Introduction
Brexpa Tablet 1 mg is a novel D2 dopamine and serotonin 1A partial agonist, called serotonin-dopamine activity modulator (SDAM), and a potent antagonist of serotonin 2A receptors, noradrenergic alpha 1B and 2C receptors. Brexpa Tablet 1 mg is approved for the treatment of schizophrenia, and as an adjunctive treatment for major depressive disorder (MDD). Although it failed Phase II clinical trials for ADHD, it has been designed to provide improved efficacy and tolerability (e.g., less akathisia, restlessness and/or insomnia) over established adjunctive treatments for major depressive disorder (MDD).
Uses
Brexpa Tablet 1 mg is a serotonin–dopamine activity modulator used in the treatment of major depressive disorder as an adjunct and schizophrenia.
As an adjunctive treatment of major depressive disorder (MDD) and for treatment of schizophrenia.
Associated Conditions
Mechanism of Action
Although the mechanism of action of brexpiprazole in the treatment of MDD and schizophrenia is unclear, the efficacy of brexpiprazole may be attributed to partial agonist activity at serotonin 1A and dopamine D2 receptors, and antagonist activity at serotonin 2A receptors.
Absorption
Brexpa Tablet 1 mg reaches peak plasma concentration within 4 hours of administration, and steady state occurs within 10-12 days of dosing. Oral bioavailability is 95%, and can be administered with or without food.
Volume of Distribution
Intravenous volume of distribution is 1.56L/kg.
Protein Binding
>99% protein bound in plasma to serum albumin and α1-acid glycoprotein. Based on in vitro studies, protein binding is not affected by warfarin, diazepam, or digitoxin.
Route of Elimination
Approximately 25% urinary and 46% fecal excretion. <1% and ~14% of the unchanged drug was recovered in the urine and feces, respectively.
Half Life
Brexpa Tablet 1 mg and its major metabolite, DM-3411 have half lives of 91 and 96 hours respectively.
Clearance
19.8mL/h/kg
Toxicity
The most commonly observed adverse effects include: weight increase, akathisia, somnolence, tremor and nasopharyngitis. Neonates are at risk for extrapyramidal and/or withdrawal symptoms if exposed to an antipsychotic drug during the third trimester of development.
Food Interactions
- Avoid St. John's Wort. This herb induces the CYP3A metabolism of brexpiprazole and may reduce its serum concentration. The dose of Brexpa Tablet 1 mg should be doubled if administered with St. John's wort.
- Drink plenty of fluids.
- Take with or without food.
Dosage
Treatment of Schizophrenia: The recommended starting dosage for Brexpa Tablet 1 mg is 1 mg once daily on Days 1 to 4, taken orally with or without food. The recommended target Brexpa Tablet 1 mg 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.
