Rexulti
Brexpiprazole · Tablet · Oral
Uses
1 INDICATIONS AND USAGE REXULTI is indicated for: Adjunctive treatment to antidepressants for major depressive disorder (MDD) in adults Treatment of schizophrenia in adults and pediatric patients ages 13 years and older Treatment of agitation associated with dementia due to Alzheimer's disease Limitations of Use: REXULTI is not indicated as an as needed ("prn") treatment for agitation associated with dementia due to Alzheimer's disease [see Clinical Studies (14.3) ] . REXULTI is an atypical antipsychotic indicated for: Use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults ( 1 , 14.1 ) Treatment of schizophrenia in adults and pediatric patients ages 13 years and older ( 1 , 14.2 ) Treatment of agitation associated with dementia due to Alzheimer's disease ( 1 , 14.3 ) Limitations of Use : REXULTI is not indicated as an as needed ("prn") treatment for agitation associated with dementia due to Alzheimer's disease ( 1 )
Dosage and administration
Administer REXULTI orally once daily with or without food. ( 2 , 12.3 ) Indication Starting Dosage Recommended Target Dosage Maximum Dosage MDD Adults ( 2.2 ) 0.5 mg/day or 1 mg/day 2 mg/day 3 mg/day Schizophrenia Adults ( 2.3 ) 1 mg/day 2 to 4 mg/day 4 mg/day Schizophrenia Pediatric (13 - 17 years) ( 2.3 ) 0.5 mg/day 2 to 4 mg/day 4 mg/day Agitation associated with dementia due to Alzheimer's disease ( 2.4 ) 0.5 mg/day 2 mg/day 3 mg/day Moderate to Severe Hepatic Impairment: Maximum recommended dosage is 2 mg once daily for patients with MDD or agitation associated with dementia due to Alzheimer's disease and 3 mg once daily for patients with schizophrenia. ( 2.5 ) CrCl<60 mL/minute: Maximum recommended dosage is 2 mg once daily for patients with MDD or agitation associated with dementia due to Alzheimer's disease and 3 mg once daily for patients with schizophrenia. ( 2.6 ) See Full Prescribing Information for dosage modifications for CYP2D6 poor metabolizers and for concomitant use with CYP inhibitors or inducers. ( 2.7 ) 2.1 Administration Information Administer REXULTI orally, once daily with or without food [see Clinical Pharmacology (12.3) ]. 2.2 Recommended Dosage for Adjunctive Treatment of Major Depressive Disorder (Adults) The recommended starting REXULTI dosage for the adjunctive treatment of MDD in adults is 0.5 mg or 1 mg orally once daily . Titrate to 1 mg once daily, then titrate to the target dosage of 2 mg once daily (based on the patient's clinical response and tolerability, increase the dosage at weekly intervals). The maximum recommended daily dosage is 3 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment. 2.3 Recommended Dosage for Schizophrenia (Adults and Pediatric Patients 13 to 17 Years) Adults The recommended starting REXULTI dosage for the treatment of schizophrenia in adults is 1 mg orally once daily on Days 1 to 4. Titrate to 2 mg once daily on Day 5 through Day 7. On Day 8, the dosage can be increased to the maximum recommended daily dosage of 4 mg based on clinical response and tolerability. The recommended target dosage is 2 mg to 4 mg once daily. Pediatric Patients (13 to 17 years of age) The recommended starting REXULTI dosage for the treatment of schizophrenia in pediatric patients 13 to 17 years of age is 0.5 mg orally once daily on Days 1 to 4. On Days 5 through 7, titrate to 1 mg per day and on Day 8 titrate to 2 mg based on clinical response and tolerability. Weekly dose increases can be made in 1 mg increments. A recommended target dosage is 2 to 4 mg once daily. The maximum recommended daily dosage is 4 mg. 2.4 Recommended Dosage for Agitation Associated with Dementia Due to Alzheimer's Disease The recommended starting REXULTI dosage for the treatment of agitation associated with dementia due to Alzheimer's disease is 0.5 mg orally once daily on Days 1 to 7 . Increase the dosage on Days 8 through 14 to 1 mg once daily, and on Day 15 to 2 mg once daily. The recommended target dose is 2 mg once daily. The dosage can be increased to the maximum recommended daily dosage of 3 mg once daily after at least 14 days, based on clinical response and tolerability. 