Brand Name: Rexulti
Generic Name: brexpiprazole 

Drug Class: Atypical antipsychotic
Similar Drugs: aripiprazole (Abilify), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal)
Manufacturer: Otsuka Pharmaceutical Company Ltd.
FDA Approval Date: July 10, 2015

What is Rexulti and its mechanism of action?

Rexulti is an atypical antipsychotic. The exact mechanism of action for treating schizophrenia or major depressive disorder (MDD) is unknown. It may work through a combination of serotonin (5-HT) and dopamine (DA) receptor activity. Primary effects of atypical antipsychotics is thought to be due to blocking 5-HT2A and D2 receptors. This leads to dopamine release in the prefrontal cortex of the brain which can explain the decrease in negative symptoms and improvement in cognition. Brexpiprazole has mixed activity for serotonin receptors, partial activity for dopamine receptors, and even has affinity for histamine (H1) and muscarinic (M1) receptors.

What are the uses for Rexulti?

Rexulti is used to treat schizophrenia and as add-on therapy for MDD.

Schizophrenia is  a chronic, severe, and disabling brain disorder that has affected people throughout history. People with schizophrenia  may believe people are controlling their thoughts, plotting to harm them, or  reading their minds. As a result they  become withdrawn or extremely agitated. Treatment can help with many symptoms, but most people must learn to cope with symptoms throughout their lives.

Unlike schizophrenia, MDD is a mood disorder. People with MDD have  depressed mood that negatively impacts  their daily life and impairs their ability to work, sleep, study, eat, and enjoy normal activities. Other symptoms of depression are fatigue, feelings of guilt or worthlessness, and suicidal behaviors or thoughts. 

How effective is Rexulti?

Rexulti was studied in two 6-week clinical trials that included 1,310 participants with schizophrenia. Patients were randomized to 2 or 4 mg once per day or placebo. Change in the baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) for symptoms of schizophrenia was measured for each group. Both studies showed a greater reduction in the PANSS score for the Rexulti groups compared to placebo with up to -8.7 difference (on a 30 to 120 scale).

The efficacy of Rexulti as an add-on treatment for MDD was also studied in two 6-week trials that included 1,046 participants who had failed previous single-antidepressant therapy. Rexulti was only studied as an add-on therapy for patients with MDD who  did not have an adequate response to traditional first-line therapies such as fluoxetine (Prozac), escitalopram (Lexapro), sertraline (Zoloft), venlafaxine (Effexor), and other antidepressants. Patients were randomized to 1, 2 or 3 mg once daily plus antidepressant or placebo plus antidepressant. The change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) was measured to determine efficacy over placebo. Both trials showed a statistically significant decrease in the MADRS score for Rexulti groups compared to placebo.

Interesting facts about Rexulti

Rexulti does not prolong the QTc interval at a dose 3-times the maximum recommended human dose (MRHD) for schizophrenia and 4-times MRHD for MDD. Prolonging the QTc interval causes abnormal heart beats. This is an advantage over other antipsychotics (e.g., thioridazine, mesoridazine, chlorpromazine, haloperidol, ziprasidone and olanzapinea) known to increase the QTc interval.

What is the dosage of Rexulti?

Rexulti is available as 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg tablets.

For MDD, the recommended starting dose is 0.5 mg or 1 mg once daily. The recommended maintenance dose is 2 mg/day and maximum dose is 3 mg/day.

For schizophrenia, the recommended starting dose is 1 mg once daily. The recommended maintenance dose is 2 to 4 mg/day and maximum is 4 mg/day.

Rexulti can be taken with or without food.

Tablets should be stored at 20 C to 25 C (68 F to 77 F).

What are the side effects and precautions for Rexulti?

The most common side effects that were experienced by participants in the trials of Rexulti were weight gain and akathisia (restlessness or the need to move). Other side effects  included fatigue, sedation, and tremors. .

Weight gain of ≥7% was experienced by 30% of patients in the long-term, open label depression studies. Twenty percent of patients in the schizophrenia long-term, open label study also experienced ≥7% weight gain.

Patients should not drive a car, operate machinery or participate in  other dangerous activities until they know how Rexulti affects them. . 

A healthcare provider should be notified immediately if any of the following symptoms start, persist, or worsen:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worsening depression
• new or worsening anxiety
• feeling very agitated or restless
• acting on dangerous impulses
• panic attacks
• trouble sleeping (insomnia)
• new or worsening irritability
• acting aggressive, being angry, or violent
• an extreme increase in activity or talking (mania)
• other unusual changes in behavior or mood

What are Rexulti drug interactions?

Strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ketoconazole) increase blood levels of brexpiprazole. The dose of brexpiprazole should be reduced if it is combined with drugs that increase its blood levels. 

Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine) increase blood levels of brexpiprazole. The dose of brexpiprazole should be reduced if it is combined with drugs that increase its blood levels. 

Strong CYP3A4 inducers (e.g., rifampin, St. John’s wort) decrease blood levels of brexpiprazole. The dose of brexpiprazole should be increased if it is combined with drugs that increase its blood levels. 

People who are fast or slow metabolizers also require dose adjustments. Pharmacogenetic testing is used to determine how people metabolize brexpiprazole and a number of other drugs. 

Can pregnant or breastfeeding women take Rexulti?

Adequate studies of Rexulti in pregnant women are not available. Neonates are at an increased risk of extrapyramidal symptoms when antipsychotic drugs similar to Rexulti are given to mothers in the third trimester of pregnancy.

Adequate studies for the presence of brexpiprazole in human milk have not been conducted. Brexpiprazole is secreted in rat milk.

What is the cost of Rexulti?

The wholesale price for all strengths of Rexulti is $34.62 per tablet. Visit Assure for a savings card for a free 30 day supply and copay help.

Resources

FDA Announcement – FDA.gov

Schizophrenia Information – National Institute of Mental Health

Depression Information – National Institute of Mental Health

Rexulti Prescribing Information (package insert) – Otsuka-us.com (Manufacturer Website)

DiPiro JT, et al. Chapter 50: Schizophrenia. Pharmacotherapy: A pathophysiologic Approach, 92. McGraw-Hill Education; 2014.

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Editor: Karine Wong, PharmD