Mexiletine Hydrochloride

Pronunciation

Pronunciation: MEX-ih-leh-teen HIGH-droe-KLOR-ide
Class: Antiarrhythmic agent

Trade Names

Mexitil
- Capsules 150 mg
- Capsules 200 mg
- Capsules 250 mg

Novo-Mexiletine (Canada)

Pharmacology

Reduces rate of rise of action potential; decreases effective refractory period in Purkinje fibers; has local anesthetic actions.

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Pharmacokinetics

Absorption

Mexiletine is well absorbed with approximately 90% from the GI tract. T max is 2 to 3 h, and the therapeutic range is 0.5 to 2 mcg/mL.

Distribution

Approximately 50% to 60% is protein bound. Vd is 5 to 7 L/kg.

Metabolism

First-pass metabolism occurs in the liver. N-methylmexiletine metabolite is the most active, but less than 20% as potent as mexiletine.

Elimination

10% is excreted unchanged by the kidney, and less than 0.5% of N-methylmexiletine is excreted in urine. The plasma t ½ is 10 to 12 h. Urinary acidification accelerates excretion.

Special Populations

Renal Function Impairment

Patients with severe renal function impairment may require lower doses. Monitor closely. Mean t ½ is 15.7 h with CrCl less than 10 mL/min.

Hepatic Function Impairment

Prolonged elimination t ½ ; mean t ½ is approximately 25 h.

Indications and Usage

Treatment of documented life-threatening ventricular arrhythmias such as sustained ventricular tachycardia (VT).

Contraindications

Preexisting second- or third-degree AV block (if pacemaker is not present); cardiogenic shock.

Dosage and Administration

Ventricular Arrhythmias
Adults

PO 200 mg every 8 h initially, increasing up to 400 mg every 8 h if necessary (max, 1,200 mg/day). Adjust dose by 50 to 100 mg increments every 2 to 3 days. For rapid control of ventricular arrhythmias, give loading dose of 400 mg followed by 200 mg in 8 h. When adequate suppression is achieved on a dose of 300 mg or less given every 8 h, the same total daily dose may be given in divided doses every 12 h (max, 450 mg every 12 h).

General Advice

  • Administer with food or antacid to reduce GI upset
  • Do not increase dose more often than every 2 days during dosage titration as optimal effect may not be achieved during the first 2 days following initiation of therapy or dose change.
  • When converting from lidocaine infusion to mexiletine, discontinue lidocaine infusion when first dose of mexiletine is administered.

Storage/Stability

Store capsules at controlled room temperature (59° to 86°F).

Drug Interactions

Aluminum-magnesium hydroxide, atropine, narcotics

May slow absorption.

Caffeine

Cl may be decreased by 50%.

Cimetidine

May increase or decrease mexiletine plasma levels.

Fluvoxamine

Cl of mexiletine may be decreased.

Hydantoins, rifampin, phenobarbital

May increase mexiletine Cl.

Metoclopramide

May accelerate absorption of mexiletine.

Propafenone

May inhibit mexiletine metabolism, which may elevate mexiletine plasma levels in extensive metabolizers and increase the risk of adverse reactions.

Theophylline

May increase serum theophylline levels.

Laboratory Test Interactions

May result in abnormal LFTs, positive ANA titer, or thrombocytopenia.

Adverse Reactions

Cardiovascular

Palpitations, chest pain (8%); increased ventricular arrhythmias/PVCs, angina or angina-like pain (2%); exacerbation of CHF (postmarketing).

CNS

Dizziness, lightheadedness (26%); tremor (13%); nervousness (11%); coordination difficulties (10%); headache (8%); changes in sleep habits (7%); weakness (5%); paresthesias, numbness, fatigue (4%); speech difficulties, confusion, clouded sensorium (3%); depression (2%); drowsiness, ataxia (postmarketing).

Dermatologic

Rash (4%).

EENT

Blurred vision, visual disturbances (8%); tinnitus (2%); nystagmus (postmarketing).

GI

Nausea, vomiting, heartburn (40%); diarrhea (5%); constipation (4%); changes in appetite, dry mouth (3%); abdominal pain, cramps, or discomfort (1%); dyspepsia (postmarketing).

Hematologic-Lymphatic

Blood dyscrasias.

Musculoskeletal

Arthralgia (1.7%); myelofibrosis.

Respiratory

Dyspnea (6%).

Miscellaneous

Non-specific edema (4%); fever (1%); hypersensitivity (postmarketing).

Precautions

Warnings

Mortality risks noted for flecainide and/or encainide (type 1C antiarrhythmics). Reserved for use in patients with life-threatening ventricular arrhythmias.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Hepatic Function

Use drug with caution in patients with hepatic function impairment. Reduce dosage in patients with severe liver disease.

Special Risk Patients

Use with caution in patients with CHF or hypotension.

CV effects

Has proarrhythmic effect; initiate therapy in hospital.

Convulsions

Have occurred; use drug with caution in patients with known seizure disorder.

Urinary pH

Marked alterations in urinary pH may alter mexiletine elimination; avoid drugs or diets that alter pH.

Overdosage

Symptoms

Coma, respiratory arrest, dizziness, drowsiness, nausea, hypotension, sinus bradycardia, paresthesia, seizures, confusion, bundle branch block, AV heart block, asystole, ventricular tachyarrhythmias including ventricular fibrillation.

Patient Information

  • Advise patient that dose of medication may be changed periodically to obtain max benefit.
  • Caution patient to take prescribed dose every 8 or 12 h exactly as ordered. Advise patient that serious heart disturbances can result from missing doses.
  • Advise patient to take each dose with food or antacid to prevent stomach upset.
  • Caution patient not to change the dose or stop taking unless advised by health care provider. Advise patient that serious adverse reactions can result from increasing or decreasing the dose without medical supervision.
  • Inform patient that drug controls, but does not cure, abnormal heart rhythm and to continue taking as prescribed once the heart rhythm has been controlled.
  • Instruct patient to continue taking other heart medications as prescribed by health care provider.
  • Instruct patient in BP and pulse measurement skills.
  • Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
  • Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
  • Advise patient to notify health care provider if any of the following occur: frequent episodes of dizziness or lightheadedness, persistent nausea, tremor, any other unusual or unexplained symptom or sign.
  • Instruct patient to immediately report fainting, pounding in chest, change in pulse or heart rhythm, yellowing of skin or eyes, unexplained fever, sore throat, bleeding, or unusual bruising to health care provider.
  • Caution patient that drug may cause dizziness, lightheadedness, or coordination difficulties, and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
  • Advise patient to carry medical identification (eg, card, bracelet) describing cardiac condition and medication regimen.
  • Offer family instruction in basic life support.

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