What the label lists and what reports show
Leflunomide side effects
Leflunomide's FDA label: “The most commonly reported adverse reactions (≥10%) regardless of relation to ARAVA treatment were diarrhea, respiratory infection, nausea, headache, rash, abnormal liver enzymes, and dyspepsia.” FAERS holds 104,036 reports naming it through July 30, 2026; the reaction reported most often, leaving out the conditions it is used for, product-use terms and outcomes, is pain (20,468 reports).
- Generic listed
- A presentation discontinued
- Boxed warning
Check it at the source: the leflunomide FDA label on DailyMed (effective June 4, 2025, sanofi-aventis U.S. LLC); the FDA FAERS public dashboard.
What does the label list?
From the label: adverse reactionsThe most commonly reported adverse reactions (≥10%) regardless of relation to ARAVA treatment were diarrhea, respiratory infection, nausea, headache, rash, abnormal liver enzymes, and dyspepsia.
Table 2: Percentage Of Patients With Adverse Events ≥5% In Any ARAVA Treated Group in all RA Studies in Patients with RA
| Reaction | ARAVA 20 mg/day (n=315) | PL (n=210) | SSZ 2 g/day (n=133) | MTX 7.5–15 mg/wk (n=182) | ARAVA 20 mg/day (n=501) | MTX 7.5–15 mg/wk (n=498) | ARAVA (n=1339) Includes all controlled and uncontrolled trials with ARAVA (duration up to… |
|---|---|---|---|---|---|---|---|
| Diarrhea | 27% | 12% | 10% | 20% | 22% | 10% | 17% |
| Headache | 13% | 11% | 12% | 21% | 10% | 8% | 7% |
| Nausea | 13% | 11% | 19% | 18% | 13% | 18% | 9% |
| Rash | 12% | 7% | 11% | 9% | 11% | 10% | 10% |
| Abnormal Liver Enzymes | 10% | 2% | 4% | 10% | 6% | 17% | 5% |
| Alopecia | 9% | 1% | 6% | 6% | 17% | 10% | 10% |
| Hypertension Hypertension as a preexisting condition was overrepresented in all ARAVA… | 9% | 4% | 4% | 3% | 10% | 4% | 10% |
| Asthenia | 6% | 4% | 5% | 6% | 3% | 3% | 3% |
| Back Pain | 6% | 3% | 4% | 9% | 8% | 7% | 5% |
| GI/Abdominal Pain | 6% | 4% | 7% | 8% | 8% | 8% | 5% |
| Abdominal Pain | 5% | 4% | 4% | 8% | 6% | 4% | 6% |
| Allergic Reaction | 5% | 2% | 0% | 6% | 1% | 2% | 2% |
| Bronchitis | 5% | 2% | 4% | 7% | 8% | 7% | 7% |
| Dizziness | 5% | 3% | 6% | 5% | 7% | 6% | 4% |
| Mouth Ulcer | 5% | 4% | 3% | 10% | 3% | 6% | 3% |
| Pruritus | 5% | 2% | 3% | 2% | 6% | 2% | 4% |
| Rhinitis | 5% | 2% | 4% | 3% | 2% | 2% | 2% |
| Vomiting | 5% | 4% | 4% | 3% | 3% | 3% | 3% |
| Tenosynovitis | 2% | 0% | 1% | 2% | 5% | 1% | 3% |
Rows and numbers as the label prints them, under its own column headings (the first rows of a longer table where it runs on). A reaction in a trial table is not necessarily caused by the medicine, and trials differ from everyday use.
From the label: adverse reactions, continuedThe following serious adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.2) ] Immunosuppression [see Warnings and Precautions (5.4) ] Bone marrow suppression [see Warnings and Precautions (5.4) ] Serious infections [see Warnings and Precautions (5.4) ] Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reactions with eosinophilia and systemic symptoms [see Warnings and Precautions (5.5) ] Skin ulcers [see Warnings and Precautions (5.6) ] Peripheral neuropathy [see Warnings and Precautions (5.8) ] Interstitial lung disease [see Warnings and Precautions (5.9) ] The most commonly reported adverse reactions (≥10%) regardless of relation to ARAVA treatment were diarrhea, respiratory infection, nausea, headache, rash, abnormal liver enzymes, and dyspepsia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. …
Source: FDA drug label, sanofi-aventis U.S. LLC, effective June 4, 2025 (SPL set 320f63f2-fac3-4aee-aff8-85724e00ef52), via openFDA; the full label on DailyMed
What do FAERS reports show?
104,036 reports list leflunomide among the medicines taken, each a report of something that happened, not proof the medicine caused it; 9,331 are coded as a death and 28,778 as a hospital stay. Counts follow how widely a medicine is used and watched, and they are not a measure of how risky it is. Of the 20 reactions below, 5 are named by the same term (in US spelling) in the label's adverse reactions, warnings or patient leaflet; a reaction the label does not name may still be there under another word, and a report does not show that the medicine caused it.
Reports received each year
The 25 most reported reactions
Source: FDA Adverse Event Reporting System (FAERS) via openFDA, reports through July 30, 2026; reactions as MedDRA preferred terms
What next?
- Leflunomide: the full record
- label, generics, price, shortages, recalls
- Report a side effect to the FDA
- MedWatch
- Side effects hub
- the most reported medicines and reactions