2.5 Recommended Dosage in Patients with Hepatic Impairment The maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score ≥7) is [see Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ]: 2 mg orally once daily in patients with MDD or agitation associated with dementia due to Alzheimer's disease, and 3 mg orally once daily in patients with schizophrenia 2.6 Recommended Dosage in Patients with Renal Impairment The maximum recommended dosage in patients with creatinine clearance CrCl<60 mL/minute is [see Use in Specific Populations (8.8) , Clinical Pharmacology (12.3) ]: 2 mg orally once daily in patients with MDD or agitation associated with dementia due to Alzheimer's disease and 3 mg orally once daily in patients with schizophrenia 2.7 Dosage Modifications for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP Inhibitors or Inducers Dosage modifications are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors, CYP2D6 inhibitors, or strong CYP3A4 inducers (see Table 1 ). If the concomitant drug is discontinued, adjust the REXULTI dosage to its original level. If the concomitant CYP3A4 inducer is discontinued, reduce the REXULTI dosage to the original level over 1 to 2 weeks [see Drug Interactions (7.1) , Clinical Pharmacology (12.3) ] . Table 1 Dosage Modifications of REXULTI for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP3A4 Inhibitors, CYP2D6 Inhibitors, or CYP3A4 Inducers Factors Adjusted REXULTI Dosage CYP2D6 Poor Metabolizers CYP2D6 poor metabolizers Administer half of the recommended dosage. Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors Administer a quarter of the recommended dosage. Patients Taking CYP2D6 Inhibitors and/or CYP3A4 Inhibitors Strong CYP2D6 inhibitors In the clinical studies examining the use of REXULTI for the adjunctive treatment of MDD, dosage was not adjusted for strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). Thus, CYP considerations are already factored into general dosing recommendations, and REXULTI may be administered without dosage adjustment in patients with MDD. Administer half of the recommended dosage. Strong CYP3A4 inhibitors Administer half of the recommended dosage. Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors Administer a quarter of the recommended dosage. Patients Taking CYP3A4 Inducers Strong CYP3A4 inducers Double the recommended dosage over 1 to 2 weeks. Dosage and Administration Advise patients that REXULTI can be taken with or without food. Advise patients regarding importance of following dosage escalation instructions [see Dosage and Administration (2) ] .
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS REXULTI tablets are available in 6 strengths: 0.25 mg tablets are light brown, round, shallow convex, bevel-edged body with "BRX" and "0.25" imprinted on one side. 0.5 mg tablets: are light orange, round, shallow convex, bevel-edged body with "BRX" and "0.5" imprinted on one side. 1 mg tablets are light yellow, round, shallow convex, bevel-edged body with "BRX" and "1" imprinted on one side. 2 mg tablets are light green, round, shallow convex, bevel-edged body with "BRX" and "2" imprinted on one side. 3 mg tablets are light purple, round, shallow convex, bevel-edged body with "BRX" and "3" imprinted on one side. 4 mg tablets are white, round, shallow convex, bevel-edged body with "BRX" and "4" imprinted on one side. Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg ( 3 )
Contraindications
4 CONTRAINDICATIONS REXULTI is contraindicated in patients with a known hypersensitivity to brexpiprazole or any of its components. Reactions have included rash, facial swelling, urticaria, and anaphylaxis. Known hypersensitivity to REXULTI or any of its components ( 4 )
Warnings and precautions
Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) ( 5.3 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. ( 5.4 ) Tardive Dyskinesia: Discontinue if clinically appropriate. ( 5.5 ) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. ( 5.6 ) Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation. ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing REXULTI if a clinically significant decline in WBC occurs in absence of other causative factors. ( 5.8 ) Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. ( 5.9 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. ( 5.11 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery. ( 5.14 ) 5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in the drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. REXULTI is not approved for the treatment of patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer's disease [see Boxed Warning , Warnings and Precautions (5.3) ] . 