mexiletine hydrochloride

mexiletine hydrochloride

[mek′silē′tin]

an oral antiarrhythmic drug.

indications It is prescribed for the treatment of symptomatic ventricular arrhythmias and suppression of premature ventricular contractions.

contraindications It is contraindicated in patients with cardiogenic shock or preexisting second- or third-degree atrioventricular block in the absence of a pacemaker.

adverse effects Among adverse effects reported are upper GI distress, lightheadedness, tremor, loss of coordination, diarrhea, sleep disorders, headache, visual disturbances, and palpitations.

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mexiletine hydrochloride

Novo-Mexiletine (CA)

Pharmacologic class: Lidocaine-like agent

Therapeutic class: Antiarrhythmic (class IB)

Pregnancy risk category C

FDA Boxed Warning

• In study of patients with asymptomatic, non-life-threatening ventricular arrhythmias who had myocardial infarction more than 6 days but less than 2 years previously, excessive mortality or nonfatal cardiac arrest rate occurred in those treated with encainide or flecainide antiarrhythmics - compared with patients in carefully matched placebo-treated groups. Given drug's known proarrhythmic properties and lack of evidence of improved survival for any antiarrhythmic in patients without life-threatening arrhythmias, reserve use of drug for patients with life-threatening ventricular arrhythmias.
• Abnormal liver function tests have occurred postmarketing, some cases in first few weeks of therapy. Most cases occurred in setting of congestive heart failure or ischemia, and their relationship to drug hasn't been established.

Action

Decreases duration of action potential and effective refractory period in cardiac conduction tissue by altering sodium transport across myocardial cell membranes

Availability

Capsules: 150 mg, 200 mg, 250 mg

⊘Indications and dosages

➣ Serious ventricular arrhythmias, including sustained ventricular tachycardia

Adults: Initially, 200 mg P.O. q 8 hours when rapid control isn't essential; may adjust dosage by 50 to 100 mg q 2 to 3 days. When rapid control is needed, give initial loading dose of 400 mg P.O., followed by 200 mg in 8 hours.

Off-label uses

• Pain, dysesthesias, paresthesias associated with diabetes mellitus

Contraindications

• Cardiogenic shock
• Second- or third-degree heart block (in patients without pacemakers)

Precautions

Use cautiously in:
• sinus node or intraventricular conduction abnormalities, heart failure, hypotension, seizure disorder, severe hepatic impairment
• pregnant or breastfeeding patients
• children (safety not established).

Administration

☞ Be aware that therapy should be initiated in hospital setting. Also, drug is reserved for life-threatening ventricular arrhythmias and shouldn't be used to treat asymptomatic premature ventricular contractions.
• When switching patient to mexiletine from lidocaine, stop lidocaine infusion as soon as first oral mexiletine dose is given, but maintain I.V. line until heart rhythm is satisfactory.
• When switching patient to mexiletine from other class I oral antiarrhythmics, give mexiletine as prescribed and titrate to response.

Route	Onset	Peak	Duration
P.O.	30 min-2 hr	2-3 hr	8-12 hr

Adverse reactions

CNS: dizziness, nervousness, confusion, fatigue, headache, sleep disorder, tremor, poor coordination, paresthesia

CV: chest pain, edema, palpitations, new or increased arrhythmias

EENT: blurred vision, tinnitus

GI: nausea, vomiting, heartburn

Hematologic: leukopenia, neutropenia, agranulocytosis, thrombocytopenia

Hepatic: hepatic necrosis

Respiratory: dyspnea

Skin: rash

Interactions

Drug-drug. Antacids, atropine, opioids: slow mexiletine absorption

Cimetidine: increased or decreased mexiletine blood level

Metoclopramide: increased mexiletine absorption

Other antiarrhythmics: additive cardiac effects

Phenobarbital, phenytoin, rifampin: increased mexiletine metabolism, decreased efficacy

Theophylline: increased theophylline blood level, greater risk of toxicity

Urine acidifiers: increased mexiletine excretion, decreased blood level

Urine alkalizers: decreased mexiletine excretion, increased blood level

Drug-diagnostic tests. Antinuclear antibodies: positive titers

Aspartate aminotransferase: transient increase

Platelets: decreased count (usually returns to normal within 1 month after drug withdrawal)

Drug-food. Foods that drastically alter urine pH: altered mexiletine blood level

Caffeine: 50% decrease in caffeine clearance

Drug-behaviors. Cigarette smoking: increased mexiletine metabolism, decreased efficacy

Patient monitoring

• Monitor vital signs and ECG frequently when initiating therapy.
• Evaluate liver function tests and hematologic studies.
☞ Watch for early evidence of toxicity (dizziness, tremor, poor coordination). With increasing toxicity, patient may develop hypotension, sinus bradycardia, ventricular arrhythmias, and seizures. Therapeutic mexiletine blood level is 0.5 to 2 mcg/ml.

Patient teaching

• Tell patient to take with food or antacids if adverse GI reactions occur.
• Advise patient to avoid dietary changes that would markedly alter urine pH.
• Inform patient that drug may cause nausea, vomiting, diarrhea, constipation, heartburn, dizziness, tremor, nervousness, poor coordination, changes in sleep pattern, headache, visual disturbances, tingling or numbness, ringing in ears, and palpitations or chest pain. Tell him to contact prescriber if these effects are bothersome or severe.
☞ Tell patient to immediately report tiredness, yellowing of skin or eyes, flulike symptoms, fever, or sore throat.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.