Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

Bianca Berghuis; Job van der Palen; Gerrit-Jan de Haan; Dick Lindhout; Bobby P.C. Koeleman; Josemir W. Sander; Rikke S. Møller; Marina Nikanorova; Andrés Ingason; Chantal Depondt; Michael R. Johnson; Sarah R Langley; Karl Martin Klein; Mark McCormack; Norman Delanty; Gianpiero L. Cavalleri; Janic van Zijl; Hiltrud Muhle; Mojgansadat Borghei; Simona Donatello; Joseph Willis; Costin Leu; Kristin Heggeli; Andreja Avbersek; Sanjay M. Sisodiya; Antonio Gamberdella; Sarah Weckhuysen; Wolfram S. Kunz; Pasquale Striano; Federico Zara; Martin J. Brodie; Kári Stefánsson; Anthony G. Marson; Andrea Jorgensen; Pauls Auce; Ben Francis; Prashant Srivastava; Graeme J. Sills; Zvonka Rener Primec; Roland Krause; Stefan Wolking; Yvonne G. Weber; Sarah Rau; Christian Hengsbach; Holger Lerche; Anja Sonsma; Martin Krenn; Fritz Zimprich; Ekaterina Pataraia

doi:10.1111/epi.13777

Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

Bianca Berghuis^*, Job van der Palen, Gerrit-Jan de Haan, Dick Lindhout, Bobby P.C. Koeleman, Josemir W. Sander, Rikke S. Møller, Marina Nikanorova, Andrés Ingason, Chantal Depondt, Michael R. Johnson, Sarah R Langley, Karl Martin Klein, Mark McCormack, Norman Delanty, Gianpiero L. Cavalleri, Janic van Zijl, Hiltrud Muhle, Mojgansadat Borghei, Simona DonatelloJoseph Willis, Costin Leu, Kristin Heggeli, Andreja Avbersek, Sanjay M. Sisodiya, Antonio Gamberdella, Sarah Weckhuysen, Wolfram S. Kunz, Pasquale Striano, Federico Zara, Martin J. Brodie, Kári Stefánsson, Anthony G. Marson, Andrea Jorgensen, Pauls Auce, Ben Francis, Prashant Srivastava, Graeme J. Sills, Zvonka Rener Primec, Roland Krause, Stefan Wolking, Yvonne G. Weber, Sarah Rau, Christian Hengsbach, Holger Lerche, Anja Sonsma, Martin Krenn, Fritz Zimprich, Ekaterina Pataraia,

^*Corresponding author for this work

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

Abstract

Objective: To ascertain possible determinants of carbamazepine (CBZ)– and oxcarbazepine (OXC)–induced hyponatremia in a large cohort of people with epilepsy. Methods: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L and severe hyponatremia as Na+ ≤128 mEq/L. Results: We identified 1,782 people who had used CBZ (n = 1,424) or OXC (n = 358), of whom 50 were treated with both drugs. Data on sodium level measurements were available in 1,132 on CBZ and in 289 on OXC. Hyponatremia occurred in 26% of those taking CBZ and 46% of those taking OXC. This was severe in 7% in the CBZ group and 22% in the OXC group. Hyponatremia was symptomatic in 48% and led to admissions in 3%. Age over 40 years, high serum levels of CBZ and OXC, and concomitant use of other antiepileptic drugs were the main risk factors for hyponatremia in both treatment groups. Female patients on OXC were at a higher risk than male patients of hyponatremia. The risk of hyponatremia on CBZ was significantly associated with the risk of hyponatremia on OXC within a subgroup that used both drugs consecutively. Significance: Hyponatremia is a common problem in people taking CBZ or OXC. Regular ascertainment of sodium levels in those taking either drug is recommended and results should be acted on.

Original language	English
Pages (from-to)	1227-1233
Number of pages	7
Journal	Epilepsia
Volume	58
Issue number	7
DOIs	https://doi.org/10.1111/epi.13777
Publication status	Published - 1 Jul 2017

Keywords

Antiepileptic drugs
Sodium levels
Adverse effects
Electrolytes.

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10.1111/epi.13777

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Berghuis, B., van der Palen, J., de Haan, G.-J., Lindhout, D., Koeleman, B. P. C., Sander, J. W., Møller, R. S., Nikanorova, M., Ingason, A., Depondt, C., Johnson, M. R., Langley, S. R., Klein, K. M., McCormack, M., Delanty, N., Cavalleri, G. L., van Zijl, J., Muhle, H., Borghei, M. (2017). Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy. Epilepsia, 58(7), 1227-1233. https://doi.org/10.1111/epi.13777

