Drug interactions
Caffeine + Methotrexate
Severity: Minor
Caffeine and Methotrexate: minor interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Caffeine blocks adenosine receptors, and adenosine mediates part of the anti-inflammatory effect of low-dose methotrexate. High caffeine intake might therefore reduce methotrexate benefit in rheumatoid arthritis, but clinical data are inconsistent and the effect is probably small.
What this interaction means in plain words
Caffeine and Methotrexate have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised.
Caffeine belongs to Miscellaneous; Methotrexate belongs to Oncology.
Why it happens
Caffeine antagonizes adenosine receptors, which may counteract methotrexate's adenosine-mediated anti-inflammatory action.
What to do
No routine change is needed. Consider asking about heavy caffeine intake if methotrexate response in inflammatory disease is poor.
What to ask your pharmacist
- Is there anything I should notice while taking both?
- Do I need to tell my doctor at the next visit?
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Other interactions of Methotrexate
- Acitretin + Methotrexate Contraindicated
- Adenovirus types 4 and 7 live + Methotrexate Contraindicated
- Influenza virus vaccine quadrivalent intranasal + Methotrexate Contraindicated
- Ketorolac + Methotrexate Contraindicated
- Measles mumps and rubella vaccine live + Methotrexate Contraindicated
- Measles mumps and rubella vaccine + Methotrexate Contraindicated
Other interactions of Caffeine
- Caffeine + Ephedrine Major
- Caffeine + Fezolinetant Major
- Caffeine + Methylenedioxymethamphetamine Major
- Caffeine + Selegiline transdermal Major
- Adenosine + Caffeine Moderate
- Benzphetamine + Caffeine Moderate
Frequently asked questions
Can I take Caffeine with Methotrexate?
MediHelp rates the interaction as minor. Caffeine and Methotrexate have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised. Caffeine blocks adenosine receptors, and adenosine mediates part of the anti-inflammatory effect of low-dose methotrexate. High caffeine intake might therefore reduce methotrexate benefit in rheumatoid arthritis, but clinical data are inconsistent and the effect is probably small.
How serious is the interaction between Caffeine and Methotrexate?
MediHelp rates it minor, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: No routine change is needed. Consider asking about heavy caffeine intake if methotrexate response in inflammatory disease is poor.
What other medicines interact with Methotrexate?
MediHelp also lists interactions of Methotrexate with, for example, Acitretin, Adenovirus types 4 and 7 live, Influenza virus vaccine quadrivalent intranasal. The full list is on the Methotrexate page.
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