| Active Ingredient | BREXPIPRAZOLE |
|---|
| Drug Name | FDA Application No. | Company | Dosage Form;Route | Strength | RLD Strength | Original Approval or Tentative Approval Date |
Exclusivity Expiration (NCE) |
Exclusivity Expiration (ODE) |
Chemical Type |
Review Classification |
Marketing Status |
TE Code |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| REXULTI | (NDA) 205422 | OTSUKA PHARM CO LTD | TABLET;ORAL | 0.25MG, 0.5MG, 1MG, 2MG, 3MG, 4MG | 4MG (RS) | July 10, 2015 | July 10, 2020 | - | 1 New molecular entity (NME) | P Priority review drug | Prescription | None |
| Parameters | Details |
|---|---|
| Structural Formula |
 |
| Chemical Name | 7-{4-[4-(1-Benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin2(1H)-one |
| CAS No | 913611-97-9 |
| Molecular Formula | C25H27N3O2S |
| Molecular Weight | 433.57 |
| Appearance | - |
| Solubility | - |
| Water Solubility | 0.00227 mg/mL (Predicted) |
| Polymorphism | - |
| pKa (Strongest Acidic) | 13.56 (Predicted) |
| pKa (Strongest Basic) | 8.4 (Predicted) |
| Log P | 5.38 (Predicted) |
| Identification | - |
| Degradation | - |
| Hygroscopic | - |
| Photostability study | - |
| Melting Point | - |
| BCS Class | - |
| Manufacture of API | - |
| Parameters | Details |
|---|---|
| Indications and Usage | Use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). Treatment of schizophrenia. |
| Dosage and Administration |
Adjunctive Treatment of Major Depressive Disorder: The recommended starting dosage for REXULTI as adjunctive treatment is 0.5 mg or 1 mg once daily, taken orally with or without food [see Clinical Pharmacology. 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. Treatment of Schizophrenia: The recommended starting dosage f o r REXULTI is 1 mg once daily on Days 1 to 4, taken orally with or without food [see Clinical Pharmacology. The recommended target REXULT I dosage is 2 mg to 4 mg once daily. 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 maximum recommended daily dosage is 4 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment. |
| Mechanism of action | The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. |
| Absorption | After single dose administration of REXULTI tablets, the peak plasma brexpiprazole concentrations occurred within 4 hours after administration; and the absolute oral bioavailability was 95%. Brexpiprazole steady-state concentrations were attained within 10-12 days of dosing. |
| Food Effect |
REXULTI can be administered with or without food. Administration of a 4 mg REXULTI tablet with a standard high fat meal did not significantly affect the Cmax or AUC of brexpiprazole. After single and multiple once daily dose administration, brexpiprazole exposure (Cmax and AUC) increased in proportion to the dose administered. In vitro studies of brexpiprazole did not indicate that brexpiprazole is a substrate of efflux transporters such as MDRI (P-gp) and BCRP. |
| Distribution |
The volume of distribution of brexpiprazole following intravenous administration is high (1.56±0.42 L/kg), indicating extravascular distribution. Brexpiprazole is highly protein bound in plasma (greater than 99%) to serum albumin and α1-acid glycoprotein, and its protein binding is not affected by renal or hepatic impairment. Based on results of in vitro studies, brexpiprazole protein binding is not affected by warfarin, diazepam, or digitoxin. |
| Metabolism |
Based on in vitro metabolism studies of brexpiprazole using recombinant human cytochrome P450 (CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4), the metabolism of brexpiprazole was shown to be mainly mediated by CYP3A4 and CYP2D6. In vivo brexpirazole is metabolized primarily by CYP3A4 and CYP2D6 enzymes. After single-and multiple-dose administrations, brexpiprazole and its major metabolite, DM-3411, were the predominant drug moieties in the systemic circulation. At steady-state, DM-3411 represented 23% to 48% of brexpiprazole exposure (AUC) in plasma. DM-3411 is considered not to contribute to the therapeutic effects of brexpiprazole. Based on in vitro data, brexpiprazole showed little to no inhibition of CYP450 isozymes. |
