What the FDA labels say about taking them together
Esomeprazole and methotrexate
Esomeprazole's FDA label of March 19, 2024 names methotrexate in its drug interactions (prescription label) section, and methotrexate's label names esomeprazole too. The esomeprazole label: “Concomitant use of esomeprazole 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 esomeprazole FDA label on DailyMed (effective March 19, 2024, Haleon US Holdings LLC); the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.).
What does the esomeprazole label say about methotrexate?
Esomeprazole label, drug interactions (prescription label)Methotrexate Clinical Impact: Concomitant use of esomeprazole 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 NEXIUM may be considered in some patients receiving high-dose methotrexate.
Esomeprazole label, warnings and precautions (prescription label)Interaction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity.
Esomeprazole Strontium label (R2 Pharma, LLC, September 22, 2016), drug interactionsCase reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate.
Esomeprazole Strontium label (R2 Pharma, LLC, September 22, 2016), warnings and precautionsUse of Esomeprazole Strontium with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities.
Source: FDA drug label (Esomeprazole Strontium, NDA202342), R2 Pharma, LLC, effective September 22, 2016 (SPL set 3c916d32-f9e9-1d15-e054-00144ff88e88), via openFDA
Source: FDA drug label (Nexium 24HR), NDA204655 (Astrazeneca Lp), as published by Haleon US Holdings LLC, effective March 19, 2024 (SPL set 4513934d-0cf0-40fc-a348-b4e75a33b094), via openFDA; the full label on DailyMed
What does the methotrexate label say about esomeprazole?
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
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
| Esomeprazole | Methotrexate | |
|---|---|---|
| Labeled for | Acid reflux and ulcers | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.145 per capsule 20 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