ptoms; two patients who had dosage interruption because of lossof consciousness did not resume the infusion.
Table 2 presents the adverse reactions that occurred in ZULRESSO-treated PPD patients at a rateof at least 2% and at a higher rate than in the placebo-treated patients during the 60-hourtreatment period.
Table 2 Adverse Reactions in Placebo-Controlled Studies in Patients with PPD
Reported in ≥ 2% of ZULRESSO-Treated Patients and Greater than
Placebo-Treated Patients
Placebo
(n=107)
Maximum dosage
60 mcg/kg/hour
(n=38)
Maximum dosage
90 mcg/kg/hour
(Recommended dosage)
(n=102)
Cardiac Disorders
Tachycardia - - 3%
Gastrointestinal Disorders
Diarrhea 1% 3% 2%
Dry mouth, 1% 11% 3%
Dyspepsia - - 2%
Oropharyngeal pain - 3% 2%
Nervous System Disorders
Dizziness, presyncope, vertigo 7% 13% 12%
Loss of consciousness - 5% 3%
Sedation, somnolence 6% 21% 13%
Vascular Disorders
Flushing, hot flush - 5% 2%
7 DRUG INTERACTIONS
7.1 CNS Depressants
Concomitant use of ZULRESSO with CNS depressants (e.g., opioids, benzodiazepines) mayincrease the likelihood or severity of adverse reactions related to sedation [see Warnings andPrecautions (5.1)].
7.2 Antidepressants
In the placebo-controlled studies, a higher percentage of ZULRESSO-treated patients who usedconcomitant antidepressants reported sedation-related events [see Warnings and Precautions(5.1)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed toantidepressants during pregnancy. Healthcare providers are encouraged to register patients bycalling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting onlineat https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/.
Risk Summary
Based on findings from animal studies of other drugs that enhance GABAergic inhibition,ZULRESSO may cause fetal harm. There are no available data on ZULRESSO use in pregnantwomen to determine a drug-associated risk of major birth defects, miscarriage, or adversematernal or fetal outcomes. In animal reproduction studies, malformations were not seen in ratsor rabbits at plasma levels up to 5 and 6 times the maximum recommended human dose(MRHD), respectively. Developmental toxicities were seen in the fetuses of rats and rabbits at 5and ≥3 times the plasma levels at the MRHD, respectively. Reproductive toxicities were seen inrabbits at ≥3 times the plasma levels at the MRHD. These effects were not seen in rats andrabbits at 2 and 1.2 times the plasma levels at the MRHD. Brexanolone administered to pregnant
rats during pregnancy and lactation resulted in lower pup survival at doses which were associatedwith ≥2 times the plasma levels at the MRHD and a neurobehavioral deficit in female offspringat 5 times the plasma levels at the MRHD. These effects were not seen at 0.8 times and 2 timesthe plasma levels at the MRHD, respectively (see Data).
In published animal studies, administration of other drugs that enhance GABAergic inhibition toneonatal rats caused widespread apoptotic neurodegeneration in the developing brain. Thewindow of vulnerability to these changes in rats (postnatal days 0-14) corresponds to the periodof brain development that takes place during the third trimester of pregnancy in humans.
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