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Indications/Uses
Used for sedation in minor surgical or investigative procedures and in intensive care, for premedication, and for induction of general anesthesia. It is also used as hypnotic in the short-term management of insomnia.
Dosage/Direction for Use
Dosage should be individualized and drug should be administered slowly. Lower doses may be required in elderly or debilitated patients, in patients, in patients with hepatic or renal insufficiency, or when Midazolam is used in conjunction with opioid analgesics. When Midazolam is used, respiratory and cardiac functions should be monitored continuously, and facilities for resuscitation should always be available. It is advisable to keep the patient supine during intravenous administration and throughout the procedure. Because serious and life-threatening cardiorespiratory adverse events have been reported, provision for monitoring, detection and correction of these reactions must be made for every patient to whom Midazolam injection is administered, regardless of age or health status.
Midazolam may be given for premedication before general anaesthesia or to provide for minor surgical or investigative procedures. A usual sedative dose for dental and minor surgical and other procedures ranges from 2.5 to 7.5 mg (about 70 mcg per kg body-weight) intravenously; an initial dose of 2 mg over 30seconds has been suggested, with further incremental doses of 0.5 to 1 mg at intervals of 2 minutes if required until the desired end-points is reached.
The dosage of Midazolam should be determined by the response of the individual patient. The usual dose of Midazolam for induction of anaesthesia is about 200mcg per kg by slow I.V. injection in premedicated patients and at least 300 mcg per kg in those who not received a premedicant. A dose of 150 mcg per kg has been recommended for the induction of anaesthesia in children over 7 years of age.
Patients in intensive care who requires continuous sedation can be given Midazolam by I.V. infusion. The dosage should be individualized and Midazolam titrated to the desired state of sedation according to the clinical need, physical status, age and concomitant medication. An initial loading dose of 30 to 300mcg per kg may be given by I.V. infusion over 5 minutes to induce sedation. The maintenance dose required varies considerable but a dose of between 20 and 200 mcg per kg per hour has been suggested. The loading dose should be reduced or omitted and the maintenance dose reduced, for patients with hypovolemia, vasoconstriction, or hypothermia. The need for continuous administration should be reassessed on a daily basis to reduce the risk of accumulation and prolonged recovery. Sedation may also be achieved by giving intermittent I.V. bolus injections of Midazolam; doses of 1 to 2 mg may be given and repeated, until the desired level of sedation has been reached. Midazolam is given intramuscularly as a premedicant about 30 to 60 minutes before surgery. The usual dose is about 5 mg; doses range from 70 to 100 mcg per kg. Or as prescribed by the physician.
Midazolam may be given for premedication before general anaesthesia or to provide for minor surgical or investigative procedures. A usual sedative dose for dental and minor surgical and other procedures ranges from 2.5 to 7.5 mg (about 70 mcg per kg body-weight) intravenously; an initial dose of 2 mg over 30seconds has been suggested, with further incremental doses of 0.5 to 1 mg at intervals of 2 minutes if required until the desired end-points is reached.
The dosage of Midazolam should be determined by the response of the individual patient. The usual dose of Midazolam for induction of anaesthesia is about 200mcg per kg by slow I.V. injection in premedicated patients and at least 300 mcg per kg in those who not received a premedicant. A dose of 150 mcg per kg has been recommended for the induction of anaesthesia in children over 7 years of age.
Patients in intensive care who requires continuous sedation can be given Midazolam by I.V. infusion. The dosage should be individualized and Midazolam titrated to the desired state of sedation according to the clinical need, physical status, age and concomitant medication. An initial loading dose of 30 to 300mcg per kg may be given by I.V. infusion over 5 minutes to induce sedation. The maintenance dose required varies considerable but a dose of between 20 and 200 mcg per kg per hour has been suggested. The loading dose should be reduced or omitted and the maintenance dose reduced, for patients with hypovolemia, vasoconstriction, or hypothermia. The need for continuous administration should be reassessed on a daily basis to reduce the risk of accumulation and prolonged recovery. Sedation may also be achieved by giving intermittent I.V. bolus injections of Midazolam; doses of 1 to 2 mg may be given and repeated, until the desired level of sedation has been reached. Midazolam is given intramuscularly as a premedicant about 30 to 60 minutes before surgery. The usual dose is about 5 mg; doses range from 70 to 100 mcg per kg. Or as prescribed by the physician.
