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MEXITIL (mexiletine hydrochloride, USP) commonly produces reversible gastrointestinal and nervous system adverse reactions but is otherwise well tolerated. MEXITIL (mexiletine hcl) 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 (mexiletine hcl) 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
|Increased Ventricular Arrhythmia /PVC's||1.9||-|
|Central Nervous System|
|Changes in Sleep Habits||7.5||16.3|
|Blurred Vision/Visual Disturbances||7.5||2.0|
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
N = 430
N = 262
N = 78
|Increased Ventricular Arrhythmias/PVC's||1.0||2.7||2.6|
|Changes in Appetite||2.6||1.9||—|
|Central Nervous System|
|Changes in Sleep Habits||7.1||2.7||11.5|
|Blurred Vision/Visual Disturbances||5.7||3.1||5.1|
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 (mexiletine hcl) 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.
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 post-marketing experience, there have been isolated, spontaneous reports of pulmonary changes including pulmonary infiltration and pulmonary fibrosis during MEXITIL (mexiletine hcl) therapy with or without other drugs or diseases that are known to produce pulmonary toxicity. A causal relationship to MEXITIL (mexiletine hcl) 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 pre-existing compromised ventricular function. There have been rare reports of pancreatitis associated with MEXITIL (mexiletine hcl) treatment.
Read the Mexitil (mexiletine hcl) Side Effects Center for a complete guide to possible side effects
Since MEXITIL (mexiletine hcl) 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 (mexiletine hcl) 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 (mexiletine hcl) ®, lowered MEXITIL (mexiletine hcl) plasma levels have been reported. Monitoring of MEXITIL (mexiletine hcl) plasma levels is recommended during such concurrent use to avoid ineffective therapy.
In a formal study, benzodiazepines were shown not to affect MEXITIL (mexiletine hcl) plasma concentrations. ECG intervals (PR, QRS, and QT) were not affected by concurrent MEXITIL (mexiletine hcl) and digoxin, diuretics, or propranolol.
Concurrent administration of cimetidine and MEXITIL (mexiletine hcl) has been reported to increase, decrease, or leave unchanged MEXITIL (mexiletine hcl) plasma levels; therefore patients should be followed carefully during concurrent therapy.
MEXITIL (mexiletine hcl) does not alter serum digoxin levels but magnesium-aluminum hydroxide, when used to treat gastrointestinal symptoms due to MEXITIL (mexiletine hydrochloride, USP) Capsules, has been reported to lower serum digoxin levels.
Concurrent use of MEXITIL (mexiletine hcl) 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 (mexiletine hcl) . Theophylline plasma levels returned to pre- MEXITIL (mexiletine hcl) values within 48 hours after discontinuing MEXITIL (mexiletine hcl) . If MEXITIL (mexiletine hcl) and theophylline are to be used concurrently, theophylline blood levels should be monitored, particularly when the MEXITIL (mexiletine hcl) 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 (mexiletine hcl) .
Read the Mexitil Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 4/8/2009
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