brexpiprazole (Rx)

Brand and Other Names:Rexulti
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 0.25mg
  • 0.5mg
  • 1mg
  • 2mg
  • 3mg
  • 4mg

Schizophrenia

Indicated for schizophrenia

Recommended starting dose: 1 mg PO qDay on Days 1 through 4

Recommended target dose: 2-4 mg PO qDay; titrate to 2 mg qDay on Days 5 through 7, and then to 4 mg/day on Day 8 based on the patient’s clinical response and tolerability

Not to exceed 4 mg/day

Periodically reassess to determine the continued need and appropriate dose

Depression

Indicated as adjunctive treatment for major depressive disorder

Recommended starting dose: 0.5 mg or 1 mg PO qDay

Recommended target dose: 2 mg PO qDay; at weekly intervals, titrate to 1 mg/day, and then up to 2 mg/day

Titrate according to clinical response and tolerability

Not to exceed 3 mg/day

Periodically reassess to determine the continued need and appropriate dose

Dosage Modifications

Hepatic impairment

  • Moderate-to-severe hepatic impairment (Child-Pugh ≥7)
    • MDD: Not to exceed 2 mg/day
    • Schizophrenia: Not to exceed 3 mg/day

Renal impairment

  • Moderate, severe, or ESRD (CrCl <60 mL/min)
    • MDD: Not to exceed 2 mg/day
    • Schizophrenia: Not to exceed 3 mg/day

CYP2D6 poor metabolizers

  • CYP2D6 poor metabolizers: Administer half of the usual brexpiprazole dose
  • Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors: Administer a quarter of the usual brexpiprazole dose

CYP2D6 or CYP3A4 inhibitors

  • Strong CYP2D6 inhibitors: Administer half of the usual brexpiprazole dose (see note below for MDD)
  • Strong CYP3A4 inhibitors: Administer half of the usual brexpiprazole dose
  • Strong/moderate CYP2D6 inhibitors plus strong/moderate CYP3A4 inhibitors: Administer a quarter of the usual brexpiprazole dose
  • If the coadministered drug is discontinued, adjust the brexpiprazole dosage to its original level
  • NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD

CYP3A4 inducers

  • Strong CYP3A4 inducers: Double usual dose over 1 to 2 weeks
  • If the coadministered CYP3A4 inducer is discontinued, reduce the brexpiprazole dosage to the original level over 1-2 weeks

Geriatric Dosage & Uses

Antipsychotic drugs increase the risk of death in elderly patients with dementia-related psychosis

Brexpiprazole is not approved for the treatment of patients with dementia-related psychosis (see Black Box Warnings)

Safety and efficacy not established

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Interactions

Interaction Checker

and brexpiprazole

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            Adverse Effects

            >10%

            Akathisia (4-14%)

            1-10%

            Headache (4-9%)

            Weight increased (3-8%)

            Nasopharyngitis (1-7%)

            Extrapyramidal symptoms, excluding akathisia (5-6%)

            Somnolence (4-6%)

            Dyspepsia (2-6%)

            Constipation (1-6%)

            Tremor (2-5%)

            Fatigue/sedation (2-5%)

            Dizziness (1-5%)

            Increased CPK blood levels (2-4%)

            Decreased cortisol levels (2-4%)

            Anxiety (2-4%)

            Restlessness (2-4%)

            Increased appetite (2-3%)

            Diarrhea (1-3%)

            Frequency Unknown

            Dystonia

            Postmarketing Reports

            Falls

            Pathological gambling and other compulsive behaviors

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            Warnings

            Black Box Warnings

            Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death; brexpiprazole is not approved for the treatment of patients with dementia-related psychosis

            Antidepressants increase the risk of suicidal thoughts and behaviors in patients aged ≤24 yr; monitor for clinical worsening and emergence of suicidal thoughts and behaviors

            Safety and effectiveness have not been established in pediatric patients

            Contraindications

            Hypersensitivity; reactions have included rash, facial swelling, urticaria, and angioedema

            Cautions

            Increased mortality in elderly patients with dementia-related psychosis (see Black Box Warnings); in placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly patients with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks), including fatalities, compared with placebo

            Suicidal thoughts and behaviors reported in children, adolescents, and young adults who are taking antidepressant drugs (see Black Box Warnings)

            Potentially fatal neuroleptic malignant syndrome (NMS) reported in association with administration of antipsychotic drugs; if NMS is suspected, immediately discontinue therapy and provide intensive symptomatic treatment and monitoring

            Potentially irreversible, involuntary, dyskinetic movements (ie, tardive dyskinesia) reported with antipsychotic drugs; incidence highest in elderly persons, especially elderly women

            Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus (including extreme cases associated with ketoacidosis or hyperosmolar coma or death), dyslipidemia, and body weight gain; assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment; before or soon after initiation of antipsychotic medications, obtain a fasting lipid profile at baseline and monitor periodically during treatment; monitor weight at baseline and frequently thereafter

            May cause leukopenia, neutropenia, and agranulocytosis; monitor and discontinue if severe neutropenia (ANC <1000/mm³); in patients with a pre-existing low WBC or ANC or a history of drug-induced leukopenia or neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy

            Orthostatic hypotension or syncope may occur (rare); generally, the risk is greatest during initial dose titration and when increasing the dose; orthostatic vital signs should be monitored in patients who are vulnerable to hypotension, (e.g., elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medication, patients with known cardiovascular disease, and patients with cerebrovascular disease)

            May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy

            Caution with a history of seizures or with conditions/drugs that potentially lower the seizure threshold

            Body temperature dysregulation: Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents

            Dysphagia: Esophageal dysmotility and aspiration pneumonia reported

            Sedation and hypersomnia reported that may cause impaired judgement, thinking, or motor skills

            Post-marketing case reports suggest that patients can experience intense urges, particularly for gambling, and inability to control urges; consider dose reduction or stopping medication if a patient develops such urges

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            Pregnancy

            Pregnancy

            Rexulti pregnancy exposure registry: Monitors pregnancy outcomes in women exposed to brexpiprazole during pregnancy; for more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancy

            Adequate and well-controlled studies have not been conducted with brexpiprazole in pregnant women to inform drug-associated risks; however, neonates whose mothers are exposed to antipsychotic drugs, like brexpiprazole, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms (eg, agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder)

            Animal reproduction studies

            • No teratogenicity was observed with oral administration of brexpiprazole to pregnant rats and rabbits during organogenesis at doses up to 73 and 146 times, respectively, of maximum recommended human dose (MRHD) of 4 mg/day on a mg/m² basis
            • However, when pregnant rats were administered brexpiprazole during the period of organogenesis through lactation, the number of perinatal deaths of pups was increased at 73 times the MRHD

            Lactation

            Unknown if distributed in human breast milk

            Present in rat milk

            The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Serotonin-dopamine activity modulator (SDAM) that acts as a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors

            Absorption

            Absolute bioavailability: 95%

            Peak plasma time: 4 hr

            Steady-state concentration: 1-12 days

            Distribution

            Protein bound: >99% to serum albumin and alpha-1-acid glycoprotein; its protein binding is not affected by renal or hepatic impairment

            Brexpiprazole protein binding is not affected by warfarin, diazepam, or digitoxin

            Vd: 1.56 L/kg

            Metabolism

            Metabolized primarily by CYP2D6 and CYP3A4 isoenzymes

            Elimination

            Half-life: 91 hr

            Clearance: 19.8 mL·hr/kg

            Excretion: 25% urine; 46% feces

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            Administration

            Instructions

            May take with or without food

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.