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Sphingosine-1-phosphate receptor 1/5 modulator Pregnancy: UK SPC section 4.6: siponimod is contraindicated during pregnancy and in women of childbearing potential not using effective contraception. A negative pregnancy test is required before initiation; effective contraception must be used during treatment and for at least 10 days after the last dose, and siponimod should be stopped at least 10 days before a planned pregnancy. Animal studies showed embryotoxicity, foetotoxicity and teratogenicity. Should not be used during breast-feeding.

Siponimod

Brand names: Mayzent

Siponimod is an oral sphingosine-1-phosphate (S1P) receptor modulator used for active secondary progressive multiple sclerosis.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 2 mg once daily maintenance (1 mg once daily in patients with a CYP2C9*2*3 or *1*3 genotype), started on day 6 after a 5-day titration
Route: Oral
Frequency: Once daily, with or without food; tablets swallowed whole with water
UK SPC (Mayzent) section 4.2. Before initiation patients MUST be genotyped for CYP2C9; siponimod should not be used in patients with a CYP2C9*3*3 genotype. Titration (5-day titration pack, taken once daily in the morning): 0.25 mg on days 1 and 2, 0.5 mg on day 3, 0.75 mg on day 4, 1.25 mg on day 5, then the prescribed maintenance dose from day 6. Maintenance is 2 mg once daily in all genotypes other than CYP2C9*2*3 or *1*3, in whom it is 1 mg once daily. Missed dose during the first 6 days: treatment needs to be re-initiated with a new titration pack. Missed dose after day 6: take the prescribed dose at the next scheduled time and do not double the next dose. If maintenance treatment is interrupted for 4 or more consecutive daily doses, re-initiate with a new titration pack. Section 4.4: confirmed absolute lymphocyte count below 0.2 x 10^9/L should lead to dose reduction to 1 mg; if already on 1 mg, interrupt therapy until the count reaches 0.6 x 10^9/L. Elderly: not studied in patients aged 65 years and above (studies included patients up to 61 years) — use with caution. Hepatic impairment: must not be used in severe impairment (Child-Pugh class C); no dose adjustment needed in mild or moderate impairment but exercise caution when initiating. Paediatrics: safety and efficacy in children and adolescents aged 0 to 18 years have not been established and no data are available — verify any paediatric use against a children's formulary. Treatment should be initiated and supervised by a physician experienced in the management of multiple sclerosis. NOTE ON INTERACTIONS: the UK SPC section 4.5 was not captured in this bundle, so the interaction list below is taken from the US label (MAYZENT) section 7 — verify against the UK SPC.

Dose adjustments

Renal

UK SPC section 4.2: based on clinical pharmacology studies, no dose adjustment is needed in patients with renal impairment.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substance, or to peanut, soya or any of the excipients
  • Immunodeficiency syndrome
  • History of progressive multifocal leukoencephalopathy or cryptococcal meningitis
  • Active malignancies
  • Severe liver impairment (Child-Pugh class C)
  • Myocardial infarction, unstable angina, stroke/TIA, decompensated heart failure requiring inpatient treatment, or NYHA class III/IV heart failure in the previous 6 months
  • History of second-degree Mobitz type II AV block, third-degree AV block, sino-atrial heart block or sick-sinus syndrome, unless the patient wears a pacemaker
  • Patients homozygous for CYP2C9*3 (CYP2C9*3*3 genotype, poor metaboliser)
  • During pregnancy and in women of childbearing potential not using effective contraception

Side effects

  • Headache (very common, 15%)
  • Hypertension (very common, 12.6%)
  • Liver function test increased (very common)
  • Bradycardia and first- or second-degree atrioventricular block (common)
  • Macular oedema (common; 1.8% versus 0.2% on placebo)
  • Lymphopenia and herpes zoster infection (common)

Interactions

  • Live-attenuated vaccines — avoid during and for up to 4 weeks after treatment (US label section 7.4)
  • Strong CYP2C9 inhibitors — increase siponimod exposure; concomitant use is not recommended (US label section 7.5)
  • Moderate CYP2C9 inhibitors or moderate dual CYP2C9/CYP3A4 inhibitors — monitor for adverse reactions during concomitant use (US label section 7.5)
  • Dual moderate CYP2C9 / strong CYP3A4 inducers — decrease siponimod exposure; concomitant use is not recommended (US label section 7.6)
  • Moderate or strong CYP3A4 inducers in patients with CYP2C9*1/*3 or *2/*3 genotypes — monitor for loss of efficacy (US label section 7.6)
  • Anti-neoplastic, immune-modulating or immunosuppressive therapies — caution because of the risk of additive immune effects (US label section 7.1)
  • Drugs that slow heart rate or AV conduction — determine whether the patient is taking these before the first dose (US label section 2.1)

Clinical monograph

How it works

It selectively modulates S1P1 and S1P5 receptors, retaining lymphocytes within lymph nodes and so reducing the number of circulating lymphocytes available to enter the central nervous system.

Prescribing in practice

  • CYP2C9 genotype must be determined before starting because patients homozygous for certain poor-metaboliser alleles are contraindicated and others require dose adjustment.
  • It can cause bradycardia and atrioventricular conduction delay at initiation, so first-dose cardiac assessment is required in those with relevant cardiac history.
  • It increases infection risk and necessitates checks of macular health, liver function and varicella immunity before treatment.

Monitoring

Monitor full blood count, liver function, blood pressure and, where indicated, cardiac rhythm at initiation and ophthalmological assessment for macular oedema.

Counselling the patient

  • Report signs of infection, and remember that immune effects can persist for some weeks after stopping.
  • Report any visual disturbance, which could indicate macular oedema.
  • Effective contraception is needed during and for a period after treatment because of the risk to a developing baby.

Evidence & guidelines

Siponimod slowed disability progression in active secondary progressive multiple sclerosis in the randomised EXPAND trial and is recommended by NICE for eligible patients.

Reference: NICE TA656; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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