RXULTI Film-coated tablet Ref.[7627] Active ingredients: Brexpiprazole

Posology

The recommended starting dose for brexpiprazole is 1 mg once daily on days 1 to 4.

The recommended target dose range is 2 mg to 4 mg once daily.

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 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.

Special populations

Elderly

The safety and efficacy of brexpiprazole in the treatment of schizophrenia in patients aged 65 years and older have not been established (see sections 4.4 and 5.2). It is not possible to advise on a minimum effective/safe dose in this population.

Renal impairment

The maximum recommended dose in patients with moderate to severe impaired renal function is reduced to 3 mg once daily (see section 5.2).

Hepatic impairment

The maximum recommended dose in patients with moderate to severe hepatic impairment (Child-Pugh score ≥7) is reduced to 3 mg once daily (see section 5.2).

CYP2D6 poor metabolisers

Dosing modifications to half the recommended doses is required for patients with known CYP2D6 poor metaboliser status. Further dosing modifications to a quarter of the recommended dose is required for known CYP2D6 poor metabolisers while taking strong or moderate CYP3A4 inhibitors (see sections 4.5 and 5.2).

Dose adjustments due to interactions

Dose adjustments should be made in patients taking concomitant strong CYP3A4 inhibitors/inducers or strong CYP2D6 inhibitors. If the CYP3A4 inhibitor/inducers or CYP2D6 inhibitor is withdrawn, the dose may need to be returned to the original dose (see section 4.5). 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.

Table 1. Dose adjustments of RXULTI in patients who are CYP2D6 poor metabolisers and for concomitant use with CYP inhibitors:

Patients taking strong CYP3A4 inducers

If brexpiprazole is used concomitantly with strong CYP3A4 inducers (e.g. 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 clinical response, further dose adjustments are required, the dose may be increased up to a maximum of three times the recommended daily dose. Daily dose must not exceed 12 mg when brexpiprazole is used concomitantly with strong CYP3A4 inducers. Twice daily divided dosing of brexpiprazole is preferable as once daily dosing results in high peak to trough fluctuation (see section 4.5). CYP3A4 inducers exert their effect in a time-dependent manner, and may take at least 2 weeks to reach maximal effect after introduction. Conversely, on discontinuation, CYP3A4 induction may take at least 2 weeks to decline.

Paediatric population

The safety and efficacy of brexpiprazole in children and adolescents aged less than 18 years have not been established. No data are available.

Method of administration

Oral use.

The film-coated tablets can be taken with or without food.

Gastric lavage and treatment with an emetic may be useful immediately after overdose. An electrocardiogram should be obtained in case of overdose and if QT interval prolongation is present, cardiac monitoring should be instituted.

Otherwise, management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers.

Oral activated charcoal and sorbitol (50 g/240 mL), administered one hour after ingesting 2 mg oral dose of brexpiprazole, decreased brexpiprazole C_max and AUC by approximately 5% to 23% and 31% to 39% respectively; however, there is insufficient information available on the therapeutic potential of activated charcoal in treating an overdose with brexpiprazole.

Although there is no information on the effect of haemodialysis in treating an overdose with brexpiprazole, haemodialysis is unlikely to be useful in overdose management since brexpiprazole is highly bound to plasma proteins.

Shelf life: 3 years.

This medicinal product does not require any special storage conditions.

RXULTI 0.25 mg, 0.5 mg, 2 mg, 3 mg and 4 mg film-coated tablets: 28 film-coated tablets in Aluminium/PVC blisters.

RXULTI 1 mg film-coated tablets: 10 or 28 film-coated tablets in Aluminium/PVC blisters.

Not all pack sizes may be marketed

This medicinal product may pose a risk to the environment (see section 5.3).

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.