Methotrexate Injection and Sars-Cov-2 (Covid-19) Vaccine, Mrna (Pfizer): Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methotrexate Injection
Sars-Cov-2 (Covid-19) Vaccine, Mrna (Pfizer)
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Decreased immune response to COVID-19 vaccine
Interaction Deep Dive
Hold methotrexate for 1 week after each vaccine dose (do not modify vaccine timing)1.
Why it happens (mechanism)
Immunomodulatory effects of methotrexate
Common questions
Can I take Methotrexate Injection and Sars-Cov-2 (Covid-19) Vaccine, Mrna (Pfizer) together?
Decreased immune response to COVID-19 vaccine Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methotrexate Injection and Sars-Cov-2 (Covid-19) Vaccine, Mrna (Pfizer) interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Methotrexate Injection or Sars-Cov-2 (Covid-19) Vaccine, Mrna (Pfizer) need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (1)
- American College of Rheumatology: COVID-19 vaccine clinical guidance summary for patients with rheumatic and musculoskeletal diseases. American College of Rheumatology. Atlanta, GA. 2021.
Keep reading about Methotrexate Injection
Keep reading about Sars-Cov-2 (Covid-19) Vaccine, Mrna (Pfizer)
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