Rexulti

— THERAPEUTIC CATEGORIES —
  • Alzheimer's dementia
  • Mood disorders
  • Psychosis

Rexulti Generic Name & Formulations

General Description

Brexpiprazole 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg; tabs.

Pharmacological Class

Atypical antipsychotic.

How Supplied

Tabs—30

Generic Availability

NO

Mechanism of Action

The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.

Rexulti Indications

Indications

Agitation associated with dementia due to Alzheimer disease. 

Limitations of Use

Not indicated as an as needed (“prn”) treatment for agitation associated with dementia due to Alzheimer disease.

Rexulti Dosage and Administration

Adult

Initially 0.5mg once daily on Days 1–7; titrate to 1mg once daily on Days 8–14, then to 2mg once daily on Day 15; target dose 2mg/day; max 3mg/day after at least 14 days based on clinical response and tolerability. Moderate to severe hepatic impairment (Child-Pugh ≥7), or renal impairment (CrCl <60mL/min): max 2mg/day. CYP2D6 poor metabolizers: give ½ of usual dose; and if taking with moderate/strong CYP3A4 inhibitors: give ¼ of usual dose. Concomitant strong CYP2D6 or strong CYP3A4 inhibitors: give ½ of usual dose. Concomitant moderate/strong CYP2D6 with moderate/strong CYP3A4 inhibitors: give ¼ of usual dose. Concomitant strong CYP3A4 inducers: double usual dose over 1–2 weeks.

Children

Not established.

Rexulti Contraindications

Not Applicable

Rexulti Boxed Warnings

Boxed Warning

Increased mortality in elderly patients with dementia-related psychosis. Suicidal thoughts and behaviors.

Rexulti Warnings/Precautions

Warnings/Precautions

Elderly with dementia-related psychosis without agitation associated with dementia due to Alzheimer disease (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor closely for worsening or unusual changes in all patients. Cardio- or cerebrovascular disease. Discontinue immediately if neuroleptic malignant syndrome is suspected; treat appropriately and monitor. Tardive dyskinesia. Pre-existing low WBC or ANC or history of leukopenia/neutropenia; monitor CBCs during 1st few months of treatment; discontinue if WBCs decline. Monitor for hyperglycemia/diabetes, dyslipidemia, weight gain. Risk of hypotension, syncope, or aspiration. Pathological gambling and other compulsive behaviors: consider dose reduction or discontinuation if develops. History of seizures or conditions that lower the seizure threshold. Strenuous exercise. Exposure to extreme heat. Dehydration. Hypovolemia. Perform fall risk assessments when initiating and recurrently on long-term therapy. CYP2D6 poor metabolizers. Renal or moderate to severe hepatic impairment. Write ℞ for smallest practical amount. Neonates: risk of extrapyramidal and/or withdrawal symptoms post-delivery (due to exposure during 3rd-trimester pregnancy). Pregnancy. Nursing mothers.

Rexulti Pharmacokinetics

Absorption

  • Peak plasma concentration occurred within 4 hours after administration.

  • Absolute oral bioavailability: 95%.

  • Steady-state concentrations were attained within 10 to 12 days of dosing.

Distribution

  • Volume of distribution after IV administration: 1.56 ± 0.42 L/kg.

  • >99% plasma protein bound.

Metabolism

  • Mainly mediated by CYP3A4 and CYP2D6. 

Elimination

  • Fecal (46%), renal (25%).

  • Half-life: 91 hours.

Rexulti Interactions

Interactions

See Adults. May be potentiated by strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin, ketoconazole) or strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine). May be antagonized by strong CYP3A4 inducers (eg, rifampin, St. John’s wort). Potentiates antihypertensives. Caution with drugs that interfere with temperature regulation (eg, anticholinergics).

Rexulti Adverse Reactions

Adverse Reactions

Weight gain, akathisia, headache, somnolence, tremor, nasopharyngitis, fatigue, increased appetite, dizziness, anxiety, restlessness.

Rexulti Clinical Trials

See Literature

Rexulti Note

Not Applicable

Rexulti Patient Counseling

See Literature

Rexulti Generic Name & Formulations

General Description

Brexpiprazole 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg; tabs.

