Brexpiprazole
These highlights do not include all the information needed to use BREXPIPRAZOLE TABLETS safely and effectively. See full prescribing information for BREXPIPRAZOLE TABLETS. BREXPIPRAZOLE tablets, for oral use Initial U.S. Approval: 2015
993b584c-7fe6-4551-899f-39146c8508ac
HUMAN PRESCRIPTION DRUG LABEL
Dec 13, 2022
Ajanta Pharma USA Inc.
DUNS: 557554156
Products 6
Detailed information about drug products covered under this FDA approval, including NDC codes, dosage forms, ingredients, and administration routes.
Brexpiprazole
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
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INGREDIENTS (11)
Brexpiprazole
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
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INGREDIENTS (9)
Brexpiprazole
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (11)
Brexpiprazole
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (11)
Brexpiprazole
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (11)
Brexpiprazole
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (11)
Drug Labeling Information
RECENT MAJOR CHANGES SECTION
RECENT MAJOR CHANGES
Boxed Warning 12/2021
Warnings and Precautions (5.6) 12/2021
USE IN SPECIFIC POPULATIONS SECTION
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to brexpiprazole tablets during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research- programs/pregnancyregistry/.
Risk Summary
Adequate and well-controlled studies have not been conducted with brexpiprazole tablets in pregnant women to inform drug-associated risks. However, neonates whose mothers are exposed to antipsychotic drugs, like brexpiprazole tablets, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. In animal reproduction studies, no teratogenicity was observed with oral administration of brexpiprazole to pregnant rats and rabbits during organogenesis at doses up to 73 and 146 times, respectively, of maximum recommended human dose (MRHD) of 4 mg/day on a mg/m2 basis. However, when pregnant rats were administered brexpiprazole during the period of organogenesis through lactation, the number of perinatal deaths of pups was increased at 73 times the MRHD [see Data]. The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder, have been reported in neonates whose mothers were exposed to antipsychotic drugs during the third trimester of pregnancy. These symptoms have varied in severity. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Data
Animal Data
Pregnant rats were treated with oral doses of 3 mg/kg/day, 10 mg/kg/day, and 30 mg/kg/day (7.3, 24, and 73 times the MRHD on a mg/m2 basis) of brexpiprazole during the period of organogenesis. Brexpiprazole was not teratogenic and did not cause adverse developmental effects at doses up to 73 times the MRHD.
Pregnant rabbits were treated with oral doses of 10 mg/kg/day, 30 mg/kg/day, and 150 mg/kg/day (49, 146, and 730 times the MRHD) of brexpiprazole during the period of organogenesis. Brexpiprazole was not teratogenic and did not cause adverse developmental effects at doses up to 146 times the MRHD. Findings of decreased body weight, retarded ossification, and increased incidences of visceral and skeletal variations were observed in fetuses at 730 times the MRHD, a dose that induced maternal toxicity.
In a study in which pregnant rats were administered oral doses of 3 mg/kg/day, 10 mg/kg/day, and 30 mg/kg/day (7.3, 24, and 73 times the MRHD) during the period of organogenesis and through lactation, the number of live-born pups was decreased, and early postnatal deaths increased at a dose 73 times the MRHD. Impaired nursing by dams, and low birth weight and decreased body weight gain in pups were observed at 73 times, but not at 24 times, the MRHD.
8.2 Lactation
Risk Summary
Lactation studies have not been conducted to assess the presence of brexpiprazole in human milk, the effects of brexpiprazole on the breastfed infant, or the effects of brexpiprazole on milk production. Brexpiprazole is present in rat milk. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for brexpiprazole tablets and any potential adverse effects on the breastfed infant from brexpiprazole tablets or from the underlying maternal condition.
8.4 Pediatric Use
Major Depressive Disorder
Safety and effectiveness in pediatric patients with major depressive disorder
have not been established. Antidepressants increased the risk of suicidal
thoughts and behaviors in pediatric patients [see Boxed Warning, Warnings and Precautions (5.2)].
Pediatric use information is approved for Otsuka Pharmaceutical Company, Ltd.’s Rexulti® (brexpiprazole) tablets. However, due to Otsuka Pharmaceutical Company, LTD.’s marketing exclusivity rights, this drug product is not labeled with that information.
8.5 Geriatric Use
Clinical studies of the efficacy of brexpiprazole tablets did not include any patients aged 65 or older to determine whether 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, and cardiac function, concomitant diseases, and other drug therapy.
Based on the results of a safety, tolerability, and pharmacokinetics trial, the pharmacokinetics of once daily oral administration of brexpiprazole (up to 3 mg/day for 14 days) as an adjunct therapy in the treatment of elderly patients (70 to 85 years old, N=11) with MDD were comparable to those observed in adult patients with MDD.
Antipsychotic drugs increase the risk of death in elderly patients with dementia-related psychosis. Brexpiprazole tablets are not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning, Warnings and Precautions (5.1)].
8.6 CYP2D6 Poor Metabolizers
Dosage adjustment is recommended in known CYP2D6 poor metabolizers, because these patients have higher brexpiprazole concentrations than normal metabolizers of CYP2D6. Approximately 8% of Caucasians and 3% to 8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
Reduce the maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score greater than or equal to 7). Patients with moderate to severe hepatic impairment (Child-Pugh score greater than or equal to 7) generally had higher exposure to brexpiprazole than patients with normal hepatic function [see Clinical Pharmacology (12.3)]. Greater exposure may increase the risk of brexpiprazole tablets-associated adverse reactions [see Dosage and Administration (2.3)].
8.8 Renal Impairment
Reduce the maximum recommended dosage in patients with moderate, severe, or end-stage renal impairment (CrCl less than 60 mL/minute). Patients with impaired renal function (CrCl less than 60 mL/minute) had higher exposure to brexpiprazole than patients with normal renal function [see Clinical Pharmacology (12.3)]. Greater exposure may increase the risk of brexpiprazole tablets-associated adverse reactions [see Dosage and Administration (2.4)].
8.9 Other Specific Populations
No dosage adjustment for brexpiprazole tablets is required on the basis of a patient’s sex, race, or smoking status [see Clinical Pharmacology (12.3)].
Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure (8.1)
Pediatric use information is approved for Otsuka Pharmaceutical Company, Ltd.’s Rexulti® (brexpiprazole) tablets. However, due to Otsuka Pharmaceutical Company, Ltd.’s marketing exclusivity rights, this drug product is not labeled with that information.