r-old man participating in a cardiac repolarization studyexperienced severe somnolence and <1 minute of apnea while receiving two times the maximumrecommended dosage of ZULRESSO (180 mcg/kg/hour). All patients with loss of or alteredstate of consciousness recovered with dose interruption.
There was no clear association between loss or alteration of consciousness and pattern or timingof dose. Not all patients who experienced a loss or alteration of consciousness reported sedationor somnolence before the episode.
During the infusion, monitor patients for sedative effects every 2 hours during planned,non-sleep periods. Immediately stop the infusion if there are signs or symptoms of excessivesedation.
After symptoms resolve, the infusion may be resumed at the same or lower dose as clinicallyappropriate [see Dosage and Administration (2.2)].
Immediately stop the infusion if pulse oximetry reveals hypoxia. After hypoxia, the infusionshould not be resumed.
Patients should be cautioned against engaging in potentially hazardous activities requiringmental alertness, such as driving after infusion until any sedative effects of ZULRESSO havedissipated. Patients must be accompanied during interactions with their child(ren) whilereceiving the infusion because of the potential for excessive sedation and sudden loss ofconsciousness.
Concomitant use of opioids, antidepressants, or other CNS depressants such as benzodiazepinesor alcohol may increase the likelihood or severity of adverse reactions related to sedation [seeWarnings and Precautions (7.1, 7.2)].
Because of the risk of serious harm resulting from excessive sedation or sudden loss ofconsciousness, ZULRESSO is available only through a restricted program under a Riskeva luation and Mitigation Strategy (REMS) called the ZULRESSO REMS [see Warnings andPrecautions (5.2)].
5.2 ZULRESSO Risk eva luation and Mitigation Strategy (REMS)
ZULRESSO is available only through a restricted program under a REMS called theZULRESSO REMS because excessive sedation or sudden loss of consciousness can result in
serious harm [see Warnings and Precautions (5.1)].
Notable requirements of the ZULRESSO REMS include the following:
• Healthcare facilities must enroll in the program and ensure that ZULRESSO is onlyadministered to patients who are enrolled in the ZULRESSO REMS.
• Pharmacies must be certified with the program and must only dispense ZULRESSOto healthcare facilities who are certified in the ZULRESSO REMS.
• Patients must be enrolled in the ZULRESSO REMS prior to administration ofZULRESSO.
• Wholesalers and distributors must be registered with the program and must onlydistribute to certified healthcare facilities and pharmacies.
Further information, including a list of certified healthcare facilities, is available atwww.zulressorems.com or 1-844-472-4379.
5.3 Suicidal Thoughts and Behaviors
In pooled analyses of placebo-controlled trials of chronically administered antidepressantdrugs (SSRIs and other antidepressant classes) that included approximately 77,000 adultpatients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors inantidepressant-treated patients age 24 years and younger was greater than in placebo-treatedpatients. There was considerable variation in risk of suicidal thoughts and behaviors amongdrugs, but there was an increased risk identified in young patien
