Mexiletine Hydrochloride
FDA Drug Information • Also known as: Mexiletine Hydrochloride
- Brand Names
- Mexiletine Hydrochloride
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
DESCRIPTION Mexiletine hydrochloride, USP is an orally active antiarrhythmic agent. It is a white to off-white crystalline powder with slightly bitter taste, freely soluble in water and in alcohol. Mexiletine hydrochloride, USP has a pKa of 9.2. The chemical name of mexiletine hydrochloride, USP is 1-methyl-2-(2,6-xylyloxy)ethylamine hydrochloride and its structural formula is: C 11 H 17 NO
What Is Mexiletine Hydrochloride Used For?
INDICATIONS AND USAGE Mexiletine hydrochloride capsules, USP are indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening. Because of the proarrhythmic effects of mexiletine, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Initiation of mexiletine treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.
Dosage and Administration
DOSAGE AND ADMINISTRATION The dosage of mexiletine hydrochloride must be individualized on the basis of response and tolerance, both of which are dose-related. Administration with food or antacid is recommended. Initiate mexiletine therapy with 200 mg every eight hours when rapid control of arrhythmia is not essential. A minimum of two to three days between dose adjustments is recommended. Dose may be adjusted in 50 or 100 mg increments up or down. As with any antiarrhythmic drug, clinical and electrocardiographic evaluation (including Holter monitoring if necessary for evaluation) are needed to determine whether the desired antiarrhythmic effect has been obtained and to guide titration and dose adjustment. Satisfactory control can be achieved in most patients by 200 to 300 mg given every eight hours with food or antacid. If satisfactory response has not been achieved at 300 mg q8h, and the patient tolerates mexiletine well, a dose of 400 mg q8h may be tried. As the severity of CNS side effects increases with total daily dose, the dose should not exceed 1200 mg/day. In general, patients with renal failure will require the usual doses of mexiletine hydrochloride. Patients with severe liver disease, however, may require lower doses and must be monitored closely. Similarly, marked right-sided congestive heart failure can reduce hepatic metabolism and reduce the needed dose. Plasma level may also be affected by certain concomitant drugs (see PRECAUTIONS, Drug Interactions ). Loading Dose When rapid control of ventricular arrhythmia is essential, an initial loading dose of 400 mg of mexiletine hydrochloride may be administered, followed by a 200 mg dose in eight hours. Onset of therapeutic effect is usually observed within 30 minutes to two hours. Q12H Dosage Schedule Some patients responding to mexiletine may be transferred to a 12 hour dosage schedule to improve convenience and compliance. If adequate suppression is achieved on a mexiletine hydrochloride dose of 300 mg or less every eight hours, the same total daily dose may be given in divided doses every 12 hours while carefully monitoring the degree of suppression of ventricular ectopy. This dose may be adjusted up to a maximum of 450 mg every 12 hours to achieve the desired response. Transferring to Mexiletine Hydrochloride The following dosage schedule, based on theoretical considerations rather than experimental data, is suggested for transferring patients from other Class I oral antiarrhythmic agents to mexiletine: mexiletine hydrochloride treatment may be initiated with a 200 mg dose, and titrated to response as described above, 6 to 12 hours after the last dose of quinidine sulfate, 3 to 6 hours after the last dose of procainamide, 6 to 12 hours after the last dose of disopryramide or 8 to 12 hours after the last dose of tocainide. In patients in whom withdrawal of the previous antiarrhythmic agent is likely to produce life-threatening arrhythmias, hospitalization of the patient is...
Side Effects (Adverse Reactions)
ADVERSE REACTIONS Mexiletine hydrochloride commonly produces reversible gastrointestinal and nervous system adverse reactions but is otherwise well tolerated. Mexiletine has been evaluated in 483 patients in one month and three month controlled studies and in over 10,000 patients in a large compassionate use program. Dosages in the controlled studies ranged from 600 to 1200 mg/day; some patients (8%) in the compassionate use program were treated with higher daily doses (1600 to 3200 mg/day). In the three month controlled trials comparing mexiletine to quinidine, procainamide and disopyramide, the most frequent adverse reactions were upper gastrointestinal distress (41%), lightheadedness (10.5%), tremor (12.6%) and coordination difficulties (10.2%). Similar frequency and incidence were observed in the one month placebo-controlled trial. Although these reactions were generally not serious, and were dose-related and reversible with a reduction in dosage, by taking the drug with food or antacid or by therapy discontinuation, they led to therapy discontinuation in 40% of patients in the controlled trials. Table 1 presents the adverse events reported in the one-month placebo-controlled trial. Table 1: Comparative Incidence (%) of Adverse Events Among Patients Treated With Mexiletine and Placebo in the 4 Week, Double-Blind Crossover Trial Mexiletine N = 53 Placebo N = 49 Cardiovascular Palpitations 7.5 10.2 Chest Pain 7.5 4.1 Increased Ventricular Arrythmia/PVCs 1.9 - Digestive Nausea/Vomiting/Heartburn 39.6 6.1 Central Nervous System Dizziness/Lightheadedness 26.4 14.3 Tremor 13.2 - Nervousness 11.3 6.1 Coordination Difficulties 9.4 - Changes in Sleep Habits 7.5 16.3 Paresthesias/Numbness 3.8 2 Weakness 1.9 4.1 Fatigue 1.9 2 Tinnitus 1.9 4.1 Confusion/Clouded Sensorium 1.9 2 Other Headache 7.5 6.1 Blurred Vision/Visual Disturbances 7.5 2 Dyspnea/Respiratory 5.7 10.2 Rash 3.8 2 Non-specific Edema 3.8 - Table 2 presents the adverse reactions occurring in one percent or more of patients in the three month controlled studies. Table 2: Comparative Incidence (%) of Adverse Events Among Patients Treated With Mexiletine or Control Drugs in the 12 Week Double-Blind Trials Mexiletine N = 430 Quinidine N = 262 Procainamide N = 78 Disopyramide N = 69 Cardiovascular Palpitations 4.3 4.6 1.3 5.8 Chest Pain 2.6 3.4 1.3 2.9 Angina/Angina-like Pain 1.7 1.9 2.6 2.9 Increased Ventricular Arrhythmias/PVCs 1 2.7 2.6 - Digestive Nausea/Vomiting/ Heartburn 39.3 21.4 33.3 14.5 Diarrhea 5.2 33.2 2.6 8.7 Constipation 4 - 6.4 11.6 Changes in Appetite 2.6 1.9 - - Abdominal Pain/Cramps/ Discomfort 1.2 1.5 - 1.4 Central Nervous System Dizziness/Lightheadedness 18.9 14.1 14.1 2.9 Tremor 13.2 2.3 3.8 1.4 Coordination Difficulties 9.7 1.1 1.3 - Changes in Sleep Habits 7.1 2.7 11.5 8.7 Weakness 5 5.3 7.7 2.9 Nervousness 5 1.9 6.4 5.8 Fatigue 3.8 5.7 5.1 1.4 Speech Difficulties 2.6 0.4 - - Confusion/Clouded Sensorium 2.6 - 3.8 - Paresthesias/Numbness 2.4 2.3 2.6 - Tinnitus 2.4 1.5 - - Depression 2.4 1.1 1.3 1.4 Other Blurred Vision/Visual Disturbances 5.7 3.1 5.1 7.2 Headache 5.7 6.9 7.7 4.3 Rash 4.2 3.8 10.3 1.4 Dyspnea/Respiratory 3.3 3.1 5.1 2.9 Dry Mouth 2.8 1.9 5.1 14.5 Arthralgia 1.7 2.3 5.1 1.4 Fever 1.2 3.1 2.6 - Less than 1%: Syncope, edema, hot flashes, hypertension, short-term memory loss, loss of consciousness, other psychological changes, diaphoresis, urinary hesitancy/retention, malaise, impotence/decreased libido, pharyngitis, congestive heart failure. An additional group of over 10,000 patients has been treated in a program allowing administration of mexiletine hydrochloride under compassionate use circumstances. These patients were seriously ill with the large majority on multiple drug therapy. Twenty-four percent of the patients continued in the program for one year or longer. Adverse reactions leading to therapy discontinuation occurred in 15 percent of patients (usually upper gastrointestinal system or nervous system effects). In general, the...
Warnings and Precautions
WARNINGS BOXED WARNING WARNINGS Mortality In the National Heart, Lung and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicentered, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than six days but less than two years previously, an excessive mortality or non-fatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3%). The average duration of treatment with encainide or flecainide in this study was ten months. The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) is uncertain. Considering the known proarrhythmic properties of mexiletine and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of mexiletine as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmia. Acute Liver Injury In postmarketing experience abnormal liver function tests have been reported, some in the first few weeks of therapy with mexiletine hydrochloride. Most of these have been observed in the setting of congestive heart failure or ischemia and their relationship to mexiletine hydrochloride has not been established. Drug Reactions with Eosinophilia and Systemic Symptoms (DRESS) Drug reactions with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking mexiletine. DRESS typically presents with eosinophilia, fever, rash, and/or lymphadenopathy in association with other organ involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Discontinue mexiletine if DRESS is suspected.
Contraindications
CONTRAINDICATIONS Mexiletine hydrochloride capsules are contraindicated in the presence of cardiogenic shock or preexisting second- or third-degree AV block (if no pacemaker is present).
Overdosage
OVERDOSAGE Clinical findings associated with mexiletine overdosage have included drowsiness, confusion, nausea, hypotension, sinus bradycardia, paresthesia, seizures, bundle branch block, AV heart block, asystole, ventricular tachyarrythmia, including ventricular fibrillation, cardiovascular collapse and coma. The lowest known dose in a fatality case was 4.4 g with postmortem serum mexiletine level of 34 to 37 mcg/mL (Jequier P. et. al., Lancet 1976: 1 (7956): 429). Patients have recovered from ingestion of 4 g to 18 g of mexiletine (Frank S. E. et. al., Am J Emerg Med 1991: 9:43-48). There is no specific antidote for mexiletine. Management of mexiletine overdosage includes general supportive measures, close observation and monitoring of vital signs. In addition, the use of pharmacologic interventions (e.g., pressor agents, atropine or anticonvulsants) or transvenous cardiac pacing is suggested, depending on the patient’s clinical condition.
How Supplied
HOW SUPPLIED Mexiletine hydrochloride capsules USP, 150 mg are white granular powder in a hard gelatin capsule with a tan opaque cap and an orange opaque body, imprinted with "A27" on the cap and “150" on the body in black ink. They are supplied as follows: NDC 63629-9179-1 bottles of 100 with child-resistant closure. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.