Drug · FAERS side-effect profile with label screen
Siponimod side effects: what 8,869 FDA adverse event reports show
Drug class
Sphingosine 1-phosphate Receptor Modulator
FDA label (Established Pharmacologic Class)
Brand names
Mayzent
openFDA label
Who reports
8,869 reports · 50% serious · 207 with death outcome · 75% female
openFDA FAERS counts, all years, deduplication not applied
Used for
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) .
FDA label, Indications and Usage
What it is
MAYZENT tablets contains siponimod, an S1P receptor modulator, as 2:1 co-crystal of siponimod and fumaric acid and has the following chemical name: 1-[[4-[(1 E )-1-[[[4-Cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino]ethyl]-2-ethylphenyl]methyl]-3-azetidinecarboxylic acid (2 E )-2-butenedioate (2:1).
FDA label, Description section
Boxed warning
None in the current label
How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation.
Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)?
That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.
Causality screen of the 40 strongest signals
Labeled adverse reaction 5Labeled (related wording) 4Likely indication confounding 5Reporting / coding artifact 2Lab value / disease marker 4Not in label — unassessed 20
What the badges mean
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 884 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
Show:
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Gait spastic | 50 | 398.0 295.1–536.8ROR 400.2 · χ² 16,576 / p <1e-300 | 300.9 EB05 237.2 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | serious n=50 · ♀ 0% (drug 75%) | no trial data cached |
| Needle fatigue | 32 | 177.7 124.1–254.4ROR 178.3 · χ² 5,061 / p <1e-300 | 150.5 EB05 111.6 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=32 · ♀ 0% (drug 75%) | no trial data cached |
| Relapsing-remitting multiple sclerosis | 55 | 160.9 122.6–211.3ROR 161.9 · χ² 8,029 / p <1e-300 | 143.2 EB05 114.2 · IC025 +5.6 3/3 methods agree | Likely indication confounding term in indications | serious n=55 · ♀ 34% (drug 75%) | no trial data cached |
| Expanded disability status scale score increased | 77 | 155.9 123.9–196.1ROR 157.2 · χ² 10,963 / p <1e-300 | 141.1 EB05 116.6 · IC025 +5.9 3/3 methods agree | Lab value / disease marker | serious n=77 | no trial data cached |
| Multiple sclerosis pseudo relapse | 13 | 96.9 55.6–168.6ROR 97.0 · χ² 1,094 / p 4e-240 | 82.2 EB05 51.1 · IC025 +3.5 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=13 | no trial data cached |
| Secondary progressive multiple sclerosis | 69 | 89.3 70.3–113.5ROR 90.0 · χ² 5,718 / p <1e-300 | 84.1 EB05 68.7 · IC025 +5.3 3/3 methods agree | Likely indication confounding term in indications | serious n=68 | no trial data cached |
| Dysmetria | 16 | 64.4 39.2–105.9ROR 64.6 · χ² 912 / p 1e-200 | 58.6 EB05 38.2 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=16 | no trial data cached |
| Drug dose titration not performed | 43 | 60.5 44.7–81.9ROR 60.8 · χ² 2,396 / p <1e-300 | 57.6 EB05 44.5 · IC025 +4.6 3/3 methods agree | Labeled (related wording) related wording | serious n=13 · 86% consumer | no trial data cached |
| Lymphocyte count decreased | 417 | 57.1 51.9–62.8ROR 59.8 · χ² 22,390 / p <1e-300 | 55.6 EB05 51.3 · IC025 +5.5 3/3 methods agree | Lab value / disease marker | serious PRR 51.0 | no trial data cached |
| Lymphocyte count abnormal | 23 | 49.1 32.5–74.2ROR 49.2 · χ² 1,015 / p 4e-223 | 46.4 EB05 32.6 · IC025 +3.9 3/3 methods agree | Lab value / disease marker | serious n=16 | no trial data cached |
| Monoparesis | 37 | 49.0 35.4–67.9ROR 49.2 · χ² 1,658 / p <1e-300 | 47.0 EB05 35.6 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=37 · ♀ 9% (drug 75%) | no trial data cached |
| Drug titration error | 48 | 44.7 33.6–59.4ROR 44.9 · χ² 1,968 / p <1e-300 | 43.2 EB05 33.8 · IC025 +4.4 3/3 methods agree | Reporting / coding artifact | serious n=18 · 77% consumer | no trial data cached |
| Lymphopenia | 225 | 38.4 33.7–43.8ROR 39.4 · χ² 8,035 / p <1e-300 | 37.7 EB05 33.7 · IC025 +4.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 40.3 | no trial data cached |
| Hypertonic bladder | 44 | 36.7 27.3–49.4ROR 36.9 · χ² 1,469 / p <1e-300 | 35.6 EB05 27.6 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=43 · ♀ 24% (drug 75%) | no trial data cached |
