Mexitil^® (mexiletine hydrochloride, USP) is an orally active antiarrhythmic agent available as 150 mg, 200 mg and 250 mg capsules. 100 mg of mexiletine hydrochloride is equivalent to 83.31 mg of mexiletine base. It is a white to off-white crystalline powder with slightly bitter taste, freely soluble in water and in alcohol. Mexitil^® has a pKa of 9.2.

Chemically, MEXITIL is 1-methyl-2-(2, 6-xylyloxy) ethylamine hydrochloride and has the following structural formula:

MEXITIL capsules contain the following excipients: colloidal silicon dioxide, corn starch, magnesium stearate, titanium dioxide, gelatin, pharmaceutical glaze, simethicone, FD&C Red No. 40, and FD&C Blue No. 1; the MEXITIL 150 mg and 250 mg capsules also contain FD&C Yellow No. 10 and D&C Red No. 28. MEXITIL capsules may contain one or more of the following components: sodium lauryl sulfate, lecithin, shellac, and FD&C Blue No. 1 Aluminum Lake.

MEXITIL (mexiletine hydrochloride, USP) is indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgement of the physician, are life-threatening. Because of the proarrhythmic effects of Mexitil^® its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided.

Initiation of Mexitil^® 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.

The dosage of Mexitil^® (mexiletine hydrochloride, USP) must be individualized on the basis of response and tolerance, both of which are dose-related. Administration with food or antacid is recommended. Initiate Mexitil^® 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 Mexitil^® 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 Mexitil^®. 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 DRUG INTERACTIONS section).

Loading Dose: When rapid control of ventricular arrhythmia is essential, an initial loading dose of 400 mg of Mexitil^® 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 Mexitil^® may be transferred to a 12-hour dosage schedule to improve convenience and compliance. If adequate suppression is achieved on a Mexitil^® 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 Mexitil: 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 Mexitil^®: Mexitil^® treatment may be initiated with a 200 mg dose, and titrated to response as described above, 6-12 hours after the last dose of quinidine sulfate, 3-6 hours after the last dose of procainamide, 6-12 hours after the last dose of disopryramide or 8-12 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 Mexitil^®, the lidocaine infusion should be stopped when the first oral dose of Mexitil 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 Mexitil^® and the possibility that they may be additive.

MEXITIL (mexiletine hydrochloride, USP) is supplied in bottles of 100 hard gelatin capsules containing 150 mg, 200 mg or 250 mg of mexiletine hydrochloride:

MEXITIL 150 mg capsules are red and caramel with the marking Bl 66 (NDC 0597-0066-01).

MEXITIL 200 mg capsules are red with the marking Bl 67 (NDC 0597-0067-01).

MEXITIL 250 mg capsules are red and aqua green with the marking Bl 68 (NDC 0597-0068-01).

Store at 25^°C (77^°F); excursions permitted to 15-30^°C (59-86^°F). [see USP Controlled Room Temperature].

Rx Only

Distributed by;
Boehringer Ingelheim
Pharmaceuticals, Inc.
Ridgefield, Connecticut 06877 USA

Licensed from;
Boehringer Ingelheim
nternational GmbH

© Copyright Boehringer Ingelheim International GmbH
20013, ALL RIGHTS RESERVED
Revised 05/30/03

MEXITIL (mexiletine hydrochloride, USP) commonly produces reversible gastrointestinal and nervous system adverse reactions but is otherwise well tolerated. MEXITIL 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 600-1200 mg/day; some patients (8%) in the compassionate use program were treated with higher daily doses (1600-3200 mg/day). In the three-month controlled trials comparing MEXITIL 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.

Comparative Incidence (%) Of Adverse Events Among Patients Treated With Mexiletine And Placebo In The 4-Week, Double-Blind Crossover Trial

Table 2 presents the adverse reactions occurring in one percent or more of patients in the three-month controlled studies.

