Dosage & Administration
Advise patients that REXULTI can be taken with or without food. Advise patients regarding importance of following dosage escalation instructions
Administer REXULTI orally once daily with or without food.
| Indication | Starting Dosage | Recommended Target Dosage | Maximum Dosage |
|---|---|---|---|
| MDD Adults | 0.5 mg/day or 1 mg/day | 2 mg/day | 3 mg/day |
| Schizophrenia Adults | 1 mg/day | 2 to 4 mg/day | 4 mg/day |
| Schizophrenia Pediatric (13 - 17 years) | 0.5 mg/day | 2 to 4 mg/day | 4 mg/day |
| Agitation associated with dementia due to Alzheimer's disease | 0.5 mg/day | 2 mg/day | 3 mg/day |
Administer REXULTI orally, once daily with or without food
The recommended starting REXULTI dosage for the adjunctive treatment of MDD in adults is 0.5 mg or 1 mg orally once daily
The recommended starting REXULTI dosage for the treatment of schizophrenia in adults is 1 mg orally once daily on Days 1 to 4. Titrate to 2 mg once daily on Day 5 through Day 7. On Day 8, the dosage can be increased to the maximum recommended daily dosage of 4 mg based on clinical response and tolerability. The recommended target dosage is 2 mg to 4 mg once daily.
The recommended starting REXULTI dosage for the treatment of schizophrenia in pediatric patients 13 to 17 years of age is 0.5 mg orally once daily on Days 1 to 4. On Days 5 through 7, titrate to 1 mg per day and on Day 8 titrate to 2 mg based on clinical response and tolerability. Weekly dose increases can be made in 1 mg increments. A recommended target dosage is 2 to 4 mg once daily. The maximum recommended daily dosage is 4 mg.
The recommended starting REXULTI dosage for the treatment of agitation associated with dementia due to Alzheimer's disease is 0.5 mg orally once daily on Days 1 to 7
The maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score ≥7) is
2 mg orally once daily in patients with MDD or agitation associated with dementia due to Alzheimer's disease, and
3 mg orally once daily in patients with schizophrenia
The maximum recommended dosage in patients with creatinine clearance CrCl<60 mL/minute is
2 mg orally once daily in patients with MDD or agitation associated with dementia due to Alzheimer's disease and
3 mg orally once daily in patients with schizophrenia
Dosage modifications are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors, CYP2D6 inhibitors, or strong CYP3A4 inducers (see Table 1). If the concomitant drug is discontinued, adjust the REXULTI dosage to its original level. If the concomitant CYP3A4 inducer is discontinued, reduce the REXULTI dosage to the original level over 1 to 2 weeks
| Factors | Adjusted REXULTI Dosage |
|---|---|
CYP2D6 Poor Metabolizers | |
| CYP2D6 poor metabolizers | Administer half of the recommended dosage. |
| Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors | Administer a quarter of the recommended dosage. |
Patients Taking CYP2D6 Inhibitors and/or CYP3A4 Inhibitors | |
| Strong CYP2D6 inhibitorsIn the clinical studies examining the use of REXULTI for the adjunctive treatment of MDD, dosage was not adjusted for strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). Thus, CYP considerations are already factored into general dosing recommendations, and REXULTI may be administered without dosage adjustment in patients with MDD. | Administer half of the recommended dosage. |
| Strong CYP3A4 inhibitors | Administer half of the recommended dosage. |
| Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors | Administer a quarter of the recommended dosage. |
Patients Taking CYP3A4 Inducers | |
| Strong CYP3A4 inducers | Double the recommended dosage over 1 to 2 weeks. |
By using PrescriberAI, you agree to the AI Terms of Use.
Rexulti Prescribing Information
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS
- Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. REXULTI is not approved for the treatment of patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer's disease. ()
5.1 Increased Mortality in Elderly Patients with Dementia-Related PsychosisElderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in the drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. REXULTI is not approved for the treatment of patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer's disease
[seeBoxed Warning, Warnings and Precautions (5.3)]. - Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Safety and effectiveness of REXULTI have not been established in pediatric patients with MDD. (,
5.2 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young AdultsIn pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in patients 24 years of age and younger was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 2.
No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide.