Overdosage
Symptoms of Overdosage: The manifestation of Midazolam overdosage are similar to those observed with other benzodiazepines, including sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma and untoward effects on vital signs and cerebrovascular perfusion. Hepatic function should be monitored.
Treatment of Overdosage: Treatment of Midazolam overdosage is the same as that followed for overdosage with other benzodiazepines. Respiration, pulse rate and blood pressure should be monitored and general supportive measures should be employed. Flumazenil can be used to reverse the effects of Midazolam. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the judicious use of other accepted antihypotensive measures. There is no information as to whether peritoneal dialysis, forced diuresis or haemodialysis are of any value in the treatment of overdosage.
Treatment of Overdosage: Treatment of Midazolam overdosage is the same as that followed for overdosage with other benzodiazepines. Respiration, pulse rate and blood pressure should be monitored and general supportive measures should be employed. Flumazenil can be used to reverse the effects of Midazolam. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the judicious use of other accepted antihypotensive measures. There is no information as to whether peritoneal dialysis, forced diuresis or haemodialysis are of any value in the treatment of overdosage.
Contraindications
Midazolam should not be administered to patients with Myasthenia gravis, hypersensitivity to benzodiazepines; patient in shock or coma, or in acute alcoholic intoxication with depression of vital signs. Benzodiazepines are contraindicated in patients with acute narrow angle glaucoma.
Special Precautions
Intravenous Midazolam should only be used in settings with equipment and skilled personnel for continuous monitoring of cardiorespiratory function and resuscitation procedures. Patients should be continuously monitored for early signs of under ventillation or apnea. Vital signs should continue to be monitored during the recovery period. During intravenous application of Midazolam respiratory depression, apnea, respiratory arrest and/or cardiac arrest have occurred. In some cases where this was not recognized promptly and treated, hypoxic encephalopathy or death has resulted. These life-threatening incidents may occur especially in elderly patients or patients with pre-existing respiratory insufficiency, especially if the injection is given too rapidly or with excessive dose. Particular care must be used in administering the drug by the I.V. route to the elderly to very ill patients, high risk surgical patients and to those with significant hepatic impairment, chronic renal insufficiency, or with limited pulmonary reserve because of the possibility that apnea or respiratory depression may occur. These patients require lower doses whether premedicated or not.
Dependence and Withdrawal: The development of dependence is common after regular use of Midazolam, even in the therapeutic doses for short periods.
Dependence is particularly likely in patients with a history of alcohol or drug abuse and in patients with marked personality disorders. Abrupt withdrawal of Midazolam should be avoided to prevent withdrawal symptoms. Therefore, a gradual reduction of Midazolam is recommended. The time needed for withdrawal can vary from about 4 weeks to a year or more. The extent to which tolerance occurs involves psychomotor performance more than anxiolytic effects. Drug-seeking behavior is uncommon with therapeutic doses of benzodiazepines.
Dependence and Withdrawal: The development of dependence is common after regular use of Midazolam, even in the therapeutic doses for short periods.
Dependence is particularly likely in patients with a history of alcohol or drug abuse and in patients with marked personality disorders. Abrupt withdrawal of Midazolam should be avoided to prevent withdrawal symptoms. Therefore, a gradual reduction of Midazolam is recommended. The time needed for withdrawal can vary from about 4 weeks to a year or more. The extent to which tolerance occurs involves psychomotor performance more than anxiolytic effects. Drug-seeking behavior is uncommon with therapeutic doses of benzodiazepines.
Adverse Reactions
There have been reports of life-threatening adverse respiratory and cardiovascular events occurring after administration of Midazolam. Deaths have been reported due to respiratory depression, hypotension, or cardiac arrest in patients given intravenous Midazolam for conscious sedation. Pain, tenderness, and thrombophlebitis have occurred following injection of Midazolam. Hiccups have also been reported.
