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Drug Interactions between methotrexate and prednisone

This report displays the potential drug interactions for the following 2 drugs:

  • methotrexate
  • prednisone

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Interactions between your drugs


methotrexate predniSONE

Applies to: methotrexate and prednisone

MONITOR: Although they are often used together in clinical practice, limited data suggest that corticosteroids may increase the risk of methotrexate toxicity. Individual cases of severe and fatal bone marrow suppression and fatal systemic moniliasis have been reported. Data have been conflicting. A pediatric study found no increased methotrexate toxicity; however, hepatic enzyme elevations were noted. The mechanism is unknown.

MANAGEMENT: Close monitoring for signs and symptoms of bone marrow suppression and nephrotoxicity is advisable during concomitant administration. Patients should be advised to report possible symptoms of toxicity including nausea, vomiting, diarrhea, stomatitis, sore throat, chills, fever, rash, unusual bruising or bleeding, jaundice, dark urine, swelling of the extremities, or shortness of breath to their physician.


  1. Wolff JE, Hauch H, Kuhl J, Egeler RM, Jurgens H "Dexamethasone increases hepatotoxicity of MTX in children with brain tumors." Anticancer Res 18 (1998): 2895-900
  2. Roenigk HH, Fowler-Bergfeld W, Curtis GH "Methotrexate for psoriasis in weekly oral doses." Arch Dermatol 99 (1969): 86-93
  3. Lafforgue P, Monjanel-Mouterde S, Durand A, Catalin J, Acquaviva PC "Is there an interaction between low doses of corticosteroids and methotrexate in patients with rheumatoid arthritis? A pharmacokinetic study in 33 patients." J Rheumatol 20 (1993): 263-7

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Drug and food interactions


methotrexate food

Applies to: methotrexate

MONITOR: Limited data suggest that consumption of greater than 180 mg/day of caffeine may interfere with the efficacy of methotrexate (MTX) in patients with rheumatoid arthritis. The exact mechanism of interaction is unknown but may be related to the antagonistic effect of caffeine on adenosine receptors, as anti-inflammatory properties of MTX is thought to result from the accumulation of adenosine. In a study of 39 patients treated with MTX 7.5 mg/week (without folate supplementation) for 3 months, patients with high caffeine intake (more than 180 mg/day) experienced significantly less improvement in morning stiffness and joint pain from baseline than patients with low caffeine intake (less than 120 mg/day). There were no significant differences between the responses of patients with moderate caffeine intake (120 to 180 mg/day) and those of the other 2 groups. In an interview of 91 patients treated with MTX, 26% of patients who discontinued the drug were regular coffee drinkers compared to only 2% of those still receiving the drug. Because treatment failure was the reason for MTX discontinuation in 80% of patients who discontinued, the investigators suggested that caffeine may have interfered with MTX efficacy.

MANAGEMENT: Until further information is available, the potential for interaction should be considered in patients who consume substantial amounts of caffeine and caffeine-containing foods and are prescribed methotrexate for rheumatoid arthritis. It may be appropriate to limit caffeine intake if an interaction is suspected in cases of treatment failure.


  1. Nesher G, Mates M, Zevin S "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum 48 (2003): 571-572

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.