Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Mayzent is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity (see section 5.1).
Treatment with siponimod should be initiated and supervised by a physician experienced in the management of multiple sclerosis.
Before initiation of treatment, patients must be genotyped for CYP2C9 to determine their CYP2C9 metaboliser status (see sections 4.4, 4.5 and 5.2).
In patients with a CYP2C9*3*3 genotype, siponimod should not be used (see sections 4.3, 4.4 and 5.2).
Treatment has to be started with a titration pack that lasts for 5 days. Treatment starts with 0.25 mg once daily on days 1 and 2, followed by once-daily doses of 0.5 mg on day 3, 0.75 mg on day 4, and 1.25 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.
Table 1. Dose titration regimen to reach maintenance dosage:
| Titration | Titration dose | Titration regimen | Dose |
|---|---|---|---|
| Day 1 | 0.25 mg | 1 × 0.25 mg | TITRATION |
| Day 2 | 0.25 mg | 1 × 0.25 mg | |
| Day 3 | 0.5 mg | 2 × 0.25 mg | |
| Day 4 | 0.75 mg | 3 × 0.25 mg | |
| Day 5 | 1.25 mg | 5 × 0.25 mg | |
| Day 6 | 2 mg1 | 1 × 2 mg1 | MAINTENANCE |
1 In patients with CYP2C9*2*3 or *1*3 genotype, the recommended maintenance dose is 1 mg taken once daily (4 × 0.25 mg) (see above and sections 4.4 and 5.2). Additional exposure of 0.25 mg on day 5 does not compromise patient safety.
In patients with a CYP2C9*2*3 or *1*3 genotype, the recommended maintenance dose is 1 mg (see sections 4.4 and 5.2).
The recommended maintenance dose of siponimod in all other CYP2C9 genotype patients is 2 mg.
Mayzent is taken once daily.
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.
If a dose is missed, the prescribed dose should be taken at the next scheduled time; the next dose should not be doubled.
If maintenance treatment is interrupted for 4 or more consecutive daily doses, siponimod needs to be re-initiated with a new titration pack.
Siponimod has not been studied in patients aged 65 years and above. Clinical studies included patients up to the age of 61 years. Siponimod should be used with caution in the elderly due to insufficient data on safety and efficacy (see section 5.2).
Based on clinical pharmacology studies, no dose adjustment is needed in patients with renal impairment (see section 5.2).
Siponimod must not be used in patients with severe hepatic impairment (Child-Pugh class C) (see section 4.3). Although no dose adjustment is needed in patients with mild or moderate hepatic impairment, caution should be exercised when initiating treatment in these patients (see sections 4.4 and 5.2).
The safety and efficacy of siponimod in children and adolescents aged 0 to 18 years have not yet been established. No data are available.
Oral use. Siponimod is taken with or without food.
The film-coated tablets should be swallowed whole with water.
In healthy subjects, the single maximum tolerated dose was determined to be 25 mg based upon the occurrence of symptomatic bradycardia after single doses of 75 mg. A few subjects received unintended doses of up to 200 mg daily for 3 to 4 days and experienced asymptomatic mild to moderate transient elevations of liver function tests.
One patient (with a history of depression) who took 84 mg siponimod experienced a slight elevation in liver transaminases.
If the overdose constitutes first exposure to siponimod or occurs during the dose titration phase of siponimod it is important to observe for signs and symptoms of bradycardia, which could include overnight monitoring. Regular measurements of pulse rate and blood pressure are required and electrocardiograms should be performed (see sections 4.2 and 4.4).
There is no specific antidote to siponimod available. Neither dialysis nor plasma exchange would result in meaningful removal of siponimod from the body.
2 years.
Do not store above 25°C.
Mayzent 0.25 mg film-coated tablets:
Titration packs of 12 film-coated tablets in PA/alu/PVC/alu blister in wallet.
Packs of 84 or 120 film-coated tablets in PA/alu/PVC/alu blisters.
Mayzent 1 mg film-coated tablets:
Packs of 28 or 98 film-coated tablets in PA/alu/PVC/alu blisters.
Mayzent 2 mg film-coated tablets:
Packs of 14, 28 or 98 film-coated tablets in PA/alu/PVC/alu blisters.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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