Prevalence and consequences of drug-drug interactions between high-dose methotrexate and common co-medications on an inpatient hematology unit

Abstract

Background: High-dose methotrexate (HD-MTX) is a chemotherapeutic agent that is used to treat a range of hematological cancers. Certain medications, when administered concurrently with HD-MTX, have been associated with delayed MTX clearance, which may increase the risk of adverse effects including nephrotoxicity and febrile neutropenia. The prevalence and consequences of drug-drug interactions (DDI) with HD-MTX have not previously been described at our centre. Objectives: To determine the proportion of HD-MTX cycles administered to adult hematology inpatients where at least one DDI was present. To compare the incidence of delayed MTX clearance, increased serum creatinine grade two or higher and febrile neutropenia between cycles with and without DDIs. Methods: A single-centre, retrospective cohort analysis was conducted on HD-MTX cycles administered to adult inpatients diagnosed with hematological cancer. The patient cycles were screened and allocated to the DDI and non-DDI group based on the presence of DDI during MTX clearance. The two groups were then compared. Results: From January 2020 to November 2023, DDIs were present in 53 out of 100 patient cycles. There were no statistically significant differences between the DDI and non-DDI group regarding the incidence of delayed MTX clearance, increased serum creatinine grade two or higher and febrile neutropenia. Subgroup analyses on cycles with fluoroquinolones and proton pump inhibitors co-administered also did not reveal any significant differences when compared to the non-DDI group. Conclusion: DDIs were identified in 53% of the HD-MTX cycles, but significant consequences of DDIs were not demonstrated in this study. Future larger-scale studies are required.