Midazolam is a potent sedative agent that requires slow administration and individualisation of dosage.
The dose should be individualized and titration is strongly recommended to safely obtain the desired state of sedation according to the clinical need, physical status, age and concomitant medication.
In adults over 60 years of age, critically ill patients, high risk patients and paediatric patients, the dose should be determined with caution and risk factors related to each patient should be taken into account.
The drug takes effect in about 2 minutes after intravenous injection. Maximum effect is obtained in about 5 to 10 minutes.
Standard dosage are provided in the table as follows. Additional details are given in the text following the table. (See table.)
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Conscious sedation: For basal (conscious) sedation prior to diagnostic or surgical intervention, Midazolam injection is administered i.v. The dose must be individualized and titrated and should not be administered by rapid or single bolus injection. The onset of sedation may vary individually depending on the physical status of the patient and the detailed circumstances of dosing (e.g. speed of administration, amount of dose). If necessary, subsequent doses may be administered according to the individual need. Special caution is required for the indication of conscious sedation in patients with impaired respiratory function. See Precautions.
Adults: The i.v. injection of Midazolam injection should be given slowly at a rate of approximately 1mg in 30 seconds.
In adults below the age of 60 the initial dose is 2 to 2.5 mg given 5-10 minutes before the beginning of the procedure. Further doses of 1 mg may be given as necessary. Mean total doses have been found to range from 3.5-7.5 mg. A total dose greater than 5.0 mg is not usually not necessary.
In adults over 60 years of age, critically ill patients, high-risk patients the initial dose must be reduced to 0.5-1.0 mg and given 5-10 minutes before the beginning of the procedure. Further doses of 0.5-1 mg may be given as necessary. Since in these patients the peak effect may be reached less rapidly, additional Midazolam Injection should be titrated very slowly and carefully.
A total dose greater than 3.5 mg is not usually necessary.
Paediatrics: I.V. administration: Midazolam Injection should be titrated slowly to the desired clinical effect. The initial dose of Midazolam Injection should be administered over 2 to 3 minutes and, it is recommended to wait an additional 2 to 5 minutes to fully evaluate the sedative effect before initiating a procedure or repeating a dose. If further sedation is necessary, continue to titrate with small increments until the appropriate level of sedation is achieved. Infants and young children less than 5 years of age may require substantially higher doses than older children and adolescents.
Paediatric patients less than 6 months of age: Paediatric patients less than 6 months of age are particularly vulnerable to airway obstruction and hypoventilation. For this reason, the use in conscious sedation in children less than 6 months of age is not recommended unless the benefits outweigh the risks. In such cases titration with small increments to clinical effect and careful monitoring are essential.
Paediatric patients >6 months to 5 years of age: initial dose 0.05 to 0.1 mg/kg. A total dose up to 0.6 mg/kg may be necessary to reach the desired endpoint but the total dose should not exceed 6mg. Prolonged sedation and risk of hyperventilation may be associated with the higher doses.
Paediatric patients 6 to 12 years of age: initial dose 0.025 to 0.05 mg/kg. A total dose up to 0.4 mg/kg to a maximum of 10 mg may be necessary. Prolonged sedation and risk of hyperventilation may be associated with the higher doses.
Paediatric patients 13 to 16 years of age: should be dosed as adults.
I.M. administration (paediatrics 1-16 years): The recommended dose range is 0.05 and 0.15 mg/kg given 5-10 minutes before the beginning of the procedure. A total dose greater than 10.0 mg is not usually necessary. This route should only be used in exceptional cases. Rectal administration should be preferred as IM injection may be painful.
In paediatrics less than 15 kg of body weight, midazolam solutions with concentrations higher than 1 mg/ml are not recommended.
Higher concentrations should be diluted to 1 mg/ml.
Rectal administration: The total dose of midazolam usually ranges from 0.3 to 0.5 mg/kg. Total dose should be administered at once and repeated rectal administration avoided. The use in paediatrics less than 6 months of age is not recommended, as available data in this population are limited. Rectal administration of the ampoule/vial solution is performed by means of a plastic applicator fixed on the end of the syringe. If the volume to be administered is too small, water may be added up to a total volume of 10 ml.