5.2 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in patients 24 years of age and younger was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 2 . No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide. Table 2 Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric REXULTI is not approved in pediatric patients with MDD. and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1,000 Patients Treated Increases Compared to Placebo <18 14 additional patients 18 to 24 5 additional patients Decreases Compared to Placebo 25 to 64 1 fewer patient ≥65 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance studies in adults with MDD that antidepressants delay the recurrence of depression. Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing REXULTI, in patients whose depression is persistently worse or who are experiencing emergent suicidal thoughts or behaviors. 5.3 Cerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials in elderly patients with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer's disease [see Boxed Warning , Warnings and Precautions (5.1) ]. 5.4 Neuroleptic Malignant Syndrome (NMS) Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with administration of antipsychotic drugs, including REXULTI. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue REXULTI and provide intensive symptomatic treatment and monitoring. 5.5 Tardive Dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. The risk appears to be highest among the elderly, especially elderly women, but it is impossible to predict which patients will develop the syndrome.
Side effects
The following adverse reactions are discussed in more detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning , Warnings and Precautions (5.1) ] Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Boxed Warning , Warnings and Precautions (5.2) ] Cerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.3) ] Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions (5.4) ] Tardive Dyskinesia [see Warnings and Precautions (5.5) ] Metabolic Changes [see Warnings and Precautions (5.6) ] Pathological Gambling and Other Compulsive Behaviors [see Warnings and Precautions (5.7) ] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.8) ] Orthostatic Hypotension and Syncope [see Warnings and Precautions (5.9) ] Falls [see Warnings and Precautions (5.10) ] Seizures [see Warnings and Precautions (5.11) ] Body Temperature Dysregulation [see Warnings and Precautions (5.12) ] Dysphagia [see Warnings and Precautions (5.13) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.14) ] Most common adverse reactions in adults were ( 6.1 ): Adult patients with major depressive disorder (adjunctive treatment to antidepressant therapy): Weight increased, somnolence, and akathisia (≥5% and at least twice the rate for placebo) Adult Patients with schizophrenia : Weight increased (≥4% and at least twice the rate for placebo) Pediatric patients (13 to 17 years) with schizophrenia : Extrapyramidal symptoms, excluding akathisia (≥5% and at least twice the rate for placebo) Adult patients with agitation associated with dementia due to Alzheimer's disease: Nasopharyngitis, dizziness (≥4% and at least twice the rate for placebo) To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most common adverse reactions in adult patients in clinical trials (≥5%) were weight increased, akathisia, headache, somnolence, and insomnia. The most common adverse reactions in pediatric patients in clinical trials (≥5%) were weight increased, somnolence, headache, akathisia, and nasopharyngitis. Brexpiprazole has been evaluated for safety in 12,550 adult patients who participated in multiple-dose clinical trials for major depressive disorder, schizophrenia, agitation associated with dementia due to Alzheimer's disease, attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), bipolar mania, and borderline personality disorder (BPD). Among them, 3,870 patients were treated with brexpiprazole for at least 180 days, and 1,910 patients were treated for at least one year of exposure. Additionally, brexpiprazole has been evaluated for safety in 119 pediatric patients who participated in short-term trials, and 314 patients in long-term multiple-dose clinical trials for pediatric schizophrenia and autism spectrum disorders (ASD). Adjunctive Treatment in Major Depressive Disorder (MDD) The safety of REXULTI was evaluated in 1054 adult patients (18 to 65 years of age) diagnosed with MDD who participated in two 6-week placebo-controlled, fixed-dose clinical studies in patients with major depressive disorder in which REXULTI was