Mexiletine (Mexitil) is a class 1B antiarrhythmic drug that is used in the treatment of patients with ventricular arrhythmias, premature ventricular beats, and painful muscle spasms.

Mexiletine (Mexitil) Uses:

• Ventricular arrhythmias:

  • It is indicated for the management of life-threatening ventricular arrhythmias.

Note: The American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) states that mexiletine can be given for long QT syndrome type 3 who present with torsades de pointes

• Off Label Use of Mexiletine in Adults:

  • Amyotrophic lateral sclerosis, painful muscle spasms
  • Myotonic dystrophy (type 1)
  • Ventricular premature beats

Mexiletine Dose in Adults:

Mexiletine (Mexitil) Dose to treat painful muscle spasms in patients with amyotrophic lateral sclerosis (off-label):

• Initial: 150 mg once a day for 3 days, then increase the dose to 150 mg twice a day
• Alternatively, starting doses up to 450 mg twice a daily have been given but it showed less tolerability

Mexiletine (Mexitil) Dose in the treatment of Myotonic dystrophy (type 1) (off-label):

• Oral: 150 mg 3 times a day

Note: It is prudent to obtain a cardiology consult before starting therapy.

Mexiletine (Mexitil) Dose in the treatment of life-threatening ventricular arrhythmias:

• Oral: Initial: 150 - 200 mg every twice or thrice a day (may load with 400 mg if necessary); adjust the dose as required, dose can be increased 50 or 100 mg every 2 to 3 days up to 300 mg every 8 to 12 hours
• Usual dose: 150 - 300 mg every 8 to 12 hours
• Maximum dose: 1.2 g/day.

Mexiletine (Mexitil) dose in the suppression of symptomatic ventricular premature beat (off-label):

• Oral: Initial: 100 - 150 mg twice or thrice a day; Adjust dose as required, dose can be increased 50 or 100 mg every 2 to 3 days up to 300 mg
• The usual dose: 150 - 300 mg every 8 - 12 hours.

• Conversion from and to other antiarrhythmic drugs:

  • Switching from other oral antiarrhythmics (eg, disopyramide, quinidine sulfate): start 200 mg of mexiletine 6 - 12 hours after the last dose of the former agent.
  • Switching from IV lidocaine: start 200 mg of mexiletine when lidocaine infusion is stopped.
  • Switching from oral procainamide: start 200 mg of mexiletine 3 - 6 hours after the last dose of procainamide.

Mexiletine Dose in Childrens:

Mexiletine (Mexitil) Dose in the treatment of life-threatening ventricular arrhythmias including Long QT Syndrome Type 3:

• Children and Adolescents:

  • Oral: Initial: 6 - 8 mg/kg/day in 2 or 3 divided doses for 2 - 3 days, then increase to 2 - 5 mg/kg/dose every 8 - 12 hours
  • Continue to increase by 1 to 2 mg/kg/dose every 2 - 3 days until the desired effect
  • Monitor serum concentrations.
  • Maximum daily dose: 15 mg/kg/day or 1,200 mg/day whichever is less

Pregnancy Risk Factor C

• Studies on animal reproduction have shown adverse effects
• A few cases have shown that mexiletine is safe for pregnant women.

Use during breastfeeding:

• Breast milk contains mexiletine
• The manufacturer doesn't recommend breastfeeding

Dose in Kidney Disease:

No dosage adjustment required.

Dose in Liver disease:

• The manufacturer has not provided any dose adjustment in labeling.
• Half-life is approximately doubled in patients with hepatic impairment, dose reduction may be required

Common Side Effects of Mexiletine (Mexitil):

• Cardiovascular:

  • Exacerbation of cardiac arrhythmia

• Central nervous system:

  • Dizziness
  • Ataxia
  • Nervousness
  • Unsteady gait

• Gastrointestinal:

  • Gastrointestinal distress
  • Nausea
  • Vomiting

• Neuromuscular & skeletal:

  • Tremor

Less Common Side Effects of Mexiletine (Mexitil):

• Cardiovascular:

  • Palpitations
  • Chest Pain
  • Angina Pectoris
  • Ventricular Premature Contractions

• Central Nervous System:

  • Insomnia
  • Numbness
  • Depression
  • Paresthesia
  • Confusion
  • Headache

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Constipation
  • Diarrhea
  • Xerostomia
  • Abdominal Pain

• Neuromuscular & Skeletal:

  • Weakness
  • Arthralgia

• Ophthalmic:

  • Blurred Vision
  • Nystagmus

• Otic:

  • Tinnitus

• Respiratory:

  • Dyspnea

Contraindications to Mexiletine (Mexitil):

• Cardiogenic shock
• Second- and third-degree AV Block (except for patients with an artificial pacemaker).

