Posology : מינונים

2 DOSAGE AND ADMINISTRATION
2.1 Administration Information
Administer REXULTI orally, once daily with or without food [see Clinical Pharmacology (12.3)] 
2.2 Recommended Dosage for Adjunctive Treatment of Major Depressive Disorder (Adults)
The recommended starting REXULTI dosage for the adjunctive treatment of MDD in adults is 0.5 mg or 1 mg once daily.

Titrate to 1 mg once daily, then titrate to the target dosage of 2 mg once daily (based on the patient’s clinical response and tolerability, increase the dosage at weekly intervals). The maximum recommended daily dosage is 3 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment.

2.3 Recommended Dosage for Schizophrenia (Adults and Pediatric Patients 13 to 17 Years)
Adults
The recommended starting REXULTI dosage for the treatment of schizophrenia in adults is 1 mg once daily on Days 1 to 4.

Titrate to 2 mg once daily on Day 5 through Day 7. On Day 8 , the dosage can be increased to the maximum recommended daily dosage of 4 mg based on clinical response and tolerability. The recommended target dosage is 2 mg to 4 mg once daily.

Pediatric Patients (13 to 17 years of age)
The recommended starting REXULTI dosage for the treatment of schizophrenia in pediatric patients 13 to 17 years of age is 0.5 mg taken orally once daily on Days 1 to 4. On days 5 through 7, titrate to 1 mg per day and on Day 8 titrate to 2 mg based on clinical response and tolerability. Weekly dose increases can be made in 1 mg increments. A recommended target dosage is 2 to 4 mg once daily. The maximum recommended daily dosage is 4 mg.


2.4 Recommended Dosage for Agitation Associated with Dementia Due to Alzheimer’s Disease
The recommended starting REXULTI dosage for the treatment of agitation associated with dementia due to Alzheimer’s disease is 0.5 mg taken once daily on Days 1 to 7. Increase the dosage on Days 8 through 14 to 1 mg once daily, and on Day 15 to 2 mg once daily. The recommended target dose is 2 mg once daily. The dosage can be increased to the maximum recommended daily dosage of 3 mg once daily after at least 14 days, based on clinical response and tolerability.


2.5 Recommended Dosage in Patients with Hepatic Impairment
The maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score ≥7) ) is [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)] 2 mg once daily in patients with MDD or agitation associated with dementia due to Alzheimer’s disease, and 3 mg orally once daily in patients with schizophrenia.

2.6 Recommended Dosage in Patients with Renal Impairment
The maximum recommended dosage in patients with creatinine clearance CrCl<60 mL/minute is [see Use in Specific Populations (8.8), Clinical Pharmacology (12.3)] 2 mg orally once daily in patients with MDD or agitation associated with dementia due to Alzheimer’s disease and 3 mg orally once daily in patients with schizophrenia.

2.7 Dosage Modifications for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP Inhibitors or
Inducers
Dosage modifications are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors , CYP2D6 inhibitors, or strong CYP3A4 inducers (see Table 1). If the concomitant drug is discontinued, adjust the REXULTI dosage to its original level. If the concomitant 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 Modifications of REXULTI for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP3A4 Inhibitors, CYP2D6 Inhibitors, or CYP3A4 Inducers

Factors                                                          Adjusted REXULTI Dosage 
CYP2D6 Poor Metabolizers

Administer half of the
CYP2D6 poor metabolizers recommended dosage.
Known CYP2D6 poor metabolizers taking strong/moderate                 Administer a quarter of the CYP3A4 inhibitors                                                     recommended dosage.

Patients Taking CYP2D6 Inhibitors and/or CYP3A4 Inhibitors

Administer half of the
Strong CYP2D6 inhibitors* recommended dosage.
Administer half of the
Strong CYP3A4 inhibitors recommended dosage.

Strong/moderate CYP2D6 inhibitors with strong/moderate                Administer a quarter of the CYP3A4 inhibitors                                                     recommended dosage.

Patients Taking CYP3A4 Inducers

Double the recommended
Strong CYP3A4 inducers dosage over 1 to 2 weeks.
*In the clinical studies examining the use of REXULTI for the adjunctive 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.