administered at doses of 1 mg to 3 mg daily as adjunctive treatment to continued antidepressant therapy; patients in the placebo group continued to receive antidepressant therapy [see Clinical Studies (14.1) ] . Adverse Reactions Reported as Reasons for Discontinuation of Treatment A total of 3% (17/643) of REXULTI-treated patients and 1% (3/411) of placebo-treated patients discontinued due to adverse reactions. Adverse Reactions in REXULTI Studies for Adjunctive MDD in Adults Adverse reactions associated with the adjunctive use of REXULTI (incidence of 2% or greater and adjunctive REXULTI incidence greater than adjunctive placebo) that occurred during acute therapy (up to 6-weeks in patients with MDD) are shown in Table 8. Table 8 Adverse Reactions in ≥2% of REXULTI-Treated Patients and Greater than Placebo in Pooled 6-Week Placebo-Controlled, Fixed-Dose Adjunctive MDD Studies in Adults (Study 1 and Study 2) Placebo (N=411) % REXULTI 1 mg/day (N=226) % 2 mg/day (N=188) % 3 mg/day (N=229) % All REXULTI (N=643) % Gastrointestinal Disorders Constipation 1 3 2 1 2 General Disorders and Administration Site Conditions Fatigue 2 3 2 5 3 Infections and Infestations Nasopharyngitis 2 7 1 3 4 Investigations Weight Increased 2 7 8 6 7 Blood Cortisol Decreased 1 4 0 3 2 Metabolism and Nutrition Increased Appetite 2 3 3 2 3 Nervous System Disorders Akathisia 2 4 7 14 9 Headache 6 9 4 6 7 Somnolence 0.5 4 4 6 5 Tremor 2 4 2 5 4 Dizziness 1 1 5 2 3 Psychiatric Disorders Anxiety 1 2 4 4 3 Restlessness 0 2 3 4 3 Dose-Related Adverse Reactions in the Adjunctive MDD Studies In Studies 1 and 2, among the adverse reactions that occurred at ≥2% incidence in the patients treated with REXULTI plus ADT, the incidences of akathisia and restlessness increased with increases in dose. Schizophrenia Adults The safety of REXULTI was evaluated in 852 adult patients (18 to 65 years of age) diagnosed with schizophrenia who participated in two 6-week placebo-controlled, fixed-dose clinical studies in which REXULTI was administered at daily doses of 1 mg, 2 mg, and 4 mg [see Clinical Studies (14.2) ].
Drug interactions
Factors Dosage Adjustments for REXULTI ( 2.7 ) Strong CYP2D6 REXULTI may be administered without dosage adjustment in patients with MDD when administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). or CYP3A4 inhibitors Administer half of recommended dosage. Strong/moderate CYP2D6 with Strong/moderate CYP3A4 inhibitors Administer a quarter of the recommended dosage. Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors Administer a quarter of the recommended dosage. Strong CYP3A4 inducers Double the recommended dosage and further adjust based on clinical response. 7.1 Drugs Having Clinically Important Interactions with REXULTI See Table 12 for clinically important drug interactions with REXULTI. Table 12 Clinically Important Drug Interactions with REXULTI Strong CYP3A4 Inhibitors Clinical Impact: Concomitant use of REXULTI with strong CYP3A4 inhibitors increased the exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3) ] . Intervention: With concomitant use of REXULTI with a strong CYP3A4 inhibitor, reduce the REXULTI dosage [see Dosage and Administration (2.7) ] . Strong CYP2D6 Inhibitors In the clinical studies examining the adjunctive use of REXULTI in the treatment of MDD, dosage was not adjusted for strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). Thus, CYP considerations are already factored into general dosing recommendations, and REXULTI may be administered without dosage adjustment in patients with MDD. Clinical Impact: Concomitant use of REXULTI with strong CYP2D6 inhibitors increased the exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3) ] . Intervention: With concomitant use of REXULTI with a strong CYP2D6 inhibitor, reduce the REXULTI dosage [see Dosage and Administration (2.7) ] . Both CYP3A4 Inhibitors and CYP2D6 Inhibitors Clinical Impact: Concomitant use of REXULTI with 1) a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 2) a moderate CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 3) a strong CYP3A4 inhibitor and a moderate CYP2D6 inhibitor; or 4) a moderate CYP3A4 inhibitor and a moderate CYP2D6 inhibitor increased the exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3) ]. Intervention: With concomitant use of REXULTI with 1) a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 2) a moderate CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 3) a strong CYP3A4 inhibitor and a moderate CYP2D6 inhibitor; or 4) a moderate CYP3A4 inhibitor and a moderate CYP2D6 inhibitor, decrease the REXULTI dosage [see Dosage and Administration (2.7) ]. Strong CYP3A4 Inducers Clinical Impact: Concomitant use of REXULTI and a strong CYP3A4 inducer decreased the exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3) ]. Intervention: With concomitant use of REXULTI with a strong CYP3A4 inducer, increase the REXULTI dosage [see Dosage and Administration (2.7) ]. 