Table 2 Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in PediatricREXULTI is not approved in pediatric patients with MDD.and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1,000 Patients Treated Increases Compared to Placebo<18 14 additional patients 18 to 24 5 additional patients Decreases Compared to Placebo25 to 64 1 fewer patient ≥65 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance studies in adults with MDD that antidepressants delay the recurrence of depression.
Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing REXULTI, in patients whose depression is persistently worse or who are experiencing emergent suicidal thoughts or behaviors.
)8.4 Pediatric UseSchizophreniaThe safety and effectiveness of REXULTI for treatment of schizophrenia have been established in pediatric patients 13 years of age and older. Use of REXULTI in this population is supported by evidence from adequate and well-controlled studies in adults and pediatric patients with schizophrenia, pharmacokinetic data from adults and pediatric patients, and safety data in pediatric patients 13 to 17 years of age
[see Warnings and Precautions (5.6), Adverse Reactions (6.1), Clinical Pharmacology (12.3),Clinical Studies (14.2)].The safety and effectiveness of REXULTI for the treatment of schizophrenia have not been established in pediatric patients less than 13 years of age.
Major Depressive DisorderThe safety and effectiveness of REXULTI for treatment of major depressive disorder have not been established in pediatric patients. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients
[see Boxed Warning, Warnings and Precautions (5.2)].Irritability Associated with Autism Spectrum DisorderThe safety and effectiveness of REXULTI for the treatment of irritability associated with autism spectrum disorder have not been established in pediatric patients. Effectiveness was not demonstrated, in an 8-week, double-blind, placebo-controlled, flexible-dose clinical study conducted in 119 REXULTI-treated pediatric patients 5 to 17 years of age with irritability associated with autism spectrum disorder diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, 5thEdition [DSM-5] criteria. In this study, somnolence (including sedation) occurred at a higher rate than reported in other REXULTI studies evaluating adults and elderly patients (16% in REXULTI-treated pediatric patients versus 5% for placebo). The mean increase in age-and-gender adjusted body weight z-score from baseline to last visit was 0.3 for REXULTI-treated patients versus 0.1 for placebo-treated patients. Increases in age-and-gender adjusted body weight z-score of at least 0.5 SD from baseline was higher in REXULTI-treated patients versus placebo (19% versus 5%).
Of the 119 patients from this study, 95 patients entered the open-label treatment study and received up to 26 weeks of daily treatment with brexpiprazole. During the open-label treatment period, 2% of patients discontinued due to weight increase. In patients previously treated with REXULTI for 8 weeks, the mean increase in weight from the open-label study baseline to last visit was 4.5 kg. and 26% of patients had an increase in age-and-gender-adjusted body weight z-score of at least 0.5 SD from baseline.
Juvenile Animal Studies
Juvenile rats were administered oral doses of brexpiprazole of 3, 10, and 20 mg/kg/day once daily beginning from weaning (postnatal day 21) through adulthood (postnatal day 90), followed by a 4-week recovery (non-dosing) period. Results were similar to those observed in previous repeat‑dose toxicity studies in adolescent (8-week-old) rats. Mortality occurred at the high-dose of 20 mg/kg/day, as well as delayed sexual maturation in males and decreased rearing and motor activity. There was no evidence of neurotoxicity or effects on fertility and reproductive function. Histopathologic changes in reproductive organs and mammary glands occurred at all doses, were related to the pharmacology of brexpiprazole and were comparable to those in adult rats. All findings were at least partially reversible. Juvenile dogs were administered oral doses of brexpiprazole of 1, 3, and 30 mg/kg/day once daily starting at 8 or 9 weeks of age for 26 weeks, followed by an 8-week recovery (non-dosing) period. Decreases in body weight, lethargy, changes in heart rate, and immature male sex organs were observed at 30 mg/kg/day. These findings were at least partially reversible.
