Brexpiprazole

Brexpiprazole is an FDA-registered drug product whose active ingredient is BREXPIPRAZOLE. It is labelled by Ajanta Pharma USA Inc. taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 27241-204, application ANDA213718, label effective 20221213. It is one of 3 FDA drug label records sharing the active ingredient BREXPIPRAZOLE. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing BREXPIPRAZOLE are most often described in connection with: brexpiprazole tablets, treatment major, depressive disorder, mdd adults, atypical antipsychotic, adjunctive therapy. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE Brexpiprazole tablets are indicated for: Adjunctive treatment of major depressive disorder (MDD) in adults. Treatment of schizophrenia in adults. Brexpiprazole tablets 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

2 DOSAGE AND ADMINISTRATION Administer brexpiprazole tablets once daily with or without food. ( 2.1 , 2.2 , 12.3 ) Indication Starting Dose Recommended Dose Maximum Dose MDD Adults ( 2.1 ) 0.5 mg/day or 1 mg/day 2 mg/day 3 mg/day Schizophrenia Adults ( 2.2 ) 1 mg/day 2 to 4 mg/day 4 mg/day Moderate to Severe Hepatic Impairment (Child-Pugh score greater than or equal to 7): Maximum recommended dosage is 2 mg once daily for patients with MDD and 3 mg once daily for patients with schizophrenia. ( 2.3 ) Moderate, Severe or End-Stage Renal Impairment (CrCl less than 60 mL/minute): Maximum recommended dosage is 2 mg once daily for patients with MDD and 3 mg once daily for patients with schizophrenia. ( 2.4 ) Known CYP2D6 Poor Metabolizers: Reduce the usual dosage by half. ( 2.5 ) 2.1 Adjunctive Treatment of Major Depressive Disorder (Adults) The recommended starting dosage for brexpiprazole tablets as adjunctive treatment of MDD in adults is 0.5 mg or 1 mg once daily, taken orally with or without food [see Clinical Pharmacology ( 12.3 )]. Titrate to 1 mg once daily, then up to the target dosage of 2 mg once daily. Dosage increases should occur at weekly intervals based on the patient’s clinical response and tolerability. The maximum recommended daily dosage is 3 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment. 2.2 Treatment of Schizophrenia (Adults) Adults The recommended starting dosage for brexpiprazole tablets for the treatment of schizophrenia in adults is 1 mg once daily on Days 1 to 4, taken orally with or without food [see Clinical Pharmacology ( 12.3 )]. Titrate to 2 mg once daily on Day 5 through Day 7, then to 4 mg on Day 8 based on the patient’s clinical response and tolerability. The recommended target brexpiprazole tablets dosage is 2 mg to 4 mg once daily. The maximum recommended daily dosage is 4 mg. 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. 2.3 Dosage Adjustments for Hepatic Impairment For patients with moderate to severe hepatic impairment (Child-Pugh score greater than or equal to 7), the maximum recommended dosage is 2 mg once daily for patients with MDD, and 3 mg once daily for patients with schizophrenia [see Use in Specific Populations ( 8.7 ), Clinical Pharmacology ( 12.3 )]. 2.4 Dosage Adjustments for Renal Impairment For patients with moderate, severe, or end-stage renal impairment (creatinine clearance CrCl less than 60 mL/minute), the maximum recommended dosage is 2 mg once daily for patients with MDD and 3 mg once daily for patients with schizophrenia [see Use in Specific Populations ( 8.8 ), Clinical Pharmacology ( 12.3 )]. 2.5 Dosage Modifications for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP Inhibitors or Inducers Dosage adjustments are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers (see Table 1). If the coadministered drug is discontinued, adjust the brexpiprazole tablets dosage to its original level. If the coadministered CYP3A4 inducer is discontinued, reduce the brexpiprazole tablets dosage to the original level over 1 to 2 weeks [see Drug Interactions ( 7.1 ),Clinical Pharmacology ( 12.3 )]. Table 1: Dosage Adjustments of Brexpiprazole Tablets for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP3A4 and CYP2D6 Inhibitors and/or CYP3A4 Inducers *In the clinical trials examining the adjunctive use of brexpiprazole tablets 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 brexpiprazole tablets may be administered without dosage adjustment in patients with MDD. Factors Adjusted Brexpiprazole Tablets Dosage CYP2D6 Poor Metabolizers CYP2D6 poor metabolizers Administer half of the usual dose. Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors Administer a quarter of the usual dose. Patients Taking CYP2D6 Inhibitors and/or CYP3A4 Inhibitors Strong CYP2D6 inhibitors* Administer half of the usual dose. Strong CYP3A4 inhibitors Administer half of the usual dose. Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors Administer a quarter of the usual dose. Patients Taking CYP3A4 Inducers Strong CYP3A4 inducers Double usual dose over 1 to 2 weeks.

