Midazolam (injection)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
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Black Box Warning
|
BOXED WARNING
See full prescribing information for complete Boxed Warning.
Adults and Pediatric:
Intravenous midazolam hydrochloride has been associated with respiratory depression and respiratory arrest, especially when used for sedation in noncritical care settings. In some cases, where this was not recognized promptly and treated effectively, death or hypoxic encephalopathy has resulted. Intravenous midazolam should be used only in hospital or ambulatory care settings, including physicians and dental offices, that provide for continuous monitoring of respiratory and cardiac function, ie., pulse oximetry. Immediate availability of resuscitative drugs and age- and size-appropriate equipment for bag/valve/mask ventilation and intubation, and personnel trained in their use and skilled in airway management should be assured (see WARNINGS). For deeply sedated pediatric patients, a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure. The initial intravenous dose for sedation in adult patients may be as little as 1 mg, but should not exceed 2.5 mg in a normal healthy adult. Lower doses are necessary for older (over 60 years) or debilitated patients and in patients receiving concomitant narcotics or other central nervous system (CNS) depressants. The initial dose and all subsequent doses should always be titrated slowly; administer over at least 2 minutes and allow an additional 2 or more minutes to fully evaluate the sedative effect. The use of the 1 mg/mL formulation or dilution of the 1 mg/mL or 5 mg/mL formulation is recommended to facilitate slower injection. Doses of sedative medications in pediatric patients must be calculated on a mg/kg basis, and initial doses and all subsequent doses should always be titrated slowly. The initial pediatric dose of midazolam for sedation /anxiolysis/amnesia is age, procedure, and route dependent (see DOSAGE AND ADMINISTRATION for complete dosing information). Neonates: Midazolam should not be administered by rapid injection in the neonatal population. Severe hypotension and seizures have been reported following rapid IV administration, particularly with concomitant use of fentanyl (see DOSAGE AND ADMINISTRATION for complete information). |
Overview
Midazolam (injection) is a general anesthetic that is FDA approved for the {{{indicationType}}} of anxiety - induction of amnesia - preoperative sedation, induction of general anesthesia, procedural sedation, sedation for a mechanically ventilated patient.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include neurologic: excessive somnolence] (1.6%), [[]headache]] (1.3% to 1.5%), somnolence(1.2%), respiratory: hiccoughs (3.6% ).
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Anxiety good-risk patients less than 60 years of age, 0.07 to 0.08 mg/kg IM (approximately 5 mg) up to 1 hour before surgery.
- Anxiety - Induction of amnesia - Preoperative sedation: patients 60 years or older, patients with COPD, other higher-risk surgical patients, and patients who have received concomitant narcotics or other CNS depressants, 0.02 to 0.05 mg/kg IM (approximately 2 to 3 mg) 1 hour before surgery.
- Anxiety - Induction of amnesia - older patients when the anticipated intensity and duration of sedation is less critical, 1 mg IM 1 hour before surgery.
- Anxiety - Induction of amnesia - Preoperative sedation: healthy adults less than 60 years of age, initial, 1 to 2.5 mg IV over at least 2 minutes, may titrate using small increments to desired level of sedation (allowing 2 additional minutes to evaluate full effect after each increment); reduce dose by 30% with narcotic premedication or other CNS depressants (MAX total dose: 5 mg).
- Anxiety - Induction of amnesia - Preoperative sedation: patients 60 years or older, and debilitated or chronically ill patients, initial, 1 to 1.5 mg IV over at least 2 minutes, may titrate by no more than 1-mg increments (allowing 2 additional minutes to evaluate full effect after each increment); reduce dose by 50% with narcotic premedication or other CNS depressants (MAX total dose: 3.5 mg) [2]
- Anxiety - Induction of amnesia - Preoperative sedation: maintenance, additional doses of 25% of total initial dose required to achieved desired sedation may be administered IV if additional sedation is required.
- Induction of general anesthesia: unpremedicated patients less than 55 years of age, initial, 0.3 to 0.35 mg/kg IV over 20 to 30 seconds; may increase by 25% of initial dose to desired effect (allowing 2 minutes for effect) to MAX total dose of 0.6 mg/kg.
- Induction of general anesthesia: unpremedicated patients greater than 55 years of age, initial, 0.3 mg/kg IV over 20 to 30 seconds.
- Induction of general anesthesia: unpremedicated patients with severe systemic disease or other debilitation, initial, 0.15 to 0.25 mg/kg IV over 20 to 30 seconds.
- Induction of general anesthesia: premedicated patients less than 55 years of age, initial, 0.25 mg/kg IV over 20 to 30 seconds.
- Induction of general anesthesia: premedicated good-risk patients greater than 55 years of age, initial, 0.2 mg/kg IV over 20 to 30 seconds.