Effects on children: The bolus I.V. administration of Midazolam should be avoided in neonates due to the occurrences of hypotension. For patients already receiving other receiving other drugs which provide sedation in the early postoperative period, the use of Midazolam should be limited to a continuous infusion. The initial dosage of Midazolam used for continuous intravenous sedation may need to be reduced in critically ill children under 3 years of age.
Effects on the elderly: There is an increase in sensitivity of the CNS to Midazolam in elderly patients, who frequently have inefficient function of one or more organ systems, and dosage requirements have been shown to be reduced with age. Patients with chronic renal failure and congestive heart failure eliminate Midazolam more slowly.
Effects on intensive care patients: Intensive care patients receiving Midazolam by I.V. infusion for prolonged sedation, the elimination half-life was found to increase by up to six times. Abrupt discontinuation of the product may be accompanied by withdrawal symptoms. Therefore, a gradual reduction of Midazolam is recommended.
Effects on mental function: Performance of tasks involving visual-spatial ability and sustained attention was poor in patients taking high doses of benzodiazepines for long periods of time but there was no evidence of impairment in global measures of intellectual functioning such as memory, flexibility, and simple reaction time. In women sedated with intravenous Midazolam, sexual fantasies have been reported.
Effects on the nervous system: Prolonged use of Midazolam with fentanyl has been associated with encephalopathy in infants sedated. Myoclinic twitching of all four limbs was also noted in neonates who received a continuous I.V. infusion of Midazolam at a rate of 30 to 60 mcg per kg body weight per hour. Myoclonus ceased a few hours after discontinuing the infusion and never reoccurred during the myoclonus.
Effects on pregnancy: Midazolam crosses the placenta. Therefore the risk benefit must be carefully considered when using Midazolam.
Effects on children: The bolus I.V. administration of Midazolam should be avoided in neonates due to the occurrences of hypotension. For patients already receiving other receiving other drugs which provide sedation in the early postoperative period, the use of Midazolam should be limited to a continuous infusion. The initial dosage of Midazolam used for continuous intravenous sedation may need to be reduced in critically ill children under 3 years of age.
Effects on the elderly: There is an increase in sensitivity of the CNS to Midazolam in elderly patients, who frequently have inefficient function of one or more organ systems, and dosage requirements have been shown to be reduced with age. Patients with chronic renal failure and congestive heart failure eliminate Midazolam more slowly.
Effects on intensive care patients: Intensive care patients receiving Midazolam by I.V. infusion for prolonged sedation, the elimination half-life was found to increase by up to six times. Abrupt discontinuation of the product may be accompanied by withdrawal symptoms. Therefore, a gradual reduction of Midazolam is recommended.
Effects on mental function: Performance of tasks involving visual-spatial ability and sustained attention was poor in patients taking high doses of benzodiazepines for long periods of time but there was no evidence of impairment in global measures of intellectual functioning such as memory, flexibility, and simple reaction time. In women sedated with intravenous Midazolam, sexual fantasies have been reported.
Effects on the nervous system: Prolonged use of Midazolam with fentanyl has been associated with encephalopathy in infants sedated. Myoclinic twitching of all four limbs was also noted in neonates who received a continuous I.V. infusion of Midazolam at a rate of 30 to 60 mcg per kg body weight per hour. Myoclonus ceased a few hours after discontinuing the infusion and never reoccurred during the myoclonus.
Effects on pregnancy: Midazolam crosses the placenta. Therefore the risk benefit must be carefully considered when using Midazolam.
Drug Interactions
Enhanced sedation or respiratory and cardiovascular depression may occur if Midazolam are given with other drugs that have CNS depressant properties such as alcohol antidepressants, antihistamines, antipsychotic, general anesthetics, other hypnotics or sedatives, and opioid analgesics.
Analgesics: Aspirin shortens the time to induce anesthetics with Midazolam possibly due to competition for plasma protein binding sites. Opioid analgesics maybe used with Midazolam in anesthetic or analgesics regimens. An additive sedative effect is to be expected but there are also reports of severe respiratory depression with Midazolam and fentayl or sudden hypotension with Midazolam and fentayl or sufentanil. The clearance of Midazolam appears to be reduced by fentanyl. Careful monitoring is required during concomitant administration of Midazolam with opioid and the dose of both drugs may need to be reduced. Synergic potentiation of the induction of anaesthesia has been reported between Midazolam and fentanyl, but Midazolam can diminish the analgesic effects of sufentanil.
