Journal of Pediatric Neurology 2024; 22(06): 425-428
DOI: 10.1055/s-0043-1778102
Review Article

Use of Mexiletine in Children: A Minireview

1   Centre de Référence Maladies Rares des Pathologies Neuromusculaires, Service de Génétique Médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France
,
Sarah Barrière
1   Centre de Référence Maladies Rares des Pathologies Neuromusculaires, Service de Génétique Médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France
2   Centre de Compétence Maladies Rares des Epilepsies, Service de Pédiatrie et Service de Néonatalogie, CHU Clermont-Ferrand, Clermont-Ferrand, France
,
Ganaelle Remerand
2   Centre de Compétence Maladies Rares des Epilepsies, Service de Pédiatrie et Service de Néonatalogie, CHU Clermont-Ferrand, Clermont-Ferrand, France
,
Grégoire Massoullie
3   Centre de Compétence Maladies Rares des Malformations Cardiaques Complexes, Service de Cardiologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
,
Aurélie Chalard
3   Centre de Compétence Maladies Rares des Malformations Cardiaques Complexes, Service de Cardiologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
,
Claire Dauphin
3   Centre de Compétence Maladies Rares des Malformations Cardiaques Complexes, Service de Cardiologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
,
Bénédicte Pontier
1   Centre de Référence Maladies Rares des Pathologies Neuromusculaires, Service de Génétique Médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France
,
Fanny Laffargue
1   Centre de Référence Maladies Rares des Pathologies Neuromusculaires, Service de Génétique Médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France
› Author Affiliations
Funding None.

Abstract

Mexiletine is well-established sodium channel blocker that acts on cardiac myocytes and neurons. It has recently been repositioned as an orphan drug in the treatment of rare neuromuscular diseases in adults with nondystrophic myotonia. It has also long been used in some rare pediatric diseases in the areas of cardiopathy, epilepsy, neuromuscular diseases, and pain disorders. Here, we review the different uses of mexiletine reported in pediatrics, stating indications, efficacy, and tolerance. Special attention by health authorities to maintain access to mexiletine in rare pediatric diseases and further pediatric research in these rare syndromes are required.