4 CONTRAINDICATIONS Brexpiprazole tablets are 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 brexpiprazole tablets or any of its components ( 4 )

6 ADVERSE REACTIONS 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 ): MDD: Weight increased and akathisia (greater than or equal to 5% and at least twice the rate for placebo) Schizophrenia: Weight increased (greater than or equal to 4% and at least twice the rate for placebo) To report SUSPECTED ADVERSE REACTIONS, contact Ajanta Pharma USA Inc. at 1-855-664-7744 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial 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. Major Depressive Disorder The safety of brexpiprazole tablets 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 trials in patients with major depressive disorder in which brexpiprazole tablets 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 brexpiprazole tablets-treated patients and 1% (3/411) of placebo-treated patients discontinued due to adverse reactions. Common Adverse Reactions Adverse reactions associated with the adjunctive use of brexpiprazole tablets (incidence of 2% or greater and adjunctive brexpiprazole tablets incidence greater than adjunctive placebo) that occurred during acute therapy (up to 6-weeks in patients with MDD) are shown in Table 7. Table 7: Adverse Reactions in Pooled 6-Week Placebo-Controlled, Fixed-Dose MDD Trials in Adults (Studies 1 and 2)* Placebo (N=411) Brexpiprazole Tablets 1 mg/day (N=226) 2 mg/day (N=188) 3 mg/day (N=229) All Brexpiprazole Tablets (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% * Adverse reactions that occurred in greater than or equal to 2% of brexpiprazole tablets-treated patients and greater incidence than in placebo-treated patients Dose-Related Adverse Reactions in the MDD Trials In Studies 1 and 2, among the adverse reactions that occurred at greater than or equal to 2% incidence in the patients treated with brexpiprazole tablets plus ADT, the incidences of akathisia and restlessness increased with increases in dose. Schizophrenia Adults The safety of brexpiprazole tablets 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 trials in which brexpiprazole tablets was administered at daily doses of 1 mg, 2 mg and 4 mg [see Clinical Studies ( 14.2)]. Common Adverse Reactions Adverse reactions associated with brexpiprazole tablets (incidence of 2% or greater and brexpiprazole tablets incidence greater than placebo) during short-term (up to 6 weeks) trials in adult patients with schizophrenia are shown in Table 8. Table 8: Adverse Reactions in Pooled 6-Week Placebo-Controlled, Fixed-Dose Schizophrenia Trials in Adult Patients (Studies 3 and 4)* Placebo (N=368) Brexpiprazole Tablets 1 mg/day (N=120) 2 mg/day (N=368) 4 mg/day (N=364) ALL Brexpiprazole Tablets (N=852) Gastrointestinal Disorders Dyspepsia 2% 6% 2% 3% 3% Diarrhea 2% 1% 3% 3% 3% Investigations Weight Increased 2% 3% 4% 4% 4% Blood Creatinine Phosphokinase Increased 1% 4% 2% 2% 2% Nervous System Disorders Akathisia 5% 4% 5% 7% 6% Tremor 1% 2% 2% 3% 3% Sedation 1% 2% 2% 3% 2% * Adverse reactions that occurred in greater than or equal to 2% of brexpiprazole tablets-treated patients and greater incidence than in placebo-treated patients Extrapyramidal Symptoms Major Depressive Disorder The incidence of reported extrapyramidal symptoms (EPS)-related adverse reactions, excluding akathisia, was 6% for brexpiprazole tablets plus ADT-treated patients versus 3% for placebo plus ADT-treated patients. The incidence of akathisia events for brexpiprazole tablets plus ADT-treated patients was 9% versus 2% for placebo plus ADT-treated patients. In the 6-week placebo-controlled MDD studies, data was objectively collected on the Simpson-Angus Rating Scale (SAS) for