| Band sensation | 16 | 30.0 18.3–49.1ROR 30.0 · χ² 414 / p 2e-92 | 28.7 EB05 18.7 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=9 | no trial data cached |
| Macular oedema | 68 | 29.1 22.9–36.9ROR 29.3 · χ² 1,793 / p <1e-300 | 28.5 EB05 23.3 · IC025 +4.2 3/3 methods agree | Labeled adverse reaction exact term | serious n=67 | no trial data cached |
| Jc polyomavirus test positive | 13 | 26.4 15.3–45.6ROR 26.4 · χ² 289 / p 3e-65 | 25.2 EB05 15.5 · IC025 +2.8 3/3 methods agree | Lab value / disease marker | serious n=6 | no trial data cached |
| Multiple sclerosis | 486 | 24.1 22.1–26.3ROR 25.5 · χ² 10,672 / p <1e-300 | 23.9 EB05 22.2 · IC025 +4.4 3/3 methods agree | Likely indication confounding term in indications | serious PRR 40.5 · 72% consumer | no trial data cached |
| Obstructive sleep apnoea syndrome | 14 | 23.9 14.1–40.5ROR 24.0 · χ² 282 / p 1e-63 | 23.0 EB05 14.4 · IC025 +2.8 3/3 methods agree | Labeled (related wording) related wording | serious n=14 | no trial data cached |
| Drug monitoring procedure not performed | 17 | 22.8 14.1–36.7ROR 22.8 · χ² 329 / p 6e-74 | 22.0 EB05 14.4 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | – | no trial data cached |
| Paraparesis | 17 | 22.7 14.1–36.6ROR 22.7 · χ² 328 / p 1e-73 | 21.9 EB05 14.4 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=17 | no trial data cached |
| Paresis | 21 | 22.4 14.6–34.4ROR 22.4 · χ² 404 / p 4e-90 | 21.8 EB05 14.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=21 · 90% clinician | no trial data cached |
| Trigeminal neuralgia | 36 | 21.3 15.4–29.6ROR 21.4 · χ² 671 / p 3e-148 | 20.9 EB05 15.8 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=27 · ♀ 53% (drug 75%) | no trial data cached |
| Muscle spasticity | 98 | 18.8 15.4–22.9ROR 19.0 · χ² 1,624 / p <1e-300 | 18.6 EB05 15.7 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious PRR 27.6 · ♀ 34% (drug 75%) | no trial data cached |
| Multiple sclerosis relapse | 546 | 18.8 17.3–20.4ROR 20.0 · χ² 9,149 / p <1e-300 | 18.7 EB05 17.4 · IC025 +4.1 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 29.3 | no trial data cached |
| Central nervous system lesion | 106 | 18.3 15.1–22.1ROR 18.5 · χ² 1,699 / p <1e-300 | 18.1 EB05 15.3 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 20.7 | no trial data cached |
| Atrioventricular block first degree | 32 | 17.5 12.3–24.7ROR 17.5 · χ² 477 / p 4e-106 | 17.1 EB05 12.6 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious n=8 | no trial data cached |
| Heart rate decreased | 243 | 16.4 14.5–18.6ROR 16.8 · χ² 3,477 / p <1e-300 | 16.3 EB05 14.6 · IC025 +3.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.5 | no trial data cached |
| Melanocytic naevus | 30 | 16.3 11.4–23.3ROR 16.3 · χ² 412 / p 6e-92 | 15.9 EB05 11.5 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=26 · 83% consumer | no trial data cached |
| Basal cell carcinoma | 101 | 15.4 12.7–18.7ROR 15.5 · χ² 1,336 / p 8e-293 | 15.2 EB05 12.9 · IC025 +3.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 17.6 | no trial data cached |
| Electric shock sensation | 17 | 15.0 9.3–24.2ROR 15.1 · χ² 208 / p 2e-47 | 14.2 EB05 8.8 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Concomitant disease aggravated | 39 | 15.0 11.0–20.6ROR 15.1 · χ² 493 / p 1e-109 | 14.7 EB05 11.1 · IC025 +3.1 3/3 methods agree | Labeled (related wording) related wording | serious n=35 | no trial data cached |
| Peroneal nerve palsy | 32 | 13.4 9.5–18.9ROR 13.4 · χ² 352 / p 7e-79 | 12.9 EB05 9.3 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=24 | no trial data cached |
| Optic neuritis | 51 | 13.3 10.1–17.5ROR 13.4 · χ² 564 / p 5e-125 | 13.0 EB05 10.2 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 17.4 | no trial data cached |
| Fine motor skill dysfunction | 15 | 12.4 7.4–20.5ROR 12.4 · χ² 145 / p 1e-33 | 11.1 EB05 6.5 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Neurogenic bladder | 11 | 12.3 6.8–22.3ROR 12.3 · χ² 103 / p 2e-24 | 10.5 EB05 5.5 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| Micturition urgency | 52 | 10.9 8.3–14.3ROR 10.9 · χ² 455 / p 3e-101 | 10.5 EB05 8.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 19.1 · ♀ 18% (drug 75%) | no trial data cached |
| Hemiparesis | 75 | 10.4 8.3–13.1ROR 10.5 · χ² 629 / p 5e-139 | 10.2 EB05 8.3 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 12.8 | no trial data cached |
