Generic
Brexpiprazole
4 brands available in the market
At a glance
Brexpiprazole is an atypical antipsychotic used for the treatment of schizophrenia and as adjunctive therapy to antidepressants for major depressive disorder (MDD). It works through modulatory activity at serotonin and dopamine systems.
Description
Brexpiprazole is an atypical antipsychotic agent. Its pharmacology is mediated by modulatory activity at serotonin and dopamine systems, combining partial agonist activity at serotonergic 5-HT1A and dopaminergic D2 receptors with antagonist activity at serotonergic 5-HT2A receptors. It also shows antagonist activity at noradrenergic α1B/2C receptors.
Brexpiprazole is indicated for the treatment of schizophrenia and as adjunctive therapy to antidepressants for major depressive disorder.
Indications
- Schizophrenia
- Major Depressive Disorder (MDD) - adjunctive therapy with antidepressants
Therapeutic class
Benzodiazepine antagonist
Pharmacological class
Atypical Antipsychotic / Serotonin-Dopamine Activity Modulator
Pharmacology
Brexpiprazole is an atypical antipsychotic agent. Its pharmacology is mediated by modulatory activity at serotonin and dopamine systems, combining partial agonist activity at serotonergic 5-HT1A and dopaminergic D2 receptors (at similar potency) with antagonist activity at serotonergic 5-HT2A and noradrenergic α1B/2C receptors.
Mechanism of action
Brexpiprazole acts as a partial agonist at 5-HT1A and D2 receptors and as an antagonist at 5-HT2A and α1B/2C receptors, regulating serotonin and dopamine system balance.
Dosage
Schizophrenia:
Recommended starting dose: 1 mg PO qDay on Days 1-4 (with or without food).
Recommended target dose: 2-4 mg PO qDay.
Titration: 2 mg/day on Days 5-7, then 4 mg/day on Day 8 (based on clinical response and tolerability).
Maximum daily dose: 4 mg.
Major Depressive Disorder (Adjunctive Therapy):
Recommended starting dose: 0.5 mg or 1 mg PO qDay (with or without food).
Recommended target dose: 2 mg PO qDay.
Titration: Weekly intervals to 1 mg/day, then up to 2 mg/day (based on clinical response and tolerability).
Maximum daily dose: 3 mg.
Hepatic impairment (Moderate-severe, Child-Pugh ≥7):
MDD: Not to exceed 2 mg/day; Schizophrenia: Not to exceed 3 mg/day.
Renal impairment (Moderate, severe, or ESRD, CrCl <60 mL/min):
MDD: Not to exceed 2 mg/day; Schizophrenia: Not to exceed 3 mg/day.
Periodically reassess to determine the continued need and appropriate dose.
Administration
Take with or without food. Follow the dose and duration as advised by your physician. Take at a fixed time each day for best results.
Missed dose
If you miss a dose, take it as soon as you remember. Skip the missed dose if it is almost time for your next dose. Do not double the dose.
Side effects
>10%: Akathisia (4-14%)
1-10%: Headache (4-9%), Weight increased (3-8%), Nasopharyngitis (1-7%), Extrapyramidal symptoms (excluding akathisia) (5-6%), Somnolence (4-6%), Dyspepsia (2-6%), Constipation (1-6%), Tremor (2-5%), Fatigue/sedation (2-5%), Dizziness (1-5%), Increased CPK blood levels (2-4%), Decreased cortisol levels (2-4%), Anxiety (2-4%), Restlessness (2-4%), Increased appetite (2-3%), Diarrhea (1-3%)
Frequency Unknown: Dystonia, QT prolongation, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Leukopenia, Neutropenia, Agranulocytosis, Orthostatic hypotension, Syncope.
Precautions & warnings
- Increased mortality in elderly patients with dementia-related psychosis (cerebrovascular adverse reactions).
- Suicidal thoughts and behaviors reported in children, adolescents, and young adults taking antidepressant drugs.
- Neuroleptic malignant syndrome (NMS): If suspected, immediately discontinue therapy and provide intensive symptomatic treatment and monitoring.
- Tardive dyskinesia: Potentially irreversible, involuntary dyskinetic movements reported with antipsychotic drugs (highest in elderly women).
- Monitor for metabolic changes including hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain.
- May cause leukopenia, neutropenia, and agranulocytosis; monitor CBC.
- Orthostatic hypotension or syncope may occur (rare); risk greatest during initial dose titration and dose increases.
- May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and fractures.
- Caution with history of seizures or conditions/drugs that lower seizure threshold.
Contraindications
- Hypersensitivity to brexpiprazole or any of its components (reactions include rash, facial swelling, urticaria, and angioedema)
Drug interactions
- CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine): May increase brexpiprazole levels; dose adjustment may be required.
- CYP3A4 inhibitors (ketoconazole, itraconazole): May increase brexpiprazole levels; dose adjustment may be required.
- CYP3A4 inducers (rifampin, carbamazepine): May decrease brexpiprazole levels; dose adjustment may be required.
Food interactions
No food restrictions (may take with or without food).
Use in pregnancy
Adequate and well-controlled studies have not been conducted in pregnant women. Neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms. Animal studies showed no teratogenicity but increased perinatal deaths at high doses.
Use in lactation
Unknown if distributed in human breast milk; present in rat milk. Consider developmental and health benefits of breastfeeding along with mother's clinical need and potential adverse effects on the infant.
Pediatric use
Safety and effectiveness in pediatric patients have not been established. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients.
Geriatric use
Dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range (considering decreased hepatic, renal, and cardiac function, concomitant diseases, and other drug therapy).
Renal / hepatic impairment
Hepatic impairment (Moderate-severe, Child-Pugh ≥7): MDD: Not to exceed 2 mg/day; Schizophrenia: Not to exceed 3 mg/day.
Overdose effects
Overdose symptoms: Somnolence, dizziness, orthostatic hypotension, nausea, vomiting, tachycardia. Consult your doctor immediately if overdose is suspected.
Storage conditions
Do not store above 30°C. Keep away from light and moisture. Keep out of reach of children.
Chemical structure
Brexpiprazole