Folic acid supplementation for Children Using Methotrexate

Folic acid dosing: How much and how often?

Methotrexate is an immunosuppressive medication used for a range of immunological conditions. The drug itself is a folic acid antagonist that irreversibly binds and inhibits the dihydrofolate reductase (DHFR) and thus inhibits RNA and DNA synthesis resulting in cell cycle arrest. In the hair clinic, I commonly use for advanced forms of alopecia areata as well as some patients with lichen planopilaris, frontal fibrosing alopecia and discoid lupus. 

Users of methotrexate are generally very familiar with folic acid. Folic acid is a vitamin that is routinely given to help improve tolerability and reduce side effects such as nausea, macrocytic anemia, pancytopenia and elevation of liver enzymes (hepatitis). Generally speaking, the  tolerability of MTX in children is better compared to the tolerability in adults, given that adults usually have other complicating factors present such as liver problems to begin with, use of chronic medications and frequent use of alcohol.  About 15 % of children have abnormalities of liver enzymes (i.e. 2 times above normal); kidney and blood cell abnormalities are rare in children.

How much folic acid should be used in children ? How often should it be given?

The optimal dose of folic acid and how often it should be given are still unclear. Most physicians, including myself, prescribe 1 to 5 mg folic acid every day except on the methotrexate day. However, other physicians prescribe folic acid (often 5 mg) a day or two after the MTX dose. 

Why the variability?

One of the reasons that experts can't seen to agree on the proper dose and frequency is that there is a lack of evidence based guidelines published in the medical literature to guide physicians. 

In 2013, Amarillo and colleagues surveyed 214 pediatric rheumatologists around the globe regarding their use of folic acid when prescribing MTX. Interestingly, 71 (seventy one) unique folate supplementation regimens were reported for this study! This study highlighted that folate supplementation (either in the form of folic acid or folinic acid) is inconsistent and highly variable within the United States as well as between the United States and other countries. 

REFERENCE

Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol. 2009;60:824–837. doi: 10.1016/j.jaad.2008.11.906.  

Ståhle M, Atakan N, Boehncke WH, et al. Juvenile psoriasis and its clinical management: a European expert group consensus. J Dtsch Dermatol Ges. 2010;8:812–818. 

Gisondi P, Fantuzzi F, Malerba M, Girolomoni G. Folic acid in general medicine and dermatology. J Dermatolog Treat. 2007;18:138–146. doi: 10.1080/09546630701247930. 

Amarilyo G, et al. Folate usage in MTX-treated juvenile idiopathic arthritis (JIA) patients is inconsistent and highly variable. Rheumatol Int. 2013.