**BEERS Drug**

Genetic Implications: Genetic Implications


Trade Name(s)

  • Rexulti

Ther. Class.

none assigned



Pharm. Class.

serotonin-dopamine activity modulators (SDAM)


  • Treatment of schizophrenia.
  • Adjunctive treatment of major depressive disorder.


Psychotropic activity may be due to partial agonist activity at dopamine D2  and serotonin 5-HT1A  receptors and antagonist activity at the 5-HT2A  receptor.

Therapeutic Effect(s):

  • Decreased manifestations of schizophrenia including excitable, paranoic, or withdrawn behavior.
  • Improvement in symptoms of depression with increased sense of wellbeing.


Absorption: Well absorbed (95%) following oral administration.

Distribution: Displays extravascular distribution.

Protein Binding: >99%.

Metabolism and Excretion: Metabolized by CYP3A4 and CYP2D6; Genetic implication the CYP2D6 enzyme system exhibits genetic polymorphism (~7% of population may be poor metabolizers and may have significantly ↑ brexpiprazole concentrations and an ↑ risk of adverse effects). 25% excreted in urine (<1% unchanged), 46% in feces (14% unchanged).

Half-life: 91 hr.

TIME/ACTION PROFILE (improvement in symptoms)

PO (schizophrenia)within 1–2 wk4–6 wkunknown
PO (depression)within 1 wk5 wkunknown


Contraindicated in:

  • Hypersensitivity.

Use Cautiously in:

  • History of seizures, concurrent use of medications that may ↓ seizure threshold;
  • Pre-existing cardiovascular disease, dehydration, hypotension, concurrent antihypertensives, diuretics, electrolyte imbalance (↑ risk of orthostatic hypotension, correct deficits before treatment);
  • Pre-existing low WBC (may ↑ risk of leukopenia/neutropenia;
  • History of diabetes, metabolic syndrome or dyslipidemia (may exacerbate);
  • Patients <24 yr (may ↑ suicidal ideation/behaviors, monitor carefully);
  • Patients at risk for falls;
  • Genetic implication Poor CYP2D6 metabolizers (PM), dose ↓ required;
  • OB:  Use during third trimester may result in extrapyramidal/withdrawal symptoms in infant; use during pregnancy only if potential maternal benefit justifies potential fetal risk;
  •  Lactation: Safety not established during breastfeeding;
  • Pedi:  Antidepressants may ↑ risk of suicidal ideation/behaviors in children; safety and effectiveness not established in children.
  • Geri:  ↑ risk of mortality in older adults with dementia-related psychosis; consider age, concurrent medical conditions and medications, and renal/hepatic/cardiac function when initiating therapy.

Adverse Reactions/Side Effects

EENT: blurred vision

CV: cerebrovascular adverse reactions (↑ in elderly patients with dementia-related psychoses), orthostatic hypotension/syncope

GI: abdominal pain, constipation, diarrhea, dry mouth, dysphagia, excess salivation, flatulence

Hemat: agranulocytosis, leukopenia, neutropenia

Metabolic: ↑ appetite, ↑ weight, hyperglycemia/diabetes, dyslipidemia

Neuro: akathisia, dystonia, extrapyramidal symptoms, tardive dyskinesia, tremor, SEIZURES, abnormal dreams, dizziness, drowsiness, headache, restlessness, urges (eating, gambling, sexual, shopping)

Misc: NEUROLEPTIC MALIGNANT SYNDROME, allergic reactions including ANAPHYLAXIS, body temperature dysregulation

* CAPITALS indicate life-threatening.
Underline indicate most frequent.



  • Concurrent use with strong CYP3A4 inhibitors including  clarithromycin,  itraconazole  or  ketoconazole  ↑ blood levels, effects and risk of adverse reactions; ↓ dose of brexpiprazole required.
  • Concurrent use with strong CYP2D6 inhibitors including  fluoxetine,  paroxetine, or  quinidine ↑ blood levels, effects and risk of adverse reactions; ↓ dose of brexpiprazole required.
  • Combined use of  strong or moderate CYP3A4 inhibitors with strong or moderate CYP2D6 inhibitors  in addition to brexpiprazole including the following combinations  itraconazole + quinidine,  fluconazole + paroxetine,  itraconazole + duloxetine  or  fluconazole + duloxetine  ↑ blood levels, effects and risk of toxicity; ↓ dose of brexpiprazole required.
  • Concurrent use of  strong inducers of CYP3A4  including  rifampin ↓ blood levels and effectiveness; ↑ dose of brexpiprazole required.
  • Concurrent use of  antihypertensives  or  diuretics  (↑ risk of hypotension).
  • Concurrent use of  medications that may ↓ seizure threshold  (↑ risk of seizures).

