Multiple sclerosis therapy

Siponimod

One of the few medicines that cannot be prescribed at all until the test has been done. Here the genotype is not advice about a dose — it is part of the prescription.

What this drug connects to

The genes involved

CYP2C9

Multiple Sclerosis →

Siponimod is one of the few medicines a person cannot be prescribed at all without a genetic test first. CYP2C9 clears it, and someone carrying two copies of the least-active form — the *3/*3 genotype, roughly one person in 250 of European ancestry — is exposed to about four times as much drug as a normal metaboliser. The US label makes that genotype an outright contraindication and halves the maintenance dose for two of the intermediate genotypes. Genotyping before the first dose is a requirement rather than a recommendation, which is what separates this from almost everything else on this site: here the test is part of the prescription.

US prescribing information for MAYZENT (siponimod). CPIC lists the pair at level A; the requirement to genotype comes from the label, not from a CPIC guideline.

Variants MyGeneLog™ reports for these genes

These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.

Urine X-24354 levels in chronic kidney disease

CYP2C9 · rs111667734

Omega-3 fatty acid levels

CYP2C9 · rs55891451

X-11787 levels

CYP2C9 · rs9332172

Warfarin maintenance dose

CYP2C9 · rs4918798

X-11787 levels

CYP2C9 · rs1934963

X-21849 levels

CYP2C9 · rs9332217

X-17654 levels

CYP2C9 · rs1934969

Appendicular lean mass

CYP2C9 · rs28371678

Omega-3 Fatty Acids to Polyunsaturated Fatty Acids percentage

CYP2C9 · rs9332238

Questions about Siponimod

What is siponimod?

Siponimod is a multiple sclerosis therapy and one of the few medicines a person cannot be prescribed at all without a genetic test first.

Can I be prescribed siponimod without a CYP2C9 genetic test?

No — genotyping before the first dose is a requirement, not a recommendation, because CYP2C9 clears siponimod and certain genotypes change exposure dramatically.

What does the CYP2C9 *3/*3 genotype mean for siponimod exposure?

Someone carrying two copies of the least-active form — roughly one person in 250 of European ancestry — is exposed to about four times as much siponimod as a normal metaboliser.

What does the siponimod label do with the CYP2C9 *3/*3 finding?

It makes the *3/*3 genotype an outright contraindication and halves the maintenance dose for two of the intermediate genotypes.

Quoting this page

Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.

Siponimod. MyGeneLog™. https://www.mygenelog.com/drugs/siponimod

This page is educational and contains no dosing information. Where a clinical guideline covers one of these gene-drug pairs it is written for prescribers and works through validated algorithms alongside clinical monitoring. Nothing here is a reason to start, stop, or change a medication — that conversation belongs with the clinician or pharmacist managing your treatment.