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brexpiprazole (Rxulti)

Indications: - adults with major depression on antidepressant therapy - psychosis & agitation in the elderly, including Alzheimer's disease* - schizophrenia * improves agitation in Alzheimer' disease vs placebo over 12 weeks [2,3] Contraindications: - pregnancy category: C Dosage: - start 0.5-1.0 mg/day - 2-3 mg/day (agitation, major depression) - 2-4 mg/day (schizophrenia) - maximum 4 mg/day Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg Pharmacokinetics: - metabolized in the liver mainly by CYP3A4 - protein binding: 99% Dosage adjustment in renal failure: - maximum dose 2 mg (depression or agitation), 3 mg (schizophrenia) Adverse effects: - discontinuance 5.3% vs 4.3% for placebo - stroke, TIA (elderly with dementia-related psychosis) - neuroleptic malignant syndrome - tardive dyskinesia - leukopenia, neutropenia, granulocytopenia - orthostatic hypotension, syncope - seizures - weight gain (twice risk of placebo) * Boxed Warning - increased mortality in elderly with dementia-related psychosis & suicidal thoughts & behaviors Drug interactions: - CYP3A4 inhibitors increase levels of brexpiprazole - cut brexpiprazole dose in 1/2 - CYP3A4 inducers decrease levels of brexpiprazole - double brexpiprazole dose - drugs that lower the seizure threshold Mechanism of action: - partial serotonin 5-HT1A receptor agonist & dopamine D2 receptor agonist - serotonin 5-HT2A receptor agonist

Interactions

drug adverse effects of antipsychotic agents monitor with atypical antipsychotic agents

General

pyrrole atypical antipsychotic agent; second generation antipsychotic

Database Correlations

PUBCHEM cid=11978813

References

  1. FDA News Release. July 13, 2015 FDA approves new drug to treat schizophrenia and as an add on to an antidepressant to treat major depressive disorder. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm454647.htm
  2. Monaco K Rexulti Calms Alzheimer's Dementia-Related Agitation. But atypical antipsychotic disappoints in borderline personality disorder. MedPage Today September 19, 2022 https://www.medpagetoday.com/meetingcoverage/psychcongress/100805 - DePeau-Wilson M Rexulti Works for Agitation in Alzheimer's, Despite Risks, Says FDA Staff. Increased mortality risk consistent with other antipsychotics in elderly dementia patients. MedPage Today April 13, 2023 https://www.medpagetoday.com/neurology/dementia/104000
  3. US Food & Drug Administration News Release. May 11, 2023 FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer's Disease. https://www.fda.gov/news-events/press
  4. Lee D, Slomkowski M, Hefting N et al. Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial. JAMA Neurol. 2023 Nov 6:e233810. PMID: 37930669 PMCID: PMC10628834 Free PMC article
  5. HIGHLIGHTS OF PRESCRIBING INFORMATION REXULTI (brexpiprazole) tablets, for oral use https://www.otsuka-us.com/sites/g/files/qhldwo8676/files/media/static/Rexulti-PI.pdf