Methotrexate is used in cancer chemotherapy as well as for treating inflammatory diseases such as rheumatoid arthritis and psoriasis.
Potassium citrate and other forms of citrate (e.g., calcium citrate, 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. 1
It may be advisable to avoid these citrate compounds during methotrexate therapy except under medical supervision.
St. John's wort (Hypericum perforatum) is primarily used to treat mild to moderate depression.
The herb dong quai (Angelica sinensis) is often recommended for menstrual disorders such as dysmenorrhea, 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 wear a sunscreen or protective clothing during sun exposure if you take one of these herbs while using methotrexate.
The herb white willow (Salix alba) , also known as willow bark, is used to treat pain and fever. White willow contains a substance that is converted by the body into a salicylate similar to aspirin.
Case reports suggest that salicylates can increase methotrexate blood levels and toxicity. 2 For this reason, you should avoid combining white willow with methotrexate.
The supplement ipriflavone is used to treat osteoporosis. A 3-year double-blind trial of almost 500 women, as well as a small study, found worrisome evidence that ipriflavone can reduce white blood cell count in some people. 3,4 For this reason, anyone taking medications that suppress the immune system should avoid taking ipriflavone.
Potassium citrate, sodium citrate, and potassium-magnesium citrate are sometimes used to prevent kidney stones . These supplements reduce urinary acidity, and can therefore lead to decreased blood levels and effectiveness of methotrexate. 19
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 you are taking any medication that depletes or impairs folate even slightly, you 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 individuals who take methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis can safely use folate supplements. 5–9, 14 Not only does the methotrexate continue to work properly, but its usual side effects may decrease also.
For example, in a 48-week double-blind placebo-controlled trial of 434 individuals with active rheumatoid arthritis, use of folate helped prevent liver inflammation caused by methotrexate. 10 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 individuals receiving methotrexate for rheumatoid arthritis 11-15 and in those with psoriasis. 16
In addition, two studies of individuals with rheumatoid arthritis found that use of folate supplements corrected the methotrexate-induced rise in homocysteine without affecting disease control. 17-18
Note: Folate supplements have only been found safe as supportive treatment in the specific conditions noted above. It is not known, for example, whether folate supplements are safe for use by individuals taking methotrexate for cancer treatment.
References
REF1 A to Z Drug Facts [book on CD-ROM]. 2nd ed. St. Louis, Mo: Facts and Comparisons; 2000.
REF2 Tracy TS, Krohn K, Jones DR, et al. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol. 1992;42:121–125.
REF3 Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int. 1997;61(suppl 1):S23–S27.
REF4 Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 2001;285:1482–1488.
REF5 Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med. 1994;121:833–841.
REF6 Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol. 1993;28:466–469.
REF7 Hunt PG, Rose CD, McIlvain-Simpson G, et al. The effects of daily intake of folic acid on the efficacy of methotrexate therapy in children with juvenile rheumatoid arthritis. A controlled study. J Rheumatol. 1997;24:2230–2232.
REF8 van Ede AE, Laan RF, Rood MJ, et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2001;44:1515–1524.
REF9 Griffith SM, Fisher J, Clarke S, 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 (Oxford). 2000;39:1102–1109.
REF10 van Ede AE, Laan RF, Rood MJ, et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2001;44:1515–1524.
REF11 Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med. 1994;121:833–841.
REF12 Griffith SM, Fisher J, Clarke S, 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 (Oxford). 2000;39:1102–1109.
REF13 Hunt PG, Rose CD, McIlvain-Simpson G, et al. The effects of daily intake of folic acid on the efficacy of methotrexate therapy in children with juvenile rheumatoid arthritis. A controlled study. J Rheumatol. 1997;24:2230–2232.
REF14 Ortiz Z, Shea B, Suarez-Almazor ME, et al. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J Rheumatol. 1998;25:36-43.
REF15 Hunt PG, Rose CD, McIlvain-Simpson G, et al. The effects of daily intake of folic acid on the efficacy of methotrexate therapy in children with juvenile rheumatoid arthritis. A controlled study. J Rheumatol. 1997;24:2230–2232
REF16 Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol. 1993;28:466–469.
REF17 Van Ede AE, Laan RF, Blom HJ, et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatology (Oxford). 2002;41(6):658-665.
REF18 Morgan SL, Baggott JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol. 1998;25:441-446.
REF19 Tatro D, ed. Drug Interaction Facts. St. Louis, Mo: Facts and Comparisons; 1999.