Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences?

Abstract The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high‐dose methotrexate (≥1 g/m2) for haematological malignancy and to identify the impact of interacting drugs, especially proton‐pump inhibitors (PPIs) and ranitidine. All patients treated with high‐dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton‐pump inhibitors were co‐administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety‐three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delay...
Source: Hematological Oncology - Category: Hematology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research