Pharmacological Class

Atypical antipsychotic.

How Supplied

Tabs—30

Generic Availability

NO

Mechanism of Action

The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.

Rexulti Indications

Indications

Adjunct therapy for major depressive disorder (MDD).

Rexulti Dosage and Administration

Adult

Initially 0.5mg or 1mg once daily; titrate weekly up to target dose of 2mg/day; max 3mg/day. Moderate to severe hepatic impairment (Child-Pugh ≥7), or renal impairment (CrCl <60mL/min): max 2mg/day. CYP2D6 poor metabolizers: give ½ of usual dose; and if taking with moderate/strong CYP3A4 inhibitors: give ¼ of usual dose. Concomitant strong CYP3A4 inhibitors: give ½ of usual dose. Concomitant moderate/strong CYP2D6 with moderate/strong CYP3A4 inhibitors: give ¼ of usual dose. Concomitant strong CYP3A4 inducers: double usual dose over 1–2 weeks.

Children

Not established.

Rexulti Contraindications

Not Applicable

Rexulti Boxed Warnings

Boxed Warning

Increased mortality in elderly patients with dementia-related psychosis. Suicidal thoughts and behaviors.

Rexulti Warnings/Precautions

Warnings/Precautions

Elderly with dementia-related psychosis without agitation associated with dementia due to Alzheimer disease (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor closely for worsening or unusual changes in all patients. Cardio- or cerebrovascular disease. Discontinue immediately if neuroleptic malignant syndrome is suspected; treat appropriately and monitor. Tardive dyskinesia. Pre-existing low WBC or ANC or history of leukopenia/neutropenia; monitor CBCs during 1st few months of treatment; discontinue if WBCs decline. Monitor for hyperglycemia/diabetes, dyslipidemia, weight gain. Risk of hypotension, syncope, or aspiration. Pathological gambling and other compulsive behaviors: consider dose reduction or discontinuation if develops. History of seizures or conditions that lower the seizure threshold. Strenuous exercise. Exposure to extreme heat. Dehydration. Hypovolemia. Perform fall risk assessments when initiating and recurrently on long-term therapy. CYP2D6 poor metabolizers. Renal or moderate to severe hepatic impairment. Write ℞ for smallest practical amount. Neonates: risk of extrapyramidal and/or withdrawal symptoms post-delivery (due to exposure during 3rd-trimester pregnancy). Pregnancy. Nursing mothers.

Rexulti Pharmacokinetics

Absorption

  • Peak plasma concentration occurred within 4 hours after administration.

  • Absolute oral bioavailability: 95%.

  • Steady-state concentrations were attained within 10 to 12 days of dosing.

Distribution

  • Volume of distribution after IV administration: 1.56 ± 0.42 L/kg.

  • >99% plasma protein bound.

Metabolism

  • Mainly mediated by CYP3A4 and CYP2D6. 

Elimination

  • Fecal (46%), renal (25%).

  • Half-life: 91 hours.

Rexulti Interactions

Interactions

See Adults. May be potentiated by strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin, ketoconazole) or strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine). May be antagonized by strong CYP3A4 inducers (eg, rifampin, St. John’s wort). Potentiates antihypertensives. Caution with drugs that interfere with temperature regulation (eg, anticholinergics).

Rexulti Adverse Reactions

Adverse Reactions

Weight gain, akathisia, headache, somnolence, tremor, nasopharyngitis, fatigue, increased appetite, dizziness, anxiety, restlessness.

Rexulti Clinical Trials

See Literature

Rexulti Note

Not Applicable

Rexulti Patient Counseling

See Literature

Rexulti Generic Name & Formulations

General Description

Brexpiprazole 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg; tabs.

Pharmacological Class

Atypical antipsychotic.

How Supplied

Tabs—30

Generic Availability

NO

Mechanism of Action

The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.

Rexulti Indications

Indications

Schizophrenia.