Anaesthesia-premedication: Premedication with Midazolam injection given shortly before a procedure produces sedation (induction of sleepiness or drowsiness and relief of apprehension) and preoperative impairment of memory. Midazolam injection can also be administered in combination with anticholinergics. For this indication Midazolam injection should be administered i.v. or i.m. (deep into a large muscle mass 20-60 minutes before induction of anaesthesia) or preferably via the rectal route in paediatrics. Adequate observation of the patient after administration is mandatory as interindividual sensitivity varies and symptoms of overdose may occur.
Adults: For preoperative sedation and to impair memory of preoperative events, the recommended dose for adults of ASA Physical Status I & II and patients below 60 years is 1-2 mg i.v. repeated as needed, or 0.07-0.1 mg/kg i.m.
The dose must be reduced and individualized when Midazolam injection is administered to adult over 60 years of age, critically ill, high-risk patients. The recommended initial i.v. dose is 0.5 mg and should be slowly uptitrated as needed. Allow 2-3 minutes to fully evaluate the effect between doses. An i.m. dose of 0.025-0.05 mg/kg is recommended if there is no concomitant administration of narcotics.
I.M. administration (1-15 years): As i.m. injection may be painful this route should only be used in exceptional cases. Rectal administration should be preferred. However, a dose range from 0.08-0.2 mg/kg of Midazolam injection administered i.m. has been shown to be effective and safe.
In children between ages 1 and 15, proportionally higher doses are required than in adults in relation to body-weight. It is recommended that Midazolam injection should be administered deep into a large muscle mass 30-60 minutes prior to the induction of anaesthesia.
In paediatrics less than 15 kg of body weight, midazolam solutions with concentrations higher than 1mg/ml are not recommended. Higher concentrations should be diluted to 1 mg/ml.
Rectal administration (Children over 6 months of age): The total dose of midazolam, usually ranging from 0.4 mg/kg, ranging from 0.3-0.5 mg/kg, should be should be administered 20-30 minutes before induction of anaesthesia. Rectal administration of the ampoule solution is performed by means of a plastic applicator fixed on the end of the syringe. If the volume to be administered is too small, water may be added up to a total volume of 10 ml.
The use in paediatrics less than 6 months of age is not recommended as available data are limited.
Induction of anaesthesia: Adults: If Midazolam injection is used for induction of anaesthesia before other anaesthetic agents have been administered, the individual response is variable. The dose should be titrated to the desired effect according to the patient's age and clinical status.
When Midazolam injection is used before or in combination with other i.v. or inhalation agents for induction of anaesthesia, the initial dose of each agent may be significantly reduced, at times to as low as 25% of the usual initial dose of the individual agents.
The desired level of anaesthesia is reached by stepwise titration. The i.v. induction dose of Midazolam injection should be given slowly in increments. Each increment of not more than 5 mg should be injected over 20 - 30 seconds allowing 2 minutes between successive increments.
Adults below the age of 60 years: A dose of 0.15-0.2 mg/kg, administered i.v. over 20-30 seconds and allowing 2 minutes for effect, will usually suffice.
In non-premedicated patients the dose may be higher (0.3-0.35 mg/kg), administered i.v. over 20-30 seconds and allowing about 2 minutes for effect. If needed to complete induction, increments of approximately 25% of the patient’s initial dose may be used. Induction may instead be completed with volatile liquid inhalational anaesthetics. In resistant cases, a total dose of up to 0.6 mg/kg may be used for induction, but such larger doses may prolong recovery.
Adults above the age of 60 years and/or critically ill and/or high-risk patients: In non-premedicated patients the lowest initial dose of 0.15-0.2 mg/kg is recommended.
In premedicated patients a dose of 0.05-0.15 mg/kg administered i.v. over 20-30 seconds and allowing 2 minutes for effect, will usually suffice.