@article{c29cf4b5f2b64e23a40750f7eb086534,

title = "Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy",

abstract = "Objective: To ascertain possible determinants of carbamazepine (CBZ)– and oxcarbazepine (OXC)–induced hyponatremia in a large cohort of people with epilepsy. Methods: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L and severe hyponatremia as Na+ ≤128 mEq/L. Results: We identified 1,782 people who had used CBZ (n = 1,424) or OXC (n = 358), of whom 50 were treated with both drugs. Data on sodium level measurements were available in 1,132 on CBZ and in 289 on OXC. Hyponatremia occurred in 26% of those taking CBZ and 46% of those taking OXC. This was severe in 7% in the CBZ group and 22% in the OXC group. Hyponatremia was symptomatic in 48% and led to admissions in 3%. Age over 40 years, high serum levels of CBZ and OXC, and concomitant use of other antiepileptic drugs were the main risk factors for hyponatremia in both treatment groups. Female patients on OXC were at a higher risk than male patients of hyponatremia. The risk of hyponatremia on CBZ was significantly associated with the risk of hyponatremia on OXC within a subgroup that used both drugs consecutively. Significance: Hyponatremia is a common problem in people taking CBZ or OXC. Regular ascertainment of sodium levels in those taking either drug is recommended and results should be acted on.",

keywords = "Antiepileptic drugs, Sodium levels, Adverse effects, Electrolytes.",

author = "Bianca Berghuis and {van der Palen}, Job and {de Haan}, Gerrit-Jan and Dick Lindhout and Koeleman, {Bobby P.C.} and Sander, {Josemir W.} and M{\o}ller, {Rikke S.} and Marina Nikanorova and Andr{\'e}s Ingason and Chantal Depondt and Johnson, {Michael R.} and Langley, {Sarah R} and Klein, {Karl Martin} and Mark McCormack and Norman Delanty and Cavalleri, {Gianpiero L.} and {van Zijl}, Janic and Hiltrud Muhle and Mojgansadat Borghei and Simona Donatello and Joseph Willis and Costin Leu and Kristin Heggeli and Andreja Avbersek and Sisodiya, {Sanjay M.} and Antonio Gamberdella and Sarah Weckhuysen and Kunz, {Wolfram S.} and Pasquale Striano and Federico Zara and Brodie, {Martin J.} and K{\'a}ri Stef{\'a}nsson and Marson, {Anthony G.} and Andrea Jorgensen and Pauls Auce and Ben Francis and Prashant Srivastava and Sills, {Graeme J.} and Primec, {Zvonka Rener} and Roland Krause and Stefan Wolking and Weber, {Yvonne G.} and Sarah Rau and Christian Hengsbach and Holger Lerche and Anja Sonsma and Martin Krenn and Fritz Zimprich and Ekaterina Pataraia",

note = "Funding Information: The European Union Seventh Framework Programme (FP7/2007-2013) supported this work under grant agreement n? 279062, as part of the EpiPGX project. JWS is based at UCLH/UCL Comprehensive Biomedical Research Centre, which receives a proportion of funding from the U.K. Department of Health's National Institute for Health Research Biomedical Research Centre's funding scheme. He receives support from the Dr Marvin Weil Epilepsy Research Fund. We thank Janic van Zijl, Marita Devile, Trusjen Punte, and Anja Sonsma, for helping with data collection. We are grateful to Gail Bell for reviewing the manuscript. Publisher Copyright: Wiley Periodicals, Inc. {\textcopyright} 2017 International League Against Epilepsy",

year = "2017",

month = jul,

day = "1",

doi = "10.1111/epi.13777",

language = "English",

volume = "58",

pages = "1227--1233",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "Wiley-Blackwell",

number = "7",

}

Berghuis, B, van der Palen, J, de Haan, G-J, Lindhout, D, Koeleman, BPC, Sander, JW, Møller, RS, Nikanorova, M, Ingason, A, Depondt, C, Johnson, MR, Langley, SR, Klein, KM, McCormack, M, Delanty, N, Cavalleri, GL, van Zijl, J, Muhle, H, Borghei, M, Donatello, S, Willis, J, Leu, C, Heggeli, K, Avbersek, A, Sisodiya, SM, Gamberdella, A, Weckhuysen, S, Kunz, WS, Striano, P, Zara, F, Brodie, MJ, Stefánsson, K, Marson, AG, Jorgensen, A, Auce, P, Francis, B, Srivastava, P, Sills, GJ, Primec, ZR, Krause, R, Wolking, S, Weber, YG, Rau, S, Hengsbach, C, Lerche, H, Sonsma, A, Krenn, M, Zimprich, F, Pataraia, E 2017, 'Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy', Epilepsia, vol. 58, no. 7, pp. 1227-1233. https://doi.org/10.1111/epi.13777

TY - JOUR

T1 - Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

AU - Berghuis, Bianca

AU - van der Palen, Job

AU - de Haan, Gerrit-Jan

AU - Lindhout, Dick

AU - Koeleman, Bobby P.C.

AU - Sander, Josemir W.

AU - Møller, Rikke S.

AU - Nikanorova, Marina

AU - Ingason, Andrés

AU - Depondt, Chantal

AU - Johnson, Michael R.

