Medical Editor: John P. Cunha, DO, FACOEP
What Is Rexulti?
Rexulti (brexpiprazole) is an atypical antipsychotic indicated for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) and for treatment of schizophrenia.
What Are Side Effects of Rexulti?
Common side effects of Rexulti include:
- weight gain,
- agitation,
- distress,
- restlessness,
- constipation,
- fatigue,
- runny or stuffy nose,
- increased appetite,
- headache,
- drowsiness,
- tremor,
- dizziness, and
- anxiety.
- Children, teenagers, and young adults may have suicidal thoughts while taking Rexulti. Tell your doctor if this occurs.
Dosage for Rexulti
The recommended starting dosage for Rexulti as adjunctive treatment for MDD is 0.5 mg or 1 mg once daily, taken orally. The recommended target Rexulti dosage to treat schizophrenia is 2 mg to 4 mg once daily.
What Drugs, Substances, or Supplements Interact with Rexulti?
Rexulti may interact with:
- strong/moderate CYP2D6 or
- CYP3A4 inhibitors or strong CYP3A4 inducers
Tell your doctor all medications and supplements you use.
Rexulti During Pregnancy and Breastfeeding
The effects of Rexulti on a fetus are unknown. 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. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Rexulti during pregnancy. It is unknown if Rexulti passes into breast milk or if it would affect a nursing infant. Consult your doctor before breastfeeding.
Additional Information
Our Rexulti (brexpiprazole) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
SLIDESHOW
Schizophrenia: Symptoms, Types, Causes, Treatment See SlideshowGet emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.
High doses or long-term use of brexpiprazole can cause a serious movement disorder that may not be reversible. The longer you use brexpiprazole, the more likely you are to develop this disorder, especially if you are a diabetic or an older adult.
Call your doctor at once if you have:
- uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);
- trouble swallowing;
- feelings of warmth, intolerance to heat;
- a seizure (convulsions);
- a light-headed feeling, like you might pass out;
- high blood sugar--increased thirst, increased urination, dry mouth, fruity breath odor;
- low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing;
- severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors; or
- signs of a blood clot--sudden numbness or weakness, problems with vision or speech, swelling or redness in an arm or leg.
You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medicine. Talk with your doctor if this occurs.
Common side effects may include:
- weight gain; or
- feeling restless or being unable to sit still.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
QUESTION
Schizophrenia is the most disabling mental illness. See AnswerSIDE EFFECTS
The following adverse reactions are discussed in more detail in other sections of the labeling:
- Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Cerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis [see WARNINGS AND PRECAUTIONS]
- Neuroleptic Malignant Syndrome (NMS) [see WARNINGS AND PRECAUTIONS]
- Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS]
- Metabolic Changes [see WARNINGS AND PRECAUTIONS]
- Pathological Gambling and Other Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
- Leukopenia, Neutropenia, and Agranulocytosis [see WARNINGS AND PRECAUTIONS]
- Orthostatic Hypotension and Syncope [see WARNINGS AND PRECAUTIONS]
- Falls [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
- Body Temperature Dysregulation [see WARNINGS AND PRECAUTIONS]
- Dysphagia [see WARNINGS AND PRECAUTIONS]
- Potential for Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Major Depressive Disorder
The safety of REXULTI was evaluated in 1054 adult patients (18 to 65 years of age) diagnosed with MDD who participated in two 6-week placebo-controlled, fixed-dose clinical trials in patients with major depressive disorder in which REXULTI was administered at doses of 1 mg to 3 mg daily as adjunctive treatment to continued antidepressant therapy; patients in the placebo group continued to receive antidepressant therapy [see Clinical Studies].
Adverse Reactions Reported As Reasons For Discontinuation Of Treatment
A total of 3% (17/643) of REXULTI-treated patients and 1% (3/411) of placebo-treated patients discontinued due to adverse reactions.
Common Adverse Reactions
Adverse reactions associated with the adjunctive use of REXULTI (incidence of 2% or greater and adjunctive REXULTI incidence greater than adjunctive placebo) that occurred during acute therapy (up to 6-weeks in patients with MDD) are shown in Table 7.
