Mexiletine

Mexiletine
Names
Trade namesMexitil, NaMuscla, others
IUPAC name
  • (RS)-1-(2,6-dimethylphenoxy)propan-2-amine
    OR
    2-(2-aminopropoxy)-1,3-dimethylbenzene
Clinical data
Main usesVentricular arrhythmias, myotonia[1][2]
Side effectsChest discomfort, headache, lightheadedness, nausea, arrhythmias, heart failure, liver problems[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B1
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth, intravenous
    Onset of actionWithin 2 hr[1]
    Typical dose200 mg TID[1]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa607064
    Legal
    License data
    Legal status
    Pharmacokinetics
    Bioavailability90%
    Protein binding50–60%
    MetabolismLiver (CYP2D6 and 1A2-mediated)
    Elimination half-life10–12 hours
    ExcretionKidney (10%)
    Chemical and physical data
    FormulaC11H17NO
    Molar mass179.263 g·mol−1
    3D model (JSmol)
    ChiralityRacemic mixture
    SMILES
    • O(c1c(cccc1C)C)CC(N)C
    InChI
    • InChI=1S/C11H17NO/c1-8-5-4-6-9(2)11(8)13-7-10(3)12/h4-6,10H,7,12H2,1-3H3 checkY
    • Key:VLPIATFUUWWMKC-UHFFFAOYSA-N checkY

    Mexiletine, sold under the brand name Mexitil among others, is a medication used to treat ventricular arrhythmias that are life threatening and certain types of myotonia.[1][2] It may be used when other treatments do not work.[1] While it has been used for diabetic neuropathy such use is not well supported.[1] It is taken by mouth.[1]

    Common side effects include chest discomfort, headache, lightheadedness, and nausea.[1] Other side effects may include arrhythmias, heart failure, liver problems, low platelets, seizures, and low white blood cells.[1] It is a class IB anti-arrhythmic and works as a sodium channel blocker.[1][2]

    Mexiletine was approved for medical use in 1985.[1] It is available as a generic medication.[3] In the United Kingdom 100 pills of 167 mg costs the NHS about £5,000 as of 2021.[2] In the United States 100 pills of 150 mg costs about 47 USD.[3]

    Medical uses

    Mexiletine has several uses including the treatment of abnormal heart rhythms or arrhythmias, chronic pain, and myotonia.

    Arrhythmia

    In general when treating arrhythmias, mexiletine is reserved for use in dangerous heart rhythm disturbances such as ventricular tachycardia.[4] It is of particular use when treating arrhythmias caused by long QT syndrome.[5] The LQT3 form of long QT syndrome is amenable to treatment with mexiletine as this form is caused by defective sodium channels that continue to release a sustained current rather than fully inactivating, however other forms of long QT syndrome can also be treated with this medication.[5]

    Muscle problems

    Mexiletine has been used to treat chronic pain and may also be used to treat muscle stiffness resulting from myotonic dystrophy (Steinert's disease) or nondystrophic myotonias such as myotonia congenita (Thomsen syndrome or Becker syndrome).[6][7]

    Dosage

    It is generally taken at a dose of 200 mg three times per day.[1] If a faster onset is required the initial dose may be 400 mg.[1]

    Side effects

    Mexiletine induced red macules and plaques

    Common side effects of mexiletine include abdominal pain, chest discomfort, drowsiness, headache, nausea and skin reactions.[8] Uncommon or rare side effects include seizures and liver dysfunction.[8]

    Pharmacology

    Mexiletine is an oral analogue of lidocaine.[7] It is a class IB antiarrhythmic which shorten the refractory period and action potential duration (APD). Decrease in APD more than that of ERP so there is increase ERP/APD ratio.[4] The drug has a bioavailability of 90%, and peak plasma concentrations are seen after 2–4 hours.[4] The mean drug half-life is approximately 11 hours.[4]

    Mexiletine is predominantly metabolised by the liver. The pharmacokinetics of mexiletine are preserved with even moderate to severe renal impairment, but dose adjustment may be required when creatinine clearance falls below 10 mL/minute.[4]

    Synthesis

    Mexiletine synthesis:[9]

    Society and culture

    Mexiletine is available for human use in the US, and has been reintroduced in the UK as a licensed product, having previously only been available as a 'named patient' import. The drug is sold under the trade name Mexitil for use in arrhythmias and NaMuscla for use in myotonia.[10][11]

    NaMuscla in the United Kingdom is sold by Lupin Healthcare UK.[2]

    Veterinary uses

    Mexiletine is available to veterinarians in the US for the treatment of heart disease in dogs and cats. It is commonly used for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxer dogs in combination with sotalol.

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "Mexiletine Monograph for Professionals". Drugs.com. Archived from the original on 17 January 2021. Retrieved 18 November 2021.
    2. 1 2 3 4 5 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1172. ISBN 978-0857114105.
    3. 1 2 "Mexiletine Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 18 November 2021.
    4. 1 2 3 4 5 Manolis AS, Deering TF, Cameron J, Estes NA (May 1990). "Mexiletine: pharmacology and therapeutic use". Clinical Cardiology. 13 (5): 349–59. doi:10.1002/clc.4960130509. PMID 2189614. S2CID 269453.
    5. 1 2 Li G, Zhang L (November 2018). "The role of mexiletine in the management of long QT syndrome". Journal of Electrocardiology. 51 (6): 1061–1065. doi:10.1016/j.jelectrocard.2018.08.035. PMID 30497731.
    6. ↑ Romman A, Salama-Hanna J, Dwivedi S (September 2018). "Mexiletine Usage in a Chronic Pain Clinic: Indications, Tolerability, and Side Effects". Pain Physician. 21 (5): E573–E579. doi:10.36076/ppj.2018.5.E573. PMID 30282405.
    7. 1 2 Sweetman S, ed. (2002). Martindale: The complete drug reference (33rd ed.). London: Pharmaceutical Press. ISBN 0-85369-499-0.
    8. 1 2 "British National Formulary - Mexiletine". NICE. Archived from the original on 2021-10-31. Retrieved 2019-06-17.
    9. ↑ US 3954872, Koppe R, Kummer W, issued 1976 
    10. ↑ "Mexiletine". www.drugbank.ca. Archived from the original on 2019-06-27. Retrieved 2019-06-17.
    11. ↑ "Lupin announces launch of NaMuscla". www.biospectrumindia.com. Archived from the original on 2019-06-17. Retrieved 2019-06-17.
    • Peck T, Hill S, Williams M, eds. (2004). Pharmacology for Anaesthesia and Intensive Care (2nd ed.). Cambridge University Press. ISBN 0-521-68794-2.
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