Interactions : אינטראקציות

7 DRUG INTERACTIONS

7.1 Drugs Having Clinically Important Interactions with REXULTI
See Table 11 for clinically important drug interactions with REXULTI.

Table 11          Clinically Important Drug Interactions with REXULTI 
Strong CYP3A4 Inhibitors

Concomitant use of REXULTI with strong CYP3A4 inhibitors increased the Clinical Impact:     exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3)]

With concomitant use of REXULTI with a strong CYP3A4 inhibitor, reduce Intervention: the REXULTI dosage [see Dosage and Administration (2.7)]

Strong CYP2D6 Inhibitors*

Concomitant use of REXULTI with strong CYP2D6 inhibitors increased the Clinical Impact:     exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3)]

With concomitant use of REXULTI with a strong CYP2D6 inhibitor, reduce Intervention: the REXULTI dosage [see Dosage and Administration (2.7)]

Both CYP3A4 Inhibitors and CYP2D6 Inhibitors

Concomitant use of REXULTI with 1) a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 2) a moderate CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 3) a strong CYP3A4 inhibitor and a moderate
Clinical Impact:
CYP2D6 inhibitor; or 4) a moderate CYP3A4 inhibitor and a moderate
CYP2D6 inhibitor increased the exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3)]

With concomitant use of REXULTI with 1) a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 2) a moderate CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 3) a strong CYP3A4 inhibitor and a moderate Intervention:
CYP2D6 inhibitor; or 4) a moderate CYP3A4 inhibitor and a moderate
CYP2D6 inhibitor, decrease the REXULTI dosage [see Dosage and
Administration (2.7)]

Strong CYP3A4 Inducers

Concomitant use of REXULTI and a strong CYP3A4 inducer decreased the
Clinical Impact:     exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3)]

With concomitant use of REXULTI with a strong CYP3A4 inducer,
Intervention: increase the REXULTI dosage [see Dosage and Administration (2.7)]
* In the clinical studies 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.

7.2 Drugs Having No Clinically Important Interactions with REXULTI
Based on pharmacokinetic studies, no dosage adjustment of REXULTI is required when administered concomitantly with CYP2B6 inhibitors (e.g., ticlopidine) or gastric pH modifiers (e.g., omeprazole). Additionally, no dosage adjustment for substrates of CYP2D6 (e.g., dextromethorphan), CYP3A4 (e.g., lovastatin), CYP2B6 (e.g., bupropion), BCRP (e.g., rosuvastatin), or P-gp (e.g., fexofenadine) is required when administered concomitantly with REXULTI.