What the FDA labels say about taking them together
Leflunomide and methotrexate
Leflunomide's FDA label of June 4, 2025 names methotrexate in its drug interactions section; the methotrexate labels PlainMeds reads (4) do not name leflunomide. The leflunomide label: “In patients taking ARAVA, exposure of drugs which are OAT3 substrates may be increased.”
Check it at the source: the leflunomide FDA label on DailyMed (effective June 4, 2025, sanofi-aventis U.S. LLC); the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.).
What does the leflunomide label say about methotrexate?
Leflunomide label, drug interactionsIn patients taking ARAVA, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased.
Leflunomide label, warnings and precautionsIf ARAVA and methotrexate are given concomitantly, follow the American College of Rheumatology (ACR) guidelines for monitoring methotrexate liver toxicity with ALT, AST, and serum albumin testing.
Source: FDA drug label (Arava), sanofi-aventis U.S. LLC, effective June 4, 2025 (SPL set 320f63f2-fac3-4aee-aff8-85724e00ef52), via openFDA; the full label on DailyMed
What does the methotrexate label say about leflunomide?
Methotrexate's label (effective May 27, 2026) and its 3 other brand-application labels do not name leflunomide in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (Methotrexate), Accord Healthcare Inc., effective May 27, 2026 (SPL set 874c7f43-a3be-4236-89cc-24c44e3c5813), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Leflunomide | Methotrexate | |
|---|---|---|
| Labeled for | Rheumatoid arthritis | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.324 per tablet 10 mg tablet | $0.158 per tablet 2.5 mg tablet |
| Shortage now | A presentation being discontinued | In shortage |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once