Dosing and uses of Mexiletine
Adult dosage forms and strengths
capsule
- 150mg
- 200mg
- 250mg
Ventricular Arrhythmias (Life-Threatening)
Initial: 200 mg PO q8hr; may load with 400 mg followed by 200 mg PO q8hr if necessary for rapid control of ventricular arrhythmia
Dose range: 200-300 mg PO q8hr
May increase to 400 mg q8hr; not to exceed 1200 mg/day
Take with food or antacid
Therapeutic range: 0.5-2 mg/L
Organ Transplant Rejection (Orphan)
Prevention of acute and chronic rejection in patients who have received solid organ transplants
Orphan indication sponsor
- James W Williams, MD; Rush-Presbyterian-St. Luke's Medical Ctr, Dept o, 1653 West Congress Parkway; Chicago, IL 60612-3833
Myotonia (Orphan)
Treatment of nondystrophic myotonia
Orphan indication sponsor
- University of Rochester Medical Center; 1351 Mt. Hope Ave, Suite 203; Rochester, NY 14620
Renal Impairment
CrCl<10 mL/min: 50-75% of normal dose
Hepatic Impairment
Liver impairment or CHF: 25-30% of normal dose
Pediatric dosage forms and strengths
Not FDA approved
Usual dose for arrhythmias: 2.5-5 mg/kg PO q8hr
Mexiletine adverse (side) effects
>10%
Nausea (40%)
Vomiting (40%)
Heartburn (40%)
Ataxia (20%)
Dizziness (20-25%%)
Lightheadedness (11-25%)
Tremor (13%)
1-10%
Coordination difficulties (10%)
Palpitation (4-7%)
Hypotension (4-8%)
Angina (2%)
Headache (5-7%)
Depression (2%)
Xerostomia (3%)
Proarrythmia (10-15%)
Rash (4%)
Insomnia (5-7%)
Confusion (5-7%)
Chest pain (3-8%)
Abdominal pain (1%)
Dyspnea (3%)
Constipation or diarrhea (4-5%)
Premature ventricular contractions (1-2%)
Blurred vision (5-7%)
Nystagmus (6%)
Frequency not defined
Edema
Exacerbation of CHF
Puilmonary fibrosis
Proarrhythmia
Convulsions
Mouth sores
Tinnitus
Systemic lupus erythematosus
Warnings
Black box warnings
National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST): Excessive mortality or nonfatal cardiac arrest (7.7%) shown with encainide or flecainide compared with placebo (3%)
CAST was a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction (MI) >6 days but <2 yr previously
Average duration of treatment w/ encainide or flecainide in CAST was 10 months
Applicability of CAST results to other populations (eg, patients without recent MI) is uncertain
Reserve use of Class IC antiarrhythmics for life-threatening ventricular arrhythmias: Considering the known proarrhythmic properties of mexiletine & lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, mexiletine use, as well as other antiarrhythmic agents, should be reserved for patients with life-threatening ventricular arrhythmias
Contraindications
Hypersensitivity to mexiletine
Cardiogenic shock, 2°/3° AV block w/o pacemaker
Cautions
Use caution in CHF, hypotension, history of seizures
Use in less severe arrhythmias not recommended; avoid in treatment of asymptomatic ventricular premature contractions or conduction disturbances
Hepatic toxicity may occur
Correct electrolyte inbalances
Prior to use electrolyte imbalences (especially hypokalemia or hypomagnesemia) must be corrected
Monitor and adjust dose to prevent QTc prolongation
Seizure disorders, pregnancy
Good for automatic and reentrant arrhythmias, not PSVT's
Pregnancy and lactation
Pregnancy category: C
Lactation: enters breast milk at concs comparable to maternal plasma (AAP Committee states compatible w/ nursing)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Mexiletine
Mechanism of action
Class 1B antidysrhythmic; combines with fast Na channels & thereby inhibits recovery after repolarization resulting in decreasing myocardial excitability & conduction velocity
Pharmacokinetics
Bioavailability: 80-90%
Protein Bound: 50-60%
Half-Life: 10-14 hr (adults)
Peak Plasma Time: 2-3 hr (PO)
Therapeutic range: 0.5-2 mcg/mL
Toxicity range: >2 mcg/mL
Vd: 5-7 L/kg
Metabolism: in liver to form parahydroxymexiletine & 2-hydroxymexiletine mainly by hepatic P450 enzyme CYP2D6 & partially by CYP1A2
Metabolites: parahydroxymexiletine & 2-hydroxymexiletine (inactive)
Excretion: urine 10-15%
Dialyzable: HD: No; PD: No