When Should Rexulti Be Taken?
Rexulti (brexpiprazole) should be administered once daily, either with or without food, as timing relative to meals does not affect its absorption or efficacy. 1
Dosing Schedule
- Administer brexpiprazole orally once daily at any time of day 1
- Food does not impact administration - the medication can be taken with or without food based on patient preference 1
- Consistency in timing is recommended - while not explicitly required by the FDA label, taking the medication at the same time each day helps maintain steady plasma levels and improves adherence 1
Titration Requirements
The medication requires gradual dose escalation to reach target doses:
- For Major Depressive Disorder (MDD): Start at 0.5-1 mg/day, titrate to target dose of 2 mg/day (maximum 3 mg/day) 1
- For Schizophrenia: Start at 1 mg/day, titrate to target dose of 2-4 mg/day (maximum 4 mg/day) 1
- Titration should occur over 1-2 weeks to reach the target therapeutic dose 2
Pharmacokinetic Considerations
- Time to peak concentration (tmax) occurs at 4-5 hours after administration 3
- Steady-state is achieved after approximately 10 days of consistent daily dosing 3
- Elimination half-life is 52-92 hours, supporting once-daily dosing and providing flexibility in timing 3
- Accumulation occurs over 2.5- to 5.5-fold by day 14 compared to initial dosing, which is why gradual titration is necessary 3
Special Population Adjustments
- Moderate to severe hepatic impairment: Maximum 2 mg/day for MDD, 3 mg/day for schizophrenia 1
- Renal impairment (CrCl <60 mL/min): Maximum 2 mg/day for MDD, 3 mg/day for schizophrenia 1
- CYP2D6 poor metabolizers: Dose adjustments required due to higher drug exposure 1, 3
Clinical Pearls
- No specific time-of-day advantage - unlike some antipsychotics that cause sedation (requiring bedtime dosing) or activation (requiring morning dosing), brexpiprazole demonstrates a balanced profile with relatively low incidence of both activating and sedating effects 4
- Akathisia monitoring is most relevant during dose titration, occurring in 5.5% of schizophrenia patients and 8.6% of MDD patients, but timing of administration does not mitigate this risk 5
- Do not abruptly discontinue - if stopping brexpiprazole, consider gradual tapering (approximately 10% per week) to minimize withdrawal symptoms, though this is more critical when switching to other antipsychotics 6