Canadian labeling: Additional contraindications not in US labeling

• Hypersensitivity to any ingredient of the formulation, or amide-type local painkillers.

Warnings and precautions

• Blood dyscrasias:

  • Rarely, it can cause cell line suppressions, including leukopenia and agranulocytosis. These effects are often reversible
  • If the patient develops dyscrasias, discontinue therapy

• Systemic symptoms and drug reactions to eosinophilia:

  • Drug reactions may include eosinophilia or systemic symptoms (DRESS).
  • If DRESS is suspected, discontinue.
  • Eosinophilia, fever and/or lymphadenopathy are some of the symptoms of DRESS. Other organ involvement can also occur, such as myocarditis or myositis.

• Hepatotoxicity: [US Boxed Warning]

  • LFTs (liver function tests) can become abnormal at the beginning of therapy. 
  • These abnormalities are most common in congestive cardiac failure and ischemia.
  • Rarely, severe liver injury or elevation AST > 1000 units/L may occur.
  • If the patient has abnormal liver function tests, be sure to monitor them.
  • Consider quitting therapy if LFTs rise significantly.

• Proarrhythmic effects

  • It is particularly effective for people with life-threatening arrhythmias, such as sustained ventricular tachycardia.
  • It is possible to get arrhythmia worsened by its use.

• Conduction disturbances:

  • Be cautious with conduction delays, heart block of the first degree, and/or sinus dysfunction.
  • Contraindicated for second- and third-degree AV blocks
  • Patients with an artificial pacemaker in use

• Electrolyte imbalance:

  • Its use may cause or worsen electrolyte disturbance. 
  • If you have had electrolyte disturbances in the past, make sure to correct them before using it, particularly hypokalaemia and hypomagnesemia.
  • Also, monitor its usage throughout its duration

• Heart failure (HF):

  • Be cautious with severe HF. It can either exacerbate or precipitate the condition.

• Hepatic impairment

  • Be cautious if you have hepatic impairment. The half-life of the drug may be extended and there is a greater chance of adverse side effects.

• Seizure:

  • Use cautiously in a seizure disorder, it may exacerbate seizures.

Mexiletine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Liver function tests
• ECG

How to administer Mexiletine (Mexitil)?

Administer around-the-clock rather than 3 times daily to promote less variation in peak and trough serum levels. Can be taken with food or antacid

Mechanism of action of Mexiletine (Mexitil):

It is an antiarrhythmic drug of class IB, structurally similar to lidocaine. It prevents sodium from moving inwardly, reduces phase 1's rate of rising and increases the effective refractory time/action potential duration ratio. Start of action30 to 120 minutes (with loading program)

Absorption:

• Well absorbed.

Protein binding:

• 50-60%

Metabolism:

• • Mainly hepatic via CYP2D6 metabolism to inactive metabolites (~90%) and major metabolites p-hydroxymexiletine, hydroxy-methylmexiletine, and N-hydroxy-mexiletine. It has a low first pass effect.

Bioavailability:

• 90%

Half-life elimination:

• About 10 - 12 hours;
• ~ 15 hours in severe renal impairment (CrCl < 10 ml/min);
• ~ 25 hours in moderate to severe hepatic impairment

Time to peak, serum:

• 2 - 3 hours

Excretion:

• Mainly through Urine (10% as unchanged drug); urinary acidification increases excretion while alkalinization decreases

International Brand Names of Mexiletine:

• TEVA-Mexiletine
• Lefotil (KR);
• Meletin
• Mexaritm
• Mexicord
• Mexilate
• Mexitec
• Mexitil
• Mexitilen
• Ritalmex
• Tumetil

Mexiletine Brand Names in Pakistan:

No Brands Available in Pakistan.