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

David J. Reeves; Elizabeth S. Moore; Devon Bascom; Brandon Rensing

doi:10.1111/bcp.12384

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

David J. Reeves, Elizabeth S. Moore, Devon Bascom, Brandon Rensing

Butler University

Research output: Contribution to journal › Article › peer-review

Abstract

<p> <h3> Aims </h3></p><p> The aim was to assess potential interaction between methotrexate (MTX) and proton pump inhibitors (PPIs) in patients receiving high-dose MTX. <h3> Methods </h3></p><p> 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. <h3> Results </h3></p><p> Despite a significant difference between those receiving a PPI and not receiving a PPI in median MTX levels at 24 (8.0 <em> vs. </em> 3.9 μmol l <sup> −1 </sup> , respectively, <em> P </em> = 0.013) and 72 h after MTX administration (0.08 <em> vs. </em> 0.05 μmol l <sup> −1 </sup> , respectively, <em> P </em> = 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% <em> vs. </em> 20.2%, respectively, <em> P </em> = 1.000) and 72 h (36.2% <em> vs. </em> 33.7%, respectively, <em> P </em> = 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 <sup> −1 </sup> . 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 ( <em> P </em> = 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 ( <em> P </em> = 0.607). <h3> Conclusions </h3></p><p> 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.</p>

Original language	American English
Journal	Scholarship and Professional Work – COPHS
Volume	78
Issue number	3
DOIs	https://doi.org/10.1111/bcp.12384
State	Published - Jan 1 2014

Keywords

methotrexate elimination
proton pump inhibitors

Disciplines

Pharmaceutics and Drug Design
Pharmacy and Pharmaceutical Sciences

Access to Document

10.1111/bcp.12384License: Unspecified

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243907

Cite this

@article{7fa8939c339047e9acc740cfdc861714,

title = "Retrospective Evaluation of Methotrexate Elimination when Co-Administered with Proton Pump Inhibitors",

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.",

keywords = "methotrexate elimination, proton pump inhibitors",

author = "Reeves, \{David J.\} and Moore, \{Elizabeth S.\} and Devon Bascom and Brandon Rensing",

year = "2014",

month = jan,

day = "1",

doi = "10.1111/bcp.12384",

language = "American English",

volume = "78",

journal = "Scholarship and Professional Work – COPHS",

number = "3",

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TY - JOUR

T1 - Retrospective Evaluation of Methotrexate Elimination when Co-Administered with Proton Pump Inhibitors

AU - Reeves, David J.

AU - Moore, Elizabeth S.

AU - Bascom, Devon

AU - Rensing, Brandon

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - methotrexate elimination

KW - proton pump inhibitors

UR - https://digitalcommons.butler.edu/cophs_papers/215

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243907

U2 - 10.1111/bcp.12384

DO - 10.1111/bcp.12384

M3 - Article

VL - 78

JO - Scholarship and Professional Work – COPHS

JF - Scholarship and Professional Work – COPHS

IS - 3

ER -

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

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