What are the potential interactions between Rexulti (brexpiprazole) and pramipexole?

Potential Interactions Between Rexulti (Brexpiprazole) and Pramipexole

There is a significant risk of reduced therapeutic efficacy when brexpiprazole (Rexulti) and pramipexole are used together, as brexpiprazole's dopamine antagonist properties may diminish the effectiveness of pramipexole. 1

Pharmacological Mechanism of Interaction

• Brexpiprazole is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors 2
• Pramipexole is a dopamine receptor agonist commonly used for Parkinson's disease and sometimes for REM sleep behavior disorder (RBD) 3
• The opposing mechanisms on dopamine receptors create a pharmacodynamic interaction where brexpiprazole may counteract pramipexole's therapeutic effects 1

Clinical Implications

Reduced Efficacy

• Brexpiprazole may diminish pramipexole's effectiveness for treating Parkinson's disease symptoms 1
• For patients using pramipexole for RBD, brexpiprazole may reduce its already variable efficacy 3
• The antagonistic effect at D2 receptors from brexpiprazole could potentially worsen motor symptoms in patients with Parkinson's disease 1, 2

Safety Considerations

• Both medications can affect the central nervous system, potentially leading to additive effects on:
  • Sedation and somnolence 4
  • Risk of orthostatic hypotension, particularly in older adults 1
• Brexpiprazole has minimal drug-drug interaction potential through metabolic pathways, as it showed weak inhibitory effects on most CYP enzymes in vitro 5

Management Recommendations

• Consider alternative antipsychotic options with less D2 antagonism if pramipexole therapy is essential 1
• If co-administration cannot be avoided:
  • Start with the lowest effective doses of both medications 1
  • For pramipexole, begin with 0.125 mg three times daily or 0.125 mg at bedtime (for RBD) 1
  • Monitor closely for:
    • Reduced efficacy of pramipexole 1
    • Worsening of Parkinson's symptoms if applicable 1
    • Orthostatic hypotension, particularly in older adults 1
    • Excessive sedation or CNS depression 1, 4

Special Populations

• Older Adults: Use this combination with particular caution due to increased risk of orthostatic hypotension and sedation 1
• Patients with RBD: Be aware that pramipexole has shown contradictory results for RBD treatment, and this efficacy may be further compromised by brexpiprazole 3

Monitoring Parameters

• Motor symptoms in patients with Parkinson's disease 1
• Efficacy of pramipexole for its intended indication 1
• Blood pressure (sitting and standing) to assess for orthostatic hypotension 1
• Level of sedation and cognitive function 1, 4