[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Multiple sclerosis disease-modifying therapies](https://durgical.com/en/pharmacology/classes/multiple-sclerosis-disease-modifying-therapies/) › Siponimod # Siponimod ## Multiple sclerosis disease-modifying therapies? Multiple sclerosis disease-modifying therapies An oral S1P receptor modulator for relapsing and active secondary progressive MS. A CYP2C9 gene test decides whether and how it can be used. Updated Nov 1, 2026 ## Quick facts **Group** [Multiple sclerosis disease-modifying therapies](https://durgical.com/en/pharmacology/classes/multiple-sclerosis-disease-modifying-therapies/) **Target** Sphingosine-1-phosphate receptor 1 (S1PR1) **Used for** Relapsing forms of multiple sclerosis **Key effects** Headache and dizziness · Pain in the arms or legs **Monitor** CYP2C9 genotype before starting · Blood count **ATC** L04AE03 No doses: the clinician sets them by the current guideline. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ◎**Sphingosine-1-phosphate receptor 1 (S1PR1)**Siponimod ⓘ The figure shows siponimod bound to the human S1P1 receptor coupled to its Gi protein. **Target in 3D:** Sphingosine-1-phosphate receptor 1 (S1PR1). PDB structure 7EVY (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/7EVY) · Drag to rotate · pinch to zoom Siponimod acts directly on the S1P1 and S1P5 receptors. It behaves as a functional antagonist of S1P1: the receptor is internalized and degraded, lymphocytes cannot follow the S1P signal to leave the lymph nodes, and fewer of them enter the central nervous system. - Siponimod binds S1P1 (and S1P5) - S1P1 is internalized and degraded - Lymphocytes remain in lymph nodes - Fewer relapses and slower disability ## Indications - Relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting and active secondary progressive disease [Multiple sclerosis →](https://durgical.com/en/conditions/multiple-sclerosis/) ## Adverse effects ### Common - Headache and dizziness - Pain in the arms or legs - Diarrhoea - Raised blood pressure ### Serious (rare, important) - Slow heartbeat or heart block, mainly when starting - Serious infections, including meningitis and progressive multifocal leukoencephalopathy (PML) - Macular oedema (blurred vision, a blind spot in the centre of vision) - Liver injury - Posterior reversible encephalopathy syndrome (sudden severe headache, confusion, seizures) - Skin cancer - Severe worsening of MS after stopping ## Contraindications - CYP2C9*3/*3 genotype - Heart attack, unstable angina, stroke, TIA or heart failure in the previous 6 months - Some heart rhythm disorders without a pacemaker ## Key interactions **Moderate or strong CYP2C9/CYP3A4 inducers (rifampicin, carbamazepine)** Lower siponimod levels; the combination is not recommended **Moderate or strong inhibitors (fluconazole)** Higher siponimod levels; the combination is not recommended **Medicines that slow the heart** More bradycardia **Live vaccines** Avoided from 1 week before starting until 1 month after the last dose unless the treating team advises otherwise ## What is monitored - CYP2C9 genotype before starting - ECG before the first dose and 6 hours after it - Blood count, liver tests, eye (macula) and skin checks - Blood pressure - Varicella immunity ## Administration and safety - Oral tablet raised over the first days - The first dose is given in a health facility, with an ECG before it and 6 hours after it ## Pregnancy and breastfeeding Effective contraception is used during treatment and for at least 10 days after the last dose. ## Nursing care - Confirm the CYP2C9 test result before the first dose - Check pulse and ECG at the start - Teach sun protection and skin self-checks - Teach the signs of infection and of PML (one-sided weakness, confusion) - Advise contraception during treatment and for 10 days after the last dose ## Pharmacokinetics **Absorption** Oral, with good bioavailability **Metabolism** By CYP2C9, a highly polymorphic enzyme, and then CYP3A4 **Elimination** Mainly in bile and faeces ## Memory aid «SIPONIMOD = See If Polymorphism (CYP2C9) Okays the MODulator»: genotype first, then the dose. ## Test yourself Think of the answer, then tap the question to see it. ## Which genetic test is done before siponimod? CYP2C9 genotyping. ## Which CYP2C9 genotype contraindicates siponimod? Homozygous CYP2C9*3/*3. ## Which form of MS is siponimod notable for treating among S1P modulators? Active secondary progressive multiple sclerosis. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/siponimod/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Connections ## Related drugs 3 - [Fingolimod](https://durgical.com/en/pharmacology/fingolimod/) - [Ozanimod](https://durgical.com/en/pharmacology/ozanimod/) - [Ocrelizumab](https://durgical.com/en/pharmacology/ocrelizumab/) ## Related conditions 1 - [Multiple sclerosis](https://durgical.com/en/conditions/multiple-sclerosis/) [← Back to the class: Multiple sclerosis disease-modifying therapies](https://durgical.com/en/pharmacology/classes/multiple-sclerosis-disease-modifying-therapies/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Siponimod: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a619027.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L04AE03) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [RCSB PDB - 7EVY: Cryo-EM structure of siponimod -bound Sphingosine-1-phosphate receptor 1 in complex with Gi protein](https://www.rcsb.org/structure/7EVY) (RCSB Protein Data Bank, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/siponimod/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/siponimod/