Daily folate supplementation is adequate prophylaxis against methotrexate-induced nausea and vomiting and avoids the need for expensive anti-emetic prescription

A. R. Lorenzi, A. H. Johnson and A. Gough

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 1–10)], 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 1Go). 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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TABLE 1. Patients taking MTX for any reason at the time of writing.

 
In a meta-analysis of randomized controlled trials assessing the efficacy of folic and folinic acid in reducing MTX GI toxicity in patients with RA, Ortiz et al. [3] report an 80% reduction in mucosal and GI side effects of MTX with low-dose folic acid. Folic acid was superior to folinic acid and there was no difference in disease activity between placebo, folinic acid and folic acid. High-dose folinic acid was associated with deterioration in joint activity scores. The efficacy of MTX has been shown previously not to be reduced by the co-administration of folate [4].

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].

Notes

Correspondence to: A. Gough. Back

References

  1. Devlin J, Wagstaff K, Arthur V, Emery P. Granisetron (Kytril) suppresses methotrexate induced nausea and vomiting among patients with inflammatory arthritis and is superior to prochlorperazine (Stemetil). Rheumatology1999;38:280–82.[Abstract]
  2. Blanco R, Gonzalez-Gay MA, Garcia-Porrua C, Ibannez D, Garcia-Pais MJ, Sanchez-Andrade A, Vazquez-Caruncho M. Ondansetron prevents refractory and severe methotrexate-induced nausea in rheumatoid arthritis. Br J Rheumatol1998;37:590–2.[ISI][Medline]
  3. Ortiz Z, Shea B, Suarez-Almazor ME, Moher D, Wells GA, Tugwell P. The efficacy of folic acid and folinic acid in reducing methotrexate induced gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomised controlled trials. J Rheumatology1998;25:36–43.[ISI][Medline]
  4. Shiroky JB, Neville C, Esdaile JM. Low dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multi-centre randomised, double blind, placebo controlled trial. Arthritis Rheum1993;36:795–80.[ISI][Medline]
  5. British National Formulary 1999; March.
  6. Laroche F, Perrot S, Menkes CJ. [Pancytopenia in rheumatoid arthritis with methotrexate]. [French]. Presse Medical1996;25:1144–6.[ISI]
  7. Berthelot JM, Maugars Y, Prost A. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis: comment on the article by Gutierrez-Urena et al. Arthritis Rheum1997;40:193–4.[Medline]
Accepted 24 January 2000





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