Methotrexate and folic acid: what is the optimal combination?

A. Bamji

Department of Rheumatology, Queen Mary's Hospital, Sidcup, UK

Correspondence to: E-mail: andrewbamji{at}lineone.net

SIR, A few papers change my practice, and Whittle and Hughes's review of methotrexate supplementation with folate [1] is likely to be one. While I have not been in the habit of prescribing folic acid as a routine, the argument that by doing so one may reduce the risk of cardiovascular adverse events seems compelling. The question is how best to give the folate.

There seem to be as many different regimes of folic acid administration as there are rheumatology departments and the trials quoted in the review reflect this. However, their pragmatic selection of a weekly dose of 5 mg of folate, given the morning after the methotrexate, would not be my choice. Most patients who have physical side-effects get what I term the ‘Monday blues’: taking their methotrexate on a Sunday, they feel sick and unwell the following day. If we want to block this effect then the folate should be given the day before, not the day after. This is supported anecdotally by the clinical improvement of patients inherited from elsewhere who are on daily or day-after folate (or, in one case, taking the folate 3 days before the methotrexate) and who are switched to day-before folate. Other unnoticed side-effects (such as bone marrow suppression and liver dysfunction) will be unaffected by such a change.

So I vote for a pragmatic (but patient-friendly) regime of 15 mg of folate given the day before. Any more bids?

The author has declared no conflicts of interest.

References

  1. Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology 2004;43:267–71.[Abstract/Free Full Text]
Accepted 8 April 2004





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