usion of ZULRESSO. The calculatedmaximum relative infant dose for ZULRESSO during the infusion was 1% to 2%.
8.4 Pediatric Use
The safety and effectiveness of ZULRESSO in pediatric patients have not been established.
8.5 Geriatric Use
PPD is a condition associated with pregnancy; there is no geriatric experience with ZULRESSO.
8.6 Hepatic Impairment
Dosage adjustment in patients with hepatic impairment is not necessary. Modest increases inexposure to unbound brexanolone and modest decreases in exposure to total brexanolone wereobserved in patients with moderate to severe hepatic impairment (Child-Pugh≥7) with noassociated change in tolerability [see Clinical Pharmacology (12.3)].
8.7 Renal Impairment
No dosage adjustment is recommended in patients with mild (eGFR 60 to 89 mL/minute/1.73m2), moderate (eGFR 30 to 59 mL/minute/1.73 m2) or severe (eGFR 15 to 29 mL/minute/1.73m2) renal impairment [see Clinical Pharmacology (12.3)].
Avoid use of ZULRESSO in patients with end stage renal disease (ESRD) with eGFR of< 15 mL/minute/1.73 m2because of the potential accumulation of the solubilizing agent, betadexsulfobutyl ether sodium [see Clinical Pharmacology (12.3, 12.6)].
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
ZULRESSO contains brexanolone. (Controlled substance schedule to be determined after reviewby the Drug Enforcement Administration.)
9.2 Abuse
In a human abuse potential study, 90 mcg/kg, 180 mcg/kg (two times the maximumrecommended infusion rate), and 270 mcg/kg (three times the maximum recommended infusion
rate) ZULRESSO infusions over a one hour period were compared to oral alprazolamadministration (1.5 mg and 3 mg). On positive subjective measures of "drug liking”, “overalldrug liking”, “high” and “good drug effects”, the 90 mcg/kg dosage produced scores that weresimilar to placebo. Scores on these positive subjective measures for both dosages ofZULRESSO 90 mcg/kg and 180 mcg/kg were lower than both alprazolam doses. However, thescores on the positive subjective measures for ZULRESSO 270 mcg/kg dosage were similar tothose produced by both doses of alprazolam. In this study, 3% of subjects administeredZULRESSO 90 mcg/kg and 13% administered ZULRESSO 270 mcg/kg reported euphoricmood, compared to none administered placebo during the one-hour administration.
9.3 Dependence
In the PPD clinical studies conducted with ZULRESSO, end of treatment occurred throughtapering. Thus, in these studies it was not possible to assess whether abrupt discontinuation ofZULRESSO produced withdrawal symptoms indicative of physical dependence. It isrecommended that ZULRESSO be tapered according to the dosage recommendations, unlesssymptoms warrant immediate discontinuation [see Dosage and Administration (2.2), Warningsand Precautions (5.1)].
10 OVERDOSAGE
Human Experience
There is limited clinical trial experience regarding human overdosage with ZULRESSO. Inpremarketing clinical studies, two cases of accidental overdosage due to infusion pumpmalfunction resulted in transient loss of consciousness. Both patients regained consciousnessapproximately 15 minutes after discontinuation of the infusion without supportive measures.
After full resolution of symptoms, both patients subsequently resumed and completed treatment.
Overdosage may result in excessive sedation, including loss of consci |