Comparative Incidence (%) Of Adverse Events Among Patients Treated With Mexiletine Or Control Drugs In The 12-Week Double-Blind Trials

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 Mexitil^® (mexiletine hydrochloride, USP) 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 events possibly related to Mexitil^® 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 Mexitil^® (mexiletine hydrochloride, USP) treatment have been reported.

Laboratory: Abnormal liver function tests, about 5 in 1000 patients; 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 fibrosis during Mexitil^® therapy with or without other drugs or diseases that are known to produce pulmonary toxicity. A causal relationship to Mexitil^® therapy has not been established. In addition, there have been isolated reports of exacerbation of congestive heart failure in patients with pre-existing compromised ventricular function. There have been rare reports of pancreatitis associated with Mexitil^® treatment.

Since MEXITIL is a substrate for the metabolic pathways involving CYP2D6 and CYP1A2 enzymes, inhibition or induction of either of these enzymes would be expected to alter mexiletine plasma concentrations. In a formal, single-dose interaction study (n = 6 males) the clearance of mexiletine was decreased by 38% following the coadministration of fluvoxamine, an inhibitor of CYP1A2. In another formal study (n = 8 extensive and n = 7 poor metabolizers of CYP2D6), coadministration of propafenone did not alter the kinetics of mexiletine in the poor CYP2D6 metabolizer group. However, the metabolic clearance of mexiletine in the extensive metabolizer phenotype decreased by about 70% making the poor and extensive metabolizer groups indistinguishable. In this crossover steady state study, the pharmacokinetics of propafenone were unaffected in either phenotype by the coadministration of mexiletine. Addition of mexiletine to propafenone did not lead to further electrocardiographic parameters changes of QRS, QTc, RR, and PR intervals than propafenone alone. When concomitant administration of either of these two drugs with mexiletine is initiated, the dose of mexiletine should be slowly titrated to desired effect.

In a large compassionate use program Mexitil^® has been used concurrently with commonly employed antianginal, antihypertensive, and anticoagulant drugs without observed interactions. A variety of antiarrhythmics such as quinidine or propranolol were also added, sometimes with improved control of ventricular ectopy. When phenytoin or other hepatic enzyme inducers such as rifampin and phenobarbital have been taken concurrently with Mexitil^®, lowered Mexitil^® plasma levels have been reported. Monitoring of Mexitil^® plasma levels is recommended during such concurrent use to avoid ineffective therapy.

In a formal study, benzodiazepines were shown not to affect Mexitil^® plasma concentrations. ECG intervals (PR, QRS, and QT) were not affected by concurrent Mexitil^® and digoxin, diuretics, or propranolol.

Concurrent administration of cimetidine and Mexitil^® has been reported to increase, decrease, or leave unchanged Mexitil^® plasma levels; therefore patients should be followed carefully during concurrent therapy.

Mexitil^® does not alter serum digoxin levels but magnesium-aluminum hydroxide, when used to treat gastrointestinal symptoms due to Mexitil^®, has been reported to lower serum digoxin levels.

Concurrent use of Mexitil^® and theophylline may lead to increased plasma theophylline levels. One controlled study in eight normal subjects showed a 72% mean increase (range 35-136%) in plasma theophylline levels. This increase was observed at the first test point which was the second day after starting Mexitil^®. Theophylline plasma levels returned to pre-Mexitil^® values within 48 hours after discontinuing Mexitil^®. If Mexitil and theophylline are to be used concurrently, theophylline blood levels should be monitored, particularly when the Mexitil^® dose is changed. An appropriate adjustment in theophylline dose should be considered.

Additionally, in one controlled study in five normal subjects and seven patients, the clearance of caffeine was decreased 50% following the administration of Mexitil^®.

Acute Liver Injury

In postmarketing experience abnormal liver function tests have been reported, some in the first few weeks of therapy with Mexitil^® (mexiletine hydrochloride, USP). Most of these have been observed in the setting of congestive heart failure or ischemia and their relationship to Mexitil^® has not been established.

General

If a ventricular pacemaker is operative, patients with second or third degree heart block may be treated with Mexitil^® (mexiletine hydrochloride, USP) if continuously monitored. A limited number of patients (45 of 475 in controlled clinical trials) with pre-existing first degree AV block were treated with Mexitil^®; none of these patients developed second or third degree AV block. Caution should be exercised when it is used in such patients or in patients with pre-existing sinus node dysfunction or intraventricular conduction abnormalities.

Like other antiarrhythmics Mexitil^® (mexiletine hydrochloride, USP) can cause worsening of arrhythmias. This has been uncommon in patients with less serious arrhythmias (frequent premature beats or non-sustained ventricular tachycardia: see ADVERSE REACTIONS), but is of greater concern in patients with life-threatening arrhythmias such as sustained ventricular tachycardia. In patients with such arrhythmias subjected to programmed electrical stimulation or to exercise provocation, 10-15% of patients had exacerbation of the arrhythmia, a rate not greater than that of other agents.

Mexitil^® should be used with caution in patients with hypotension and severe congestive heart failure because of the potential for aggravating these conditions.

Since Mexitil^® is metabolized in the liver, and hepatic impairment has been reported to prolong the elimination half-life of Mexitil^®, patients with liver disease should be followed carefully while receiving Mexitil^®. The same caution should be observed in patients with hepatic dysfunction secondary to congestive heart failure.

Concurrent drug therapy or dietary regimens which may markedly alter urinary pH should be avoided during Mexitil^® therapy. The minor fluctuations in urinary pH associated with normal diet do not affect the excretion of Mexitil^®.

SGOT Elevation and Liver Injury

In three-month controlled trials, elevations of SGOT greater than three times the upper limit of normal occurred in about 1% of both mexiletine-treated and control patients. Approximately 2% of patients in the mexiletine compassionate use program had elevations of SGOT greater than or equal to three times the upper limit of normal. These elevations frequently occurred in association with identifiable clinical events and therapeutic measures such as congestive heart failure, acute myocardial infarction, blood transfusions and other medications. These elevations were often asymptomatic and transient, usually not associated with elevated bilirubin levels and usually did not require discontinuation of therapy. Marked elevations of SGOT (> 1000 U/L) were seen before death in four patients with end-stage cardiac disease (severe congestive heart failure, cardiogenic shock).

Rare instances of severe liver injury, including hepatic necrosis, have been reported in association with Mexitil^® treatment. It is recommended that patients in whom an abnormal liver test has occurred, or who have signs or symptoms suggesting liver dysfunction, be carefully evaluated. If persistent or worsening elevation of hepatic enzymes is detected, consideration should be given to discontinuing therapy.

Blood Dyscrasias

Among 10,867 patients treated with mexiletine in the compassionate use program, marked leukopenia (neutrophils less than 1000/mm3 )or agranulocytosis were seen in 0.06% and milder depressions of leukocytes were seen in 0.08%, and thrombocytopenia was observed in 0.16%. Many of these patients were seriously ill and receiving concomitant medications with known hematologic adverse effects. Rechallenge with mexiletine in several cases was negative. Marked leukopenia or agranulocytosis did not occur in any patient receiving Mexitil^® alone; five of the six cases of agranulocytosis were associated with procainamide (sustained release preparations in four) and one with vinblastine. If significant hematologic changes are observed, the patient should be carefully evaluated, and, if warranted, Mexitil^® should be discontinued. Blood counts usually return to normal within one month of discontinuation. (See ADVERSE REACTIONS).

Convulsions (seizures) did not occur in Mexitil^® controlled clinical trials. In the compassionate use program, convulsions were reported in about 2 of 1000 patients. Twenty-eight percent of these patients discontinued therapy. Convulsions were reported in patients with and without a prior history of seizures. Mexiletine should be used with caution in patients with known seizure disorder.

Drug Interactions

See DRUG INTERACTIONS section.

