Safety Concerns Persist for Low-Dose Methotrexate

Patient Safety Monitor Insider

December 30, 2015

For patients with severe, disabling rheumatoid arthritis (RA), oral methotrexate is often the preferred disease-modifying antirheumatic drug, unless it is specifically contraindicated (Bykerk et al., 2012; Saag et al., 2008; Singh et al., 2012). Compared to dosing for antineoplastic indications, methotrexate for RA is administered once weekly as low-dose therapy (Sing et al., 2012).

According to official prescribing information, the recommended starting dose is a single oral dose of 7.5 mg once weekly or divided oral doses of 2.5 mg every 12 hours for three doses per week. The dosing schedule may be adjusted to achieve optimal response, with doses up to about 25 mg weekly.

Since early 1996 and as recently as May 2015, harmful or fatal errors with low-dose oral methotrexate have been reported to ISMP and published in more than 50 of our newsletters. Most errors involved accidental daily dosing of oral methotrexate that was intended for weekly administration. In 2004, we published a study of methotrexate errors over a 4-year period that resulted in 25 deaths and 48 serious outcomes, many due to daily dosing (Moore, Walsh, & Cohen, 2004). Our sister organization, ISMP Canada, has also received multiple reports of severe harm or death in patients taking low-dose methotrexate for RA and other autoimmune diseases.

Editor’s Note: This article was written by The Institute for Safe Medication Practices and appears in the November/December issue of PSQH. Continue reading this article on