Siponimod

Siponimod is an S1P receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5.

• MAYZENT is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. MAYZENT is a sphingosine 1-phosphate (S1P) receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.ICD-10: G35

• MAYZENT is contraindicated in patients who have: A CYP2C9*3/*3 genotype [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.5)] In the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure Presence of Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker [see Warnings and Precautions (5.4)] Patients with a CYP2C9*3/*3 genotype. ( 4 ) In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure.contraindicated

Assessments are required prior to initiating MAYZENT. ( 2.1 ) Titration is required for treatment initiation. ( 2.2 , 2.3 ) The recommended maintenance dosage is 2 mg. ( 2.2 ) The recommended maintenance dosage in patients with a CYP2C9*1/*3 or *2/*3 genotype is 1 mg. ( 2.3 ) Administer tablets whole; do not split, crush, or chew. ( 2.2 , 2.3 ) First-dose monitoring is recommended for patients with sinus bradycardia, first- or second-degree [Mobitz type I] atrioventricular (AV) block, or a history of myocardial infarction or heart failure. ( 2.4 ) 2.1 Assessments Prior to First Dose of MAYZENT Before initiation of treatment with MAYZENT, assess the following: CYP2C9 Genotype Determination Test patients for CYP2C9 variants to determine CYP2C9 genotype [see Dosage and Administration (2.2, 2.3), Contraindications (4) and Use in Specific Populations (8.6)] . An FDA-cleared or -approved test for the detection of CYP2C9 variants to direct the use of siponimod is not currently available. Cardiac Evaluation Obtain an electrocardiogram (ECG) to determine whether preexisting conduction abnormalities are present. In patients with certain preexisting conditions, advice from a cardiologist and first-dose monitoring is recommended [see Dosage and Administration (2.4) and Warnings and Precautions (5.4)] . Determine whether patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction [see Drug Interactions (7.2, 7.3)] . Complete Blood Count Review results of a recent complete blood count (CBC) [see Warnings and Precautions (5.1)] .

Infections: MAYZENT may increase the risk. Obtain a complete blood count (CBC) before initiating treatment. Monitor for infection during treatment. Do not start in patients with active infection. ( 5.1 ) Progressive Multifocal Leukoencephalopathy (PML): Withhold MAYZENT at the first sign or symptom of PML. ( 5.2 ) Macular Edema: Increases the risk of macular edema. Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with MAYZENT. Conduct an evaluation of the fundus, including the macula, periodically while on therapy and any time there is a change in vision. Consider discontinuing MAYZENT if macular edema develops. Diabetes mellitus and uveitis increase the risk. ( 5.3 ) Bradyarrhythmia and Atrioventricular Conduction Delays: MAYZENT may result in a transient decrease in heart rate; titration is required for treatment initiation. Consider resting heart rate with concomitant beta-blocker use; obtain cardiologist consultation before concomitant use with other drugs that decrease heart rate. ( 5.4 , 7.2 , 7.3 ) Respiratory Effects: May cause a decline in pulmonary function. Assess pulmonary function (e.g., spirometry) if clinically indicated. ( 5.5 ) Liver Injury: Obtain liver enzyme results before initiation. Closely monitor patients with severe hepatic impairment. Discontinue if significant liver injury occurs. ( 5.6 ) Cutaneous Malignancies: Skin examination prior to or shortly after the start of treatment and periodically thereafter is recommended. Suspicious skin lesions should be evaluated.

The following serious adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions (5.1)] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.2)] Macular Edema [see Warnings and Precautions (5.3)] Bradyarrhythmia and Atrioventricular Conduction Delays [see Warnings and Precautions (5.4)] Respiratory Effects [see Warnings and Precautions (5.5)] Liver Injury [see Warnings and Precautions (5.6)] Cutaneous Malignancies [see Warnings and Precautions (5.7)] Increased Blood Pressure [see Warnings and Precautions (5.8)] Fetal Risk [see Warnings and Precautions (5.9)] Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.10)] Unintended Additive Immunosuppressive Effects From Prior Treatment With Immunosuppressive or Immune-Modulating Therapies [see Warnings and Precautions (5.11)] Severe Increase in Disability After Stopping MAYZENT [see Warnings and Precautions (5.12)] Immune System Effects After Stopping MAYZENT [see Warnings and Precautions (5.13)] Most common adverse reactions (incidence greater than 10%) are headache, hypertension, and transaminase increases. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to MAYZENT during pregnancy. Healthcare providers are encouraged to enroll pregnant patients, or pregnant women may register themselves in the MotherToBaby Pregnancy Study in Multiple Sclerosis by calling 1-877-311-8972, sending an email to MotherToBaby@health.ucsd.edu, or visiting www.mothertobaby.org/join-study . Risk Summary There are no adequate data on the developmental risk associated with the use of MAYZENT in pregnant women. Based on animal data and its mechanism of action, MAYZENT can cause fetal harm when administered to a pregnant woman ( see Data ). Reproductive and developmental studies in pregnant rats and rabbits have demonstrated MAYZENT-induced embryotoxicity and fetotoxicity in rats and rabbits and teratogenicity in rats. Increased incidences of post-implantation loss and fetal abnormalities (external, urogenital, and skeletal) in rat and of embryo-fetal deaths, abortions, and fetal variations (skeletal and visceral) in rabbit were observed following prenatal exposure to siponimod starting at a dose 2 times the exposure in humans at the highest recommended dose of 2 mg/day.

