Rexulti (Brexpiprazole) Drug Information
Indications
Brexpiprazole is FDA-approved for two specific indications: adjunctive treatment of major depressive disorder (MDD) in adults and treatment of schizophrenia in adults. 1
Dosing for Major Depressive Disorder (Adjunctive Treatment)
Starting and Target Doses
- Start with 0.5 mg or 1 mg orally once daily, then titrate to 1 mg once daily 1
- The target dose is 2 mg once daily, with weekly dose increases based on clinical response and tolerability 1
- Maximum dose is 3 mg once daily 1
Titration Schedule
- Increase dosage at weekly intervals to reach the target of 2 mg/day 1
- Periodically reassess to determine continued need and appropriate dosage 1
Clinical Efficacy in MDD
- When pooling data from Phase III trials at recommended doses (1-3 mg), 23.2% of brexpiprazole-treated patients were responders versus 14.5% for placebo, yielding a number needed to treat (NNT) of 12 2
- Brexpiprazole 2 mg/day is the recommended target dose for adjunctive treatment 2, 3
Dosing for Schizophrenia
Starting and Target Doses
- Start with 1 mg orally once daily on Days 1-4 1
- Titrate to 2 mg once daily on Days 5-7 1
- On Day 8, increase to the target range of 2-4 mg once daily based on clinical response 1
- Maximum dose is 4 mg once daily 1
Clinical Efficacy in Schizophrenia
- Pooled responder rates were 45.5% for brexpiprazole 2-4 mg/day versus 31.0% for placebo, resulting in an NNT of 7 2
- In a 52-week relapse prevention study, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs 38.5%), yielding an NNT of 4 4, 2
Administration
Dose Adjustments for Special Populations
Hepatic Impairment
- For moderate to severe hepatic impairment (Child-Pugh score ≥7):
Renal Impairment
- For creatinine clearance <60 mL/minute:
CYP2D6 Poor Metabolizers and Drug Interactions
- For CYP2D6 poor metabolizers: administer half the recommended dosage 1
- With strong CYP2D6 or CYP3A4 inhibitors: administer half the recommended dosage 1
- With strong/moderate CYP2D6 AND strong/moderate CYP3A4 inhibitors: administer one-quarter the recommended dosage 1
- With strong CYP3A4 inducers: double the recommended dosage over 1-2 weeks 1
- Exception: For MDD patients taking strong CYP2D6 inhibitors (paroxetine, fluoxetine), no dose adjustment needed as this was factored into clinical trial dosing 1
Pharmacology
- Brexpiprazole is a dopamine D2 partial agonist with partial agonist activity at serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A and adrenergic alpha-1B and alpha-2C receptors 4
- Compared to aripiprazole, brexpiprazole is more potent at 5-HT1A receptors and displays less intrinsic activity at D2 receptors 4
Safety and Tolerability
Most Common Adverse Effects
For MDD:
- Weight gain, somnolence, and akathisia (≥5% and at least twice the rate of placebo) 1
- Akathisia occurred in 8.6% of MDD patients, with an NNH of 15 2
- Discontinuation due to adverse events: 3% for brexpiprazole versus 1% for placebo (NNH of 53) 2
For Schizophrenia:
- Weight gain (≥4% and at least twice the rate of placebo) 1
- Akathisia occurred in 5.5% versus 4.6% for placebo, yielding an NNH of 112 4
- Discontinuation rates due to adverse events were lower for brexpiprazole (7.1-9.2%) versus placebo (14.7%) 3
Weight and Metabolic Effects
- Approximately 10% of patients receiving brexpiprazole 1-4 mg/day gained ≥7% body weight from baseline, compared with 4% for placebo (NNH of 17) 4
- More outliers with ≥7% weight gain were evident in 52-week open-label studies 4
- Effects on glucose and lipids were small 4
- Minimal effects on prolactin 4
Cardiovascular Effects
- No clinically relevant effects on ECG QTc interval 4
Boxed Warnings
Increased Mortality in Elderly with Dementia-Related Psychosis
- Elderly patients with dementia-related psychosis treated with antipsychotics are at increased risk of death 1
- Brexpiprazole is NOT approved for dementia-related psychosis 1
Suicidal Thoughts and Behaviors
- Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients 1
- Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts 1
- Safety and effectiveness have NOT been established in pediatric patients with MDD 1
Important Warnings and Precautions
- Neuroleptic malignant syndrome: manage with immediate discontinuation and close monitoring 1
- Tardive dyskinesia: discontinue if clinically appropriate 1
- Metabolic changes: monitor for hyperglycemia/diabetes, dyslipidemia, and weight gain 1
- Pathological gambling and other compulsive behaviors: consider dose reduction or discontinuation 1
- Orthostatic hypotension and syncope: monitor heart rate and blood pressure, especially in patients with cardiovascular disease 1
- Seizures: use cautiously in patients with history of seizures or conditions that lower seizure threshold 1
- Potential for cognitive and motor impairment: use caution when operating machinery 1
Available Strengths
- Tablets available in: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg 1