Regulatory Decision Summary for Rexulti

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

Product type:


Medicinal ingredient(s):


Therapeutic area:

Antipsychotic agent

Type of submission:

New Drug Submission (New Active Substance)

Control number:

What was the purpose of this submission?


With this New Drug Submission, the sponsor is seeking marketing authorization of Rexulti (brexpiprazole) for an indication for schizophrenia in adults.


Why was the decision issued?


The efficacy of Rexulti (brexpiprazole) in the treatment of schizophrenia in adults was demonstrated in 2 randomised, double-blind, placebo-controlled trials. A longer-term, double-blind, placebo-controlled randomised-withdrawal study was also positive in delaying relapse in patients who continued on brexpiprazole following open-label treatment, compared to those switched to placebo. However, as for other studies of similar design submitted to Health Canada for other drugs in the class, this study was not considered supportive of a specific indication for maintenance treatment in schizophrenia, and a general indication in schizophrenia was recommended.

Overall, the safety profile of brexpiprazole in schizophrenia was expected for an atypical antipsychotic. Brexpiprazole was associated with orthostatic hypotension, increase in metabolic parameters (for example, weight gain and triglycerides), extrapyramidal symptoms including akathisia, and prolactin elevations.

Brexpiprazole caused a statistically significant, concentration-dependent suppression of hERG currents in vitro. In the dedicated QT/QTc study, brexpiprazole showed prolongation of the QTcI interval at the therapeutic dose (4 mg, the maximum recommended dose), but not the supratherapeutic dose (12 mg).

The Rexulti Product Monograph (PM) was revised according to the data reviewed and for consistency in the drug class. These revisions included new warnings (QT prolongation, hyperprolactinemia, diabetic ketoacidosis, impulsive behaviours, dependence/tolerance, and use in pediatrics) and other class labelling (constipation, sleep apnea in the Adverse Reactions section).

The Rexulti PM also carries other class labelling warnings as proposed by the sponsor: a boxed warning on elderly patients with dementia, venous thromboembolism, body temperature regulation, priapism, leucopenia/neutropenia, Neuroleptic Malignant syndrome, tardive dyskinesia, seizures, potential cognitive and motor impairment, and suicide.

The benefit-harm-uncertainty for Rexulti for schizophrenia in adults is considered favourable at this time.


Decision issued

Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations