Methotrexate (drug interactions)
Methotrexate is a medication commonly used in cancer chemotherapy and for treating inflammatory conditions such as rheumatoid arthritis and psoriasis. However, it has notable drug interactions that can complicate its use. Certain supplements and medications, including potassium citrate, St. John's wort, dong quai, and white willow, can lead to harmful effects when taken alongside methotrexate. For instance, potassium citrate may reduce the drug's efficacy, while St. John's wort and dong quai could increase skin sensitivity, raising the risk of sunburn. Additionally, white willow can elevate methotrexate toxicity due to its salicylate content.
Conversely, folate supplementation may be beneficial for patients on methotrexate, as it can help alleviate some side effects without compromising the drug's effectiveness. However, caution is advised, especially in cancer treatment contexts, where the safety of folate supplements remains unclear. Furthermore, interactions with prescription medications, including NSAIDs and certain antibiotics, can increase the risk of toxicity, emphasizing the importance of discussing all concurrent medications with healthcare providers. Overall, patients should be well-informed and consult their healthcare team to navigate potential interactions effectively.
Methotrexate (drug interactions)
DEFINITION: Used in cancer chemotherapy and for treating inflammatory diseases such as rheumatoid arthritis and psoriasis.
INTERACTIONS: Citrate, dong quai, folate, ipriflavone, potassium citrate, St. John’s wort, white willow, various prescription medications
TRADE NAMES: Trexall, Otrexup and Rasuvo
Potassium Citrate
Effect: Possible Harmful Interaction
Potassium citrate and other forms of citrate (such as calcium citrate and magnesium citrate) may be used to prevent kidney stones. These agents work by making the urine less acidic. This effect on the urine may lead to decreased blood levels and therapeutic effects of methotrexate. It may be advisable to avoid these citrate compounds during methotrexate therapy except under medical supervision.
St. John’s Wort, Dong Quai
Effect: Possible Harmful Interaction
St. John’s wort (Hypericum perforatum) is used primarily to treat mild to moderate depression. The herb dong quai (Angelica sinensis) is often recommended for menstrual disorders such as dysmenorrhea, premenstrual syndrome (PMS), and irregular menstruation. Methotrexate has been reported to cause increased sensitivity to the sun, amplifying the risk of sunburn or skin rash. Because St. John’s wort and dong quai may also cause this problem, taking these herbal supplements during methotrexate therapy might add to this risk. It may be a good idea to use sunscreen or to wear protective clothing during sun exposure if taking one of these herbs while using methotrexate.
White Willow
Effect: Possible Harmful Interaction
The herb white willow (Salix alba), also known as willow bark, is used to treat pain and fever. White willow contains a substance the body converts into a salicylate similar to aspirin. Case reports suggest that salicylates can increase methotrexate blood levels and toxicity. For this reason, one should avoid combining white willow with methotrexate.
Ipriflavone
Effect: Possible Harmful Interaction
The supplement ipriflavone is used to treat osteoporosis. A three-year double-blind trial of almost five hundred women and a smaller study found worrisome evidence that ipriflavone can reduce white blood cell count in some people. For this reason, anyone taking medications that suppress the immune system should avoid taking ipriflavone.
Citrate
Effect: Possible Harmful Interaction
Potassium citrate, sodium citrate, and potassium-magnesium citrate are sometimes used to prevent kidney stones. These supplements reduce urinary acidity, which can, therefore, decrease blood levels and the effectiveness of methotrexate.
Folate
Effect: Supplementation Possibly Helpful
Folate (also known as folic acid) is a B vitamin that plays an important role in many vital aspects of health, including preventing neural tube birth defects and possibly reducing the risk of heart disease. Because inadequate intake of folate is widespread, if one is taking any medication that depletes or impairs folate even slightly, one may need supplementation.
Methotrexate is called a folate antagonist because it prevents the body from converting folate to its active form. In fact, this inactivation of folate plays a role in methotrexate’s therapeutic effects. This leads to an interesting Catch-22: Methotrexate use can lead to folate deficiency, but taking extra folate could theoretically prevent methotrexate from working properly. However, evidence suggests that people who take methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis can safely use folate supplements. Not only does the methotrexate continue to work properly, but also its usual side effects may decrease.
For example, in a forty-eight-week double-blind, placebo-controlled trial of 434 persons with active rheumatoid arthritis, use of folate helped prevent liver inflammation caused by methotrexate. Other side effects did not improve. A slightly higher dose of methotrexate was needed to reach the same level of benefit as taking methotrexate alone, but researchers felt this was worth it.
In the study just described, folate supplements did not help reduce the incidence of mouth sores and nausea. However, in other studies, folate supplements did reduce these side effects, both in persons receiving methotrexate for rheumatoid arthritis and in those with psoriasis. In addition, two studies of persons with rheumatoid arthritis found that use of folate supplements corrected the methotrexate-induced rise in homocysteine without affecting disease control.
Folate supplements are only safe as supportive treatment in the specific conditions noted above. It is not known, for example, whether folate supplements are safe for use by persons taking methotrexate for cancer treatment.
Other Interactions
Patients should be aware of several other interactions between methotrexate and prescription medications. Non-steroidal anti-inflammatory drugs (NSAIDs) can impair kidney function and increase the risk of methotrexate toxicity. Certain antibiotics can increase methotrexate's side effects. Proton pump inhibitors may increase methotrexate levels, and live vaccines should be avoided while taking methotrexate, as the drug can suppress the immune system. Patients should discuss all medications, herbs, and supplements they are taking with their healthcare provider, as many other substances may interact with methotrexate. Alcohol should be avoided due to liver toxicity, and women who are pregnant or breastfeeding should not take methotrexate.
Bibliography
Alexandersen, P., et al. "Ipriflavone in the Treatment of Postmenopausal Osteoporosis." Journal of the American Medical Association, vol. 285, 2001, pp. 1482-1488.
Bottaro, Angelica. "Drug and Food Interactions: What Should You Avoid While Taking Methotrexate?" Verywell Health, 24 Aug. 2024, www.verywellhealth.com/methotrexate-interactions-5112866. Accessed 11 Sept. 2024.
Chronstein, Bruce N. and Thomas M. Aune. "Methotrexate and Its Mechanisms of Action in Inflammatory Arthritis." Nature Reviews Rheumatology, vol. 16, pp. 145-54, 7 Feb. 2020, doi.org/10.1038/s41584-020-0373-9. Accessed 19 Dec. 2022.
Griffith, S. M., et al. "Do Patients with Rheumatoid Arthritis Established on Methotrexate and Folic Acid 5 Mg Daily Need to Continue Folic Acid Supplements Long Term?" Rheumatology, vol. 39, 2000, pp. 1102-1109.
Hunt. P. G., et al. "The Effects of Daily Intake of Folic Acid on the Efficacy of Methotrexate Therapy in Children with Juvenile Rheumatoid Arthritis." Journal of Rheumatology, vol. 24, 1997, pp. 2230-2232.
"Taking Methotrexate with Other Medicines and Herbal Supplements." NHS, 14 Mar. 2023, www.nhs.uk/medicines/methotrexate/taking-methotrexate-with-other-medicines-and-herbal-supplements. Accessed 11 Sept. 2024.
Van Ede, A. E., et al. "Effect of Folic or Folinic Acid Supplementation on the Toxicity and Efficacy of Methotrexate in Rheumatoid Arthritis." Arthritis and Rheumatology, vol. 44, 2001, pp. 1515-1524.