AU - Langley, Sarah R

AU - Klein, Karl Martin

AU - McCormack, Mark

AU - Delanty, Norman

AU - Cavalleri, Gianpiero L.

AU - van Zijl, Janic

AU - Muhle, Hiltrud

AU - Borghei, Mojgansadat

AU - Donatello, Simona

AU - Willis, Joseph

AU - Leu, Costin

AU - Heggeli, Kristin

AU - Avbersek, Andreja

AU - Sisodiya, Sanjay M.

AU - Gamberdella, Antonio

AU - Weckhuysen, Sarah

AU - Kunz, Wolfram S.

AU - Striano, Pasquale

AU - Zara, Federico

AU - Brodie, Martin J.

AU - Stefánsson, Kári

AU - Marson, Anthony G.

AU - Jorgensen, Andrea

AU - Auce, Pauls

AU - Francis, Ben

AU - Srivastava, Prashant

AU - Sills, Graeme J.

AU - Primec, Zvonka Rener

AU - Krause, Roland

AU - Wolking, Stefan

AU - Weber, Yvonne G.

AU - Rau, Sarah

AU - Hengsbach, Christian

AU - Lerche, Holger

AU - Sonsma, Anja

AU - Krenn, Martin

AU - Zimprich, Fritz

AU - Pataraia, Ekaterina

N1 - Funding Information: The European Union Seventh Framework Programme (FP7/2007-2013) supported this work under grant agreement n? 279062, as part of the EpiPGX project. JWS is based at UCLH/UCL Comprehensive Biomedical Research Centre, which receives a proportion of funding from the U.K. Department of Health's National Institute for Health Research Biomedical Research Centre's funding scheme. He receives support from the Dr Marvin Weil Epilepsy Research Fund. We thank Janic van Zijl, Marita Devile, Trusjen Punte, and Anja Sonsma, for helping with data collection. We are grateful to Gail Bell for reviewing the manuscript. Publisher Copyright: Wiley Periodicals, Inc. © 2017 International League Against Epilepsy

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Objective: To ascertain possible determinants of carbamazepine (CBZ)– and oxcarbazepine (OXC)–induced hyponatremia in a large cohort of people with epilepsy. Methods: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L and severe hyponatremia as Na+ ≤128 mEq/L. Results: We identified 1,782 people who had used CBZ (n = 1,424) or OXC (n = 358), of whom 50 were treated with both drugs. Data on sodium level measurements were available in 1,132 on CBZ and in 289 on OXC. Hyponatremia occurred in 26% of those taking CBZ and 46% of those taking OXC. This was severe in 7% in the CBZ group and 22% in the OXC group. Hyponatremia was symptomatic in 48% and led to admissions in 3%. Age over 40 years, high serum levels of CBZ and OXC, and concomitant use of other antiepileptic drugs were the main risk factors for hyponatremia in both treatment groups. Female patients on OXC were at a higher risk than male patients of hyponatremia. The risk of hyponatremia on CBZ was significantly associated with the risk of hyponatremia on OXC within a subgroup that used both drugs consecutively. Significance: Hyponatremia is a common problem in people taking CBZ or OXC. Regular ascertainment of sodium levels in those taking either drug is recommended and results should be acted on.

AB - Objective: To ascertain possible determinants of carbamazepine (CBZ)– and oxcarbazepine (OXC)–induced hyponatremia in a large cohort of people with epilepsy. Methods: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L and severe hyponatremia as Na+ ≤128 mEq/L. Results: We identified 1,782 people who had used CBZ (n = 1,424) or OXC (n = 358), of whom 50 were treated with both drugs. Data on sodium level measurements were available in 1,132 on CBZ and in 289 on OXC. Hyponatremia occurred in 26% of those taking CBZ and 46% of those taking OXC. This was severe in 7% in the CBZ group and 22% in the OXC group. Hyponatremia was symptomatic in 48% and led to admissions in 3%. Age over 40 years, high serum levels of CBZ and OXC, and concomitant use of other antiepileptic drugs were the main risk factors for hyponatremia in both treatment groups. Female patients on OXC were at a higher risk than male patients of hyponatremia. The risk of hyponatremia on CBZ was significantly associated with the risk of hyponatremia on OXC within a subgroup that used both drugs consecutively. Significance: Hyponatremia is a common problem in people taking CBZ or OXC. Regular ascertainment of sodium levels in those taking either drug is recommended and results should be acted on.

KW - Antiepileptic drugs

KW - Sodium levels

KW - Adverse effects

KW - Electrolytes.

UR - http://www.scopus.com/inward/record.url?scp=85021814480&partnerID=8YFLogxK

U2 - 10.1111/epi.13777

DO - 10.1111/epi.13777

M3 - Article

C2 - 28542738

AN - SCOPUS:85021814480

SN - 0013-9580

VL - 58

SP - 1227

EP - 1233

JO - Epilepsia

JF - Epilepsia

IS - 7

ER -

Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

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Keywords

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