Warnings and Precautions (Atypical antipsychotic drugs, including REXULTI, have caused metabolic changes including hyperglycemia, diabetes mellitus, dyslipidemia, and body weight gain. Although all of the drugs in the class to date have been shown to produce some metabolic changes, each drug has its own specific risk profile. Hyperglycemia/Diabetes Mellitus Hyperglycemia and diabetes mellitus, in some cases extreme and associated with diabetic ketoacidosis hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics. There have been reports of hyperglycemia in patients treated with REXULTI. Assess fasting plasma glucose before or soon after initiation of antipsychotic medication and monitor periodically during long-term treatment. Adjunctive Treatment of Major Depressive Disorder In the 6-week placebo-controlled, fixed-dose clinical studies in adult patients with MDD, the proportions of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL) and borderline (≥100 and <126 mg/dL) to high were similar in patients treated with REXULTI and placebo. In the long-term, open-label depression studies, 5% of adult patients with normal baseline fasting glucose experienced a shift to high while taking REXULTI plus an antidepressant (ADT); 25% of patients with borderline fasting glucose experienced shifts to high. Combined, 9% of patients with normal or borderline fasting glucose experienced shifts to high fasting glucose during the long-term depression studies. Schizophrenia (Adults) In the 6-week placebo-controlled, fixed-dose clinical studies in adult patients with schizophrenia, the proportions of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL) or borderline (≥100 and <126 mg/dL) to high were similar in patients treated with REXULTI and placebo. In the long-term, open-label schizophrenia studies, 8% of adult patients with normal baseline fasting glucose experienced a shift from normal to high while taking REXULTI; 17% of patients with borderline fasting glucose experienced shifts from borderline to high. Combined, 10% of patients with normal or borderline fasting glucose experienced shifts to high fasting glucose during the long-term schizophrenia studies. Schizophrenia Pediatric Patients (13 to 17 years of age) In a 6-week, placebo-controlled study in pediatric patients with schizophrenia, the proportion of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL) or borderline (≥100 and <126 mg/dL) to high were similar in patients treated with REXULTI and placebo. In this study, 1.1% of pediatric patients with normal baseline fasting glucose experienced a shift from normal (<100 mg/dL) to high (≥126 mg/dL) while taking REXULTI. In the long-term, open-label study in pediatric patients with schizophrenia, 2.7% of pediatric patients with normal baseline fasting glucose experienced a shift from normal (<100 mg/dL) to high (≥126 mg/dL) while taking REXULTI. Agitation Associated with Dementia Due to Alzheimer's Disease In the 12-week placebo-controlled, fixed-dose studies in patients (51 to 90 years of age) with agitation associated with dementia due to Alzheimer's disease, the proportions of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL) or impaired (≥100 and <126 mg/dL) to high were similar in patients treated with REXULTI (14%) and patients treated with placebo (16%). Of the patients who were previously treated with REXULTI for 12-weeks and continued into a 12-week, active-treatment extension study, 15% of patients with normal baseline fasting glucose experienced a shift from normal (<100 mg/dL) to high (≥126 mg/dL) fasting glucose while taking REXULTI; 30% of patients with impaired fasting glucose experienced shifts from impaired fasting glucose (≥100 and <126 mg/dL) to high fasting glucose. Combined, 20% of patients with normal or impaired fasting glucose experienced shifts to high fasting glucose. Dyslipidemia Atypical antipsychotics cause adverse alterations in lipids. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment. Adjunctive Treatment of Major Depressive Disorder In the 6-week placebo-controlled, fixed-dose clinical studies in adult patients with MDD, changes in fasting total cholesterol, LDL cholesterol, and HDL cholesterol were similar in REXULTI- and placebo-treated patients. Table 3 shows the proportions of patients with changes in fasting triglycerides.
In the long-term, open-label depression studies, shifts in baseline fasting cholesterol from normal to high were reported in 9% (total cholesterol), 3% (LDL cholesterol), and shifts in baseline from normal to low were reported in 14% (HDL cholesterol) of patients taking REXULTI. Of patients with normal baseline triglycerides, 17% experienced shifts to high, and 0.2% experienced shifts to very high. Combined, 0.6% of patients with normal or borderline fasting triglycerides experienced shifts to very high fasting triglycerides during the long-term depression studies. Schizophrenia (Adults) In the 6-week placebo-controlled, fixed-dose clinical studies in adult patients with schizophrenia, changes in fasting total cholesterol, LDL cholesterol, and HDL cholesterol were similar in REXULTI- and placebo-treated patients. Table 4 shows the proportions of patients with changes in fasting triglycerides.
