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. Periodically reassess to determine the continued need and appropriate dosage for treatment.
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
Factors
Adjusted REXULTI Dosage
CYP2D6 Poor Metabolizers
CYP2D6 poor metabolizers
Administer half of the usual dose
Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors
Administer a quarter of the usual dose
Patients Taking CYP2D6 Inhibitors and/or CYP3A4 Inhibitors
Strong CYP2D6 inhibitors*
Administer half of the usual dose
Strong CYP3A4 inhibitors
Administer half of the usual dose
Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors
Administer a quarter of the usual dose
Patients Taking CYP3A4 Inducers
Strong CYP3A4 inducers
Double usual dose over 1 to 2 weeks
*In 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.
