Methotrexate and bone marrow suppression

Editor—Two points arise from the lesson of the week by Sosin and Handa on methotrexate toxicity.¹

Firstly, bone marrow toxicity with methotrexate is a late complication of treatment. Only one of the cases described (case 2) had been treated for less than 12 months, and the authors suspect he had been taking methotrexate daily rather than weekly as would have been recommended. This is consistent with what we showed in our observational study,² in which the median delay to neutropenia with methotrexate was 16.9 months, in contrast to other disease modifying antirheumatic drugs such as sulphasalazine, with which the median delay was 2.1 months.

This has important implications for monitoring protocols as current guidelines specify more frequent monitoring early in treatment. Whereas with drugs such as sulphasalazine toxicity may reflect hypersensitivity, with methotrexate accumulation seems a more likely cause.³

Secondly, there is a further potential source of serious drug errors with methotrexate other than the weekly dosing regimen. The drug comes in 2.5 mg and 10 mg tablets, which look identical in colour, size, and shape. The 2.5 mg tablet is preferred in secondary care, as this allows ready dose titration. However, patients taking 10 mg or 20 mg weekly may be dispensed the 10 mg tablet from community pharmacies. Unless the different tablet dose is highlighted, patients are at risk of a fourfold overdose. Drug errors with the 10 mg tablet have been implicated in at least one death.⁴

This is partially a matter for patients' education—we regularly emphasise the importance of checking the tablet dose to our patients—and partially a matter for the manufacturers and the National Patient Safety Agency (www.npsa.org.uk). The 10 mg tablet is to change shape soon, but while stocks of the old shape remain in circulation the potential for this error remains.