Methotrexate (MTX) is a folic acid analogue classed as an immunosuppressant and antineoplastic drug. However, MTX is cytotoxic, impacting various organs when used to treat patients even at low dosages over time.

This study aimed to examine patterns of MTX-related toxicity among Egyptian patients and investigate the possible effects of the MTX level and GFR on low-dose MTX toxicity.

The present work is a cohort study involving patients treated with methotrexate at a tertiary hospital in Cairo. Recruited patients were followed for one and a half years to detect the pattern of MTX toxicity. Then, the GFR was calculated, and MTX levels were assayed and compared to those of an equivalent sample of patients with no toxicity.

The patients in both groups were mainly males, with a mean age of 40 years. The pattern of toxicity among patients was 66.7% hepatotoxicity, 30% myelosuppression, 27% GIT toxicity, 13% skin toxicity, 8% renal toxicity, and 10% other toxicities. The toxicity group had a higher mean cumulative dose of MTX (>1000mg) with a history of other concurrent drugs such as NSAIDs; lower glomerular filtration rates, with a cut-off point of 72 according to the receiver operating characteristic curve, with a sensitivity of 100% and specificity of 95%; and higher methotrexate levels, with cut-off points of 7.85ng/mL, with a sensitivity of 58% and specificity of 85%.

The toxicity of low-dose MTX was associated mainly with hepatotoxicity and haematological effects. MTX toxicity can be predicted by therapeutic drug monitoring at a serum concentration of 7.85ng/mL or higher and glomerular filtration rates less than 71 in patients.