In the long-term, open-label schizophrenia studies in adult patients, shifts in baseline fasting cholesterol from normal to high were reported in 6% (total cholesterol), 2% (LDL cholesterol), and shifts in baseline from normal to low were reported in 17% (HDL cholesterol) of patients taking REXULTI. Of patients with normal baseline triglycerides, 13% experienced shifts to high, and 0.4% experienced shifts to very high triglycerides. Combined, 0.6% of patients with normal or borderline fasting triglycerides experienced shifts to very high fasting triglycerides during the long-term schizophrenia studies. Schizophrenia [Pediatric Patients (13 to 17 years of age)] The safety and efficacy of REXULTI have not been established in patients under the age of 13 years. In a 6-week, placebo-controlled study in pediatric patients with schizophrenia, no clinically meaningful changes in fasting cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were observed between the REXULTI and placebo groups. In the long-term, open-label study in pediatric patients with schizophrenia, shifts in baseline fasting total cholesterol from normal to high (<170 to ≥200 mg/dL) were reported in 7% of patients taking REXULTI, and shifts in baseline HDL cholesterol from normal to low (>45 to <40 mg/dL) were reported in 10%% of patients taking REXULTI. Of patients with normal baseline triglycerides, 15% experienced shifts from normal to high (<90 to ≥130 mg/dL). Agitation Associated with Dementia Due to Alzheimer's Disease In the 12-week placebo-controlled, fixed-dose clinical studies in patients (55 to 90 years of age) with agitation associated with dementia due to Alzheimer's disease, changes in total cholesterol, LDL cholesterol, and HDL cholesterol were similar in REXULTI- and placebo-treated patients. Table 5 shows the proportions of patients with changes in fasting triglycerides in REXULTI- and placebo-treated patients.
Of the patients who were previously treated with REXULTI for 12 weeks and continued into a 12-week, active-treatment extension study, 9% of patients taking REXULTI showed shifts in baseline fasting total cholesterol from normal (<200 mg/dL) to high (≥240 mg/dL), and 16% of patients taking REXULTI showed shifts in baseline HDL cholesterol from normal to low (≥40 to <40 mg/dL). Of the patients with normal baseline triglycerides, 18% experienced shifts from normal (<150 mg/dL) to high (200 to <500 mg/dL). Weight Gain Weight gain has been observed in patients treated with atypical antipsychotics, including REXULTI. Monitor weight at baseline and frequently thereafter. Adjunctive Treatment of Major Depressive Disorder: Table 6 shows weight gain data at last visit and percentage of adult patients with ≥7% increase in body weight at endpoint from the 6-week placebo-controlled, fixed-dose clinical studies in patients with MDD.
In the long-term, open-label depression studies, 4% of patients discontinued due to weight increase. REXULTI was associated with mean change from baseline in weight of 2.9 kg at Week 26 and 3.1 kg at Week 52. In the long-term, open-label depression studies, 30% of patients demonstrated a ≥7% increase in body weight, and 4% demonstrated a ≥7% decrease in body weight. Schizophrenia ( Adults)Table 7 shows weight gain data at last visit and percentage of adult patients with ≥7% increase in body weight at endpoint from the 6-week placebo-controlled, fixed-dose clinical studies in adult patients with schizophrenia.