Carcinogenesis, Mutagenesis and Impairment of Fertility

Studies of carcinogenesis in rats (24 months) and mice (18 months) did not demonstrate any tumorigenic potential. Mexitil^® was found to be non-mutagenic in the Ames test. Mexitil^® did not impair fertility in the rat.

Pregnancy

Teratogenic Effects. Pregnancy Category C: Reproduction studies performed with Mexitil^® (mexiletine hydrochloride, USP) in rats, mice and rabbits at doses up to four times the maximum human oral dose (24 mg/kg in a 50 kg patient) revealed no evidence of teratogenicity or impaired fertility but did wshow an increase in fetal resorption. There are no adequate and well-controlled studies in pregnant women; this drug should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Mexitil^® appears in human milk in concentrations similar to those observed in plasma. Therefore, if the use of Mexitil^® is deemed essential, an alternative method of infant feeding should be considered.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established.

Clinical findings associated with MEXITIL (mexiletine hydrochloride, USP) overdosage have included 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 4.4g with postmortem serum mexiletine level of 34-37 mcg/ml (Jequier P. et al. Lancet 1976:1 (7956):429). Patients have recovered from ingestion of 4g to 18g of mexiletine (Frank S. E. et al. Am J E merg Med 1991:9:43-48).

There is no specific antidote for Mexitil^®. Management of Mexitil^® 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.

Mexitil^® (mexiletine hydrochloride, USP) is contraindicated in the presence of cardiogenic shock or pre-existing second- or third-degree AV block (if no pacemaker is present).

Mechanism of Action

Mexitil^® (mexiletine hydrochloride, USP) is a local anesthetic, antiarrhythmic agent, structurally similar to lidocaine, but orally active. In animal studies, Mexitil^® has been shown to be effective in the suppression of induced ventricular arrhythmias, including those induced by glycoside toxicity and coronary artery ligation. Mexitil^®, like lidocaine, inhibits the inward sodium current, thus reducing the rate of rise of the action potential, Phase 0. Mexitil^® decreased the effective refractory period (ERP) in Purkinje fibers. The decrease in ERP was of lesser magnitude than the decrease in action potential duration (APD), with a resulting increase in the ERP/APD ratio.

Electrophysiology in Man Mexiletine is a Class 1 B antiarrhythmic compound with electrophysiologic properties in man similar to lidocaine, but dissimilar from quinidine, procainamide, and disopyramide.

In patients with normal conduction systems, Mexitil^® has a minimal effect on cardiac impulse generation and propagation. In clinical trials, no development of second-degree or third-degree AV block was observed. Mexitil^® did not prolong ventricular depolarization (QRS duration) or repolarization (QT intervals) as measured by electrocardiography. Theoretically, therefore, Mexitil^® may be useful in the treatment of ventricular arrhythmias associated with a prolonged QT interval.

In patients with pre-existing conduction defects, depression of the sinus rate, prolongation of sinus node recovery time, decreased conduction velocity and increased effective refractory period of the intraventricular conduction system have occasionally been observed.

The antiarrhythmic effect of Mexitil^® has been established in controlled comparative trials against placebo, quinidine, procainamide and disopyramide. Mexitil^®, at doses of 200-400 mg q8h, produced a significant reduction of ventricular premature beats, paired beats, and episodes of non-sustained ventricular tachycardia compared to placebo and was similar in effectiveness to the active agents. Among all patients entered into the studies, about 30% in each treatment group had a 70% or greater reduction in PVC count and about 40% failed to complete the 3 month studies because of adverse effects. Follow-up of patients from the controlled trials has demonstrated continued effectiveness of Mexitil^® in long-term use.

Hemodynamics

Hemodynamic studies in a limited number of patients, with normal or abnormal myocardial function, following oral administration of Mexitil^®, have shown small, usually not statistically significant, decreases in cardiac output and increases in systemic vascular resistance, but no significant negative inotropic effect. Blood pressure and pulse rate remain essentially unchanged. Mild depression of myocardial function, similar to that produced by lidocaine, has occasionally been observed following intravenous Mexitil^® therapy in patients with cardiac disease.