- Induction of general anesthesia: premedicated patients with severe systemic disease or debilitation, initial, 0.15 mg/kg IV over 20 to 30 seconds.
- Induction of general anesthesia: maintenance dose, incremental injections of approximately 25% of the induction dose should be given in response to signs of lightening of anesthesia .and repeated as necessary.
- Procedural sedation: healthy adults below 60 years of age, initial, 1 to 2.5 mg IV over at least 2 minutes, may titrate using small increments to desired level of sedation (allowing 2 additional minutes to evaluate full effect after each increment); reduce dose by 30% with narcotic premedication or other CNS depressants (MAX total dose: 5 mg).
- Procedural sedation: patients 60 years or older, and debilitated or chronically ill patients, initial, 1 to 1.5 mg IV over at least 2 minutes, may titrate by no more than 1-mg increments (allowing 2 additional minutes to evaluate full effect after each increment); reduce dose by 50% with narcotic premedication or other CNS depressants (MAX total dose: 3.5 mg).
- Procedural sedation: maintenance, additional doses of 25% of total initial dose required to achieved desired sedation may be administered IV if additional sedation is required.
- Sedation for a mechanically ventilated patient: loading dose, 0.01 to 0.05 mg/kg IV administered over several minutes; may repeat at 10- to 15-minute intervals until adequate sedation is achieved.
- Sedation for a mechanically ventilated patient: maintenance, continuous IV infusion initiated at a rate of 0.02 to 0.1 mg/kg/hr; may adjust rate up or down by 25% to 50% of initial infusion rate to achieve adequate sedation.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Midazolam in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
- High amounts of benzyl alcohol have been associated with toxicity, particularly in neonates; consider the daily metabolic load of benzyl alcohol being given.
- Anxiety - Induction of amnesia - Preoperative sedation: (6 months or older) 0.25 to 0.5 mg/kg orally as a single dose; up to 1 mg/kg for younger (6 months to less than 6 years) or uncooperative patients (MAX dose: 20 mg).
- Anxiety - Induction of amnesia - Preoperative sedation: 0.1 to 0.15 mg/kg IM as a single dose; 0.5 mg/kg for more anxious patients (MAX total dose: 10 mg).
- Anxiety - Induction of amnesia - Preoperative sedation: (6 months to 5 years of age) initial, 0.05 to 0.1 mg/kg IV over 2 to 3 minutes; may titrate to desired level of sedation (allowing 2 to 3 additional minutes to evaluate full effect after each increment); a total dose up to 0.6 mg/kg may be necessary (MAX total dose: 6 mg).
- Anxiety - Induction of amnesia - Preoperative sedation: (6 to 12 years of age) initial, 0.025 to 0.05 mg/kg IV over 2 to 3 minutes, may titrate to desired level of sedation (allowing 2 to 3 additional minutes to evaluate full effect after each increment); a total dose up to 0.4 mg/kg may be necessary (MAX total dose: 10 mg).
- Anxiety - Induction of amnesia - Preoperative sedation: (12 years or older) initial, 1 to 2.5 mg IV over at least 2 minutes, may titrate using small increments to desired level of sedation (allowing 2 additional minutes to evaluate full effect after each increment) (MAX total dose: 10 mg).
- Procedural sedation: (6 months or older) 0.25 to 0.5 mg/kg ORALLY as a single dose; up to 1 mg/kg for younger (6 months to less than 6 years) or uncooperative patients (MAX dose: 20 mg).
- Procedural sedation: 0.1 to 0.15 mg/kg IM as a single dose; 0.5 mg/kg for more anxious patients (MAX total dose: 10 mg).
- Procedural sedation: (6 months to 5 years of age) initial, 0.05 to 0.1 mg/kg IV over 2 to 3 minutes; may titrate to desired level of sedation (allowing 2 to 3 additional minutes to evaluate full effect after each increment); a total dose up to 0.6 mg/kg may be necessary (MAX total dose: 6 mg).
- Procedural sedation: (6 to 12 years of age) initial, 0.025 to 0.05 mg/kg IV over 2 to 3 minutes, may titrate to desired level of sedation (allowing 2 to 3 additional minutes to evaluate full effect after each increment); a total dose up to 0.4 mg/kg may be necessary (MAX total dose 10 mg).
- Procedural sedation: (12 years or older) initial, 1 to 2.5 mg IV over at least 2 minutes, may titrate using small increments to desired level of sedation (allowing 2 additional minutes to evaluate full effect after each increment) (MAX total dose: 10 mg).
- Sedation for a mechanically ventilated patient: (non-neonatal) loading dose, 0.05 to 0.2 mg/kg IV over at least 2 to 3 minutes.
- Sedation for a mechanically ventilated patient: (non-neonatal), maintenance, continuous IV infusion initiated at a rate of 0.06 to 0.12 mg/kg/hr (1 to 2 mcg/kg/min), may adjust rate up or down by 25% of initial or subsequent rate to achieve adequate sedation.