Rexulti Dosage and Administration

Adult

>17yrs: Initially 1mg once daily on Days 1–4; titrate to 2mg once daily on Day 5–7, then to 4mg once daily on Day 8; target dose 2–4mg/day; max 4mg/day. Moderate to severe hepatic impairment (Child-Pugh ≥7), or renal impairment (CrCl <60mL/min): max 3mg/day. CYP2D6 poor metabolizers: give ½ of usual dose; and if taking with moderate/strong CYP3A4 inhibitors: give ¼ of usual dose. Concomitant strong CYP2D6 or strong CYP3A4 inhibitors: give ½ of usual dose. Concomitant moderate/strong CYP2D6 with moderate/strong CYP3A4 inhibitors: give ¼ of usual dose. Concomitant strong CYP3A4 inducers: double usual dose over 1–2 weeks.

Children

<13yrs: not established. 13–17yrs: Initially 0.5mg once daily on Days 1–4; titrate to 1mg once daily on Day 5–7, then to 2mg once daily on Day 8; target dose 2–4mg/day; max 4mg/day. Moderate to severe hepatic impairment (Child-Pugh ≥7), or renal impairment (CrCl <60mL/min): max 3mg/day. CYP2D6 poor metabolizers: give ½ of usual dose; and if taking with moderate/strong CYP3A4 inhibitors: give ¼ of usual dose. Concomitant strong CYP2D6 or strong CYP3A4 inhibitors: give ½ of usual dose. Concomitant moderate/strong CYP2D6 with moderate/strong CYP3A4 inhibitors: give ¼ of usual dose. Concomitant strong CYP3A4 inducers: double usual dose over 1–2 weeks.

Rexulti Contraindications

Not Applicable

Rexulti Boxed Warnings

Boxed Warning

Increased mortality in elderly patients with dementia-related psychosis. Suicidal thoughts and behaviors.

Rexulti Warnings/Precautions

Warnings/Precautions

Elderly with dementia-related psychosis without agitation associated with dementia due to Alzheimer disease (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor closely for worsening or unusual changes in all patients. Cardio- or cerebrovascular disease. Discontinue immediately if neuroleptic malignant syndrome is suspected; treat appropriately and monitor. Tardive dyskinesia. Pre-existing low WBC or ANC or history of leukopenia/neutropenia; monitor CBCs during 1st few months of treatment; discontinue if WBCs decline. Monitor for hyperglycemia/diabetes, dyslipidemia, weight gain. Risk of hypotension, syncope, or aspiration. Pathological gambling and other compulsive behaviors: consider dose reduction or discontinuation if develops. History of seizures or conditions that lower the seizure threshold. Strenuous exercise. Exposure to extreme heat. Dehydration. Hypovolemia. Perform fall risk assessments when initiating and recurrently on long-term therapy. CYP2D6 poor metabolizers. Renal or moderate to severe hepatic impairment. Write ℞ for smallest practical amount. Neonates: risk of extrapyramidal and/or withdrawal symptoms post-delivery (due to exposure during 3rd-trimester pregnancy). Pregnancy. Nursing mothers.

Rexulti Pharmacokinetics

Absorption

  • Peak plasma concentration occurred within 4 hours after administration.

  • Absolute oral bioavailability: 95%.

  • Steady-state concentrations were attained within 10 to 12 days of dosing.

Distribution

  • Volume of distribution after IV administration: 1.56 ± 0.42 L/kg.

  • >99% plasma protein bound.

Metabolism

  • Mainly mediated by CYP3A4 and CYP2D6. 

Elimination

  • Fecal (46%), renal (25%).

  • Half-life: 91 hours.

Rexulti Interactions

Interactions

See Adults. May be potentiated by strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin, ketoconazole) or strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine). May be antagonized by strong CYP3A4 inducers (eg, rifampin, St. John’s wort). Potentiates antihypertensives. Caution with drugs that interfere with temperature regulation (eg, anticholinergics).

Rexulti Adverse Reactions

Adverse Reactions

Weight gain, akathisia, headache, somnolence, tremor, nasopharyngitis, fatigue, increased appetite, dizziness, anxiety, restlessness.

Rexulti Clinical Trials

See Literature

Rexulti Note

Not Applicable

Rexulti Patient Counseling

See Literature