What the FDA labels say about taking them together
Methotrexate and omeprazole
Methotrexate's FDA label (Rasuvo) of December 15, 2025 names omeprazole in its drug interactions section, and omeprazole's label names methotrexate too. The omeprazole label: “Concomitant use of omeprazole with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate …”
Check it at the source: the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.); the omeprazole FDA label on DailyMed (effective April 22, 2024, Apotex Corp).
What does the methotrexate label say about omeprazole?
Rasuvo label (Medexus Pharma Inc., December 15, 2025), drug interactionsCase reports and published population pharmacokinetic studies suggest that concomitant use of some PPIs, such as omeprazole, esomeprazole, and pantoprazole, with methotrexate (primarily at high dose), may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.
Source: FDA drug label (Rasuvo, NDA205776), Medexus Pharma Inc., effective December 15, 2025 (SPL set d0075461-0e7e-4967-9c9b-d6440e912c0e), 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 omeprazole label say about methotrexate?
Omeprazole label, drug interactionsMethotrexate Clinical Impact: Concomitant use of omeprazole 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 omeprazole may be considered in some patients receiving high-dose methotrexate.
Omeprazole label, warnings and precautionsIncreased Chromogranin A (CgA) levels may interfere with diagnostic investigations for neuroendocrine tumors; temporarily stop omeprazole at least 14 days before assessing CgA levels. ( 5.11 , 7 ) Interaction with Methotrexate:
Prilosec label (Covis Pharma US, Inc, March 19, 2024), warnings and precautionsInteraction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity.
Source: FDA drug label (Prilosec, NDA022056), Covis Pharma US, Inc, effective March 19, 2024 (SPL set b6761f84-53ac-4745-a8c8-1e5427d7e179), via openFDA
Source: FDA drug label (Omeprazole), Apotex Corp, effective April 22, 2024 (SPL set b83329ac-a65e-b3af-a3fb-c5a6c740e5e7), 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 | Omeprazole | |
|---|---|---|
| Labeled for | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer | Acid reflux and ulcers |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.158 per tablet 2.5 mg tablet | $0.0295 per capsule 20 mg capsule |
| 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