- Sedation for a mechanically ventilated patient: (neonatal younger than 32 weeks) continuous IV infusion initiated at a rate of 0.03 mg/kg/hr (0.5 mcg/kg/min).
- Sedation for a mechanically ventilated patient: (neonatal older than 32 weeks) continuous IV infusion initiated at a rate of 0.06 mg/kg/hr (1 mcg/kg/min).
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Midazolam in pediatric patients.
Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Midazolam in pediatric patients.
Contraindications
Injectable midazolam hydrochloride is contraindicated in patients with a known hypersensitivity to the drug. Benzodiazepines are contraindicated in patients with acute narrow-angle glaucoma. Benzodiazepines may be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. Measurements of intraocular pressure in patients without eye disease show a moderate lowering following induction with midazolam hydrochloride; patients with glaucoma have not been studied.
Warnings
|
BOXED WARNING
See full prescribing information for complete Boxed Warning.
Adults and Pediatric:
Intravenous midazolam hydrochloride has been associated with respiratory depression and respiratory arrest, especially when used for sedation in noncritical care settings. In some cases, where this was not recognized promptly and treated effectively, death or hypoxic encephalopathy has resulted. Intravenous midazolam should be used only in hospital or ambulatory care settings, including physicians and dental offices, that provide for continuous monitoring of respiratory and cardiac function, ie., pulse oximetry. Immediate availability of resuscitative drugs and age- and size-appropriate equipment for bag/valve/mask ventilation and intubation, and personnel trained in their use and skilled in airway management should be assured (see WARNINGS). For deeply sedated pediatric patients, a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure. The initial intravenous dose for sedation in adult patients may be as little as 1 mg, but should not exceed 2.5 mg in a normal healthy adult. Lower doses are necessary for older (over 60 years) or debilitated patients and in patients receiving concomitant narcotics or other central nervous system (CNS) depressants. The initial dose and all subsequent doses should always be titrated slowly; administer over at least 2 minutes and allow an additional 2 or more minutes to fully evaluate the sedative effect. The use of the 1 mg/mL formulation or dilution of the 1 mg/mL or 5 mg/mL formulation is recommended to facilitate slower injection. Doses of sedative medications in pediatric patients must be calculated on a mg/kg basis, and initial doses and all subsequent doses should always be titrated slowly. The initial pediatric dose of midazolam for sedation /anxiolysis/amnesia is age, procedure, and route dependent (see DOSAGE AND ADMINISTRATION for complete dosing information). Neonates: Midazolam should not be administered by rapid injection in the neonatal population. Severe hypotension and seizures have been reported following rapid IV administration, particularly with concomitant use of fentanyl (see DOSAGE AND ADMINISTRATION for complete information). |
Midazolam hydrochloride must never be used without individualization of dosage particularly when used with other medications capable of producing central nervous system depression. Prior to the intravenous administration of midazolam hydrochloride in any dose, the immediate availability of oxygen, resuscitative drugs, age- and size-appropriate equipment for bag/valve/mask ventilation and intubation, and skilled personnel for the maintenance of a patent airway and support of ventilation should be ensured. Patients should be continuously monitored with some means of detection for early signs of hypoventilation, airway obstruction, or apnea, i.e., pulse oximetry. Hypoventilation, airway obstruction, and apnea can lead to hypoxia and/or cardiac arrest unless effective countermeasures are taken immediately. The immediate availability of specific reversal agents (flumazenil) is highly recommended. Vital signs should continue to be monitored during the recovery period. Because intravenous midazolam depresses respiration (see CLINICAL PHARMACOLOGY) and because opioid agonists and other sedatives can add to this depression, midazolam should be administered as an induction agent only by a person trained in general anesthesia and should be used for sedation/anxiolysis/amnesia only in the presence of personnel skilled in early detection of hypoventilation, maintaining a patent airway and supporting ventilation. When used for sedation/anxiolysis/amnesia, midazolam should always be titrated slowly in adult or pediatric patients. Adverse hemodynamic events have been reported in pediatric patients with cardiovascular instability; rapid intravenous administration should also be avoided in this population. See DOSAGE AND ADMINISTRATION for complete information.
Serious cardiorespiratory adverse events have occurred after administration of midazolam. These have included respiratory depression, airway obstruction, oxygen desaturation, apnea, respiratory arrest and/or cardiac arrest, sometimes resulting in death or permanent neurologic injury. There have also been rare reports of hypotensive episodes requiring treatment during or after diagnostic or surgical manipulations particularly in adult or pediatric patients with hemodynamic instability. Hypotension occurred more frequently in the sedation studies in patients premedicated with a narcotic.
