b'T:7.875"S:7"USE IN SPECIFIC POPULATIONS CYP2D6 Poor Metabolizers: Approximately 8% of Caucasians and 3-8% of Black/34 Pregnancy African Americans cannot metabolize CYP2D6 substrates and are classified as poor Pregnancy Exposure Registry: There is a pregnancy exposure registry thatmetabolizers (PM). Avoid use of ARISTADA INITIO in these patients because dosage monitors pregnancy outcomes in women exposed to ARISTADA INITIO duringadjustments are not possible (it is only available in one strength in a single-dose pregnancy. For more information, contact the National Pregnancy Registry for pre-filled syringe).Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/ Hepatic and Renal Impairment: No dosage adjustment for ARISTADA INITIO is clinical-and-research-programs/pregnancyregistry/. required based on a patients hepatic function (mild to severe hepatic impairment, Risk Summary: Neonates exposed to antipsychotic drugs during the third trimesterChild-Pugh score between 5 and 15), or renal function (mild to severe renal of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms followingimpairment, glomerular filtration rate between 15 and 90 mL/minute).delivery. Limited published data on aripiprazole use in pregnant women are notOther Specific Populations: No dosage adjustment for ARISTADA INITIO is required sufficient to inform any drug-associated risks for birth defects or miscarriage. on the basis of a patients sex, race, or smoking status.No teratogenicity was observed in animal reproductive studies with intramuscularOVERDOSAGEadministration of aripiprazole lauroxil to rats and rabbits during organogenesis atHuman Experience: Common adverse reactions (reported in at least 5% of all doses up to 8 and 23 times, respectively, the maximum recommended human dose (MRHD) of 675 mg based on body surface area (mg/m2). However, aripiprazoleoverdose cases) reported with oral aripiprazole overdosage (alone or in combination caused developmental toxicity and possible teratogenic effects in rats and rabbits.with other substances) include vomiting, somnolence, and tremor. Other clinically The background risk of major birth defects and miscarriage for the indicatedimportant signs and symptoms observed in one or more patients with aripiprazole population are unknown. In the U.S. general population, the estimated backgroundoverdoses (alone or with other substances) include acidosis, aggression, aspartate risk of major birth defects and miscarriage in clinically recognized pregnancies isaminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, 2-4% and 15-20%, respectively. Advise pregnant women of the potential risk to convulsion, blood creatine phosphokinase increased, depressed level of a fetus.consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, Clinical Considerations: Fetal/Neonatal Adverse Reactions: Extrapyramidal and/orrespiratory arrest, status epilepticus, and tachycardia.withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor,Management of Overdosage: In case of overdosage, call the Poison control center somnolence, respiratory distress and feeding disorder have been reported inimmediately at 1-800-222-1222. neonates who were exposed to antipsychotic drugs during the third trimester ofTo report SUSPECTED ADVERSE REACTIONS, contact Alkermes, Inc. atpregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.1-866-274-7823 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.Some neonates recover within hours or days without specific treatment; othersPATIENT COUNSELING INFORMATIONrequired prolonged hospitalization. Physicians are advised to discuss the FDA-approved patient labeling (Medication Data: Animal Data for ARISTADA (Aripiprazole Lauroxil): Aripiprazole lauroxil did notGuide) with patients for whom they prescribe ARISTADA INITIO.cause adverse developmental or maternal effects in rats or rabbits when administered intramuscularly during the period of organogenesis at doses of 18, 49,This Brief Summary is based on ARISTADA INITIO Full Prescribing Informationor 144 mg/animal in pregnant rats which are approximately 1 to 8 times the MRHD 2 RevMarch2021. of 675 mg based on mg/m , and at doses of 241, 723, and 2893 mg/animal in pregnant rabbits which are approximately 2 to 23 times the MRHD based on mg/m2.Manufactured and marketed by Alkermes, Inc., Waltham, MA 02451-1420.However, aripiprazole caused developmental toxicity and possible teratogenic effects in rats and rabbits [see Data below].ALKERMES is a registered trademark of Alkermes, Inc. ARISTADA and logo, and Animal Data for Aripiprazole: Pregnant rats were treated with oral doses of 3, 10, and ARISTADA INITIO, are registered trademarks of Alkermes Pharma Ireland Limited, 30 mg/kg/day which are approximately 1 to 10 times the oral MRHD of 30 mg/dayused by Alkermes, Inc., under license.based on mg/m2 of aripiprazole during the period of organogenesis. Treatment at the highest dose caused a slight prolongation of gestation and delay in fetal2021 Alkermes, Inc. All rights reserved. ARI-004456- v2development, as evidenced by decreased fetal weight, and undescended testes.S:10" T:10.75"Delayed skeletal ossification was observed at 3 and 10 times the oral MRHD based on mg/m2. At 3 and 10 times the oral MRHD based on mg/m2, 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/m2 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 are2 to 11 times human exposure at the oral MRHD based on AUC and 6 to 65 times the oral MRHD based on mg/m2 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/m2 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 mothers 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.'