Antibacterials: An increase in peak plasma concentrations of Midazolam with profound and prolonged sedation have been reported following administration of erythromycin. The use of Midazolam with erythromycin should be avoided or the dose of Midazolam reduced to 50 to 75%. Roxithromycin has some effects on the pharmacokinetics and pharmacodynamics of Midazolam but these changes were not clinically relevant. However, it was recommended that as a precaution the lowest possible dose of Midazolam should be used when given with roxithromycin. Ciprofloxacin can cause a significant rise in steady-state blood- Midazolam concentration. Rifampicin can decrease the half-life of Midazolam.
Antifungals: Ketoconazole and itraconazole can produce marked pharmacokinetic interactions with Midazolam and greatly increase the intensity and duration of action of the drug. It is recommended that the concomitant use of these antifungals and benzodiazepines should be avoided or the dose of benzodiazepines should be greatly reduced. Similarly, a less pronounced interaction occurs between fluconazole and Midazolam, but the dosage of the Midazolam should be reduced during concomitant use.
Antivirals: Concomitant use of Midazolam with HIV-protease inhibitors should be avoided.
Calcium-channel blockers: Peak plasma concentrations of Midazolam were doubled and the elimination half-life of Midazolam prolonged when Midazolam was administered to healthy subjects receiving diltiazem or verapamil. Concomitant use should be avoided or the dose of Midazolam reduced.
Clozapine: Cardiorespiratory collapse has been observed in patients taking both Clozapine and benzodiazepines. Hypersalivation associated with Clozapine and benzodiazepines may be exacerbated when these drugs are used together.
Gastrointestinal Drugs: Simultaneous administration of cimetidine (but not ranitidine) has been reported to reduce clearance of Midazolam. The sedative effect of benzodiazepines is enhanced by cisapride.
General Anaesthetics: A synergistic interaction has been demonstrated for the hypnotic effects of Midazolam and thiopental. Similar synergistic have been observed between Midazolam and both methohexital and propofol. Midazolam has also been reported to be able to produce a marked reduction in the concentration of halothane required for anaesthesia. The effects of Midazolam can be reversed by the benzodiazepines antagonist flumazenil.
Analgesics: Aspirin shortens the time to induce anesthetics with Midazolam possibly due to competition for plasma protein binding sites. Opioid analgesics maybe used with Midazolam in anesthetic or analgesics regimens. An additive sedative effect is to be expected but there are also reports of severe respiratory depression with Midazolam and fentayl or sudden hypotension with Midazolam and fentayl or sufentanil. The clearance of Midazolam appears to be reduced by fentanyl. Careful monitoring is required during concomitant administration of Midazolam with opioid and the dose of both drugs may need to be reduced. Synergic potentiation of the induction of anaesthesia has been reported between Midazolam and fentanyl, but Midazolam can diminish the analgesic effects of sufentanil.
Antibacterials: An increase in peak plasma concentrations of Midazolam with profound and prolonged sedation have been reported following administration of erythromycin. The use of Midazolam with erythromycin should be avoided or the dose of Midazolam reduced to 50 to 75%. Roxithromycin has some effects on the pharmacokinetics and pharmacodynamics of Midazolam but these changes were not clinically relevant. However, it was recommended that as a precaution the lowest possible dose of Midazolam should be used when given with roxithromycin. Ciprofloxacin can cause a significant rise in steady-state blood- Midazolam concentration. Rifampicin can decrease the half-life of Midazolam.
Antifungals: Ketoconazole and itraconazole can produce marked pharmacokinetic interactions with Midazolam and greatly increase the intensity and duration of action of the drug. It is recommended that the concomitant use of these antifungals and benzodiazepines should be avoided or the dose of benzodiazepines should be greatly reduced. Similarly, a less pronounced interaction occurs between fluconazole and Midazolam, but the dosage of the Midazolam should be reduced during concomitant use.
