What the FDA labels say about taking them together
Dexlansoprazole and methotrexate
Dexlansoprazole's FDA label of February 17, 2025 names methotrexate in its drug interactions section; methotrexate's label does not name dexlansoprazole itself but warns about its class (Proton pump inhibitors (PPIs)). The dexlansoprazole label: “Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. …”
Check it at the source: the dexlansoprazole FDA label on DailyMed (effective February 17, 2025, Takeda Pharmaceuticals America, Inc.); the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.).
What does the dexlansoprazole label say about methotrexate?
Dexlansoprazole label, drug interactionsMethotrexate Clinical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted. Intervention: A temporary withdrawal of DEXILANT may be considered in some patients receiving high-dose methotrexate.
Dexlansoprazole label, warnings and precautionsIncreases in intragastric pH may result in hypergastrinemia and enterochromaffin-like cell hyperplasia and increased chromogranin A levels which may interfere with diagnostic investigations for neuroendocrine tumors. ( 5.9 , 7 ) Interaction with Methotrexate:
Source: FDA drug label (Dexilant), Takeda Pharmaceuticals America, Inc., effective February 17, 2025 (SPL set 9819f033-3bbe-442e-8e92-45fec77b237d), via openFDA; the full label on DailyMed
What does the methotrexate label say about dexlansoprazole?
Methotrexate's label does not name dexlansoprazole itself; it warns about its class (Proton pump inhibitors (PPIs)):
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 …
Methotrexate label, drug interactionsDRUG INTERACTIONS Aspirin, NSAIDs, and steroids: concomitant use may elevate and prolong serum methotrexate levels and cause increased toxicity ( 7.1 ) Proton pump inhibitors: concomitant use may elevate and prolong serum methotrexate levels and cause increased toxicity
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
| Dexlansoprazole | Methotrexate | |
|---|---|---|
| Labeled for | Acid reflux and ulcers | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $3.71 per capsule 60 mg capsule | $0.158 per tablet 2.5 mg tablet |
| Shortage now | No current entry | 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