7.2 Drugs Having No Clinically Important Interactions with REXULTI Based on pharmacokinetic studies, no dosage adjustment of REXULTI is required when administered concomitantly with CYP2B6 inhibitors (e.g., ticlopidine) or gastric pH modifiers (e.g., omeprazole). Additionally, no dosage adjustment for substrates of CYP2D6 (e.g., dextromethorphan), CYP3A4 (e.g., lovastatin), CYP2B6 (e.g., bupropion), BCRP (e.g., rosuvastatin), or P-gp (e.g., fexofenadine) is required when administered concomitantly with REXULTI.
Use in specific populations
Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure ( 8.1 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to REXULTI during pregnancy. For more information contact the National Pregnancy Registry for Psychiatric Medications 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 REXULTI in pregnant women to inform drug-associated risks. However, neonates whose mothers are exposed to antipsychotic drugs, like REXULTI, 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/m 2 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, 10, and 30 mg/kg/day (7.3, 24, and 73 times the MRHD on a mg/m 2 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, 30, 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, 10, 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 REXULTI and any potential adverse effects on the breastfed infant from REXULTI or from the underlying maternal condition. 8.4 Pediatric Use Schizophrenia The safety and effectiveness of REXULTI for treatment of schizophrenia have been established in pediatric patients 13 years of age and older. Use of REXULTI in this population is supported by evidence from adequate and well-controlled studies in adults and pediatric patients with schizophrenia, pharmacokinetic data from adults and pediatric patients, and safety data in pediatric patients 13 to 17 years of age [see Warnings and Precautions (5.6) , Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.2) ] . The safety and effectiveness of REXULTI for the treatment of schizophrenia have not been established in pediatric patients less than 13 years of age. Major Depressive Disorder The safety and effectiveness of REXULTI for treatment of major depressive disorder have not been established in pediatric patients. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions (5.2) ] . Irritability Associated with Autism Spectrum Disorder The safety and effectiveness of REXULTI for the treatment of irritability associated with autism spectrum disorder have not been established in pediatric patients. Effectiveness was not demonstrated, in an 8-week, double-blind, placebo-controlled, flexible-dose clinical study conducted in 119 REXULTI-treated pediatric patients 5 to 17 years of age with irritability associated with autism spectrum disorder diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition [DSM-5] criteria. In this study, somnolence (including sedation) occurred at a higher rate than reported in other REXULTI studies evaluating adults and elderly patients (16% in REXULTI-treated pediatric patients versus 5% for placebo). The mean increase in age-and-gender adjusted body weight z-score from baseline to last visit was 0.3 for REXULTI-treated patients versus 0.1 for placebo-treated patients.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to REXULTI during pregnancy. For more information contact the National Pregnancy Registry for Psychiatric Medications 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 REXULTI in pregnant women to inform drug-associated risks. However, neonates whose mothers are exposed to antipsychotic drugs, like REXULTI, 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/m 2 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, 10, and 30 mg/kg/day (7.3, 24, and 73 times the MRHD on a mg/m 2 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, 30, 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, 10, 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.
