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Incidence of Acute Renal Failure in Patients Using Levetiracetam Versus Other Antiseizure Medications: A Voluntary Post-Authorization Safety Study

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Abstract

Introduction

Acute kidney injury is an expected adverse drug reaction listed in the European Union (EU) Summary of Product Characteristics (SmPC) for levetiracetam, one of the most widely used modern antiseizure medications (ASMs).

Objective

We conducted a voluntary post-authorization safety study to characterize the rate of acute renal failure (ARF) in patients exposed to levetiracetam versus other ASMs.

Methods

New users of ASMs without prior renal dysfunction were identified and followed for 30 days in the IBM® MarketScan® database (USA, January 2008–December 2017). ARF was defined as a diagnosis on inpatient or emergency department claims. We estimated adjusted incidence rates, incidence rate ratios (IRRs), and incidence rate differences (IRDs) of ARF in patients initiating levetiracetam versus other ASMs.

Results

Overall, 110,336 patients were eligible for the monotherapy cohort and 96,215 were eligible for the polytherapy cohort. The overall crude rate of ARF following a new ASM was 6.0 and 6.5 per 10,000 patients for the ‘monotherapy’ and ‘polytherapy’ cohorts, respectively, in the first 30 days after the index date. In the monotherapy cohort, the IRR for ARF was 1.37 (95% confidence interval [CI] 0.80–2.34) and the corresponding IRD was 2.0 (95% CI − 1.12 to 5.12) additional ARFs per 10,000 patient-months. In the polytherapy cohort, the adjusted IRR for ARF was 0.94 (95% CI 0.51–1.74) and the corresponding IRD was − 0.42 cases per 10,000 patient-months (95% CI − 4.01 to 3.17).

Conclusions

The rate of ARFs in ASM new users was very low. In patients without prior ASMs, the estimated difference in risk of ARF associated with initiation of levetiracetam versus initiation of other ASMs was small, with 95% CIs compatible with small protective or harmful effects. In patients receiving polytherapy, the difference was compatible with the null and the 95% CI with small protective or harmful effects.

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Acknowledgments

Nada Boudiaf, David Friesen, and Kathrin Haeffs contributed to the validation of the analysis. The authors acknowledge Kathleen Richards, PhD (UCB Pharma, Smyrna, GA, USA) for publication coordination.

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Authors and Affiliations

  1. UCB Pharma, Bulle, Switzerland

    Raphaelle Beau-Lejdstrom

  2. Redsen Limited, Bournemouth, UK

    Lai San Hong

  3. Pharmacoepidemiology and Risk Management, RTI Health Solutions, Barcelona, Spain

    Xabier Garcia de Albeniz & Susana Perez-Gutthann

  4. UCB Pharma, Monheim am Rhein, Germany

    Florin Floricel & Christian Loesch

  5. University Hospital Zurich, Zurich, Switzerland

    Johan Lorenzen

  6. UCB Pharma, Brussels, Belgium

    Francois Bonfitto & Isabelle Mottet

  7. UCB Pharma, Morrisville (formerly Raleigh), NC, USA

    Linda Kalilani

  8. UCB Pharma, Slough, UK

    Graham Luscombe & Nadia Foskett

Authors
  1. Raphaelle Beau-Lejdstrom
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  2. Lai San Hong
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  3. Xabier Garcia de Albeniz
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  4. Florin Floricel
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  7. Linda Kalilani
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Corresponding author

Correspondence to Raphaelle Beau-Lejdstrom.

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Funding

Work on this manuscript was funded by UCB Pharma.

Conflicts of interest/competing interests

Lai San Hong was an independent contractor for UCB Pharma. Xabier Garcia de Albeniz and Susana Perez-Gutthann are employees of RTI-HS and were contracted to perform work on this study and manuscript, funded by UCB Pharma. Raphaelle Beau-Lejdstrom is a salaried employee of UCB Pharma and stockholder. Francois Bonfitto, Florin Floricel, Christian Loesch, and Isabelle Mottet are salaried UCB Pharma employees and stockholders. Linda Kalilani, Graham Luscombe, and Nadia Foskett were employees of UCB Pharma at the time this study was conducted. Johan Lorenzen has received fees for consulting and expert testimony relating to the subject matter discussed in this manuscript.

Availability of data and material

The dataset (IBM® MarketScan® Research Databases) generated and/or analyzed during the current study are not publicly available but are available from IBM® on reasonable request.

Code availability

Available from David Friesen (David.Friesen@ucb.com).

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Authors’ contributions

RBL designed the study, contributed to the analysis, interpreted the data, and revised and approved the final version to be published. LSH contributed to the design of the study, analyzed the data, revised the manuscript, and approved the final version to be published. FF, JL, FB, LK, GL, CL, SPG, IM, and NF contributed to the design of the study and revised and approved the final version to be published. XGA contributed to the analysis and interpretation of the data, drafted the manuscript, and approved the final version to be published.

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Beau-Lejdstrom, R., Hong, L.S., Garcia de Albeniz, X. et al. Incidence of Acute Renal Failure in Patients Using Levetiracetam Versus Other Antiseizure Medications: A Voluntary Post-Authorization Safety Study. Drug Saf 45, 781–790 (2022). https://doi.org/10.1007/s40264-022-01193-0

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  • DOI: https://doi.org/10.1007/s40264-022-01193-0

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