What the FDA labels say about taking them together
Methotrexate and pantoprazole
Methotrexate's FDA label (Rasuvo) of December 15, 2025 names pantoprazole in its drug interactions section, and pantoprazole's label names methotrexate too. The pantoprazole 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 methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.); the pantoprazole FDA label on DailyMed (effective May 18, 2026, Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.).
What does the methotrexate label say about pantoprazole?
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 pantoprazole label say about methotrexate?
Pantoprazole 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 PROTONIX may be considered in some patients receiving high-dose methotrexate.
Pantoprazole label, warnings and precautionsUse of PROTONIX 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.
Protonix I.V. label (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., December 22, 2025), warnings and precautionsUse of PROTONIX I.V. 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 (Pantoprazole Sodium, NDA217512), Baxter Healthcare Company, effective February 14, 2024 (SPL set a476e063-9450-4793-9a22-16b0a0a61cd0), via openFDA
Source: FDA drug label (Protonix I.V., NDA020988), Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., effective December 22, 2025 (SPL set f39b3e7d-39d2-4c8a-9974-4ab885241880), via openFDA
Source: FDA drug label (Protonix Delayed-Release), Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., effective May 18, 2026 (SPL set 08098cb2-c048-4640-f387-6beec4a38936), 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 | Pantoprazole | |
|---|---|---|
| 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 | $0.0358 per tablet 40 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