Pediatric use
8.4 Pediatric Use Schizophrenia The safety and effectiveness of REXULTI for treatment of schizophrenia have been established in pediatric patients 13 years of age and older. Use of REXULTI in this population is supported by evidence from adequate and well-controlled studies in adults and pediatric patients with schizophrenia, pharmacokinetic data from adults and pediatric patients, and safety data in pediatric patients 13 to 17 years of age [see Warnings and Precautions (5.6) , Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.2) ] . The safety and effectiveness of REXULTI for the treatment of schizophrenia have not been established in pediatric patients less than 13 years of age. Major Depressive Disorder The safety and effectiveness of REXULTI for treatment of major depressive disorder have not been established in pediatric patients. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions (5.2) ] . Irritability Associated with Autism Spectrum Disorder The safety and effectiveness of REXULTI for the treatment of irritability associated with autism spectrum disorder have not been established in pediatric patients. Effectiveness was not demonstrated, in an 8-week, double-blind, placebo-controlled, flexible-dose clinical study conducted in 119 REXULTI-treated pediatric patients 5 to 17 years of age with irritability associated with autism spectrum disorder diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition [DSM-5] criteria. In this study, somnolence (including sedation) occurred at a higher rate than reported in other REXULTI studies evaluating adults and elderly patients (16% in REXULTI-treated pediatric patients versus 5% for placebo). The mean increase in age-and-gender adjusted body weight z-score from baseline to last visit was 0.3 for REXULTI-treated patients versus 0.1 for placebo-treated patients. Increases in age-and-gender adjusted body weight z-score of at least 0.5 SD from baseline was higher in REXULTI-treated patients versus placebo (19% versus 5%). Of the 119 patients from this study, 95 patients entered the open-label treatment study and received up to 26 weeks of daily treatment with brexpiprazole. During the open-label treatment period, 2% of patients discontinued due to weight increase. In patients previously treated with REXULTI for 8 weeks, the mean increase in weight from the open-label study baseline to last visit was 4.5 kg and 26% of patients had an increase in age-and-gender-adjusted body weight z-score of at least 0.5 SD from baseline. Juvenile Animal Studies Juvenile rats were administered oral doses of brexpiprazole of 3, 10, and 20 mg/kg/day once daily beginning from weaning (postnatal day 21) through adulthood (postnatal day 90), followed by a 4-week recovery (non-dosing) period. Results were similar to those observed in previous repeat‑dose toxicity studies in adolescent (8-week-old) rats. Mortality occurred at the high dose of 20 mg/kg/day, as well as delayed sexual maturation in males and decreased rearing and motor activity. There was no evidence of neurotoxicity or effects on fertility and reproductive function. Histopathologic changes in reproductive organs and mammary glands occurred at all doses, were related to the pharmacology of brexpiprazole and were comparable to those in adult rats. All findings were at least partially reversible. Juvenile dogs were administered oral doses of brexpiprazole of 1, 3, and 30 mg/kg/day once daily starting at 8 or 9 weeks of age for 26 weeks, followed by an 8-week recovery (non-dosing) period. Decreases in body weight, lethargy, changes in heart rate, and immature male sex organs were observed at 30 mg/kg/day. These findings were at least partially reversible.
