Midazolam - Warnings and Precautions

WARNINGS Personnel and Equipment for Monitoring and Resuscitation 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 for early signs of hypoventilation, airway obstruction, or apnea with means readily available (e.g., 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 can depress respiration (see CLINICAL PHARMACOLOGY ), especially when used concomitantly with opioid agonists and other sedatives (see DOSAGE AND ADMINISTRATION ), it 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).

Risks from Concomitant Use With Opioids Concomitant use of benzodiazepines, including midazolam, and opioids may result in profound sedation, respiratory depression, coma, and death.

If a decision is made to use midazolam concomitantly with opioids, monitor patients closely for respiratory depression and sedation (see PRECAUTIONS ; Drug Interactions ).

Risk of Respiratory Adverse Events 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.

Individualization of Dosage Midazolam must never be used without individualization of dosage particularly when used with other medications capable of producing central nervous system depression.

See DOSAGE AND ADMINISTRATION for complete information.

Other Adverse Events 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 Central Nervous System Depressants 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.

Debilitation and Comorbid Considerations 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.