What the FDA labels say about taking them together
Methotrexate and pyrimethamine
Methotrexate's FDA label of May 27, 2026 names pyrimethamine in its drug interactions section, and pyrimethamine's label names methotrexate too. The pyrimethamine label: “… sulfamethoxazole combinations, proguanil, zidovudine, or cytostatic agents (e.g., methotrexate), while the patient is receiving pyrimethamine, may increase the risk of bone marrow suppression.”
Check it at the source: the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.); the pyrimethamine FDA label on DailyMed (effective December 7, 2023, TILDE Sciences LLC).
What does the methotrexate label say about pyrimethamine?
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 pyrimethamine label say about methotrexate?
Pyrimethamine label, drug interactionsHowever, the concomitant use of other antifolic drugs or agents associated with myelosuppression including sulfonamides or trimethoprim- sulfamethoxazole combinations, proguanil, zidovudine, or cytostatic agents (e.g., methotrexate), while the patient is receiving pyrimethamine, may increase the risk of bone marrow suppression.
Source: FDA drug label (Daraprim), TILDE Sciences LLC, effective December 7, 2023 (SPL set f634f34b-0952-4dd3-9da3-f84b6ab823de), 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 | Pyrimethamine | |
|---|---|---|
| Labeled for | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer | n/a |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.158 per tablet 2.5 mg tablet | $137.01 per tablet 25 mg tablet |
| Shortage now | In shortage | No current entry |
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