Geriatric use
8.5 Geriatric Use Antipsychotic drugs increase the risk of death in elderly patients with dementia-related psychosis. REXULTI is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions (5.1) ] . Adjunctive Treatment of Major Depressive Disorder (MDD) and Schizophrenia Of the total number of REXULTI-treated patients in the clinical studies for the adjunctive therapy to antidepressants for MDD and for schizophrenia, 248 (3%) were 65 years of age and older (which included 45 (18%) patients who were 75 years of age and older). Clinical studies of REXULTI in these patients did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients. In general, dosage selection for the treatment of MDD or schizophrenia in a geriatric 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. Agitation Associated with Dementia Due to Alzheimer's Disease The total number of REXULTI-treated patients 65 years of age and older in the clinical studies for agitation associated with dementia due to Alzheimer's disease (Studies 6 and 7) was 448 (86%) including 170 (33%) patients 65 to 74 years of age, 228 (44%) patients 75 to 84 years of age, and 50 (10%) patients 85 years of age and older [see Clinical Studies (14.3) ] . In clinical studies of REXULTI for the treatment of agitation associated with dementia due to Alzheimer's disease did not include sufficient numbers of younger adult patients to determine if patients 65 years of age and older respond differently than younger adult patients.
Overdosage
There is limited clinical trial experience regarding human overdosage with REXULTI. Management of a REXULTI overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers. Consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Oral activated charcoal and sorbitol (50 g/240 mL), administered one hour after ingesting oral REXULTI, decreased brexpiprazole C max and area under the curve (AUC) by approximately 5% to 23% and 31% to 39% respectively; however, there is insufficient information available on the therapeutic potential of activated charcoal in treating an overdose with REXULTI. There is no information on the effect of hemodialysis in treating an overdose with REXULTI; hemodialysis is unlikely to be useful because brexpiprazole is highly bound to plasma proteins.
Description
Brexpiprazole, an atypical antipsychotic, is available as REXULTI ® (brexpiprazole) tablets. Brexpiprazole is 7-{4-[4-(1-Benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1 H )-one. The empirical formula is C 25 H 27 N 3 O 2 S, and its molecular weight is 433.57. The chemical structure is: REXULTI tablets are for oral administration and are available in 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg strengths. Inactive ingredients include lactose monohydrate, corn starch, microcrystalline cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate, hypromellose, and talc. Colorants include titanium dioxide, iron oxide, and ferrosoferric oxide. Chemical Structure
How supplied
How Supplied REXULTI (brexpiprazole) tablets have markings on one side and are available in the following strengths and package configurations (see below): 0.25 mg tablets are light brown, round, shallow convex, bevel-edged body with "BRX" and "0.25" imprinted on one side NDC 59148-035-13 Bottles of 30 0.5 mg tablets: are light orange, round, shallow convex, bevel-edged body with "BRX" and "0.5" imprinted on one side NDC 59148-036-13 Bottles of 30 1 mg tablets are light yellow, round, shallow convex, bevel-edged body with "BRX" and "1" imprinted on one side NDC 59148-037-13 Bottles of 30 2 mg tablets are light green, round, shallow convex, bevel-edged body with "BRX" and "2" imprinted on one side NDC 59148-038-13 Bottles of 30 3 mg tablets are light purple, round, shallow convex, bevel-edged body with "BRX" and "3" imprinted on one side NDC 59148-039-13 Bottles of 30 4 mg tablets are white, round, shallow convex, bevel-edged body with "BRX" and "4" imprinted on one side NDC 59148-040-13 Bottles of 30 Storage and Handling Store REXULTI tablets at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Storage
