Department of Rheumatology, Harrogate District Hospital, Harrogate, N. Yorkshire HG2 7SX, UK
SIR, In a recent issue of this journal, Devlin et al. [1] state that folate supplementation in patients treated with methotrexate (MTX) is often ineffective in preventing gastrointestinal (GI) toxicity. They propose that in patients unable to tolerate MTX because of GI side effects, granistron, an anti-emetic with 5HT3 antagonist action, could be used to allow patients to continue with treatment. In a similar trial, also reported in this journal, ondansetron (with the same class action) was reported to reduce MTX-associated nausea [2].
We recently took over the care of a 41-yr-old female patient who was receiving intramuscular MTX at a dose of 10 mg weekly as treatment for her rheumatoid arthritis (RA). She took co-proxamol and tramadol as required. Her principle complaint was of severe nausea and vomiting in association with her MTX injections. The MTX was controlling her disease activity as assessed by inflammatory markers [C-reactive protein <5 mg/l (normal range 110)], but she was severely disabled by the GI symptoms. The MTX was stopped, and on review at 2 weeks she was asymptomatic. She declined any further MTX despite a full explanation.
We reviewed our computerized patient database to assess the number of patients we have with a current prescription for MTX (Table 1). All 341 patients are also routinely taking 5 mg of folic acid, which they take every day of the week except the day of their MTX. Of our patients, fewer than 1 in 100 have experienced GI toxicity (nausea and vomiting). The case reported is the third time we have had to stop MTX because of nausea. The patient was not taking folate supplements.
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Whilst we agree that granistron (or similar) is effective, we believe it is important to use daily folic acid supplements routinely (excluding the day on which MTX is taken). This is effective in preventing GI toxicity, has no side effects and is cheap. Four weeks' supply of granisetron, as used by Devlin et al. [1] in their study (1 mg weekly) costs £36.57. This compares with folic acid supplementation, which costs only £0.11 [5].
No firm guidelines for the use of folic acid with MTX currently exist. We believe it is widely underused. Our regime is simple and patient compliance is excellent. The prescription of folic acid in conjunction with MTX has the additional important benefit of protecting against MTX-induced pancytopenia, which can be fatal [6, 7].
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