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Yes, over-the-counter (OTC) medications can interact with methotrexate, a prescription medication used to treat certain types of cancer, rheumatoid arthritis, and psoriasis. It is crucial to inform healthcare providers about all medications, including OTC drugs, supplements, and vitamins, being taken to avoid potential adverse interactions [1].

Some OTC medications can reduce methotrexate's effectiveness or increase its toxicity. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, are commonly used to treat pain and inflammation [2]. When taken with methotrexate, NSAIDs may decrease methotrexate's effectiveness in treating rheumatoid arthritis [1].

Probenecid, an OTC medication used to treat gout, can increase methotrexate levels in the blood, potentially leading to toxicity [1]. Trimethoprim-sulfamethoxazole, an antibiotic available over the counter in some countries, can also increase methotrexate levels, causing similar issues [1].

Patients should consult their healthcare providers before starting any new medications, including OTC drugs, to ensure they do not interact with methotrexate [1]. Regular monitoring of methotrexate levels and potential side effects is essential for patients taking this medication [1].

Sources:

[1] Methotrexate. (2021). Mayo Clinic. Retrieved from https://www.mayoclinic.org/drugs-supplements/methotrexate-oral-route/precautions/drg-20063431
[2] Nonsteroidal Anti-inflammatory Drugs (NSAIDs). (2021). Arthritis Foundation. Retrieved from https://www.arthritis.org/diseases/treatments/medication/drug-types/anti-inflammatory/ngf-nsaids