RXULTI

Posology Adult population The recommended starting dose for brexpiprazole is 1 mg once daily on days 1 to 4. Based on the patient’s clinical response and tolerability, the brexpiprazole dose can be titrated to 2 mg once daily on day 5 through day 7 and then to 4 mg on day 8.

The recommended target dose range is 2 mg to 4 mg once daily. The maximum recommended daily dose is 4 mg. 5 mg once daily on days 1 to 4. The brexpiprazole dose should be titrated to 1 mg once daily on day 5 through day 7 and then to 2 mg on day 8.

Weekly dose increases can be made in 1 mg increments based on clinical response and tolerability. The recommended target dose range is 2 mg to 4 mg once daily. The maximum recommended daily dose is 4 mg. Switching from other antipsychotics to brexpiprazole When switching from other antipsychotics to brexpiprazole, gradual cross-titration should be considered, with gradual discontinuation of the previous treatment while brexpiprazole treatment is initiated.

Switching to other antipsychotics from brexpiprazole When switching to other antipsychotics from brexpiprazole, no gradual cross-titration is needed. The new antipsychotic should be initiated in its lowest dose while brexpiprazole is discontinued.

It should be considered that plasma concentration of brexpiprazole will decline gradually and will be completely washed out in 1 to 2 weeks. 2). It is not possible to advise on a minimum effective/safe dose in this population. 2). 2). CYP2D6 poor metabolisers Dosing modifications to half the recommended doses is required for patients with known CYP2D6 poor metaboliser status.

2). Dose adjustments due to interactions Dose adjustments should be made in patients taking concomitant strong CYP3A4 inhibitors/inducers or strong CYP2D6 inhibitors. 5). In case of adverse reactions despite dose adjustments of RXULTI, the necessity of concomitant use of RXULTI and CYP2D6 or CYP3A4 inhibitor should be reassessed.

, rifampicin), in a patient stabilised on brexpiprazole it is necessary to titrate the daily dose of brexpiprazole stepwise up to double the recommended dose over the course of 1 to 2 weeks. Thereafter, if according to the clinical response, further dose adjustments are required, the dose may be increased up to a maximum of three times the recommended daily dose.

6%). Tabulated list of adverse reactions The incidences of the ADRs associated with brexpiprazole therapy are tabulated below. The table is based on adverse reactions reported in short-term placebo-controlled phase 2 and 3 adult clinical trials with relevant therapeutic doses (2 mg to 4 mg) and short-term placebo- controlled phase 3 paediatric clinical trials with relevant therapeutic doses (1 mg to 4 mg).

All ADRs are listed by system organ class (SOC) and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000) and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 6) SOC Very common Common Uncommon Not known Investigations Blood prolactin increased2 Blood creatine phosphokinase increased Blood pressure increased Blood triglycerides increased Hepatic enzymes increased 1 Includes also sedation and hypersomnia 2 The categorisation of blood prolactin increased is based on Potentially Clinically Relevant (PCR) criteria of > 1 × upper limit of normal (ULN).

2 % in placebo. 4 %). 4. Akathisia From fixed-dose trials there appears to be a dose-response relationship for akathisia in patients treated with brexpiprazole, with an increasing frequency with higher doses. 2 % of subjects in the placebo group.

7 %). 4 %, none-serious) in the placebo group. 6 %). Overall, in the brexpiprazole clinical development program for schizophrenia, one death due to suicide occurred but was not considered drug related by the investigator. Spontaneous cases reporting completed suicide and suicide attempt have been reported in the post-marketing setting.

4. 5 %) reported in subjects receiving placebo. The incidence of TEAEs in long-term trials was similar to that of the short-term trials. The effects of brexpiprazole at therapeutic (4 mg) and supra-therapeutic (12 mg) doses on QT interval were evaluated in subjects with schizophrenia or schizoaffective disorder in a randomised, double-blind, placebo- and positive-controlled (moxifloxacin), parallel-arm trial.

During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored throughout this period. 8). Close supervision of high-risk patients should accompany antipsychotic treatment.

Cardiovascular disorders Brexpiprazole has not been evaluated in patients with a history of myocardial infarction/ischaemic heart disease or clinically significant cardiovascular disease since such patients were excluded from clinical trials.

Brexpiprazole should be used with caution in patients with known cardiovascular disease (history of myocardial infarction or ischaemic heart disease, heart failure, or conduction abnormalities), cerebrovascular disease, conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medicinal products) or hypertension (including accelerated or malignant).

QT prolongation QT prolongation can develop in patients treated with antipsychotics. In clinical trials, only a few, non-serious QT prolongations have been reported with brexpiprazole. 1). Venous thromboembolism Cases of venous thromboembolism (VTE) have been reported with antipsychotics.

Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with brexpiprazole, and preventive measures should be undertaken.

Orthostatic hypotension and syncope Adverse reactions related to orthostatic hypotension can include dizziness, light-headedness and tachycardia. Generally, these risks are greatest at the beginning of treatment with antipsychotics and during dose escalation.

, heart failure, myocardial infarction, ischemia, or conduction abnormalities), history of cerebrovascular disease, as well as patients who are antipsychotic-naïve. 2). 8). Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia).

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