Rexulti

Rexulti (brexpiprazole) is an atypical antipsychotic indicated for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of schizophrenia, and for the treatment of agitation associated with Alzheimer's disease.

Rexulti is a prescription medicine used to treat:

• Major depressive disorder (MDD) in adults: Rexulti is used with antidepressant medicines, when your healthcare provider determines that an antidepressant alone is not enough to treat your depression.
• Schizophrenia in adults and children 13 years of age and older.
• Agitation associated with dementia due to Alzheimer's disease. It is not indicated as an as needed ("prn") treatment.

Do not take Rexulti if you are allergic to brexpiprazole or any of the ingredients in Rexulti.

Before taking Rexulti, tell your healthcare provider if you:

• have diabetes or high blood sugar or a family history of diabetes or high blood sugar. Your healthcare provider should check your blood sugar before you start Rexulti and during your treatment.
• have high levels of cholesterol, triglycerides, LDL-cholesterol, or low levels of HDL cholesterol
• have or had seizures (convulsions)
• have or had low or high blood pressure
• have or had heart problems or a stroke
• have or had a low white blood cell count

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 an 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.

Suicidal Thoughts and Behaviors

• Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years and younger in short-term studies.
• Monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors.
• The safety and efficacy of Rexulti have not been established in pediatric patients with MDD.

Rexulti may cause serious side effects, including:

• Stroke in elderly people (cerebrovascular problems) that can lead to death.
• Neuroleptic Malignant Syndrome (NMS): Tell your healthcare provider right away if you have some or all of the following symptoms: high fever, stiff muscles, confusion, sweating, changes in pulse, heart rate, and blood pressure. These may be symptoms of a rare and serious condition that can lead to death. Call your healthcare provider right away if you have any of these symptoms.
• Uncontrolled body movements (tardive dyskinesia): Rexulti may cause movements that you cannot control in your face, tongue or other body parts. Tardive dyskinesia may not go away, even if you stop taking Rexulti. Tardive dyskinesia may also start after you stop taking Rexulti.
• Unusual urges. Some people taking REXULTI have had unusual urges, such as gambling, binge eating or eating that you cannot control (compulsive), compulsive shopping and sexual urges. If you or your family members notice that you are having unusual urges or behaviors, talk to your healthcare provider.
• Low white blood cell count
• Decreased blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.
• Seizures (convulsions)
• Problems controlling your body temperature so that you feel too warm.
• Difficulty swallowing that can cause food or liquid to get into your lungs.
• Problems with your metabolism such as:
  • high blood sugar (hyperglycemia): Increases in blood sugar can happen in some people who take Rexulti. Extremely high blood sugar can lead to coma or death. If you have diabetes or risk factors for diabetes (such as being overweight or having a family history of diabetes), your healthcare provider should check your blood sugar before you start taking Rexulti and during your treatment.
    • increased fat levels (cholesterol and triglycerides) in your blood.
    • weight gain: You and your healthcare provider should check your weight regularly.

Call your healthcare provider if you have any of these symptoms of high blood sugar while taking Rexulti:

• feel very thirsty
• feel sick to your stomach
• need to urinate more than usual
• feel very hungry
• feel weak or tired
• feel confused, or your breath smells fruity

The most common side effects of Rexulti include weight gain and an inner sense of restlessness such as feeling like you need to move.

These are not all the possible side effects of Rexulti. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Administer Rexulti orally, once daily with or without food

Recommended Dosage for Adjunctive Treatment of Major Depressive Disorder (Adults)

The recommended starting Rexulti dosage for the adjunctive treatment of MDD in adults is 0.5 mg or 1 mg once daily. Titrate to 1 mg once daily, then titrate to the target dosage of 2 mg once daily (based on the patient’s clinical response and tolerability, increase the dosage at weekly intervals). The maximum recommended daily dosage is 3 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment.

Recommended Dosage for Schizophrenia (Adults and Pediatric Patients 13 to 17 Years)

Adults

The recommended starting Rexulti dosage for the treatment of schizophrenia in adults is 1 mg 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.

Pediatric Patients (13 to 17 Years Of Age)

The recommended starting Rexulti dosage for the treatment of schizophrenia in pediatric patients 13 to 17 years of age is 0.5 mg taken 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.

Recommended Dosage for Agitation Associated with Dementia Due to Alzheimer’s Disease

The recommended starting Rexulti dosage for the treatment of agitation associated with dementia due to Alzheimer’s disease is 0.5 mg taken once daily on Days 1 to 7. Increase the dosage on Days 8 through 14 to 1 mg once daily, and on Day 15 to 2 mg once daily. The recommended target dose is 2 mg once daily. The dosage can be increased to the maximum recommended daily dosage of 3 mg once daily after at least 14 days, based on clinical response and tolerability.

Recommended Dosage in Patients with Hepatic Impairment

The maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score ≥7) is.

• 2 mg 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

Recommended Dosage in Patients with Renal Impairment

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 for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP Inhibitors or Inducers

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.

Table 1 Dosage Modifications of Rexulti for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP3A4 Inhibitors, CYP2D6 Inhibitors, or CYP3A4 Inducers

Drugs Having Clinically Important Interactions with Rexulti

Table 10: Clinically Important Drug Interactions with Rexulti

Before taking Rexulti, tell your healthcare provider if you:

• are pregnant or plan to become pregnant. It is not known if Rexulti may harm your unborn baby. Using Rexulti in the last trimester of pregnancy may cause muscle movement problems, medicine withdrawal symptoms, or both of these in your newborn.
  • If you become pregnant while taking Rexulti, talk to your healthcare provider about registering with the National Pregnancy Registry for AtypicalAntipsychotics. You can register by calling 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/
• are breastfeeding or plan to breastfeed. It is not known if Rexulti passes into your breast milk. You and your healthcare provider should decide if you will take Rexulti or breastfeed.