In the long-term, open-label schizophrenia studies in adult patients, 0.6% of patients discontinued due to weight increase. REXULTI was associated with mean change from baseline in weight of 1.3 kg at Week 26 and 2.0 kg at Week 52. In the long-term, open label schizophrenia studies, 20% of patients demonstrated a ≥7% increase in body weight, and 10% demonstrated a ≥7% decrease in body weight. Schizophrenia [Pediatric Patients (13 to 17 years of age)] In a 6-week, placebo-controlled study in pediatric patients with schizophrenia, no patients discontinued due to weight increase. The mean increase in weight from baseline to last visit was 0.8 kg in the REXULTI group and no changes were seen in the placebo groups. The percentage of pediatric patients demonstrating a ≥7% increase in body weight was 8.2% in the REXULTI group and 4.9% in the placebo group. In the long-term, open label study in pediatric patients with schizophrenia, 0.5% of patients discontinued due to weight increase. The mean increase in weight from the open-label study baseline to last visit was 3.8 kg. To adjust for normal growth, z-scores were derived (measured in standard deviations [SD]), which normalize for natural growth of children and adolescents by comparisons to age- and gender- matched population standards. A z-score change <0.5 SD is considered not clinically significant. In this study, the mean change in z-score from open-label baseline to last visit was 0.10 SD for body weight, while 20% of patients had an increase in age-and-gender-adjusted body weight z-score of at least 0.5 SD from baseline. When treating pediatric, weight gain should be monitored and assessed against that expected for normal growth. Agitation Associated with Dementia Due to Alzheimer's Disease In the 12-week placebo-controlled, fixed-dose clinical studies in patients (51 to 90 years of age) with agitation associated with dementia due to Alzheimer's disease, the proportion of the patients with a ≥7% increase in body weight (kg) at any visit were 2% in REXULTI compared to 0% in placebo group. In patients who were previously treated with REXULTI for 12 weeks and who continued into a 12-week, active-treatment extension study, there was no mean change in weight (kg) from baseline to last visit in association with REXULTI. In this extension study, 4% of patients demonstrated ≥7% increase in body weight, and 5% demonstrated a ≥7% decrease in body weight from baseline to last visit. | 5/2025 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
REXULTI is indicated for:
- Adjunctive treatment to antidepressants for major depressive disorder (MDD) in adults
- Treatment of schizophrenia in adults and pediatric patients ages 13 years and older
- Treatment of agitation associated with dementia due to Alzheimer's disease
REXULTI is not indicated as an as needed ("prn") treatment for agitation associated with dementia due to Alzheimer's disease [see
The efficacy of REXULTI in the treatment of agitation associated with dementia due to Alzheimer's disease was demonstrated in two 12-week, randomized, double-blind, placebo-controlled, fixed-dose studies (Study 6, NCT01862640 and Study 7, NCT03548584). In these studies, patients were required to:
- Have a diagnosis of probable Alzheimer's disease according to NINCDS-ADRDA criteria,
- Have a Mini-Mental State Examination (MMSE) score of ≥5 and ≤22 and have a total score of ≥4 by the agitation/aggression item of the NPI/NPI-NH, and
- Exhibit sufficient agitation behaviors at time of entry to warrant use of pharmacotherapy, after excluding other factors.
Patients in:
- Study 6 were randomized to an oral dosage of either REXULTI 1 mg once a day, REXULTI 2 mg once a day, or placebo. Patients in both REXULTI groups started on 0.25 mg once daily for approximately three days, then received 0.5 mg once daily for approximately 12 days. Subsequently, patients in the 1 mg group received 1 mg once daily for the remainder of the 12-week study, and patients in the 2 mg group received 1 mg once daily for approximately two weeks and then received 2 mg for the remainder of the study.
- Study 7 were randomized to an oral dose of either REXULTI 2 mg or 3 mg once a day (combined treatment arm) or placebo. Patients in both REXULTI groups started on 0.5 mg once daily for 7 days, then received 1 mg once daily for 7 days and then 2 mg once daily for 14 days. Subsequently, patients in the 2 mg group received 2 mg once daily for the remainder of the 12-week study, and patients in the 3 mg group received 3 mg once daily for the remainder of the study.
Study 6 included 433 patients with a mean age of 74 years old, and a range of 51 and 90 years old; 45% were male; 96%, 3%, and 1%, were White, Black or African American, and Asian, respectively; and 16% and 83% were Latino/Hispanic and not Latino/Hispanic, respectively. Study 7 included 345 patients with a mean age of 74 years old, and a range of 56 and 90 years old; 44% were male; 95%, 4%, and 1% were White, Black or African American, and Asian, respectively; and 31% and 69% were Latino/Hispanic and not Latino/Hispanic, respectively.
The primary efficacy endpoint in these two studies was the change from baseline in the Cohen-Mansfield Agitation Inventory total (CMAI) score at Week 12. The CMAI is a clinician rated questionnaire consisting of 29 items, which assess the frequency of manifestations of agitated behaviors in elderly patients, based on caregiver input. Three specific factors can be derived from the CMAI scale: 1) Aggressive Behavior (e.g., screaming, throwing things, cursing/verbal aggression, kicking, pushing scratching, hurting self or others); 2) Physically Non-Aggressive Behavior (e.g., repetitive mannerisms, general restlessness, pacing); and 3) Verbally Agitated Behavior (e.g., complaining, repetitive questions, constant requests for attention). Each CMAI behavior was rated on a scale of 1 (never) to 7 (very frequent agitated behaviors); the total CMAI scores range from 29 (best) to 203 (worst). A negative change indicates improvement.
