Issue link: https://beckershealthcare.uberflip.com/i/1161749
on mg/m 2 of aripiprazole during the period of organogenesis. Treatment at the highest dose caused a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight, and undescended testes. Delayed skeletal ossification was observed at 3 and 10 times the oral MRHD based on mg/m 2 . At 3 and 10 times the oral MRHD based on mg/m 2 , delivered offspring had decreased body weights. Increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed in offspring from the highest dose group (the other dose groups were not examined for these findings). A low incidence of diaphragmatic hernia was also seen in the fetuses exposed to the highest dose. Postnatally, delayed vaginal opening was seen at 3 and 10 times the oral MRHD based on mg/m 2 and impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) along with some maternal toxicity were seen at the highest dose; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity. In pregnant rabbits treated with oral doses of 10, 30, and 100 mg/kg/day which are 2 to 11 times human exposure at the oral MRHD based on AUC and 6 to 65 times the oral MRHD based on mg/m 2 of aripiprazole during the period of organogenesis decreased maternal food consumption and increased abortions were seen at the highest dose as well as increased fetal mortality. Decreased fetal weight and increased incidence of fused sternebrae were observed at 3 and 11 times the oral MRHD based on AUC. In rats treated with oral doses of 3, 10, and 30 mg/kg/day which are 1 to 10 times the oral MRHD based on mg/m 2 of aripiprazole perinatally and postnatally (from day 17 of gestation through day 21 postpartum), slight maternal toxicity and slightly prolonged gestation were seen at the highest dose. An increase in stillbirths and decreases in pup weight (persisting into adulthood) and survival were also seen at this dose. Lactation: Risk Summary: Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for ARISTADA INITIO and any potential adverse effects on the breastfed infant from ARISTADA INITIO or from the underlying maternal condition. Pediatric Use: Safety and effectiveness of ARISTADA INITIO in pediatric patients have not been established. Geriatric Use: Safety and effectiveness of ARISTADA INITIO in patients >65 years of age have not been evaluated. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ARISTADA INITIO is not approved for the treatment of patients with dementia-related psychosis. CYP2D6 Poor Metabolizers: Approximately 8% of Caucasians and 3-8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM). Avoid use of ARISTADA INITIO in these patients because dosage adjustments are not possible (it is only available in one strength in a single-dose pre-filled syringe). Hepatic and Renal Impairment: No dosage adjustment for ARISTADA INITIO is required based on a patient's hepatic function (mild to severe hepatic impairment, Child-Pugh score between 5 and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 mL/minute). Other Specific Populations: No dosage adjustment for ARISTADA INITIO is required on the basis of a patient's sex, race, or smoking status. OVERDOSAGE Human Experience: Common adverse reactions (reported in at least 5% of all overdose cases) reported with oral aripiprazole overdosage (alone or in combination with other substances) include vomiting, somnolence, and tremor. Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia. Management of Overdosage: In case of overdosage, call the Poison control center immediately at 1-800-222-1222. To report SUSPECTED ADVERSE REACTIONS, contact Alkermes, Inc. at 1-866-274-7823 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. PATIENT COUNSELING INFORMATION Physicians are advised to discuss the FDA-approved patient labeling (Medication Guide) with patients for whom they prescribe ARISTADA INITIO. This Brief Summary is based on ARISTADA INITIO Full Prescribing Information Rev June 2018. Manufactured and marketed by Alkermes, Inc., Waltham, MA 02451-1420. ALKERMES ® is a registered trademark of Alkermes, Inc. and ARISTADA ® and logo are registered trademarks of Alkermes Pharma Ireland Limited and ARISTADA INITIO™ is a trademark of Alkermes Pharma Ireland Limited, used by Alkermes, Inc. under license. ©2018 Alkermes, Inc. All rights reserved. ARI-003280-v1