INDICATION AND USES:
REXULTI 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 and pediatric patients ages 13 years and older (1, 14.2)
DOSAGE AND ADMINISTRATION
Administer REXULTI 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 |
| Schizophrenia Pediatric (13 – 17 years) (2.2) | 0.5 mg/day | 2 to 4 mg/day | 4 mg/day |
- Moderate to Severe Hepatic Impairment (Child-Pugh score ≥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 (CLcr <60ml/min) 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)
SIDE EFFECTS:
Most common adverse reactions in adults were (6.1):
- MDD: Weight increased and akathisia (≥5% and at least twice the rate for placebo)
- Schizophrenia: Weight increased (≥4% and at least twice the rate for placebo)
To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
CONTRAINDICATIONS:
Known hypersensitivity to REXULTI or any of its components (4)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) (5.3)
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. (5.4)
- Tardive Dyskinesia: Discontinue if clinically appropriate. (5.5)
- Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain. (5.6)
- Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation. (5.7)
- Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing REXULTI if a clinically significant decline in WBC occurs in absence of other causative factors. (5.8)
- Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. (5.9)
- Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. (5.11)
DRUG INTERACTIONS:
| Factors | Dosage Adjustments for REXULTI (2.5) |
| Strong CYP2D6* or CYP3A4 inhibitors | Administer half of usual dose. |
| Strong/moderate CYP2D6 width Strong/moderate CYP3A4 inhibitors | Administer a quarter of usual dose. |
| Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors | Administer a quarter of usual dose. |
| Strong CYP3A4 inducers | Double the usual dose and further adjust based on clinical response. |
* REXULTI may be administered without dosage adjustments in patients with MDD when administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine).
OVERDOSE:
There is limited clinical trial experience regarding human overdosage with REXULTI. Consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org) for up-to-date guidance and advice regarding a REXULTI overdosage. Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers.
Charcoal: Oral activated charcoal and sorbitol (50 g/240 mL), administered one hour after ingesting oral brexpiprazole, decreased brexpiprazole Cmax and area under the curve (AUC) by approximately 5% to 23% and 31% to 39% respectively; however, there is insufficient information available on the therapeutic potential of activated charcoal in treating an overdose with REXULTI.
Hemodialysis: There is no information on the effect of hemodialysis in treating an overdose with REXULTI; hemodialysis is unlikely to be useful because brexpiprazole is highly bound to plasma proteins.
- Uses
-
INDICATION AND USES:
REXULTI 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 and pediatric patients ages 13 years and older (1, 14.2)
DOSAGE AND ADMINISTRATION
Administer REXULTI 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 Schizophrenia Pediatric (13 – 17 years) (2.2) 0.5 mg/day 2 to 4 mg/day 4 mg/day - Moderate to Severe Hepatic Impairment (Child-Pugh score ≥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 (CLcr <60ml/min) 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)
- Side Effects
-
SIDE EFFECTS:
Most common adverse reactions in adults were (6.1):
- MDD: Weight increased and akathisia (≥5% and at least twice the rate for placebo)
- Schizophrenia: Weight increased (≥4% and at least twice the rate for placebo)
To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
- Precautions
-
CONTRAINDICATIONS:
Known hypersensitivity to REXULTI or any of its components (4)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) (5.3)
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. (5.4)
- Tardive Dyskinesia: Discontinue if clinically appropriate. (5.5)
- Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain. (5.6)
- Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation. (5.7)
- Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing REXULTI if a clinically significant decline in WBC occurs in absence of other causative factors. (5.8)
- Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. (5.9)
- Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. (5.11)
- Interactions
-
DRUG INTERACTIONS:
Factors Dosage Adjustments for REXULTI (2.5) Strong CYP2D6* or CYP3A4 inhibitors Administer half of usual dose. Strong/moderate CYP2D6 width Strong/moderate CYP3A4 inhibitors Administer a quarter of usual dose. Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors Administer a quarter of usual dose. Strong CYP3A4 inducers Double the usual dose and further adjust based on clinical response. * REXULTI may be administered without dosage adjustments in patients with MDD when administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine).
- Overdose
-
OVERDOSE:
There is limited clinical trial experience regarding human overdosage with REXULTI. Consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org) for up-to-date guidance and advice regarding a REXULTI overdosage. Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers.
Charcoal: Oral activated charcoal and sorbitol (50 g/240 mL), administered one hour after ingesting oral brexpiprazole, decreased brexpiprazole Cmax and area under the curve (AUC) by approximately 5% to 23% and 31% to 39% respectively; however, there is insufficient information available on the therapeutic potential of activated charcoal in treating an overdose with REXULTI.
Hemodialysis: There is no information on the effect of hemodialysis in treating an overdose with REXULTI; hemodialysis is unlikely to be useful because brexpiprazole is highly bound to plasma proteins.