In Trial 6, patients in the REXULTI 2 mg group showed improved total CMAI scores compared to patients in the placebo group at Week 12. In Trial 7, patients in the REXULTI 2 mg/3 mg group showed improved total CMAI scores compared to patients in the placebo group at Week 12.
As shown in Table 16 and Figure 8, the mean change from baseline in the total CMAI score after 12 weeks in the 2 mg/or 3 mg REXULTI group was statistically significantly superior to the placebo group. The 1 mg REXULTI group did not demonstrate significantly greater mean changes at baseline from the placebo group in the total CMAI score in this patient population. The 1 mg once day REXULTI dosage is not approved and is not recommended for the treatment of agitation associated with dementia due to Alzheimer's disease
| Study | Treatment Group | N | Mean Baseline Score (SD) | LS Mean Change from Baseline (SE) | Placebo-subtracted DifferenceDifference (drug minus placebo) in least-squares mean change from baseline (95% CI) |
|---|---|---|---|---|---|
| SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval | |||||
| 6 | REXULTI 1 mg/day | 134 | 70.5 (16.0) | -17.6 (1.3) | 0.2 (-3.4, 3.9) |
| REXULTI 2 mg/dayDosages statistically significantly superior to placebo. | 138 | 71.0 (16.6) | -21.6 (1.3) | -3.8 (-7.4, -0.2) | |
| Placebo | 131 | 72.2 (17.9) | -17.8 (1.3) | — | |
| 7 | REXULTI 2 mg/day or 3 mg/day | 225 | 80.6 (16.6) | -22.6 (1.1) | -5.3 (-8.8, -1.9) |
| Placebo | 116 | 79.2 (17.5) | -17.3 (1.4) | — | |
Advise patients that REXULTI can be taken with or without food. Advise patients regarding importance of following dosage escalation instructions
Administer REXULTI orally once daily with or without food.
| Indication | Starting Dosage | Recommended Target Dosage | Maximum Dosage |
|---|---|---|---|
| MDD Adults | 0.5 mg/day or 1 mg/day | 2 mg/day | 3 mg/day |
| Schizophrenia Adults | 1 mg/day | 2 to 4 mg/day | 4 mg/day |
| Schizophrenia Pediatric (13 - 17 years) | 0.5 mg/day | 2 to 4 mg/day | 4 mg/day |
| Agitation associated with dementia due to Alzheimer's disease | 0.5 mg/day | 2 mg/day | 3 mg/day |
- Moderate to Severe Hepatic Impairment:Maximum recommended dosage is 2 mg once daily for patients with MDD or agitation associated with dementia due to Alzheimer's disease and 3 mg once daily for patients with schizophrenia.
- CrCl<60 mL/minute:Maximum recommended dosage is 2 mg once daily for patients with MDD or agitation associated with dementia due to Alzheimer's disease and 3 mg once daily for patients with schizophrenia.
- See Full Prescribing Information for dosage modifications for CYP2D6 poor metabolizers and for concomitant use with CYP inhibitors or inducers.
Administer REXULTI orally, once daily with or without food
The recommended starting REXULTI dosage for the adjunctive treatment of MDD in adults is 0.5 mg or 1 mg orally once daily
The recommended starting REXULTI dosage for the treatment of schizophrenia in adults is 1 mg orally once daily on Days 1 to 4. Titrate to 2 mg once daily on Day 5 through Day 7. On Day 8, the dosage can be increased to the maximum recommended daily dosage of 4 mg based on clinical response and tolerability. The recommended target dosage is 2 mg to 4 mg once daily.
The recommended starting REXULTI dosage for the treatment of schizophrenia in pediatric patients 13 to 17 years of age is 0.5 mg orally once daily on Days 1 to 4. On Days 5 through 7, titrate to 1 mg per day and on Day 8 titrate to 2 mg based on clinical response and tolerability. Weekly dose increases can be made in 1 mg increments. A recommended target dosage is 2 to 4 mg once daily. The maximum recommended daily dosage is 4 mg.
