Mayzent

Treatment with siponimod should be initiated and supervised by a physician experienced in the management of multiple sclerosis. 2). 2). Posology Treatment initiation Treatment has to be started with a titration pack that lasts for 5 days.

25 mg on day 5, to reach the patient’s prescribed maintenance dose of siponimod starting on day 6 (see Table 1). During the first 6 days of treatment initiation the recommended daily dose should be taken once daily in the morning with or without food.

2). 25 mg on day 5 does not compromise patient safety. 2). The recommended maintenance dose of siponimod in all other CYP2C9 genotype patients is 2 mg. Mayzent is taken once daily. Missed dose(s) during treatment initiation During the first 6 days of treatment, if a titration dose is missed on one day treatment needs to be re-initiated with a new titration pack.

4 Missed dose after day 6 If a dose is missed, the prescribed dose should be taken at the next scheduled time; the next dose should not be doubled. Re-initiation of maintenance therapy after treatment interruption If maintenance treatment is interrupted for 4 or more consecutive daily doses, siponimod needs to be re-initiated with a new titration pack.

Special populations Elderly Siponimod has not been studied in patients aged 65 years and above. Clinical studies included patients up to the age of 61 years. 2). 2). 3). 2). Paediatric population The safety and efficacy of siponimod in children and adolescents aged 0 to 18 years have not yet been established.

No data are available. Method of administration Oral use. Siponimod is taken with or without food. The film-coated tablets should be swallowed whole with water.

Summary of the safety profile The safety profile of siponimod was based on data from the core clinical study. 6%). The safety-related information from the extension part of the long-term study A2304 was consistent with that observed in the core part.

Tabulated list of adverse reactions Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: 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); not known (cannot be estimated from the available data).

Table 2 Tabulated list of adverse reactions Infections and infestations Common Herpes zoster Rare Progressive multifocal leukoencephalopathy Not known Meningitis cryptococcal Neoplasms benign, malignant and unspecified (incl. 1%, respectively).

7%). Cases of meningitis or meningoencephalitis caused by varicella zoster viruses have occurred with siponimod at any time during treatment. 4). 2%). 4). Some patients presented with blurred vision or decreased visual acuity, but others were asymptomatic and diagnosed on routine ophthalmological examination.

The macular oedema generally improved or resolved spontaneously after discontinuation of treatment. The risk of recurrence after re-challenge has not been evaluated. 4). 4). The maximum decline in heart rate is seen in the first 6 hours post-dose.

A transient, dose-dependent decrease in heart rate was observed during the initial dosing phase and plateaued at doses ≥5 mg. Bradyarrhythmic events (AV blocks and sinus pauses) were detected with a higher incidence under siponimod treatment compared to placebo.

Most AV blocks and sinus pauses occurred above the therapeutic dose of 2 mg, with notably higher incidence under non-titrated conditions compared to dose titration conditions. The decrease in heart rate induced by siponimod can be reversed by atropine or isoprenaline.

Infections Risk of infections A core pharmacodynamic effect of siponimod is a dose-dependent reduction of the peripheral lymphocyte count to 20-30% of baseline values. 1). 8). e. within last 6 months or after discontinuation of prior therapy) should be available.

Assessments of CBC are also recommended 3 to 4 months after treatment initiation and at least yearly thereafter, and in case of signs of infection. 2 x 109/l. 6 x 109/l when re-initiation of siponimod can be considered. Initiation of treatment should be delayed in patients with severe active infection until resolution.

Because residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 3 to 4 weeks after discontinuation, vigilance for infection should be continued throughout this period (see below section “Stopping siponimod therapy”).

Patients should be instructed to report symptoms of infection to their physician promptly. Effective diagnostic and therapeutic strategies should be employed in patients with symptoms of infection while on therapy. Suspension of treatment with siponimod should be considered if a patient develops a serious infection.

Cases of cryptococcal meningitis (CM) have been reported for siponimod. Patients with symptoms and signs consistent with CM should undergo prompt diagnostic evaluation. Siponimod treatment should be suspended until CM has been excluded.

If CM is diagnosed, appropriate treatment should be initiated. 8). Physicians should be vigilant for clinical symptoms or magnetic resonance imaging (MRI) findings that may be suggestive of PML. If PML is suspected, siponimod treatment should be suspended until PML has been excluded.

If PML is confirmed, treatment with siponimod should be discontinued. Immune reconstitution inflammatory syndrome (IRIS) has been reported in patients treated with sphingosine 1-phosphate (S1P) receptor modulators, including siponimod, who developed PML and subsequently discontinued treatment.

1. - Immunodeficiency syndrome. - History of progressive multifocal leukoencephalopathy or cryptococcal meningitis. - Active malignancies. - Severe liver impairment (Child-Pugh class C). 4). 4). - Patients homozygous for CYP2C9*3 (CYP2C9*3*3) genotype (poor metaboliser).

6). 5