Medications That Can Be Used With Rexulti (Brexpiprazole)
Rexulti can be safely used with most medications, but requires dose adjustments when combined with CYP3A4 or CYP2D6 inhibitors/inducers, and can be used without adjustment alongside common drugs including antidepressants, statins, proton pump inhibitors, and many others. 1
Medications Requiring NO Dose Adjustment
Rexulti can be administered without any dosage modifications when used with the following drug classes 1:
- Gastric pH modifiers (e.g., omeprazole) 1
- CYP2B6 inhibitors (e.g., ticlopidine) 1
- Statins (e.g., lovastatin, rosuvastatin) - no adjustment needed for these substrates 1
- Antidepressants for MDD (e.g., bupropion) - when used as adjunctive therapy, dose adjustments are already factored into general dosing 1
- Antihistamines (e.g., fexofenadine) 1
- Cough suppressants (e.g., dextromethorphan) 1
Medications Requiring Dose REDUCTION of Rexulti
Strong CYP3A4 Inhibitors
Reduce Rexulti dose to half when combined with strong CYP3A4 inhibitors, as these significantly increase brexpiprazole exposure 1. Examples include:
- Ketoconazole
- Itraconazole
- Clarithromycin
Strong CYP2D6 Inhibitors
Reduce Rexulti dose to half when combined with strong CYP2D6 inhibitors 1. Examples include:
- Paroxetine
- Fluoxetine
- Quinidine
Important caveat: In MDD clinical trials, doses were NOT adjusted for strong CYP2D6 inhibitors like paroxetine and fluoxetine, meaning CYP considerations are already built into standard MDD dosing recommendations 1.
Combination of Moderate/Strong Inhibitors
Reduce Rexulti dose to one-quarter when combining 1:
- Strong CYP3A4 inhibitor + strong CYP2D6 inhibitor, OR
- Moderate CYP3A4 inhibitor + strong CYP2D6 inhibitor, OR
- Strong CYP3A4 inhibitor + moderate CYP2D6 inhibitor, OR
- Moderate CYP3A4 inhibitor + moderate CYP2D6 inhibitor
Medications Requiring Dose INCREASE of Rexulti
Strong CYP3A4 Inducers
Double the Rexulti dose when combined with strong CYP3A4 inducers, as these decrease brexpiprazole exposure and may reduce efficacy 1. Examples include:
- Rifampin
- Carbamazepine
- Phenytoin
- St. John's Wort
Clinical Considerations
Brexpiprazole does not affect the metabolism of other drugs, meaning co-administered medications that are substrates of CYP2D6, CYP3A4, CYP2B6, BCRP, or P-gp do not require dose adjustments 1. This is a significant advantage in polypharmacy situations.
The drug's favorable interaction profile stems from its pharmacological design as a serotonin-dopamine activity modulator with lower intrinsic D2 receptor activity compared to aripiprazole, resulting in fewer activating adverse effects while maintaining efficacy 2, 3.
When used adjunctively with antidepressants (particularly SSRIs like escitalopram), brexpiprazole demonstrates enhanced efficacy without requiring complex dose adjustments in the MDD indication, as interaction considerations are already incorporated into standard dosing 1, 4, 5.