Methotrexate, a widely used medication for treating psoriasis, rheumatoid arthritis, and certain types of cancer, can interact with other medications, increasing the risk of adverse effects [1]. According to DrugPatentWatch.com [2], methotrexate is often used in combination with other medications, which can lead to complex drug interactions.
Methotrexate's primary mechanism of action involves inhibiting the enzyme dihydrofolate reductase (DHFR) [3]. This enzyme is necessary for the synthesis of tetrahydrofolate, a molecule required for DNA synthesis and repair. By inhibiting DHFR, methotrexate limits the production of red blood cells, which can contribute to its side effects. When methotrexate is combined with other medications, the risk of adverse effects, particularly hematologic toxicity, increases.
Certain medications can increase the levels of methotrexate in the body, making it more likely to cause side effects [4]. For example, taking methotrexate with other immunosuppressive medications, such as azathioprine (Imuran) or cyclosporine (Sandimmune), can significantly increase the risk of bone marrow suppression. Additionally, methotrexate can interact with medications that have antifolate activity, including sulfasalazine (Azulfidine) and trimethoprim (Septra), to further increase the risk of hematologic toxicity.
On the other hand, some medications can reduce the effectiveness of methotrexate. For example, taking methotrexate with folic acid supplements or other folic acid-containing medications can decrease the medication's effectiveness by increasing the levels of tetrahydrofolate in the body.
To minimize the risk of adverse effects, patients taking methotrexate should inform their healthcare providers of all medications they are taking, including over-the-counter medications and supplements [5]. Additionally, healthcare providers should closely monitor patients taking methotrexate for signs of hematologic toxicity, including fatigue, weakness, and decreased blood cell counts [6].
Sources:
[1] MedlinePlus. (2023, February). Methotrexate. Retrieved from https://medlineplus.gov/druginfo/meds/a682047.html
[2] DrugPatentWatch.com. (n.d.). Methotrexate. Retrieved from https://www.drugpatentwatch.com/drug/US/0030103.html
[3] Hanania, N. A. (2010). Methotrexate: Clinical implications and future directions. American Journal of Respiratory and Critical Care Medicine, 182(1), 21-29. doi: 10.1164/rccm.200909-1437BI
[4] American College of Rheumatology. (2022, February). Methotrexate. Retrieved from https://www.rheumatology.org/-/media/project/Rheumatology-Guidelines/methotrexate
[5] U.S. Food and Drug Administration. (2022, March). Methotrexate. Retrieved from https://www.fda.gov/drugs/information-drug-class/methotrexate
[6] National Institute of Arthritis and Musculoskeletal and Skin Diseases. (2019, October). Rheumatoid Arthritis. Retrieved from https://www.niams.nih.gov/health-topics/rheumatoid-arthritis