Storage and Handling Store REXULTI tablets at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [see Boxed Warning , Warnings and Precautions (5.2) ] . Dosage and Administration Advise patients that REXULTI can be taken with or without food. Advise patients regarding importance of following dosage escalation instructions [see Dosage and Administration (2) ] . Neuroleptic Malignant Syndrome (NMS) Counsel patients about a potentially fatal adverse reaction, Neuroleptic Malignant Syndrome (NMS), that has been reported in association with administration of antipsychotic drugs. Advise patients to contact a healthcare provider or report to the emergency room if they experience signs or symptoms of NMS [see Warnings and Precautions (5.4) ]. Tardive Dyskinesia Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their healthcare provider if these abnormal movements occur [see Warnings and Precautions (5.5) ]. Metabolic Changes Educate patients about the risk of metabolic changes, how to recognize symptoms of hyperglycemia and diabetes mellitus, and the need for specific monitoring, including blood glucose, lipids, and weight [see Warnings and Precautions (5.6) ]. Pathological Gambling and Other Compulsive Behaviors Advise patients and their caregivers of the possibility that they may experience compulsive urges to shop, intense urges to gamble, compulsive sexual urges, binge eating and/or other compulsive urges and the inability to control these urges while taking REXULTI. In some cases, but not all, the urges were reported to have stopped when the dose was reduced or stopped [see Warnings and Precautions (5.7) ]. Leukopenia, Neutropenia and Agranulocytosis Advise patients with a pre-existing low WBC or a history of drug-induced leukopenia/neutropenia that they should have their CBC monitored while taking REXULTI [see Warnings and Precautions (5.8) ]. Orthostatic Hypotension and Syncope Educate patients about the risk of orthostatic hypotension and syncope, especially early in treatment, and also at times of reinitiating treatment or increases in dosage [see Warnings and Precautions (5.9) ]. Heat Exposure and Dehydration Counsel patients regarding appropriate care in avoiding overheating and dehydration [see Warnings and Precautions (5.12) ]. Potential for Cognitive and Motor Impairment Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that REXULTI therapy does not adversely affect their ability to engage in such activities [see Warnings and Precautions (5.14) ] . Concomitant Medications Advise patients to inform their healthcare providers of any changes to their current prescription or over-the-counter medications because there is a potential for clinically significant interactions [see Drug Interactions (7.1) ] . Pregnancy Advise patients that third trimester use of REXULTI may cause extrapyramidal and/or withdrawal symptoms in a neonate and to notify their healthcare provider with a known or suspected pregnancy. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to REXULTI during pregnancy [see Use in Specific Populations (8.1) ] .
Label text from the FDA structured product label by Otsuka America Pharmaceutical, Inc. (revised May 6, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Brexpiprazole in 8 products
Rexulti NDC products (10)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 59148-035 | Brexpiprazole .25 mg/1 Tablet | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-036 | Brexpiprazole .5 mg/1 Tablet | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-037 | Brexpiprazole 1 mg/1 Tablet | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-038 | Brexpiprazole 2 mg/1 Tablet | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-039 | Brexpiprazole 3 mg/1 Tablet | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-040 | Brexpiprazole 4 mg/1 Tablet | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-042 | Kit | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-044 | Kit | Otsuka America Pharmaceutical, Inc. | NDA |
| 70518-3548 | Brexpiprazole 2 mg/1 Tablet | REMEDYREPACK INC. | NDA |
| 70518-4608 | Brexpiprazole 1 mg/1 Tablet | REMEDYREPACK INC. | NDA |
Frequently asked questions
What is Rexulti used for?
1 INDICATIONS AND USAGE REXULTI is indicated for: Adjunctive treatment to antidepressants for major depressive disorder (MDD) in adults Treatment of schizophrenia in adults and pediatric patients ages 13 years and older Treatment of agitation associated with dementia due to Alzheimer's disease Limitations of Use: REXULTI is not indicated as an as needed ("prn") treatment for agitation associated…
What are the side effects of Rexulti?
The following adverse reactions are discussed in more detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning , Warnings and Precautions (5.1) ] Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Boxed Warning , Warnings and Precautions (5.2) ] Cerebrovascular Adverse Reactions Including Stroke in… See the full label for the complete list.
Who makes Rexulti?
Rexulti is listed by 2 labelers in the FDA NDC directory, including Otsuka America Pharmaceutical, Inc., REMEDYREPACK INC..