Publication History

Received: 22 June 2023

Accepted: 03 December 2023

Article published online:
16 January 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Kuwabara S, Misawa S, Tamura N. et al. The effects of mexiletine on excitability properties of human median motor axons. Clin Neurophysiol 2005; 116 (02) 284-289
  • 2 Singh S, Kerndt CC, Chauhan S. et al. Mexiletine. 2022. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023
  • 3 Campbell RW. Mexiletine. N Engl J Med 1987; 316 (01) 29-34
  • 4 Talbot RG, Nimmo J, Julian DG, Clark RA, Neilson JM, Prescott LF. Treatment of ventricular arrhythmias with mexiletine (Kö 1173). Lancet 1973; 2 (7826): 399-404
  • 5 European Medicines Agency. 2018 Available at: https://www.ema.europa.eu/en/documents/assessment-report/namusclaeparpublic-assessment-report_en.pdf
  • 6 Statland JM, Bundy BN, Wang Y. et al; Consortium for Clinical Investigation of Neurologic Channelopathies. Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. JAMA 2012; 308 (13) 1357-1365
  • 7 Heatwole C, Luebbe E, Rosero S. et al. Mexiletine in myotonic dystrophy type 1: a randomized, double-blind, placebo-controlled trial. Neurology 2021; 96 (02) e228-e240
  • 8 Logigian EL, Martens WB, Moxley IV RT. et al. Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology 2010; 74 (18) 1441-1448
  • 9 Pottage A, Campbell RW, Fiddler GI, Godman MJ. Mexiletine therapy in a child with a chronic ventricular arrhythmia. Postgrad Med J 1977; 53 (Suppl. 01) 137-142
  • 10 Funasako M, Aiba T, Ishibashi K. et al. Pronounced shortening of QT interval with mexiletine infusion test in patients with type 3 congenital long QT syndrome. Circ J 2016; 80 (02) 340-345
  • 11 Bos JM, Crotti L, Rohatgi RK. et al. Mexiletine shortens the QT interval in patients with potassium channel-mediated type 2 long QT syndrome. Circ Arrhythm Electrophysiol 2019; 12 (05) e007280
  • 12 Wåström M, Pfammatter JP. Ten-year-old boy with congenital long QT syndrome type 2 (LQTS2) and life-threatening electrical storm: a case report of successful treatment with mexiletine. Cardiol Young 2022; 32 (11) 1871-1872
  • 13 Blaufox AD, Tristani-Firouzi M, Seslar S. et al. Congenital long QT 3 in the pediatric population. Am J Cardiol 2012; 109 (10) 1459-1465
  • 14 Mazzanti A, Maragna R, Faragli A. et al. Gene-specific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3. J Am Coll Cardiol 2016; 67 (09) 1053-1058
  • 15 Tunca Sahin G, Ergul Y. A case report: Is mexiletine usage effective in the shortening of QTC interval and improving the T-wave alternans in Timothy syndrome?. Ann Noninvasive Electrocardiol 2018; 23 (03) e12522
  • 16 Hermida A, Jedraszak G, Kubala M. et al. Long-term follow-up of a patient with type 2 Timothy syndrome and the partial efficacy of mexiletine. Gene 2021; 777: 145465
  • 17 Bagkaki A, Tsoutsinos A, Hatzidaki E, Tzatzarakis M, Parthenakis F, Germanakis I. Mexiletine treatment for neonatal LQT3 syndrome: case report and literature review. Front Pediatr 2021; 9: 674041
  • 18 Okuwaki H, Kato Y, Lin L, Nozaki Y, Takahashi-Igari M, Horigome H. Mexiletine infusion challenge test for neonatal long QT syndrome with 2:1 atrioventricular block. J Arrhythm 2019; 35 (04) 685-688
  • 19 Yao CT, Wang JN, Tsai YC, Lin CS, Wu JM. Congenital long QT syndrome with functionally impaired atrioventricular conduction: successful treatment by mexiletine and propranolol. J Formos Med Assoc 2002; 101 (04) 291-293
  • 20 Pereira ENS, Sacilotto L, Pessente GD. et al Mexiletina em um Recém-Nascido com Síndrome do QT Longo Tipo 3: Quando o Acesso se Impõe à Urgência [Mexiletine in a newborn with type 3 long QT syndrome: when access is difficult]. Arq Bras Cardiol 2022; 118 (05) 989-991
  • 21 Chang CC, Acharfi S, Wu MH. et al. A novel SCN5A mutation manifests as a malignant form of long QT syndrome with perinatal onset of tachycardia/bradycardia. Cardiovasc Res 2004; 64 (02) 268-278
  • 22 Schulze-Bahr E, Fenge H, Etzrodt D. et al. Long QT syndrome and life threatening arrhythmia in a newborn: molecular diagnosis and treatment response. Heart 2004; 90 (01) 13-16
  • 23 Wang DW, Crotti L, Shimizu W. et al. Malignant perinatal variant of long-QT syndrome caused by a profoundly dysfunctional cardiac sodium channel. Circ Arrhythm Electrophysiol 2008; 1 (05) 370-378
  • 24 Zeppenfeld K, Tfelt-Hansen J, de Riva M. et al; ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J 2022; 43 (40) 3997-4126
  • 25 Ruan Y, Liu N, Bloise R, Napolitano C, Priori SG. Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation 2007; 116 (10) 1137-1144
  • 26 van der Ree MH, van Dussen L, Rosenberg N. et al. Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review. Europace 2022; 24 (11) 1809-1823
  • 27 Al-Ghamdi F, Darras BT, Ghosh PS. Spectrum of nondystrophic skeletal muscle channelopathies in children. Pediatr Neurol 2017; 70: 26-33
  • 28 Modoni A, D'Amico A, Primiano G, Capozzoli F, Desaphy JF, Lo Monaco M. Long-term safety and usefulness of mexiletine in a large cohort of patients affected by non-dystrophic myotonias. Front Neurol 2020; 11: 300
  • 29 Yang MT, Yang CC, Chu LW, Lee WT, Young C, Wang PJ. Schwartz-Jampel syndrome: report of one case. Acta Paediatr Taiwan 2002; 43 (04) 220-223
  • 30 Portaro S, Rodolico C, Sinicropi S, Musumeci O, Valenzise M, Toscano A. Flecainide-responsive myotonia permanens with SNEL onset: a new case and literature review. Pediatrics 2016; 137 (04) e20153289
  • 31 Caietta E, Milh M, Sternberg D. et al. Diagnosis and outcome of SCN4A-related severe neonatal episodic laryngospasm (SNEL): 2 new cases. Pediatrics 2013; 132 (03) e784-e787
  • 32 Johnson NE, Aldana EZ, Angeard N. et al. Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1. Neurol Clin Pract 2019; 9 (05) 443-454
  • 33 Kohyama J, Shimohira M, Watanabe S, Fukuda C, Iwakawa Y. Mexiletine hydrochloride in an infant with intractable epilepsy. Brain Dev 1988; 10 (04) 258-260
  • 34 Mori K, Ito H, Toda Y. et al. Successful management of intractable epilepsy with lidocaine tapes and continuous subcutaneous lidocaine infusion. Epilepsia 2004; 45 (10) 1287-1290
  • 35 Foster LA, Johnson MR, MacDonald JT. et al. Infantile epileptic encephalopathy associated with SCN2A mutation responsive to oral mexiletine. Pediatr Neurol 2017; 66: 108-111
  • 36 Enoki H, Hata H, Ohmori I, Maniwa S, Ohta H, Kobayashi K. [Clinical applications and the effect of mexiletine on refractory epilepsies]. No To Hattatsu 2000; 32 (01) 29-34
  • 37 Nathan A, Rose JB, Guite JW, Hehir D, Milovcich K. Primary erythromelalgia in a child responding to intravenous lidocaine and oral mexiletine treatment. Pediatrics 2005; 115 (04) e504-e507
  • 38 Iqbal J, Bhat MI, Charoo BA, Syed WA, Sheikh MA, Bhat IN. Experience with oral mexiletine in primary erythromelalgia in children. Ann Saudi Med 2009; 29 (04) 316-318
  • 39 Jakob A, Creutzfeldt R, Staszewski O, Winterpacht A, Berner R, Hufnagel M. Primary erythromelalgia in a 12-year-old boy: positive response to sodium channel blockers despite negative SCN9A mutations. Klin Padiatr 2012; 224 (05) 309-312
  • 40 Faignart N, Nguyen K, Soroken C. et al. Acute monophasic erythromelalgia pain in five children diagnosed as small-fiber neuropathy. Eur J Paediatr Neurol 2020; 28: 198-204
  • 41 Zimmern V, Minassian B, Korff C. A review of targeted therapies for monogenic epilepsy syndromes. Front Neurol 2022; 13: 829116
  • 42 Themistocleous AC, Baskozos G, Blesneac I. et al. Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort. Brain Commun 2023; 5 (02) fcad037