EPS, the Barnes Akathisia Rating Scale (BARS) for akathisia and the Abnormal Involuntary Movement Score (AIMS) for dyskinesia. The mean change from baseline at last visit for brexpiprazole tablets plus ADT-treated patients for the SAS, BARS and AIMS was comparable to placebo-treated patients. The percentage of patients who shifted from normal to abnormal was greater in brexpiprazole tablets plus ADT-treated patients versus placebo plus ADT-treated patients for the BARS (4% versus 0.6%) and the SAS (4% versus 3%). Schizophrenia The incidence of reported EPS-related adverse reactions, excluding akathisia, was 5% for brexpiprazole tablets-treated patients versus 4% for placebo-treated patients. The incidence of akathisia events for brexpiprazole tablets-treated patients was 6% versus 5% for placebo-treated patients. In the 6-week placebo-controlled, fixed-dose schizophrenia studies in adults, data was objectively collected on the Simpson-Angus Rating Scale (SAS) for EPS, the Barnes Akathisia Rating Scale (BARS) for akathisia and the Abnormal Involuntary Movement Scale (AIMS) for dyskinesia. The mean change from baseline at last visit for brexpiprazole tablets-treated patients for the SAS, BARS and AIMS was comparable to placebo-treated patients. The percentage of patients who shifted from normal to abnormal was greater in brexpiprazole tablets-treated patients versus placebo for the BARS (2% versus 1%) and the SAS (7% versus 5%). Dystonia Symptoms of dystonia may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first-generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups. Other Adverse Reactions Observed during the Premarketing Evaluation of Brexpiprazole Tablets Other adverse reactions (greater than or equal to 1% frequency and greater than placebo) within the short-term, placebo-controlled trials in adult patients with MDD and schizophrenia are shown below. The following listing does not include adverse reactions: 1) already listed in previous tables or elsewhere in the labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have clinically significant implications, or 5) which occurred at a rate equal to or less than placebo. Eye Disorders: Vision Blurred Gastrointestinal Disorders: Nausea, Dry Mouth, Salivary Hypersecretion, Abdominal Pain, Flatulence Infections and Infestations: Urinary Tract Infection Investigations: Blood Prolactin Increased Musculoskeletal and Connective Tissue Disorders: Myalgia Psychiatric Disorders: Abnormal Dreams, Insomnia Skin and Subcutaneous Tissue Disorders: Hyperhidrosis 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. 6.2 Postmarketing Experience The following adverse reaction has been identified during post-approval use of brexpiprazole tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Nervous System disorders: Neuroleptic Malignant Syndrome

FDA lists 3 drug label records with BREXPIPRAZOLE as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

What is Brexpiprazole used for?
1 INDICATIONS AND USAGE Brexpiprazole tablets are indicated for: Adjunctive treatment of major depressive disorder (MDD) in adults. Treatment of schizophrenia in adults. Brexpiprazole tablets 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

Who makes Brexpiprazole?
Ajanta Pharma USA Inc. is the labeler of record for Brexpiprazole. 3 FDA label records share the active ingredient BREXPIPRAZOLE, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does Brexpiprazole come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Brexpiprazole prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing BREXPIPRAZOLE?
Yes. 3 FDA drug label records list BREXPIPRAZOLE as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has Brexpiprazole been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.