| Elimination | Following a single oral dose of [14C]-labeled brexpiprazole, approximately 25% and 46% of the administered radioactivity was recovered in the urine and feces, respectively. Less than 1% of unchanged brexpiprazole was excreted in the urine and approximately 14% of the oral dose was recovered unchanged in the feces. Apparent oral clearance of a brexpiprazole oral tablet after once daily administration is 19.8 (±11.4) mL/h/kg. After multiple once daily administration of REXULTI, the terminal elimination half-lives of brexpiprazole and its major metabolite, DM-3411, were 91 hours and 86 hours, respectively. |
| Peak plasma time (Tmax) | 4 hours |
| Half life | 91 hours (Brexipiprazole), 86 hours (Major metabolite, DM-3411) |
| Bioavailability | 95% |
| Age, gender | - |
| DMF | Status | Type | Submit Date | Holder |
|---|---|---|---|---|
| Not Available | ||||
| Parameters | Details | ||||||
|---|---|---|---|---|---|---|---|
| Strength | 0.25MG | 0.5MG | 1MG | 2MG | 3MG | 4MG | |
| Excipients used |
lactose monohydrate, corn starch, microcrystalline cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate, hypromellose, and talc Colorants include titanium dioxide, iron oxide red, iron oxide yellow and ferrosferric oxide. |
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| Composition of coating material | - | ||||||
| Composition of caspule shell | - | ||||||
| Pharmaceutical Development | - | ||||||
| Manufacture of the product | - | ||||||
| Tablet / Capsule Image |
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| Appearance | Light brown; Round; shallow convex; bevel-edged debossed with “BRX” and “0.25” oneside and plain on other side | Light orange Round; shallow convex; bevel-edged debossed with “BRX” and “0.5” oneside and plain on other side | Light yellow Round; shallow convex; bevel-edged debossed with “BRX” and “1” oneside and plain on other side | Light green Round; shallow convex; bevel-edged debossed with “BRX” and “2” oneside and plain on other side | Light purple Round; shallow convex; bevel-edged debossed with “BRX” and “3" oneside and plain on other side | White Round; shallow convex; bevel-edged debossed with “BRX” and “4” oneside and plain on other side | |
| Imprint code / Engraving / Debossment | debossed with “BRX” and “0.25” oneside and plain on other side | debossed with “BRX” and “0.5” oneside and plain on other side | debossed with “BRX” and “1” oneside and plain on other side | debossed with “BRX” and “2” oneside and plain on other side | debossed with “BRX” and “3" oneside and plain on other side | debossed with “BRX” and “4” oneside and plain on other side | |
| Score | no score | no score | no score | no score | no score | no score | |
| Color | LIGHT BROWN | LIGHT ORANGE | LIGHT YELLOW | LIGHT GREEN | LIGHT PURPLE | WHITE | |
| Shape | Round (shallow convex; bevel-edged) | Round (shallow convex; bevel-edged) | Round (shallow convex; bevel-edged) | Round (shallow convex; bevel-edged) | Round (shallow convex; bevel-edged) | Round (shallow convex; bevel-edged) | |
| Dimension | 6mm | 6mm | 6mm | 6mm | 6mm | 6mm | |
| Mfg by | Otsuka Pharmaceutical Co., Ltd (US) | ||||||
| Mfg for | - | ||||||
| Marketed by | Otsuka Pharmaceutical Co., Ltd & Lundbeck (US) | ||||||
| Distributed by | Otsuka Pharmaceutical Co., Ltd (US) | ||||||
| Application No. | Prod No | Patent No | Patent Expiration | Drug Substance Claim | Drug Product Claim | Patent Use Code | Delist Requested | Link |
|---|---|---|---|---|---|---|---|---|
| N205422 | 1 | 7888362 | February 23, 2027 | Y | - | - | - | Download |
| N205422 | 1 | 8618109 | April 12, 2026 | - | - | U - 543 | - | Download |
| N205422 | 1 | 8349840 | April 12, 2026 | - | DP | U-1529 | - | Download |
| USP Apparatus | Speed (RPMs) | Medium | Volume (mL) | Recommended Sampling Times (minutes) | Date Updated |
|---|---|---|---|---|---|
| II (Paddle) | 50 | 0.05 M Acetate buffer, pH 4.3 | 900 | 10, 15, 20, 30 and 45 | October 20, 2016 |
| Label | Link |
|---|---|
| FDA label | Download |
| FDA chemistry review | Download |
| FDA Pharmacology Review(s) | Download |
| FDA Clinical Pharmacology Biopharmaceutics Review(s) | Download |
| FDA BE Recommendation | |
| European Public Assessment Report |
| - |
| www.accessdata.fda.gov, www.drugbank.ca, www.ema.europa.eu, www.medicines.org.uk, dailymed.nlm.nih.gov |