| Limb discomfort | 131 | 10.0 8.5–11.9ROR 10.2 · χ² 1,055 / p 1e-231 | 9.9 EB05 8.5 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 12.9 · 77% consumer | no trial data cached |
| Dysgraphia | 27 | 9.7 6.6–14.1ROR 9.7 · χ² 201 / p 7e-46 | 8.9 EB05 6.2 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=11 · 96% consumer | no trial data cached |
Trial evidence (ClinicalTrials.gov)
Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Fatigue (tiredness) | 993 | 3.0 2.9–3.2ROR 3.3 · χ² 1,394 / p <1e-300 | 3.0 EB05 2.9 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.2 · 77% consumer | no trial data cached |
| Headache | 890 | 3.4 3.2–3.6ROR 3.6 · χ² 1,520 / p <1e-300 | 3.4 EB05 3.2 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.3 · 74% consumer | no trial data cached |
| Dizziness | 671 | 3.2 3.0–3.4ROR 3.4 · χ² 1,029 / p 4e-226 | 3.2 EB05 3.0 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.1 · 74% consumer | no trial data cached |
| Multiple sclerosis relapse | 546 | 18.8 17.3–20.4ROR 20.0 · χ² 9,149 / p <1e-300 | 18.7 EB05 17.4 · IC025 +4.1 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 29.3 | no trial data cached |
| Gait disturbance | 537 | 6.6 6.1–7.2ROR 7.0 · χ² 2,578 / p <1e-300 | 6.6 EB05 6.1 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 7.8 | no trial data cached |
| Fall | 511 | 3.6 3.3–4.0ROR 3.8 · χ² 989 / p 2e-217 | 3.6 EB05 3.4 · IC025 +1.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.7 | no trial data cached |
| Multiple sclerosis | 486 | 24.1 22.1–26.3ROR 25.5 · χ² 10,672 / p <1e-300 | 23.9 EB05 22.2 · IC025 +4.4 3/3 methods agree | Likely indication confounding term in indications | serious PRR 40.5 · 72% consumer | no trial data cached |
| Nausea | 423 | 1.3 1.2–1.4ROR 1.3 · χ² 25 / p 4e-7 | 1.3 EB05 1.2 · IC025 +0.2 | Labeled adverse reaction exact term | serious PRR 1.3 · 73% consumer | no trial data cached |
| Drug ineffective (drug did not work) | 417 | 0.7 0.7–0.8ROR 0.7 · χ² 37 / p 5e-10 | 0.7 EB05 0.7 · IC025 -0.6 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.0 · 70% consumer | no trial data cached |
| Lymphocyte count decreased | 417 | 57.1 51.9–62.8ROR 59.8 · χ² 22,390 / p <1e-300 | 55.6 EB05 51.3 · IC025 +5.5 3/3 methods agree | Lab value / disease marker | serious PRR 51.0 | no trial data cached |
| Product dose omission issue | 393 | 3.3 3.0–3.6ROR 3.4 · χ² 623 / p 7e-138 | 3.3 EB05 3.0 · IC025 +1.5 3/3 methods agree | Reporting / coding artifact | serious PRR 7.0 · 82% consumer | no trial data cached |
| Urinary tract infection (bladder infection) | 380 | 5.3 4.8–5.8ROR 5.5 · χ² 1,326 / p 1e-290 | 5.3 EB05 4.8 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 6.9 | no trial data cached |
| Asthenia (weakness) | 367 | 2.3 2.1–2.6ROR 2.4 · χ² 276 / p 3e-62 | 2.3 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | no trial data cached |
| Covid-19 | 366 | 4.9 4.4–5.4ROR 5.1 · χ² 1,139 / p 5e-250 | 4.9 EB05 4.5 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.2 · 72% consumer | no trial data cached |
| Pain | 342 | 1.3 1.2–1.5ROR 1.3 · χ² 26 / p 2e-7 | 1.3 EB05 1.2 · IC025 +0.2 | Labeled adverse reaction exact term | serious PRR 1.4 · 75% consumer | no trial data cached |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Gait spastic — n=50, PRR 398.0
- Needle fatigue — n=32, PRR 177.7
- Monoparesis — n=37, PRR 49.0
- Hypertonic bladder — n=44, PRR 36.7
- Paresis — n=21, PRR 22.4
- Trigeminal neuralgia — n=36, PRR 21.3
- Muscle spasticity — n=98, PRR 18.8
- Central nervous system lesion — n=106, PRR 18.3
- Melanocytic naevus — n=30, PRR 16.3
- Peroneal nerve palsy — n=32, PRR 13.4
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Siponimod?
In FDA FAERS, the most frequently co-reported reaction terms for Siponimod are fatigue, headache, dizziness, multiple sclerosis relapse, gait disturbance, fall. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Siponimod have an FDA boxed warning?
No. The FDA label retrieved for Siponimod has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Siponimod causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 44492772-5aed-4627-bd85-e8e89f308bb3, effective 20260630; matched on
openfda.generic_name.exact:"SIPONIMOD") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 924 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.