, commencing at the lower end of the range.
The dosage should be reduced or the loading dose should even be omitted in hypovolaemic, vasoconstricted and hypothermic patients.
Intravenous bolus sedation: Where analgesia is provided by a narcotic analgesic the latter should be administered first, the dose of midazolam should be carefully titrated and low doses 1 – 2mg (0.2 – 0.4ml) may be adequate. In the elderly, smaller doses as little as 0.5 – 1mg (0.1 – 0.2ml) may be adequate.
Sedation by continuous infusion in intensive care : Where analgesia is provided by narcotic analgesics, the rate of infusion of Midazolam Injection should be titrated carefully to the sedative needs of the patient.
One or more bolus intravenous injections over a single anaesthetic session.
The dose should be titrated against the individual response of the patient. Midazolam Injection should be given by slow intravenous injection until there is a loss of eyelid reflex, response to commands and voluntary movements.
In anticipating the required dose of midazolam, both the premedication already given and the age of the patient are important. Young, fit unpremedicated patients may require at least 0.3mg/kg body-weight, whereas patients premedicated with an opiate usually require only 0.2mg/kg body-weight.
OLDER PATIENTS ARE MORE SENSITIVE TO THE EFFECTS OF BENZODIAZEPINES. INDUCTION MAY BE ADEQUATE WITH 0.1MG/KG BODY-WEIGHT IN PREMEDICATED PATIENTS AND 0.2MG/KG BODY-WEIGHT IN UNPREMEDICATED PATIENTS.
Midazolam Injection has been shown to be an effective agent for induction of anaesthesia in children over 7 years of age, at a dose of 0.15mg/kg body-weight.
A single intramuscular injection of 0.07 – 0.1mg/kg body-weight, administered 30 – 60 minutes pre-operatively, has been shown to be adequate in most cases. The usual dose is about 5mg.
Atropine or hyoscine hydrobromide may be given concomitantly, bearing in mind that hyoscine hydrobromide will enhance and prolong the sedative and amnesic effects of midazolam.
Midazolam Injection can be combined with atropine or hyoscine hydrobromide in the same syringe to be given as a single intramuscular injection.
OLDER PATIENTS ARE MORE SENSITIVE TO THE EFFECTS OF BENZODIAZEPINES AND IN THESE PATIENTS A LOWER DOSE OF 2.5MG MAY BE ADEQUATE.
Midazolam Injection has not been evaluated for use as an intramuscular premedicant in children.
In patients with renal impairment (creatinine clearance <10ml/min) the pharmacokinetics of unbound midazolam following a single IV dose is similar to that reported in healthy volunteers. However, after prolonged infusion in intensive care unit (ICU) patients, the mean duration of the sedative effect in the renal failure population was considerably increased most likely due to accumulation of α-hydroxymidazolam glucuronide.
There is no specific data in patients with severe renal impairment (creatinine clearance below 30 ml/min) receiving midazolam for induction of anaesthesia.
Hepatic impairment reduces the clearance of i.v. midazolam with a subsequent increase in terminal half-life. Therefore, the clinical effects may be stronger and prolonged. The required dose of midazolam may be reduced and proper monitoring of vital signs should be established (See section 4.4).
See above and section 4.4
For the administration of Midazolam Injection, the patient should be placed in a supine position and remain there throughout the procedure. Resuscitation facilities should always be available and a second person fully trained in the use of such equipment should always be present. It is recommended that patients should remain under medical supervision until at least 1 hour has elapsed from the time of injection. They should always be accompanied home by a responsible adult.
Patients who have received Midazolam Injection alone for IV sedation prior to minor procedures should be warned not to drive or operate machinery for 12 hours. Where midazolam is used concurrently with other central nervous system depressants (e.g. potent analgesics) recovery may be prolonged. Patients should therefore be assessed carefully before being allowed to go home or resume normal activities.
Like other benzodiazepines, midazolam commonly causes drowsiness, ataxia, dysarthria and nystagmus. Overdose of midazolam is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnoea, hypotension, cardiorespiratory depression and in rare cases to coma. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease.
Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.
Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects.
If taken orally further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure.
If CNS depression is severe consider the use of flumazenil, a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil, for further information on the correct use of this drug.
The correct information for using Flumazenil can also be obtained from the UK National Poison Information Service by calling on the following telephone number. Tel: 0844-892-0111 (directs caller to relevant local centre.)
Unopened: 3 years.
After reconstitution: not applicable.
After first opening: not applicable.
Protect from light.
Store below 25°C.
Clear One Point Cut (OPC) 2ml & 10ml glass ampoules, glass type I, Ph. Eur.
Pack sizes: 5 × 2ml ampoules; 10 × 2ml ampoules. 5 × 10ml ampoules; 10 × 10ml ampoules
Not all pack sizes may be marketed.
If only part used, discard the remaining solution.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