Antivirals: Concomitant use of Midazolam with HIV-protease inhibitors should be avoided.
Calcium-channel blockers: Peak plasma concentrations of Midazolam were doubled and the elimination half-life of Midazolam prolonged when Midazolam was administered to healthy subjects receiving diltiazem or verapamil. Concomitant use should be avoided or the dose of Midazolam reduced.
Clozapine: Cardiorespiratory collapse has been observed in patients taking both Clozapine and benzodiazepines. Hypersalivation associated with Clozapine and benzodiazepines may be exacerbated when these drugs are used together.
Gastrointestinal Drugs: Simultaneous administration of cimetidine (but not ranitidine) has been reported to reduce clearance of Midazolam. The sedative effect of benzodiazepines is enhanced by cisapride.
General Anaesthetics: A synergistic interaction has been demonstrated for the hypnotic effects of Midazolam and thiopental. Similar synergistic have been observed between Midazolam and both methohexital and propofol. Midazolam has also been reported to be able to produce a marked reduction in the concentration of halothane required for anaesthesia. The effects of Midazolam can be reversed by the benzodiazepines antagonist flumazenil.
Storage
Store at temperatures not exceeding 25°C.
Action
Pharmacology: Benzodiazepines appear to intensify the physiologic inhibitory mechanisms mediated by gamma-aminobutyric acid (GABA), the most common inhibitory neurotransmitter in the brain. The effects of Midazolam on the CNS are dependent on the dose administered, the route of administration and the presence or absence of other premedications.
Mechanism of Action: Midazolam is a drug acting on psychic function, behavior, or experience which alters the mental state by affecting the neurophysiological and biochemical activity of the functional units of the CNS, or in the pharmacological sense, as narcotics.
Pharmacokinetics: The absorption of Midazolam is rapid. The peak plasma concentration is achieved within 20 to 60 minutes of administration depending on the route. The mean absolute bioavailability of Midazolam following I.M. administration is greater than 90%. In a pharmacokinetics study in children, the bioavailability of a dose of 150mcg per kg body weight was 100% and 87% after administration by the I.V. and I.M. routes respectively. Midazolam is lipophilic at physiological pH. It crosses the placenta and is distributed into breast milk. Midazolam is about 96% bound to plasma proteins. Its elimination half-life of Midazolam is about 2 hours although half lives longer than 7 hours been reported in some patients. The half-life of Midazolam is prolonged in neonates, in the elderly, and in patients with liver disorders.
The drug is rapidly metabolized to I-hydroxymethylmidazolam which is conjugated with subsequent excretion in the urine, mainly as glucuronide conjugates. The half-life of elimination of the active metabolite is similar to Midazolam.
Mechanism of Action: Midazolam is a drug acting on psychic function, behavior, or experience which alters the mental state by affecting the neurophysiological and biochemical activity of the functional units of the CNS, or in the pharmacological sense, as narcotics.
Pharmacokinetics: The absorption of Midazolam is rapid. The peak plasma concentration is achieved within 20 to 60 minutes of administration depending on the route. The mean absolute bioavailability of Midazolam following I.M. administration is greater than 90%. In a pharmacokinetics study in children, the bioavailability of a dose of 150mcg per kg body weight was 100% and 87% after administration by the I.V. and I.M. routes respectively. Midazolam is lipophilic at physiological pH. It crosses the placenta and is distributed into breast milk. Midazolam is about 96% bound to plasma proteins. Its elimination half-life of Midazolam is about 2 hours although half lives longer than 7 hours been reported in some patients. The half-life of Midazolam is prolonged in neonates, in the elderly, and in patients with liver disorders.
The drug is rapidly metabolized to I-hydroxymethylmidazolam which is conjugated with subsequent excretion in the urine, mainly as glucuronide conjugates. The half-life of elimination of the active metabolite is similar to Midazolam.
MedsGo Class
Hypnotics & Sedatives
Features
Dosage
5mg / mL
Ingredients
- Midazolam
Packaging
Solution for Injection (I.M./I.V.) 3ml x 10's
Generic Name
Midazolam
Registration Number
DR-XY41527
Classification
Prescription Drug (RX)
Product Questions
Questions
