Complete SPL Sections#
Rx only
SPL UNCLASSIFIED SECTION
DESCRIPTION
DESCRIPTION SECTION
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•HCl M.W. 215.72 Each capsule for oral administration, contains 150 mg, 200 mg, or 250 mg of mexiletine hydrochloride USP. One hundred milligrams (100 mg) of mexiletine hydrochloride USP is equivalent to 83.31 mg of mexiletine base. In addition, each capsule contains the following excipients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose and modified corn starch. The capsule shell contains: gelatin and titanium dioxide. The imprinting inks contain: ammonium hydroxide, propylene glycol and shellac. The 150 mg imprinting ink also contains black iron oxide and potassium hydroxide. The 200 mg imprinting ink also contains FD&C Blue #1. The 250 mg imprint ink also contains FD&C Red #3 and potassium hydroxide.
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
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.
CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
Mexiletine hydrochloride capsules are contraindicated in the presence of cardiogenic shock or preexisting second- or third-degree AV block (if no pacemaker is present).
WARNINGS
WARNINGS SECTION
PRECAUTIONS
PRECAUTIONS SECTION
ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
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 reactions reported in the one-month placebo-controlled trial. Table 1: Comparative Incidence (%) of Adverse Reactions 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 Reactions 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 more common adverse reactions were similar to those in the controlled trials. Less common adverse reactions possibly related to mexiletine use include: Cardiovascular System Syncope and hypotension, each about 6 in 1000; bradycardia, about 4 in 1000; angina/angina-like pain, about 3 in 1000; edema, atrioventricular block/conduction disturbances and hot flashes, each about 2 in 1000; atrial arrhythmias, hypertension and cardiogenic shock, each about 1 in 1000. Central Nervous System Short-term memory loss, about 9 in 1000 patients; hallucinations and other psychological changes, each about 3 in 1000; psychosis and convulsions/seizures, each about 2 in 1000; loss of consciousness, about 6 in 10,000. Digestive Dysphagia, about 2 in 1000; peptic ulcer, about 8 in 10,000; upper gastrointestinal bleeding, about 7 in 10,000; esophageal ulceration, about 1 in 10,000. Rare cases of severe hepatitis/acute hepatic necrosis. Skin Rare cases of exfoliative dermatitis and Stevens-Johnson syndrome with mexiletine treatment have been reported. Laboratory Abnormal liver function tests, about 5 in 1000; positive ANA and thrombocytopenia, each about 2 in 1000; leukopenia (including neutropenia and agranulocytosis), about 1 in 1000; myelofibrosis, about 2 in 10,000 patients. Other Diaphoresis, about 6 in 1000; altered taste, about 5 in 1000; salivary changes, hair loss and impotence/decreased libido, each about 4 in 1000; malaise, about 3 in 1000; urinary hesitancy/retention, each about 2 in 1000; hiccups, dry skin, laryngeal and pharyngeal changes and changes in oral mucous membranes, each about 1 in 1000; SLE syndrome, about 4 in 10,000. Hematology Blood dyscrasias were not seen in the controlled trials but did occur among 10,867 patients treated with mexiletine in the compassionate use program (see PRECAUTIONS ). Myelofibrosis was reported in two patients in the compassionate use program; one was receiving long-term thiotepa therapy and the other had pretreatment myeloid abnormalities. In postmarketing experience, there have been isolated, spontaneous reports of pulmonary changes including pulmonary infiltration and pulmonary fibrosis during mexiletine therapy with or without other drugs or diseases that are known to produce pulmonary toxicity. A causal relationship to mexiletine therapy has not been established. In addition, there have been isolated reports of drowsiness, nystagmus, ataxia, dyspepsia, hypersensitivity reaction, and exacerbation of congestive heart failure in patients with preexisting compromised ventricular function. There have been rare reports of pancreatitis associated with mexiletine treatment. To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
OVERDOSAGE
OVERDOSAGE SECTION
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.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
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 recommended. When transferring from lidocaine to mexiletine, the lidocaine infusion should be stopped when the first oral dose of mexiletine hydrochloride is administered. The infusion line should be left open until suppression of the arrhythmia appears to be satisfactorily maintained. Consideration should be given to the similarity of the adverse effects of lidocaine and mexiletine and the possibility that they may be additive.
HOW SUPPLIED
HOW SUPPLIED SECTION
Mexiletine Hydrochloride Capsules USP, 150 mg are white to yellow granular powder in a hard gelatin capsule with an opaque white cap and body, imprinted with ‘ANI’ on the cap and ‘820’ on the body in black ink. They are supplied as follows: NDC 51407-379-01 bottles of 100. Mexiletine Hydrochloride Capsules USP, 200 mg are white to yellow granular powder in a hard gelatin capsule with an opaque white cap and body, imprinted with ‘ANI’ on the cap and ‘821’ on the body in blue ink. They are supplied as follows: NDC 51407-380-01 bottles of 100. Mexiletine Hydrochloride Capsules USP, 250 mg are white to yellow granular powder in a hard gelatin capsule with an opaque white cap and body, imprinted with ‘ANI’ on the cap and ‘822’ on the body in pink ink. They are supplied as follows: NDC 51407-381-01 bottles of 100. Store at 20° to 25°C (68° to 77°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). Distributed by: ANI Pharmaceuticals, Inc. Baudette, MN 56623 Issued: 04/2025 LB4565-01 Marketed by: GSMS, Inc. Camarillo, CA 93012 USA
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Mexiletine Hydrochloride Capsules USP, 150 mg NDC 51407-379-01 TAKE WITH FOOD OR ANTACID. Rx only 100 Capsules
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Mexiletine Hydrochloride Capsules USP, 200 mg NDC 51407-380-01 TAKE WITH FOOD OR ANTACID. Rx only 100 Capsules
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Mexiletine Hydrochloride Capsules USP, 250 mg NDC 51407-381-01 TAKE WITH FOOD OR ANTACID. Rx only 100 Capsules