Reactions such as agitation, involuntary movements (including tonic/clonic movements and muscle tremor), hyperactivity and combativeness have been reported in both adult and pediatric patients. These reactions may be due to inadequate or excessive dosing or improper administration of midazolam hydrochloride; however, consideration should be given to the possibility of cerebral hypoxia or true paradoxical reactions. Should such reactions occur, the response to each dose of midazolam hydrochloride and all other drugs, including local anesthetics, should be evaluated before proceeding. Reversal of such responses with flumazenil has been reported in pediatric patients.
Concomitant use of barbiturates, alcohol or other central nervous system depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect. Narcotic premedication also depresses the ventilatory response to carbon dioxide stimulation.
Higher risk adult and pediatric surgical patients, elderly patients and debilitated adult and pediatric patients require lower dosages, whether or not concomitant sedating medications have been administered. Adult or pediatric patients with COPD are unusually sensitive to the respiratory depressant effect of midazolam hydrochloride. Pediatric and adult patients undergoing procedures involving the upper airway such as upper endoscopy or dental care, are particularly vulnerable to episodes of desaturation and hypoventilation due to partial airway obstruction. Adult and pediatric patients with chronic renal failure and patients with congestive heart failure eliminate midazolam more slowly (see CLINICAL PHARMACOLOGY). Because elderly patients frequently have inefficient function of one or more organ systems and because dosage requirements have been shown to decrease with age, reduced initial dosage of midazolam hydrochloride is recommended and the possibility of profound and/or prolonged effect should be considered.
Injectable midazolam should not be administered to adult or pediatric patients in shock or coma, or in acute alcohol intoxication with depression of vital signs. Particular care should be exercised in the use of intravenous midazolam in adult or pediatric patients with uncompensated acute illnesses, such as severe fluid or electrolyte disturbances.
There have been limited reports of intra-arterial injection of midazolam hydrochloride. Adverse events have included local reactions, as well as isolated reports of seizure activity in which no clear causal relationship was established. Precautions against unintended intra-arterial injection should be taken. Extravasation should also be avoided.
The safety and efficacy of midazolam following nonintravenous and nonintramuscular routes of administration have not been established. Midazolam hydrochloride should only be administered intramuscularly or intravenously.
The decision as to when patients who have received injectable midazolam, particularly on an outpatient basis, may again engage in activities requiring complete mental alertness, operate hazardous machinery or drive a motor vehicle must be individualized. Gross tests of recovery from the effects of midazolam (see CLINICAL PHARMACOLOGY) cannot be relied upon to predict reaction time under stress. It is recommended that no patient operate hazardous machinery or a motor vehicle until the effects of the drug, such as drowsiness, have subsided or until one full day after anesthesia and surgery, whichever is longer. For pediatric patients, particular care should be taken to assure safe ambulation.
Usage in Pregnancy:
An increased risk of congenital malformations associated with the use of benzodiazepine drugs (diazepam and chlordiazepoxide) has been suggested in several studies. If this drug is used during pregnancy, the patient should be apprised of the potential hazard to the fetus.
Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE section).
Usage In Preterm Infants And Neonates:
Rapid injection should be avoided in the neonatal population. Midazolam hydrochloride administered rapidly as an intravenous injection (less than 2 minutes) has been associated with severe hypotension in neonates, particularly when the patient has also received fentanyl. Likewise, severe hypotension has been observed in neonates receiving a continuous infusion of midazolam who then receive a rapid intravenous injection of fentanyl. Seizures have been reported in several neonates following rapid intravenous administration.
The neonate also has reduced and/or immature organ function and is also vulnerable to profound and/or prolonged respiratory effects of midazolam.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Midazolam (injection) Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Midazolam (injection) Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Midazolam (injection) Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Midazolam (injection) in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Midazolam (injection) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Midazolam (injection) during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Midazolam (injection) in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Midazolam (injection) in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Midazolam (injection) in geriatric settings.
Gender
There is no FDA guidance on the use of Midazolam (injection) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Midazolam (injection) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Midazolam (injection) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Midazolam (injection) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Midazolam (injection) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Midazolam (injection) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Midazolam (injection) Administration in the drug label.
Monitoring
There is limited information regarding Midazolam (injection) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Midazolam (injection) and IV administrations.
Overdosage
There is limited information regarding Midazolam (injection) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Midazolam (injection) Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Midazolam (injection) Mechanism of Action in the drug label.
Structure
There is limited information regarding Midazolam (injection) Structure in the drug label.
Pharmacodynamics
There is limited information regarding Midazolam (injection) Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Midazolam (injection) Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Midazolam (injection) Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Midazolam (injection) Clinical Studies in the drug label.
How Supplied
There is limited information regarding Midazolam (injection) How Supplied in the drug label.
Storage
There is limited information regarding Midazolam (injection) Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Midazolam (injection) Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Midazolam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Midazolam (injection) Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Midazolam (injection) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.