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Risk From Concomitant Use with Opiods

  • Concomitant use of benzodiazepines and opiods may result in profound sedation, respiratory depression, coma, & death.

Risk From Concomitant Use with Opioids; Abuse, Misuse, and Addiction; and Dependence and Withdrawal Reactions

  • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death (5.1, 7.2)
  • The use of benzodiazepines, including Midazolam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing Midazolam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (5.2).
  • Although Midazolam is indicated only for intermittent use (1, 2), if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of Midazolam may precipitate acute withdrawal reactions, which can be life-threatening. For patients using NAYZILAM more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue Midazolam(5.3).

Individualize Dosing

Injection and Oral Formulations

  • Respiratory Depression/Arrest has been associated with use, especially when used for sedation in noncritical care settings. Reports of respiratory depression, airway obstruction, desaturation, hypoxia, and apnea, particularly when used with concomitant CNS depressants (e.g.opioids).
  • Equipped Facility/Trained Personnel: Should only be used in settings (e.g. hospital, ambulatory care settings, including physicians' or dentists' offices) that can provide continuous monitoring of respiratory and cardiac function. Immediate availability of resuscitative drugs and age- and size- appropriate equipment for ventilation and intubation and personnel trained in their use and skilled in airway management should be assured.
  • For deeply sedated patients, a dedicated individual other than practitioner performing procedure should monitor the patient throughout the procedure.

Injection Formulation

  • 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.
  • Adult Dosing: 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.
  • Pediatric Dosing: 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 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 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.
  • When used for sedation/anxiolysis/amnesia, midazolam should always be titrated slowly in adult or pediatric patients.

FDA and Industry Communications

Index to FDA Safety Information

Package Inserts


Additional Information

Updated March 2021