Mexiletine – Class Ib (& Id?)

Mexiletine – Class Ib (& Id?)

Mexiletine is a Class Ib drug. But it has additional effect on late sodium current (INaL), which qualifies for Id inclusion, though it has not been included in that group in the Modernized Classification of Cardiac Antiarrhythmic Drugs [1]. By virtue of that effect, it has been used successfully in the treatment of Long QT syndrome 3 (LQT3) [2]. In addition to shortening QTc, it has been shown to reduce life threatening arrhythmic events in LQT3 patients. It has also been found useful in Timothy syndrome, which is long QT syndrome type 8 (LQT8) [3]. In the case reported, mexiletine shortened QTc, abolished 2:1 AV block and T wave alternans. In a mouse model it was shown to be due to inhibition of late sodium current (INaL).

Intravenous preparation used to be available earlier. Currently only oral preparation is available. It has a half life of 10-14 hours, hence 8th hourly or twice daily dosage is preferred [4]. It has a role in the treatment of ventricular ectopics, ventricular tachycardia and prevention of ventricular fibrillation.

References

  1. Ming Lei, Lin Wu, Derek A Terrar, Christopher L-H Huang. Modernized Classification of Cardiac Antiarrhythmic Drugs. Circulation. 2018 Oct 23;138(17):1879-1896.
  2. Andrea Mazzanti, Riccardo Maragna, Alessandro Faragli, Nicola Monteforte, Raffaella Bloise, Mirella Memmi, Valeria Novelli, Paola Baiardi, Vincenzo Bagnardi, Susan P Etheridge, Carlo Napolitano, Silvia G Priori. Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3. J Am Coll Cardiol. 2016 Mar 8;67(9):1053-1058.
  3. Yuanfeng Gao, Xiaolin Xue, Dayi Hu, Wenling Liu, Yue Yuan, Hongmei Sun, Lei Li, Katherine W Timothy, Li Zhang, Cuilan Li, Gan-Xin Yan. Inhibition of late sodium current by mexiletine: a novel pharmotherapeutical approach in timothy syndrome. Circ Arrhythm Electrophysiol. 2013 Jun;6(3):614-22.
  4. Sana M Al-Khatib, William G Stevenson, Michael J Ackerman, William J Bryant, David J Callans, Anne B Curtis, Barbara J Deal, Timm Dickfeld, Michael E Field, Gregg C Fonarow, Anne M Gillis, Christopher B Granger, Stephen C Hammill, Mark A Hlatky, José A Joglar, G Neal Kay, Daniel D Matlock, Robert J Myerburg, Richard L Page. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2018 Oct 2;72(14):e91-e220.
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