What the FDA labels say about taking them together
Methotrexate and pemetrexed
Methotrexate's FDA label of May 27, 2026 names pemetrexed in its drug interactions section; the pemetrexed labels PlainMeds reads (4) do not name methotrexate. The methotrexate label: “Oral antibiotics (including neomycin) Antifolate drugs Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti-inflammatory drugs Highly protein-bound drugs Hepatotoxic products …”
Check it at the source: the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.); the pemetrexed FDA label on DailyMed (effective October 8, 2025, Avyxa Pharma, LLC).
What does the methotrexate label say about pemetrexed?
Methotrexate label, drug interactionsOral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti-inflammatory drugs Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Hepatotoxic products Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.
Methotrexate label (Hospira, Inc., August 22, 2025), drug interactionsAntifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides)
Source: FDA drug label (Methotrexate, NDA011719), Hospira, Inc., effective August 22, 2025 (SPL set 0e30eaef-5a09-4104-8a11-c32933eadeab), via openFDA
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
What does the pemetrexed label say about methotrexate?
Pemetrexed's label (effective October 8, 2025) and its 3 other brand-application labels do not name methotrexate in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (AXTLE), Avyxa Pharma, LLC, effective October 8, 2025 (SPL set 9582c46c-d8b0-44b7-a2ee-9c86f5e9b7b1), 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
| Methotrexate | Pemetrexed | |
|---|---|---|
| Labeled for | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer | Lung cancer |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.158 per tablet 2.5 mg tablet | n/a |
| Shortage now | In shortage | A presentation being discontinued |
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