Drug-Natural Products:

Concurrent use of  St. John's wort  ↓ blood levels and effectiveness; ↑ dose of brexpiprazole required.


PO (Adults): Schizophrenia– 1 mg once daily for the 1st 4 days (Days 1–4), then ↑ to 2 mg once daily for the next 3 days (Days 5–8), then ↑ to 4 mg once daily on Day 8 (not to exceed 4 mg once daily);  Major depressive disorder– 0.5 or 1 mg once daily initially, may be ↑ to 2 mg once daily (not to exceed 3 mg once daily);  Known CYP2D6 poor metabolizers– use 50% of the usual dose.  Concurrent use of strong CYP2D6 inhibitors (schizophrenia only) or CYP3A4 inhibitors– use 50% of the usual dose;  Concurrent use of strong/moderate CYP2D6 inhibitors AND strong/moderate CYP3A4 inhibitors– use 25% of the usual dose;  Known CYP2D6 poor metabolizer taking concurrent strong/moderate CYP3A4 inhibitors– use 25% of the usual dose;  Concurrent use of strong CYP3A4 inducers– double usual dose over 1–2 wk; titrate by clinical response.

Hepatic Impairment 
PO (Adults): Moderate to severe hepatic impairment [Child-Pugh score ≥7]– maximum daily dose should not exceed 3 mg for schizophrenia or 2 mg for major depressive disorder.

Renal Impairment 
PO (Adults): Moderate/severe/end-stage renal impairment [CCr <60 mL/min]– maximum daily dose should not exceed 3 mg for schizophrenia or 2 mg for major depressive disorder.


Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg


  • Assess mental status (orientation, mood, behavior) before and periodically during therapy. Assess for suicidal tendencies, especially during early therapy for depression. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yrs.
  • Assess weight and BMI initially and throughout therapy.
  • Obtain fasting blood glucose and cholesterol levels initially and periodically during therapy.
  • Monitor BP (sitting, standing, lying), pulse, and respiratory rate before and periodically during therapy.
  • Observe patient carefully when administering medication to ensure that medication is actually taken and not hoarded or cheeked.
  • Monitor patient for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects ( parkinsonian– difficulty speaking or swallowing, loss of balance control, pill rolling of hands, masklike face, shuffling gait, rigidity, tremors; and  dystonic– muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) periodically throughout therapy. Report these symptoms.
  • Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue). Notify health care professional immediately if these symptoms occur; symptoms may partially or completely resolve, but may be irreversible.
  • Monitor for development of neuroleptic malignant syndrome (fever, muscle rigidity, altered mental status, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness, loss of bladder control, elevated CK, myoglobinuria/rhabdomyolysis, acute renal failure). Notify health care professional immediately if these symptoms occur.
  • Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.

Lab Test Considerations:

Monitor CBC frequently during initial mo of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if severe neutropenia (ANC <1000 mm3  occurs).

  • Monitor blood glucose and cholesterol levels initially and periodically during therapy.

Potential Diagnoses


  • PO Administer once daily without regard to meals.

Patient/Family Teaching

  • Advise patient to take medication as directed and not to skip doses or double up on missed doses. Take missed doses as soon as remembered unless almost time for the next dose. Do not stop taking brexpiprazole without consulting health care professional. Advise patient to read  Medication Guide  before starting and with each Rx refill in case of changes.
  • Inform patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Instruct patient to report these symptoms immediately.
  • Advise patient to make position changes slowly to minimize orthostatic hypotension. Protect from falls.
  • Medication may cause drowsiness and lightheadedness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking; other unusual changes in behavior or mood occur.
  • Inform patient that brexipiprazole may cause weight gain. Advise patient to monitor weight periodically. Notify health care professional of significant weight gain.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any new medications. Caution patient to avoid taking alcohol or other CNS depressants concurrently with this medication.
  • Advise patient that extremes in temperature should be avoided, because this drug impairs body temperature regulation.
  • Advise patient to notify health care professional if new or increased eating/binge eating, gambling, sexual, shopping, or other impulse control disorders occur.
  • Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
  • Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Encourage pregnant patients to enroll in registry by contacting National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit
  • Emphasize the importance of routine follow-up exams and continued participation in psychotherapy as indicated.

Evaluation/Desired Outcomes

  • Decrease in excitable, paranoic, or withdrawn behavior.
  • Increased sense of wellbeing in patients with depression.
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