Rexulti Drug Interactions

Overview: REXULTI is predominantly metabolized by cytochrome P450 (CYP)3A4 and CYP2D6.
REXULTI should be used with caution in combination with drugs known to prolong QTc interval or cause electrolyte disturbances (see Cardiovascular: QT Interval under Precautions).
Drug-Drug Interactions: Potential for other drugs to affect REXULTI: Dosage adjustments are recommended in patients who are known CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers (Table 19). If the co-administered drug is discontinued, adjust the REXULTI dosage to its original level. If the co-administered CYP3A4 inducer is discontinued, reduce the REXULTI dosage to the original level over 1 to 2 weeks (see Dosing Considerations: CYP isozymes under Dosage & Administration). (See Table 19.)

Click on icon to see table/diagram/image

The effects of other drugs on the exposure of REXULTI are summarized in Figure 1. (See Figure 1.)

Click on icon to see table/diagram/image

Potential for REXULTI to affect other drugs: Results of in vitro studies suggest that REXULTI is unlikely to cause clinically important pharmacokinetic interactions with drugs metabolized by cytochrome P450 enzymes. Clinical studies showed that oral brexpiprazole (2 mg/day, 5 days) had no effect on the metabolism of single doses of dextromethorphan (a CYP2D6 substrate), lovastatin (a CYP3A4 substrate) or bupropion (a CYP2B6 substrate). REXULTI did not affect absorption of single doses of drugs that are substrates of BCRP transporter (rosuvastatin) and PgP (P-glycoprotein) transporter (fexofenadine). No dosage adjustment of CYP2D6, CYP3A4, CYP2B6, BCRP and PgP substrates is required during concomitant administration with REXULTI.
The effects of REXULTI on the exposure of other drugs are summarized in Figure 2. (See Figure 2.)

Click on icon to see table/diagram/image

Drug-Food Interactions: REXULTI may be administered with or without food.
Drug-Herb Interactions: Interactions with herbal products have not been established.
Drug-Laboratory Interactions: Interactions with laboratory tests have not been established.
Drug-Lifestyle Interactions: Alcohol/CNS Drugs: Given the primary CNS effects of brexpiprazole, as with most psychoactive medications, combination use of REXULTI with alcohol or other CNS drugs with overlapping undesirable effects such as sedation, should be avoided.
Smoking: Based on studies utilizing human liver enzymes in vitro, brexpiprazole is not a substrate for CYP1A2. No dosage adjustment is required based on smoking status.