Paediatrics: The use of Midazolam injection for the induction of anaesthesia is limited to adults only as there is very limited experience in children.
Sedative component in combined anaesthesia: Adults: Midazolam injection can be given as a sedative component in combined anaesthesia by either further intermittent small i.v. doses (range between 0.03 and 0.1 mg/kg) or continuous infusion of i.v. Midazolam injection (range between 0.03 and 0.1 mg/kg/h) typically in combination with analgesics. The dose and the intervals between doses vary according to the patient's individual reaction.
In adults over 60 years of age, critically ill and/or high-risk patients lower maintenance doses will be required.
Paediatrics: The use of Midazolam injection as sedative component in combined anaesthesia is limited to adults only as there is very limited experience in children.
Sedation in the intensive care unit: The desired level of sedation is reached by stepwise titration of Midazolam injection followed by either continuous infusion or intermittent bolus, according to the clinical need, physical status, age and concomitant medication.
Adults: I.V. loading dose: 0.03-0.3 mg/kg should be given slowly in increments. Each increment of 1-2.5 mg should be injected over 20-30 seconds allowing 2 minutes between successive increments. In hypovolemic, vasoconstricted or hypothermic patients the loading dose should be reduced or omitted.
When Midazolam injection is given with potent analgesics, the latter should be administered first so that the sedative effects of Midazolam injection can be safely titrated on top of any sedation caused by the analgesic.
I.V. maintenance dose: doses can range from 0.03-0.2 mg/kg/h. In hypovolemic, vasoconstricted or hypothermic patients the maintenance dose should be reduced. The level of sedation should be assessed regularly if the patient’s condition permits. With long-term sedation, tolerance may develop and the dose may have to be increased.
Paediatrics: In preterm new born infants, term newborn infants, and paediatrics less than 15 kg of body weight, midazolam solutions with concentrations higher than 1 mg/ml are not recommended. Higher concentrations should be diluted to 1mg/ml.
Paediatrics up to 6 months of age: Midazolam injection should be given as a continuous i.v. infusion: Paediatrics <32 weeks of gestational age: starting dose at 0.03 mg/kg/hr (0.5μg/kg/min); Paediatrics >32 weeks of gestational age up to 6 months of age: starting dose 0.06 mg/kg/hr (1μg/kg/min).
Intravenous loading doses should not be used rather the infusion may be run more rapidly for the first several hours to establish therapeutic plasma levels. The rate of infusion should be carefully and frequently reassessed, particularly after the first 24 hours so as to administer the lowest possible effective dose and reduce the potential for drug accumulation.
Careful monitoring of respiratory rate and oxygen saturation is required.
Paediatrics over 6 months of age: In intubated and ventilated patients, a loading dose of 0.05 to 0.2 mg/kg i.v. should be administered slowly over at least 2 to 3 minutes to establish the desired clinical effect. Midazolam injection should not be administered as a rapid intravenous dose. The loading dose is followed by a continuous i.v. infusion at 0.06 to 0.12 mg/kg/h (1 to 2 μg/kg/min). The rate of infusion can be increased or decreased (generally by 25% of the initial or subsequent infusion rate) as required, or supplemental i.v. doses of Midazolam injection can be administered to increase or maintain the desired effect.
When initiating an infusion with Midazolam injection in hemodynamically compromised patients, the usual loading dose should be titrated in small increments and the patient monitored for hemodynamic instability, e.g. hypotension. These patients are also vulnerable to the respiratory depressant effects of Midazolam injection and require careful monitoring of respiratory rate and oxygen saturation.
Instruction for use/handling: The injection is for single patient use and should be used immediately after opening. The injection should not be used if particles are present. Any unused portion should be discarded. With continuous intravenous infusion, midazolam injection solution may be diluted in a ratio of 15mg midazolam to 100-1000ml with one of the infusion solution as as follows: Sodium Chloride 0.9%; Dextrose 5%; Dextrose 10%; Ringer’s Solution; Hartmann’s Solution.
Route of Administration: Parenteral.
[For IV, IM or rectal administration only.]