Pharmacokinetics

MEXITIL is well absorbed (~90%) from the gastrointestinal tract. Unlike lidocaine, its first-pass metabolism is low. Peak blood levels are reached in two to three hours. In normal subjects, the plasma elimination half-life of MEXITIL is approximately 10-12 hours. It is 50-60% bound to plasma protein, with a volume of distribution of 5-7 liters/kg. MEXITIL is mainly metabolized in the liver, the primary pathway being CYP2D6 metabolism, although it is also a substrate for CYP1A2. With involvement of CYP2D6, there can be either poor or extensive metabolizer phenotypes. Since approximately 90% of MEXITIL is metabolized in the liver into inactive metabolites, pathological changes in the liver can restrict hepatic clearance of MEXITIL and its metabolites. The metabolic degradation proceeds via various pathways including aromatic and aliphatic hydroxylation, dealkylation, deamination and N-oxidation. Several of the resulting metabolites are submitted to further conjugation with glucuronic acid (phase II metabolism); among these are the major metabolites p-hydroxymexiletine, hydroxy-methylmexiletine and N-hydroxy-mexiletine. Approximately 10% is excreted unchanged by the kidney. While urinary pH does not normally have much influence on elimination, marked changes in urinary pH influence the rate of excretion: acidification accelerates excretion, while alkalinization retards it.

Several metabolites of mexiletine have shown minimal antiarrhythmic activity in animal models. The most active is the minor metabolite N-methylmexiletine, which is less than 20% as potent as mexiletine. The urinary excretion of N-methylmexiletine in man is less than 0.5%. Thus the therapeutic activity of Mexitil^® is due to the parent compound.

Hepatic impairment prolongs the elimination half-life of Mexitil^®. In eight patients with moderate to severe liver disease, the mean half-life was approximately 25 hours.

Consistent with the limited renal elimination of Mexitil^®, little change in the half-life has been detected in patients with reduced renal function. In eight patients with creatinine clearance less than 10 ml/min, the mean plasma elimination half-life was 15.7 hours; in seven patients with creatinine clearance between 11-40 ml/mm, the mean half-life was 13.4 hours.

The absorption rate of Mexitil is reduced in clinical situations such as acute myocardial infarction in which gastric emptying time is increased. Narcotics, atropine and magnesium-aluminum hydroxide have also been reported to slow the absorption of Mexitil^®. Metoclopramide has been reported to accelerate absorption.

Mexiletine plasma levels of at least 0.5 mcg/ml are generally required for therapeutic response. An increase in the frequency of central nervous system adverse effects has been observed when plasma levels exceed 2.0 mcg/ml. Thus the therapeutic range is approximately 0.5 to 2.0 mcg/ml. Plasma levels within the therapeutic range can be attained with either three times daily or twice daily dosing but peak to trough differences are greater with the latter regimen, creating the possibility of adverse effects at peak and arrhythmic escape at trough. Nevertheless, some patients may be transferred successfully to the twice daily regimen. (See DOSAGE AND ADMINISTRATION).

See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

MEXILETINE - ORAL

(mex-ILL-ih-teen)

COMMON BRAND NAME(S): Mexitil

WARNING: Although this medication and others like it are used to treat certain kinds of abnormal heartbeats, they may rarely cause serious (sometimes fatal) irregular heartbeats. Therefore, mexiletine should be used carefully only in selected patients. Consult your doctor or pharmacist for more information.

USES: This medication is used to treat a certain serious (possibly life-threatening), persistent, abnormally fast heartbeats (sustained ventricular tachycardia). Mexiletine belongs to a class of drugs known as antidysrhythmics. It works by blocking the abnormal electrical activity of an irregular heartbeat so that the normal heartbeat can occur.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat pain, numbness, and tingling from a certain nerve problem (peripheral neuropathy) often experienced by those with diabetes, back injury, or HIV infection.

