Methotrexate dosing in renal impairment – more awareness and action needed

Christine Randall, Assistant Director, Lead pharmacist for Dental Medicines Information and Pharmacovigilance, North West Medicines Information CentreExample from Royal Cornwall Hospital NHS Trust/CCGPublished
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Summary of the example

Chronic kidney disease impacts upon prescribing for some disease modifying anti-rheumatic drugs. Methotrexate is usually hospital-initiated but rheumatology and dermatology patients will be monitored by their general practitioner, receiving repeat prescriptions in primary care.  When renal function is reduced, accumulation may lead to toxicity such as excessive bone marrow suppression, acute hepatic toxicity, and acute interstitial pneumonitis. The British Society of Rheumatology advises not exceeding 12.5mg weekly when eGFR is less than 60 mL/min/1.73m2.

For a three month period to mid-May 2018, we identified, via EclipseLive, 2,110 patients with a current methotrexate prescription, of which 1,867 (88%) had an eGFR ≥ 60 mL/min/1.73m2. There were 243 patients with a recent eGFR < 60 mL/min/1.73m2 (86% on tablets and 14% on subcutaneous injection).  No clear dose instruction was captured by data extraction for 29 of these patients on oral medication, leaving 214 whose dose could be viewed relative to an eGFR result.

Hence 121 (5.7%) of 2,110  patients received a dose greater than 12.5mg per week.

Following advice and guidance issued to primary care, a repeat database extraction for the three months to end-March 2019 identified 2,322 patients on weekly methotrexate with 3.6% (84/2322) prescribed a dose too high for their eGFR value.

Why we think it’s important

There is a need to review patients receiving methotrexate in relation to their renal function. Where primary care undertakes the prescribing there is likely to be little awareness of this need for review to avoid potential toxicity.

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Aims and objectives of the work

The primary outcome was to determine how many rheumatology/dermatology patients in primary care with impaired renal function were prescribed methotrexate at a dose exceeding 12.5mg per week as of early 2018.

We then prompted review of these patients in primary care, and undertook a follow up data extraction in early 2019.


EclipseLive (a patient safety alerting system) was used to capture anonymous data for patients prescribed methotrexate across 49 of 60 practices in one Clinical Commissioning Group (CCG). Relevant data were exported into Microsoft Excel.

Following discussion with Rheumatology and Dermatology teams, we presented a summary of the results at three meetings for GP practice prescribing leads late in 2018 and then issued a letter in early 2019 to primary care. This letter described the project, the need to review these patients and any action necessary to be taken regarding eGFR monitoring and dosing.  We have altered our local shared care guideline to emphasise caution on dosing in renal impairment. We repeated data extraction and analysis in April 2019 to ascertain if the situation had improved.

Key findings

In the primary care database from one CCG, at baseline, there were 5.7% (121/2,110) patients on methotrexate who were prescribed a dose too high for their eGFR value.

The repeat data extraction for 3 months to end of March 2019 (and hence after advice and guidance to GPs) identified 2,322 patients on methotrexate (previously 2,110) with 3.6% (84/2,322) patients on weekly methotrexate who were prescribed a dose too high for their eGFR value. This is lower than the previous value of 6% (121/2,110) patients. In addition, an eGFR value of <60 is not always an automatic binary threshold, and in the recent database there were 21of these patients with a ‘too high a dose’ who had eGFR values of between 57 and 60, and there may have been a GP view that the patient is well controlled on their existing dose and reducing this dose around the boundary of an eGFR value of 60 may lead to poorer disease control without improving patient safety.

Limitations include that we did not check for comorbidity or concomitant nephrotoxic agents (e.g non-steroidal anti-inflammatory drugs) which may have increased the potential toxicity risk, and we did not look at trends in eGFR for individual patients.


A poster was presented at the Pharmacy Management/UKCPA Conference in November  2018 and is available on the UKCPA website and in the abstract booklet, also attached below.



National guidance, data and publications

Ledingham J. et al. BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs. Rheumatology 2017;56(6): 865-868 (full text link below)