Mexiletine (NaMuscla) for the treatment of myotonia in non-dystrophic myotonic disorders

ABSTRACT

Introduction: NaMuscla, (mexiletine), is the first licensed treatment for the Non-Dystrophic Myotonias (NDM). NDM are categorized by genetic ion channel dysfunction and cause significant morbidity. To date, off-license mexiletine, although less costly, has sometimes been subject to breaches in supply causing significant regional and national variation in availability.

Areas covered: The evidence supporting mexiletine use in NDM, its mechanism of action, chemistry, and pharmacodynamics is reviewed. The evidence for other, unlicensed medications, used to treat myotonia as well as new antimyotonic compounds in development is also reviewed.

Expert opinion: Mexiletine is an effective and safe treatment for NDM. However, while mexiletine is very effective in reducing muscle stiffness, it is less effective at treating the pain associated with NDM and some SCN4A genotypes may not respond to mexiletine treatment. In addition, gastrointestinal discomfort is frequent and may prevent adequate dose titration. Since the designation of mexiletine as an orphan drug for NDM, level 1 evidence for the antimyotonic effect of lamotrigine has emerged. However, no superiority trials have been completed. A head-to-head trial to compare the efficacy of mexiletine and lamotrigine in reducing both muscle stiffness and pain and to determine variation in genotype response would facilitate greater precision medicine in NDM.

KEYWORDS:

• Non-dystrophic myotonia
• skeletal muscle channelopathy
• mexiletine
• antimyotonic

Box 1. Drug Summary Box

Acknowledgments

KS is supported by an MRC training fellowship (MR/M01827X/1). EM is supported by a Wellcome Trust Clinical Research Career Development Fellowship (209583/Z/17/Z). MGH is in receipt of an MRC Centre grant. Work in our group is supported by the UCLH NIHR Biomedical Research Centre. Our clinical muscle channel highly specialized service led by Professor Hanna is nationally commissioned by NHS England.

Declaration of Interest

M Hanna receives an MRC Centre grant, UCLH NIHR Biomedical Research Centre funding, NHS England funding to run muscle channel highly specialized service; K Suetterlin has an MRC Clinical Research Training Fellowship (MR/M01827X/1); E Matthews has a Wellcome trust Clinical Research Career Development Fellowship (209,583/Z/17/Z). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by MRC (MR/M01827X/1), Wellcome (209583/Z/17/Z), NIHR & NHS England.