The recommended starting REXULTI dosage for the treatment of agitation associated with dementia due to Alzheimer's disease is 0.5 mg orally once daily on Days 1 to 7
The maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score ≥7) is
2 mg orally once daily in patients with MDD or agitation associated with dementia due to Alzheimer's disease, and
3 mg orally once daily in patients with schizophrenia
The maximum recommended dosage in patients with creatinine clearance CrCl<60 mL/minute is
2 mg orally once daily in patients with MDD or agitation associated with dementia due to Alzheimer's disease and
3 mg orally once daily in patients with schizophrenia
Dosage modifications are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors, CYP2D6 inhibitors, or strong CYP3A4 inducers (see Table 1). If the concomitant drug is discontinued, adjust the REXULTI dosage to its original level. If the concomitant CYP3A4 inducer is discontinued, reduce the REXULTI dosage to the original level over 1 to 2 weeks
| Factors | Adjusted REXULTI Dosage |
|---|---|
CYP2D6 Poor Metabolizers | |
| CYP2D6 poor metabolizers | Administer half of the recommended dosage. |
| Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors | Administer a quarter of the recommended dosage. |
Patients Taking CYP2D6 Inhibitors and/or CYP3A4 Inhibitors | |
| Strong CYP2D6 inhibitorsIn the clinical studies examining the use of REXULTI for the adjunctive treatment of MDD, dosage was not adjusted for strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). Thus, CYP considerations are already factored into general dosing recommendations, and REXULTI may be administered without dosage adjustment in patients with MDD. | Administer half of the recommended dosage. |
| Strong CYP3A4 inhibitors | Administer half of the recommended dosage. |
| Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors | Administer a quarter of the recommended dosage. |
Patients Taking CYP3A4 Inducers | |
| Strong CYP3A4 inducers | Double the recommended dosage over 1 to 2 weeks. |
REXULTI tablets are available in 6 strengths:
- 0.25 mg tablets are light brown, round, shallow convex, bevel-edged body with "BRX" and "0.25" imprinted on one side.
- 0.5 mg tablets: are light orange, round, shallow convex, bevel-edged body with "BRX" and "0.5" imprinted on one side.
- 1 mg tablets are light yellow, round, shallow convex, bevel-edged body with "BRX" and "1" imprinted on one side.
- 2 mg tablets are light green, round, shallow convex, bevel-edged body with "BRX" and "2" imprinted on one side.
- 3 mg tablets are light purple, round, shallow convex, bevel-edged body with "BRX" and "3" imprinted on one side.
- 4 mg tablets are white, round, shallow convex, bevel-edged body with "BRX" and "4" imprinted on one side.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to REXULTI during pregnancy. For more information contact the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visit
Adequate and well-controlled studies have not been conducted with REXULTI in pregnant women to inform drug-associated risks. However, neonates whose mothers are exposed to antipsychotic drugs, like REXULTI, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. In 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/m2basis. 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
Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder, have been reported in neonates whose mothers were exposed to antipsychotic drugs during the third trimester of pregnancy. These symptoms have varied in severity. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Pregnant rats were treated with oral doses of 3, 10, and 30 mg/kg/day (7.3, 24, and 73 times the MRHD on a mg/m2basis) of brexpiprazole during the period of organogenesis. Brexpiprazole was not teratogenic and did not cause adverse developmental effects at doses up to 73 times the MRHD.
Pregnant rabbits were treated with oral doses of 10, 30, and 150 mg/kg/day (49, 146, and 730 times the MRHD) of brexpiprazole during the period of organogenesis. Brexpiprazole was not teratogenic and did not cause adverse developmental effects at doses up to 146 times the MRHD. Findings of decreased body weight, retarded ossification, and increased incidences of visceral and skeletal variations were observed in fetuses at 730 times the MRHD, a dose that induced maternal toxicity.
In a study in which pregnant rats were administered oral doses of 3, 10, and 30 mg/kg/day (7.3, 24, and 73 times the MRHD) during the period of organogenesis and through lactation, the number of live-born pups was decreased, and early postnatal deaths increased at a dose 73 times the MRHD. Impaired nursing by dams, and low birth weight and decreased body weight gain in pups were observed at 73 times, but not at 24 times, the MRHD.