HOW TO USE: This medication may be started at a low dose in the hospital so that your doctor can determine the best dose, increase it gradually as needed, and monitor you closely for side effects.

Take this medication by mouth with food or an antacid, usually 2 to 3 times daily, or exactly as directed by your doctor. Consult your pharmacist for help selecting the proper kind of antacid. Taking this medication with food or an antacid helps to decrease certain side effects (nausea, heartburn).

Dosage is based on your age, liver function, medical condition, and response to therapy.

This medication works best when the amount of drug in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals. To help you remember, take it at the same times each day. Do not run out of this medication. Order your refills several days early to avoid running out of pills.

Do not take more or less of this drug than prescribed or stop taking it (or other heart medicines) even for a short time unless directed to do so by your doctor. Skipping or changing your dose without approval from your doctor may cause your abnormal heartbeat to return.

Contact your doctor immediately and seek emergency medical attention (e.g., call -911, have someone else drive you to a hospital emergency room) if your condition persists or worsens.

SIDE EFFECTS: See also Warning section.

Nausea, vomiting, heartburn, dizziness, lightheadedness, shakiness of hands/arms, nervousness, and problems with muscle control (coordination difficulties) may occur. Less common side effects may include sleep problems, weakness, tiredness, blurred vision, dry mouth, headache, diarrhea, constipation, and mild speaking difficulties. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: shortness of breath, unusual sweating, mental/mood changes (e.g., confusion, hallucinations, depression, memory loss), tingling/numbness, ringing in the ears, loss of appetite, swelling, sore throat, decreased sexual interest/ability, problems starting the flow of urine.

Tell your doctor immediately if any of these rare but very serious side effects occur: fainting, worsening symptoms of heart failure (e.g., ankle/leg swelling, increased tiredness, increased shortness of breath when lying down), very slow heartbeat, signs of liver problems (e.g., persistent nausea/vomiting, stomach/abdominal pain, yellowing eyes/skin, dark urine, severe tiredness), butterfly-shaped facial rash with unusual tiredness, joint/muscle aches, easy bleeding/bruising, signs of serious infection (e.g., fever, severe chills, persistent sore throat).

Seek immediate medical attention if any of these rare but very serious side effects occur: seizures, chest pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: See also Warning section.

Before taking mexiletine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should generally not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain heart rhythm problems (second- or third-degree atrioventricular block unless you have a pacemaker), shock due to the heart not pumping well (e.g., very low blood pressure and loss of consciousness).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, heart failure with severe symptoms (e.g., swelling of feet/legs, severe tiredness, shortness of breath), liver problems, recent heart attack (within the past 2 years), seizures, abnormal blood minerals (high or low potassium), conditions that may make the urine more alkaline (e.g., strict vegetarian diet, renal tubular acidosis).

Contact your doctor immediately if you develop other illnesses/conditions such as prolonged or large quantities of diarrhea, excessive sweating, vomiting, prolonged loss of appetite or desire to drink water. These conditions could cause you to have serious changes in blood minerals leading to increased side effects from mexiletine.

This drug may make you dizzy or cause blurred vision. Use caution while driving, using machinery, or doing any activity that requires alertness or clear vision. Avoid alcoholic beverages.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: dofetilide, halofantrine, pimozide, disopyramide.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting mexiletine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: cimetidine, theophylline, rifampin, rifapentine, rifabutin, propafenone, fluvoxamine, caffeine, barbiturates (e.g., phenobarbital, secobarbital), tizanidine, drugs that make the urine more acid (e.g., large doses of vitamin C, methionine, ammonium chloride), drugs that make the urine more alkaline (e.g., sodium bicarbonate).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: drowsiness, severe confusion, seizures, very fast heartbeat with sudden tiredness/shortness of breath/dizziness, very slow heartbeat, fainting, inability to wake up (coma).

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., EKG, mexiletine blood levels, liver blood tests) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.