REXULTI Tablet Ref.[11112] Active ingredients: Brexpiprazole

2.1 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 (12.3)].

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.

2.2 Treatment of Schizophrenia

The recommended starting dosage for REXULTI is 1 mg once daily on Days 1 to 4, taken orally with or without food [see Clinical Pharmacology (12.3)].

The recommended target REXULTI 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.

2.3 Dosage Adjustments for Hepatic Impairment

For patients with moderate to severe hepatic impairment (Child-Pugh score ≥7), the maximum recommended dosage is 2 mg once daily for patients with MDD, and 3 mg once daily for patients with schizophrenia [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.4 Dosage Adjustments for Renal Impairment

For patients with moderate, severe or end-stage renal impairment (creatinine clearance CLcr<60 mL/minute), the maximum recommended dosage is 2 mg once daily for patients with MDD and 3 mg once daily for patients with schizophrenia [see Use in Specific Populations (8.8), Clinical Pharmacology (12.3)].

2.5 Dosage Modifications for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP Inhibitors or Inducers

Dosage adjustments are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers (see Table 1). If the coadministered drug is discontinued, adjust the REXULTI dosage to its original level. If the coadministered CYP3A4 inducer is discontinued, reduce the REXULTI dosage to the original level over 1 to 2 weeks [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Table 1. Dosage Adjustments of REXULTI for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP3A4 and CYP2D6 Inhibitors and/or CYP3A4 Inducers:

^* In the clinical trials examining the adjunctive use of REXULTI in the treatment of MDD, dosage was not adjusted for strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). Thus, CYP considerations are already factored into general dosing recommendations, and REXULTI may be administered without dosage adjustment in patients with MDD.

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 C_max 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.

Store REXULTI tablets at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].