Table 7 : Adverse Reactions in Pooled 6-Week Placebo-Controlled, Fixed-Dose MDD Trials in Adults (Studies 1 and 2)*
| Placebo (N=411) |
R | EXULTI | |||
| 1 mg/day (N=226) |
2 mg/day (N=188) |
3 mg/day (N=229) |
All REXULTI (N=643) |
||
| Gastrointestinal Disorders | |||||
| Constipation | 1% | 3% | 2% | 1% | 2% |
| General Disorders and Administration Site Conditions | |||||
| Fatigue | 2% | 3% | 2% | 5% | 3% |
| Infections and Infestations | |||||
| Nasopharyngitis | 2% | 7% | 1% | 3% | 4% |
| Investigations | |||||
| Weight Increased | 2% | 7% | 8% | 6% | 7% |
| Blood Cortisol Decreased | 1% | 4% | 0% | 3% | 2% |
| Metabolism and Nutrition | |||||
| Increased Appetite | 2% | 3% | 3% | 2% | 3% |
| Nervous System Disorders | |||||
| Akathisia | 2% | 4% | 7% | 14% | 9% |
| Headache | 6% | 9% | 4% | 6% | 7% |
| Somnolence | 0.5% | 4% | 4% | 6% | 5% |
| Tremor | 2% | 4% | 2% | 5% | 4% |
| Dizziness | 1% | 1% | 5% | 2% | 3% |
| Psychiatric Disorders | |||||
| Anxiety | 1% | 2% | 4% | 4% | 3% |
| Restlessness | 0% | 2% | 3% | 4% | 3% |
| *Adverse reactions that occurred in ≥2% of REXULTI-treated patients and greater incidence than in placebo-treated patients | |||||
Dose-Related Adverse Reactions In The MDD Trials
In Studies 1 and 2, among the adverse reactions that occurred at ≥2% incidence in the patients treated with REXULTI plus ADT, the incidences of akathisia and restlessness increased with increases in dose.
Schizophrenia
Adults
The safety of REXULTI was evaluated in 852 adult patients (18 to 65 years of age) diagnosed with schizophrenia who participated in two 6-week placebo-controlled, fixed-dose clinical trials in which REXULTI was administered at daily doses of 1 mg, 2 mg, and 4 mg [see Clinical Studies].
Common Adverse Reactions
Adverse reactions associated with REXULTI (incidence of 2% or greater and REXULTI incidence greater than placebo) during short-term (up to 6 weeks) trials in adult patients with schizophrenia are shown in Table 8.
Table 8 : Adverse Reactions in Pooled 6-Week Placebo-Controlled, Fixed-Dose Schizophrenia Trials in Adult Patients (Studies 3 and 4)*
| Placebo (N=368) |
REXULTI | ||||
| 1 mg/day (N=120) |
2 mg/day (N=368) |
4 mg/day (N=364) |
ALL REXULTI (N=852) |
||
| Gastrointestinal Disorders | |||||
| Dyspepsia | 2% | 6% | 2% | 3% | 3% |
| Diarrhea | 2% | 1% | 3% | 3% | 3% |
| Investigations | |||||
| Weight Increased | 2% | 3% | 4% | 4% | 4% |
| Blood Creatinine Phosphokinase Increased | 1% | 4% | 2% | 2% | 2% |
| Nervous System Disorders | |||||
| Akathisia | 5% | 4% | 5% | 7% | 6% |
| Tremor | 1% | 2% | 2% | 3% | 3% |
| Sedation | 1% | 2% | 2% | 3% | 2% |
| *Adverse reactions that occurred in ≥2% of REXULTI-treated patients and greater incidence than in placebo-treated patients | |||||
Extrapyramidal Symptoms
Major Depressive Disorder
The incidence of reported extrapyramidal symptoms (EPS)-related adverse reactions, excluding akathisia, was 6% for REXULTI plus ADT-treated patients versus 3% for placebo plus ADT-treated patients. The incidence of akathisia events for REXULTI plus ADT-treated patients was 9% versus 2% for placebo plus ADT-treated patients.
In the 6-week placebo-controlled MDD studies , data was objectively collected on the Simpson-Angus Rating Scale (SAS) for EPS, the Barnes Akathisia Rating Scale (BARS) for akathisia and the Abnormal Involuntary Movement Score (AIMS) for dyskinesia. The mean change from baseline at last visit for REXULTI plus ADTtreated patients for the SAS, BARS and AIMS was comparable to placebo-treated patients. The percentage of patients who shifted from normal to abnormal was greater in REXULTI plus ADT-treated patients versus placebo plus ADT-treated patients for the BARS (4% versus 0.6%) and the SAS (4% versus 3%).
Schizophrenia
The incidence of reported EPS-related adverse reactions, excluding akathisia, was 5% for REXULTI-treated patients versus 4% for placebo-treated patients. The incidence of akathisia events for REXULTI-treated patients was 6% versus 5% for placebo-treated patients.
In the 6-week placebo-controlled, fixed-dose schizophrenia studies in adults, data was objectively collected on the Simpson-Angus Rating Scale (SAS) for EPS, the Barnes Akathisia Rating Scale (BARS) for akathisia and the Abnormal Involuntary Movement Scale (AIMS) for dyskinesia. The mean change from baseline at last visit for REXULTI-treated patients for the SAS, BARS and AIMS was comparable to placebo-treated patients. The percentage of patients who shifted from normal to abnormal was greater in REXULTI-treated patients versus placebo for the BARS (2% versus 1%) and the SAS (7% versus 5%).
Dystonia
Symptoms of dystonia may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first-generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
Other Adverse Reactions Observed During The Premarketing Evaluation Of REXULTI
Other adverse reactions (≥1% frequency and greater than placebo) within the short-term, placebo-controlled trials in adult patients with MDD and schizophrenia are shown below. The following listing does not include adverse reactions: 1) already listed in previous tables or elsewhere in the labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have clinically significant implications, or 5) which occurred at a rate equal to or less than placebo.
Eye Disorders: Vision Blurred
Gastrointestinal Disorders: Nausea, Dry Mouth, Salivary Hypersecretion, Abdominal Pain, Flatulence
Infections and Infestations: Urinary Tract Infection
Investigations: Blood Prolactin Increased
Musculoskeletal and Connective Tissue Disorders: Myalgia
Psychiatric Disorders: Abnormal Dreams, Insomnia
Skin and Subcutaneous Tissue Disorders: Hyperhidrosis
Pediatric Patients (13 To 17 Years Of Age)
In an on-going, 2 year, open-label study in pediatric patients 13 to 17 years of age with schizophrenia, in which safety was assessed in 194 patients of which 140 received REXULTI for at least 6 months. Adverse reactions reported in clinical studies for this age group were generally similar to those observed in adult patients.
Postmarketing Experience
The following adverse reaction has been identified during post-approval use of REXULTI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Nervous System disorders: Neuroleptic Malignant Syndrome
DRUG INTERACTIONS
Drugs Having Clinically Important Interactions With REXULTI
| Strong CYP3A4 Inhibitors | |
| Clinical Impact: | Concomitant use of REXULTI with strong CYP3A4 inhibitors increased the exposure of brexpiprazole compared to the use of REXULTI alone [see CLINICAL PHARMACOLOGY]. |
| Intervention: | With concomitant use of REXULTI with a strong CYP3A4 inhibitor, reduce the REXULTI dosage [see DOSAGE AND ADMINISTRATION]. |
| Strong CYP2D6 Inhibitors* | |
| Clinical Impact: | Concomitant use of REXULTI with strong CYP2D6 inhibitors increased the exposure of brexpiprazole compared to the use of REXULTI alone [see CLINICAL PHARMACOLOGY]. |
| Intervention: | With concomitant use of REXULTI with a strong CYP2D6 inhibitor, reduce the REXULTI dosage [see DOSAGE AND ADMINISTRATION]. |
| Both CYP3A4 Inhibitors and CYP2D6 Inhibitors | |
| Clinical Impact: | Concomitant use of REXULTI with 1) a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 2) a moderate CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 3) a strong CYP3A4 inhibitor and a moderate CYP2D6 inhibitor; or 4) a moderate CYP3A4 inhibitor and a moderate CYP2D6 inhibitor increased the exposure of brexpiprazole compared to the use of REXULTI alone [see CLINICAL PHARMACOLOGY]. |
| Intervention: | With concomitant use of REXULTI with 1) a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 2) a moderate CYP3A4 inhibitor and a strong CYP2D6 inhibitor; or 3) a strong CYP3A4 inhibitor and a moderate CYP2D6 inhibitor; or 4) a moderate CYP3A4 inhibitor and a moderate CYP2D6 inhibitor. decrease the REXULTI dosage [see DOSAGE AND ADMINISTRATION]. |
| Strong CYP3A4 Inducers | |
| Clinical Impact: | Concomitant use of REXULTI and a strong CYP3A4 inducer decreased the exposure of brexpiprazole compared to the use of REXULTI alone [see CLINICAL PHARMACOLOGY]. |
| Intervention: | With concomitant use of REXULTI with a strong CYP3A4 inducer. increase the REXULTI dosage [see DOSAGE AND ADMINISTRATION]. |
| *In the clinical trials examining the adjunctive use of REXULTI in the 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. | |
Drugs Having No Clinically Important Interactions With REXULTI
Based on pharmacokinetic studies, no dosage adjustment of REXULTI is required when administered concomitantly with CYP2B6 inhibitors (e.g., ticlopidine) or gastric pH modifiers (e.g., omeprazole). Additionally, no dosage adjustment for substrates of CYP2D6 (e.g., dextromethorphan), CYP3A4 (e.g., lovastatin), CYP2B6 (e.g., bupropion), BCRP (e.g., rosuvastatin), or P-gp (e.g., fexofenadine) is required when administered concomitantly with REXULTI.
Read the entire FDA prescribing information for Rexulti (Brexpiprazole Tablets)
© Rexulti Patient Information is supplied by Cerner Multum, Inc. and Rexulti Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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