Mexiletine Hydrochloride Side Effects

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.