Drug Interaction Report

MONITOR CLOSELY: Coadministration with central nervous system (CNS) depressants (e.g., alcohol, benzodiazepines, opioids) or antidepressants may enhance the sedative effects of brexanolone and increase the likelihood or severity of sedation-related adverse reactions. Patients treated with brexanolone are at risk of excessive sedation or sudden loss of consciousness during administration. In clinical studies, 5% of patients receiving brexanolone infusion experienced sedation and somnolence that required dose interruption, compared to 0% of patients receiving placebo. Some patients also reported to have loss of consciousness or altered state of consciousness during the brexanolone infusion (4% vs. 0%). All patients recovered from loss or altered state of consciousness after dose interruption, with full recovery time ranging from 15 to 60 minutes. There was no clear association between loss or alteration of consciousness and pattern or timing of dose. Not all patients who experienced a loss or alteration of consciousness reported sedation or somnolence before the episode.

MANAGEMENT: Caution is advised during concomitant use of brexanolone with CNS depressants, antidepressants, or other agents that cause sedation. Patients should be closely monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring. During the brexanolone infusion, monitor for sedative effects every 2 hours during planned, non-sleep periods, and immediately stop the infusion if there are signs or symptoms of excessive sedation. After symptoms resolve, the infusion may be resumed at the same or lower dose as clinically appropriate. If pulse oximetry reveals hypoxia, immediately stop the infusion and do not resume infusion following resolution of the hypoxia. Patients should be cautioned against driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until sedative effects of brexanolone and other concomitant medications have dissipated. Patients must be accompanied during interactions with their child(ren) while receiving brexanolone because of the potential for excessive sedation and sudden loss of consciousness.

MONITOR CLOSELY: Coadministration with central nervous system (CNS) depressants (e.g., alcohol, benzodiazepines, opioids) or antidepressants may enhance the sedative effects of brexanolone and increase the likelihood or severity of sedation-related adverse reactions. Patients treated with brexanolone are at risk of excessive sedation or sudden loss of consciousness during administration. In clinical studies, 5% of patients receiving brexanolone infusion experienced sedation and somnolence that required dose interruption, compared to 0% of patients receiving placebo. Some patients also reported to have loss of consciousness or altered state of consciousness during the brexanolone infusion (4% vs. 0%). All patients recovered from loss or altered state of consciousness after dose interruption, with full recovery time ranging from 15 to 60 minutes. There was no clear association between loss or alteration of consciousness and pattern or timing of dose. Not all patients who experienced a loss or alteration of consciousness reported sedation or somnolence before the episode.

MANAGEMENT: Caution is advised during concomitant use of brexanolone with CNS depressants, antidepressants, or other agents that cause sedation. Patients should be closely monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring. During the brexanolone infusion, monitor for sedative effects every 2 hours during planned, non-sleep periods, and immediately stop the infusion if there are signs or symptoms of excessive sedation. After symptoms resolve, the infusion may be resumed at the same or lower dose as clinically appropriate. If pulse oximetry reveals hypoxia, immediately stop the infusion and do not resume infusion following resolution of the hypoxia. Patients should be cautioned against driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until sedative effects of brexanolone and other concomitant medications have dissipated. Patients must be accompanied during interactions with their child(ren) while receiving brexanolone because of the potential for excessive sedation and sudden loss of consciousness.

MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.