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      Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients

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          Background: The opioid epidemic is a public health emergency and appropriate medication prescription for pain remains challenging. Physicians have increasingly prescribed gabapentinoids for pain despite limited evidence supporting their use. We determined the prevalence of concomitant gabapentinoid and opioid prescriptions and evaluated their associations with outcomes among dialysis patients. Methods: We used the United States Renal Data System to identify patients treated with dialysis with Part A, B, and D coverage for all of 2010. Patients were grouped into 4 categories of drugs exposure status in 2010: (1) no prescriptions of either an opioid or gabapentinoid, (2) ≥1 prescription of an opioid and no prescriptions of gabapentinoids, (3) no prescriptions of an opioid and ≥1 prescription of gabapenbtinoids, (4) ≥1 prescription of both an opioid and gabapentinoid. Outcomes included 2-year all-cause death, dialysis discontinuation, and hospitalizations assessed in 2011 and 2012. Results: The study population included 153,758 dialysis patients. Concomitant prescription of an opioid and gabapentin (15%) was more common than concomitant prescription of an opioid and pregabalin (4%). In adjusted analyses, concomitant prescription of an opioid and gabapentin compared to no prescription of either was associated with increased risk of death (hazard ratio [HR] 1.16, 95% CI 1.12–1.19), dialysis discontinuation (HR 1.14, 95% CI 1.03–1.27), and hospitalization (HR 1.33, 95% CI 1.31–1.36). Concomitant prescription of an opioid and pregabalin compared to no prescription of either was associated with increased mortality (HR 1.22, 95% CI 1.16–1.28) and hospitalization (HR 1.37, 95% CI 1.33–1.41), but not dialysis discontinuation (HR 1.13, 95% CI 0.95–1.35). Prescription of opioids and gabepentinoids compared to only being prescribed opioids was associated with higher risk of hospitalizations, but not mortality, or dialysis discontinuation. Conclusions: Concomitant prescription of opioids and gabapentinoids among US dialysis patients is common, and both drugs have independent effects on outcomes. Future research should prospectively investigate the potential harms of such drugs and identify safer alternatives for treatment of pain in end-stage renal disease patients.

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          Author and article information

          Am J Nephrol
          American Journal of Nephrology
          S. Karger AG
          June 2020
          19 May 2020
          : 51
          : 6
          : 424-432
          aDepartment of Neurology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia, USA
          bDepartment of Public Health Sciences, Social and Scientific Systems, Silver Spring, Maryland, USA
          cDivision of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
          Author notes
          *Paul L. Kimmel, MD, Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 6707 Democracy Boulevard, Bethesda, MD 20892-5458 (USA), E-Mail
          507725 Am J Nephrol 2020;51:424–432
          © 2020 Published by S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Tables: 4, Pages: 9
          Patient-Oriented, Translational Research: Research Article

          Cardiovascular Medicine, Nephrology

          Mortality, Outcomes, Dialysis


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