Metabolism

Siponimod concentration increases in an apparent dose-proportional manner after multiple once-daily doses of siponimod 0.3 mg to 20 mg. Steady-state plasma concentrations are reached after approximately 6 days of once-daily dosing, and steady-state levels are approximately 2- to 3-fold greater than the initial dose.

In patients with overdosage of MAYZENT, it is important to observe for signs and symptoms of bradycardia, which may include overnight monitoring. Regular measurements of pulse rate and blood pressure are required, and ECGs should be performed [see Warnings and Precautions (5.4, 5.8) and Clinical Pharmacology (12.2)] . There is no specific antidote to siponimod available. Neither dialysis nor plasma exchange would result in meaningful removal of siponimod from the body. The decrease in heart rate induced by MAYZENT can be reversed by atropine or isoprenaline.

• Mar 26, 2019NDANDA209884Novartis

1. 1Fatigue98911%
2. 2Headache88810%
3. 3Dizziness6647.5%
4. 4Gait Disturbance5326.0%
5. 5Multiple Sclerosis Relapse5326.0%
6. 6Fall5065.8%
7. 7Multiple Sclerosis4845.5%
8. 8Drug Ineffective4174.7%
9. 9Lymphocyte Count Decreased4154.7%
10. 10Nausea4154.7%
11. 11Product Dose Omission Issue3914.4%
12. 12Urinary Tract Infection3714.2%
13. 13Covid-193654.1%
14. 14Asthenia3564.0%
15. 15Pain3393.9%

The 10 most recently updated of 33 ClinicalTrials.gov registrations naming Siponimod as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Learn More About The Safety of Diroximel Fumarate (VUMERITY®) in Participants Who Took it During Pregnancy And About the Health of Their Babies
  Active not recruiting · Observational · 1,178 enrolled · Biogen
  NCT05688436updated 2026-06-04
• Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy
  Completed · Observational · 134 enrolled · Novartis Pharmaceuticals
  NCT05376579updated 2026-05-19
• Efficacy and Safety of Ofatumumab and Siponimod Compared to Fingolimod in Pediatric Patients With Multiple Sclerosis
  Active not recruiting · Phase 3 · Interventional · 129 enrolled · Novartis Pharmaceuticals
  NCT04926818updated 2026-05-14
• Determinants of Warfarin Metabolism
  Recruiting · Interventional · 1,000 enrolled · Hadassah Medical Organization
  NCT00162474updated 2026-04-21
• Repurposing Siponimod for Alzheimer's Disease
  Recruiting · Phase 2 · Interventional · 105 enrolled · St. Joseph's Hospital and Medical Center, Phoenix
  NCT06639282updated 2026-03-04
• Survey Among Healthcare Professionals and MS Patients to Assess Their Understanding of RMP Materials
  Completed · Observational · 335 enrolled · Novartis Pharmaceuticals
  NCT05301907updated 2025-12-24
• Managed Access Program (MAP) for Patients Diagnosed With Secondary Progressive Multiple Sclerosis With Active Disease
  No longer available · Expanded access · Novartis Pharmaceuticals
  NCT04540861updated 2025-12-04
• Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial
  Active not recruiting · Interventional · 900 enrolled · Johns Hopkins University
  NCT03500328updated 2025-10-14
• A Real-world Study About the Impact of Siponimod Treatment on Secondary Progressive Multiple Sclerosis Patients in Russia
  Completed · Observational · 606 enrolled · Novartis Pharmaceuticals
  NCT07168694updated 2025-09-11
• Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS
  Active not recruiting · Phase 4 · Interventional · 800 enrolled · The Cleveland Clinic
  NCT03535298updated 2025-08-28

CPIC-curated drug–gene pairs for Siponimod. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• CYP2C9CPIC A (provisional)ClinPGx 1AFDA label: Testing Required

Frequently asked questions

How does Siponimod work?

Siponimod is an S1P receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5.

What is Siponimod used for?

According to FDA labeling, Siponimod carries indications including: MAYZENT is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. MAYZENT is a sphingosine 1-phosphate (S1P) receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Siponimod?

Siponimod is classified as Sphingosine-1-phosphate (S1P) receptor modulators, Sphingosine 1-phosphate Receptor Modulator, Sphingosine 1-Phosphate Receptor Modulators, Lymphocyte Activity Modulation.

What are the brand names for Siponimod?

Siponimod is marketed under brand names including Mayzent.

What are the contraindications for Siponimod?

Siponimod labeling lists contraindications including: MAYZENT is contraindicated in patients who have: A CYP2C9*3/*3 genotype [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.5)] In the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure Presence of Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker [see Warnings and Precautions (5.4)] Patients with a CYP2C9*3/*3 genotype. ( 4 ) In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure.. Always consult the full prescribing information and a clinician.