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Siponimod oral

Updated 2 Feb 2023 | Siponimod


Oral formulations of siponimod.

Drugs List

  • MAYZENT 250microgram tablets
  • MAYZENT 2mg tablets
  • siponimod 250microgram tablets
  • siponimod 2mg tablets
  • Therapeutic Indications


    Treatment of secondary progressive multiple sclerosis

    Treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.



    Titration dose
    Day one and two: 0.25mg.
    Day three: 0.5mg.
    Day four: 0.75mg.
    Day five: 1.25mg.
    Day six: 2mg.

    Maintenance: 2mg daily.
    In patients with CYP2C9*2*3 or *1*3 genotype, maintenance dose is 1mg.

    Additional Dosage Information

    Lymphocyte count less than 0.2 x 10 to the power of 9/L: reduce maintenance dose to 1mg.

    Lymphocyte count less than 0.2 x 10 to the power of 9/L in a patient receiving 1mg maintenance dose: interrupt treatment until lymphocyte count level reaches 0.6 x 10 to the power of 9/L.

    Switching from another disease modifying therapy

    Alemtuzumab: switch to siponimod is not recommended due to the characteristics and duration of alemtuzumab immune suppressive effects.

    Beta interferon or glatiramer acetate: switch directly to siponimod can be immediate.

    Missed doses
    During the first six days of treatment: Re-initiate with a new titration pack.

    After day six: Take the missed dose at the next scheduled time, the next dose should not be doubled.

    Maintenance treatment interrupted for four or more consecutive daily doses: Re-initiate with a new titration pack.


    Children under 18 years
    History of cryptococcal meningitis
    CYP2C9 poor metaboliser genotype
    Decompensated cardiac failure
    History of progressive multifocal leukoencephalopathy (PML)
    Immunodeficiency syndromes
    Malignant neoplasm
    New York Heart Association class III failure
    Non-paced second degree atrioventricular block
    Non-paced sinus node dysfunction
    Non-paced third degree atrioventricular block
    Progressive multifocal leukoencephalopathy (PML)
    Recent myocardial infarction
    Recurrent syncope
    Severe hepatic impairment - Child-Pugh score greater than or equal to 10
    Severe sleep apnoea
    Transient ischaemic attack
    Uncontrolled hypertension
    Unstable angina

    Precautions and Warnings

    Females of childbearing potential
    Patients over 65 years
    Diabetes mellitus
    Glucose-galactose malabsorption syndrome
    History of atrioventricular block
    History of cardiac failure
    History of hepatic impairment
    History of myocardial infarction
    History of retinal disorder
    Lactose intolerance
    QTc interval greater than or equal to 500 msec
    Severe obstructive aortic valve disease
    Sinus bradycardia

    Monitor ECG for 6 hrs after first dose in patients with cardiac conditions
    Advise patient dizziness may affect ability to drive or operate machinery
    Determine CYP2C9 metaboliser status before initiation of treatment
    Perform skin examination prior to and every 6 to 12 months during treatment
    Refer to cardiologist if QT prolonging drugs used concomitantly
    Treatment to be initiated and supervised by a specialist
    Varicella vaccination recommended for antibody-negative patients
    Contains lactose
    Contains soya or soya derivative
    Planned vaccination: Stop treatment 1 week before until 4 weeks after
    Blood counts should be performed before and periodically during treatment
    Exclude pregnancy prior to initiation of treatment
    Monitor serum transaminases before treatment
    Extend monitoring if significant cardiac effects following first dose
    Monitor bilirubin levels before treatment
    Monitor blood pressure
    Monitor levels of hepatic enzymes and bilirubin
    Perform ophthalmic examination 3-4 months after treatment initiation
    Advise patient to immediately report new skin lesions
    Advise patient to report headaches, seizures, confusion, visual disturbance
    Advise patient to report new visual problems and symptoms
    Advise patient to report signs of basal-cell carcinoma
    Advise patient to report symptoms of infection immediately
    May reduce effectiveness of vaccinations during treatment
    Risk of developing opportunistic infections
    May interfere with certain laboratory measurements
    Follow washout procedure when switching between disease modifying therapies
    Discontinue if macular oedema occurs
    Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
    Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
    Discontinue if severe hepatic changes occur
    Interrupt treatment if severe infection develops
    Suspend if drug induced liver injury is suspected
    Female: Contraception required during and for 10 days after treatment
    Advise patient to avoid exposure to sunlight and UV rays during treatment

    Residual pharmacodynamic effects, such as lowering of peripheral lymphocyte count, can persist up to three to four weeks after discontinuation. Use of immunosuppressants between these periods may lead to an additive effect on the immune system.

    A case of cryptococcal meningitis (CM) has been reported for siponimod. Patients with signs and symptoms consistent with CM should undergo prompt evaluation. If CM is suspected, siponimod should be suspended until CM has been excluded.

    Monitor symptoms or MRI imaging findings that may be suggestive of progressive multifocal leukoencephalopathy (PML). If PML is suspected, siponimod should be suspended until PML has been excluded.

    Cases of posterior reversible encephalopathy syndrome (PRES) have been reported for another sphingosine 1-phosphate (S1P) receptor module. Should patients develop signs and symptoms associated with PRES, a physical/neurological examination and MRI should be considered.

    When siponimod is added to beta-blocker therapy, the resting heart rate should be above 50bpm. If below 50bpm, beta-blocker should be suspended until heart rate is above 50bpm and treatment with siponimod can be initiated. The beta-blocker can be reinitiated once siponimod has been titrated up to maintenance dose.

    Pregnancy and Lactation


    Siponimod is contraindicated during pregnancy.

    The manufacturer recommends that siponimod should be discontinued at least 10 days before a pregnancy is planned. Animal studies have shown foetotoxic and teratogenic effects. Patient should be informed of the risks to the foetus associated with siponimod treatment and perform ultrasonography examinations if a pregnancy occurs.


    Siponimod is contraindicated during breastfeeding.

    The manufacturer states that siponimod should not be used during breastfeeding as it is unknown whether siponimod or its metabolites are excreted in human milk. Animal studies have shown siponimod and its metabolites are excreted in milk.


    Advise patient to report any signs of blurred vision or decreased visual acuity at any time.
    Advise patient to report symptoms of infection during therapy.
    Advise patient to report signs of hepatic dysfunction e.g. malaise, jaundice, dark urine or abdominal pain.
    Advise patient to report signs of basal-cell carcinoma.
    Women of childbearing potential must use effective contraception during and up to 10 days after treatment. Provide pregnancy specific Patient Guide.
    Advise patients not to drive or operate machinery if affected by side effects such as dizziness or drowsiness.
    Advise patients to immediately report new skin lesions.

    Side Effects

    Abnormal liver function tests
    Atrioventricular block
    Basal cell carcinoma
    Blurred vision
    Extremity pain
    Herpes zoster
    Macular oedema
    Melanocytic naevus
    Pulmonary function test abnormal

    Effects on Laboratory Tests

    Siponimod reduces blood lymphocyte counts via re-distribution in secondary lymphoid organs therefore peripheral blood lymphocyte counts cannot be utilised to evaluate the lymphocyte subset status of a patient treated with siponimod. Laboratory tests involving the use of circular mononuclear cells require larger blood volumes due to reduction in the number of circulating lymphocytes.


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: April 2020

    Reference Sources

    Summary of product characteristics: Mayzent 0.25mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised January 2021.
    Summary of product characteristics: Mayzent 2mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised January 2021.

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