Title

Retrospective Evaluation of Methotrexate Elimination when Co-Administered with Proton Pump Inhibitors

Document Type

Article

Publication Date

2014

Publication Title

British Journal of Clinical Pharmacology

First Page

565

Last Page

571

DOI

http://dx.doi.org/10.1111/bcp.12384

Abstract

Aims

The aim was to assess potential interaction between methotrexate (MTX) and proton pump inhibitors (PPIs) in patients receiving high-dose MTX.

Methods

Records of 56 adults receiving 201 cycles of MTX were reviewed to determine effects of PPI administration on MTX elimination. Repeated-measures logistic regressions and Cox regressions were performed to evaluate the possible drug interaction.

Results

Despite a significant difference between those receiving a PPI and not receiving a PPI in median MTX levels at 24 (8.0 vs. 3.9 μmol l−1, respectively, P = 0.013) and 72 h after MTX administration (0.08 vs. 0.05 μmol l−1, respectively, P = 0.037), there was no difference between those receiving a PPI and not receiving a PPI in the proportion of patients experiencing delayed elimination at 24 (19.2% vs. 20.2%, respectively, P = 1.000) and 72 h (36.2% vs. 33.7%, respectively, P = 0.765). When data were analysed using Cox regression, controlling for multiple cycles of MTX per patient, PPI use was not a significant predictor of time to MTX < 0.1 μmol l−1. When the clustering effect of multiple cycles of MTX per patient was controlled for, co-administration of PPIs was not a significant predictor of MTX level (P = 0.969). A comparison of patients with delayed elimination at any time point and those without delayed elimination indicated that PPI use was not a significant predictor of delayed elimination (P = 0.607).

Conclusions

This study does not support previous findings of a significant interaction between PPIs and MTX. Based on these results, the clinical significance of any potential interaction is likely to be small.

Rights

Link leads to free full text provided by PubMed Central.

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