ce area. The NOAEL dose for these effects in both species is 17 times the delivery system amount present in monthly 120 mg risperidone subcutaneous injectable suspension based on mg/m2 body surface area. These effects could be related to NMP, an excipient present in the delivery system. In published animal developmental toxicity studies, NMP administered orally daily to pregnant rats during organogenesis produced developmental toxicity below maternally toxic levels and resulted in dose-dependent decrease in fetal body weights, increased incidence of post-implantation loss, incomplete ossification and increased incidence of external, visceral and skeletal malformations. These toxicities occurred at doses that are ~3 to 12 times the NMP amount present in monthly 120 mg risperidone subcutaneous injectable suspension based on mg/m2 body surface area.
8.2 Lactation
Risk Summary
Limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3 and 4.7% of the maternal weight-adjusted dosage. There are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone (see CLINICAL CONSIDERATIONS). There is no information on the effects of risperidone on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PERSERIS and any potential adverse effects on the breastfed child from PERSERIS or from the mother's underlying condition.
Clinical Considerations
Infants exposed to PERSERIS through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements).
8.3 Females and Males of Reproductive Potential
Infertility
Females
Based on the pharmacologic action of risperidone (D2 receptor antagonism), treatment with PERSERIS may result in an increase in serum prolactin levels, which may lead to a reversible reduction in fertility in females of reproductive potential [see Warnings and Precautions (5.6)].
8.4 Pediatric Use
Safety and effectiveness of PERSERIS have not been established in pediatric patients.
8.5 Geriatric Use
Clinical studies of PERSERIS in the treatment of schizophrenia did not include patients aged 65 and older to determine whether or not they respond differently from younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Elderly patients with dementia-related psychosis treated with PERSERIS are at an increased risk of death compared to placebo. PERSERIS is not approved for the treatment of patients with dementia related psychosis [see BOXED WARNING and Warnings and Precautions (5.1, 5.2)].
8.6 Renal Impairment
In patients with renal impairment, carefully titrate with oral risperidone (up to at least 3 mg) before initiating treatment with PERSERIS at a dose of 90 mg [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
PERSERIS was not studied in patients with renal impairment, however, such effect has been investigated with oral risperidone.
8.7 Hepatic Impai |
