Mexiletine

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Mexiletine
Mexiletine.svg
Names
Trade namesMexitil, NaMuscla, others
  • (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]
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
US NLMMexiletine
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
  • O(c1c(cccc1C)C)CC(N)C
  • 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
  (verify)

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

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.[medical citation needed] It is commonly used for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxer dogs in combination with sotalol.[medical citation needed]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 "Mexiletine Monograph for Professionals". Drugs.com. Retrieved 18 November 2021.
  2. 2.0 2.1 2.2 2.3 2.4 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1172. ISBN 978-0857114105.
  3. 3.0 3.1 "Mexiletine Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 18 November 2021.
  4. 4.0 4.1 4.2 4.3 4.4 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. 5.0 5.1 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. 7.0 7.1 Sweetman S, ed. (2002). Martindale: The complete drug reference (33rd ed.). London: Pharmaceutical Press. ISBN 0-85369-499-0.
  8. 8.0 8.1 "British National Formulary - Mexiletine". NICE. Retrieved 2019-06-17.
  9. US 3954872, Koppe R, Kummer W, issued 1976 
  10. "Mexiletine". www.drugbank.ca. Retrieved 2019-06-17.
  11. "Lupin announces launch of NaMuscla". www.biospectrumindia.com. Retrieved 2019-06-17.

External links

External sites:
Identifiers: