Midazolam hydrochloride injection is indicated:intramuscularly or intravenously for preoperative sedation/anxiolysis/amnesia;intravenously as an agent for sedation/anxiolysis/amnesia prior to or during diagnostic, therapeutic or endoscopic procedures, such as bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures either alone or in combination with other CNS depressants;intravenously for induction of general anesthesia, before administration of other anesthetic agents.
With the use of narcotic premedication, induction of anesthesia can be attained within a relatively narrow dose range and in a short period of time.Intravenous midazolam can also be used as a component of intravenous supplementation of nitrous oxide and oxygen (balanced anesthesia);continuous intravenous infusion for sedation of intubated and mechanically ventilated patients as a component of anesthesia or during treatment in a critical care setting.Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours (see CLINICAL PHARMACOLOGY).
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.Midazolam hydrochloride is not intended for intrathecal or epidural administration due to the presence of the preservative benzyl alcohol in the dosage form.
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 premeditation 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.Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants.
There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol.
The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol.
Administration of high dosages of medications (including midazolam hydrochloride) containing this preservative must take into account the total amount of benzyl alcohol administered.The recommended dosage range of midazolam hydrochloride for preterm and term infants includes amounts of benzyl alcohol well below that associated with toxicity; however, the amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources.