FDA label c92c4adf-6ff2-4eda-a868-b0af18b08ae6

WARNINGS Mortality In the National Heart, Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-center, 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 increased rate of death or reversed cardiac arrest rate (7.7%; 56/730) was seen in patients treated with encainide or flecainide (class 1C antiarrhythmics) compared with that seen in patients assigned to placebo (3.0%; 22/725). 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) or other antiarrhythmic drugs is uncertain, but at present it is prudent to consider any 1C antiarrhythmic to have a significant risk in patients with structural heart disease. Given the lack of any evidence that these drugs improve survival, antiarrhythmic agents should generally be avoided in patients with non-life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs. Proarrhythmic Effects Propafenone HCl, like other antiarrhythmic agents, may cause new or worsened arrhythmias. Such proarrhythmic effects range from an increase in frequency of PVCs to the development of more severe ventricular tachycardia, ventricular fibrillation or torsade de pointes; i.e., tachycardia that is more sustained or more rapid which may lead to fatal consequences. It is therefore essential that each patient given propafenone HCl be evaluated electrocardiographically and clinically prior to, and during therapy to determine whether the response to propafenone HCl supports continued treatment. Overall in clinical trials with propafenone, 4.7% of all patients had new or worsened ventricular arrhythmia possibly representing a pro-arrhythmic event (0.7% was an increase in PVCs; 4.0% a worsening, or new appearance, of VT or ventricular fibrillation [VF]). Of the patients who had worsening of VT (4%), 92% had a history of VT and/or VT/VF, 71% had coronary artery disease, and 68% had a prior myocardial infarction. The incidence of proarrhythmia in patients with less serious or benign arrhythmias, which include patients with an increase in frequency of PVCs, was 1.6%. Although most proarrhythmic events occurred during the first week of therapy, late events also were seen and the CAST study (see above) suggests that an increased risk is present throughout treatment. In the 474 patient U.S. multicenter trial in patients with symptomatic supraventricular tachycardia (SVT), 1.9% (9/474) of these patients experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) during the study. However, in 4 of the 9 patients, the ventricular tachycardia was of atrial origin. Six of the nine patients that developed ventricular arrhythmias did so within 14 days of onset of therapy. About 2.3% (11/474) of all patients had a recurrence of SVT during the study which could have been a change in the patients' arrhythmia behavior or could represent a proarrhythmic event. Case reports in patients treated with propafenone HCl for atrial fibrillation/flutter have included increased PVCs, VT, VF, and death. Nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema) PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE PROPAFENONE or other agents with beta-adrenergic-blocking activity. Congestive Heart Failure During treatment with oral propafenone in patients with depressed baseline function (mean ejection fraction (EF)=33.5%), no significant decreases in ejection fraction were seen. In clinical trial experience, new or worsened CHF has been reported in 3.7% of patients with ventricular arrhythmia; of those 0.9% were considered probably or definitely related to propafenone HCl. Of the patients with congestive heart failure probably related to propafenone, 80% had preexisting heart failure and 85% had coronary artery disease. CHF attributable to propafenone HCl developed rarely (<0.2%) in ventricular arrhythmia patients who had no previous history of CHF. CHF occurred in 1.9% of patients studied with PAF or PSVT. As propafenone HCl exerts both beta blockade and a (dose-related) negative inotropic effect on cardiac muscle, patients with congestive heart failure should be fully compensated before receiving propafenone HCl. If congestive heart failure worsens, propafenone HCl should be discontinued (unless congestive heart failure is due to the cardiac arrhythmia) and, if indicated, restarted at a lower dosage only after adequate cardiac compensation has been established. Conduction Disturbances Propafenone HCl slows atrioventricular conduction and also causes first degree AV block. Average PR interval prolongation and increases in QRS duration are closely correlated with dosage increases and concomitant increases in propafenone plasma concentrations. The incidence of first degree, second degree, and third degree AV block observed in 2,127 ventricular arrhythmia patients was 2.5%, 0.6%, and 0.2%, respectively. Development of second or third degree AV block requires a reduction in dosage or discontinuation of propafenone HCl. Bundle branch block (1.2%) and intraventricular conduction delay (1.1%) have been reported in patients receiving propafenone. Bradycardia has also been reported (1.5%). Experience in patients with sick sinus node syndrome is limited and these patients should not be treated with propafenone. Effects on Pacemaker Threshold Propafenone HCl may alter both pacing and sensing thresholds of artificial pacemakers. Pacemakers should be monitored and programmed accordingly during therapy. Hematologic Disturbances Agranulocytosis (fever, chills, weakness, and neutropenia) has been reported in patients receiving propafenone. Generally, the agranulocytosis occurred within the first two months of propafenone therapy and upon discontinuation of therapy, the white count usually normalized by 14 days. Unexplained fever and/or decrease in white cell count, particularly during the initial three months of therapy, warrant consideration of possible agranulocytosis/granulocytopenia. Patients should be instructed to promptly report the development of any signs of infection such as fever, sore throat, or chills.

<table width="100%" ID="i8e2f879a-c761-4f3b-805b-467da4810256"> <col width="100%" align="left" valign="top"/> <tbody> <tr> <td styleCode="Lrule Rrule"> <content styleCode="bold">Mortality</content> </td> </tr> <tr> <td styleCode="Lrule Rrule"> <content styleCode="bold">In the National Heart, Lung and Blood Institute&apos;s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-center, 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 increased rate of death or reversed cardiac arrest rate (7.7%; 56/730) was seen in patients treated with encainide or flecainide (class 1C antiarrhythmics) compared with that seen in patients assigned to placebo (3.0%; 22/725). The average duration of treatment with encainide or flecainide in this study was ten months.</content> </td> </tr> <tr> <td styleCode="Lrule Rrule"> <content styleCode="bold">The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) or other antiarrhythmic drugs is uncertain, but at present it is prudent to consider any 1C antiarrhythmic to have a significant risk in patients with structural heart disease. Given the lack of any evidence that these drugs improve survival, antiarrhythmic agents should generally be avoided in patients with non-life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs.</content> </td> </tr> </tbody> </table>

ADVERSE REACTIONS Adverse reactions associated with propafenone HCl occur most frequently in the gastrointestinal, cardiovascular, and central nervous systems. About 20% of patients treated with propafenone HCl have discontinued treatment because of adverse reactions. Adverse reactions reported for >1.5% of 474 SVT patients who received propafenone in U.S. clinical trials are presented in the following table by incidence and percent discontinuation, reported to the nearest percent. Adverse Reactions Reported for >1.5% of SVT Patients Incidence (N=480) % of Patients Who Discontinued Unusual taste 14% 1.3% Nausea and/or Vomiting 11% 2.9% Dizziness 9% 1.7% Constipation 8% 0.2% Headache 6% 0.8% Fatigue 6% 1.5% Blurred Vision 3% 0.6% Weakness 3% 1.3% Dyspnea 2% 1.0% Wide Complex Tachycardia 2% 1.9% CHF 2% 0.6% Bradycardia 2% 0.2% Palpitations 2% 0.2% Tremor 2% 0.4% Anorexia 2% 0.2% Diarrhea 2% 0.4% Ataxia 2% 0.0% Results of controlled trials in ventricular arrhythmia patients comparing adverse reaction rates on propafenone and placebo, and on propafenone and quinidine are shown in the following table. Adverse reactions reported for ≥1% of the patients receiving propafenone as shown, unless they were more frequent on placebo than propafenone. The most common events were unusual taste, dizziness, first degree AV block, intraventricular conduction delay, nausea and/or vomiting, and constipation. Headache was relatively common also, but was not increased compared to placebo. Adverse Reactions Reported for ≥1% of Ventricular Arrhythmia Patients Prop./Placebo Trials Prop./Quinidine Trial Prop. Placebo Prop. Quinidine (N=247) (N=111) (N=53) (N=52) Unusual Taste 7% 1% 23% 0% Dizziness 7% 5% 15% 10% First Degree AV Block 5% 1% 2% 0% Headache(s) 5% 5% 2% 8% Constipation 4% 0% 6% 2% Intraventricular Conduction Delay 4% 0% - - Nausea and/or Vomiting 3% 1% 6% 15% Fatigue - - 4% 2% Palpitations 2% 1% - - Blurred Vision 2% 1% 6% 2% Dry Mouth 2% 1% 6% 6% Dyspnea 2% 3% 4% 0% Abdominal Pain/Cramps - - 2% 8% Dyspepsia - - 2% 8% CHF - - 2% 0% Fever - - 2% 10% Tinnitus - - 2% 2% Vision, Abnormal - - 2% 2% Esophagitis - - 2% 0% Gastroenteritis - - 2% 0% Anxiety 2% 2% - - Anorexia 2% 1% 0% 2% Proarrhythmia 1% 0% 2% 0% Flatulence 1% 0% 2% 0% Angina 1% 0% 2% 4% Second Degree AV Block 1% 0% - - Bundle Branch Block 1% 0% 2% 2% Loss of Balance 1% 0% - - Diarrhea 1% 1% 6% 39% Adverse reactions reported for ≥1% of 2,127 ventricular arrhythmia patients who received propafenone in U.S. clinical trials are presented in the following table by propafenone daily dose. The most common adverse reactions in controlled clinical trials appeared dose-related (but note that most patients spent more time at the larger doses), especially dizziness, nausea and/or vomiting, unusual taste, constipation, and blurred vision. Some less common reactions may also have been dose-related such as first degree AV block, congestive heart failure, dyspepsia, and weakness. The principal causes of discontinuation were the most common events and are shown in the table. Adverse Reactions Reported for ≥1% of Ventricular Arrhythmia Patients N=2127 Incidence by Total Daily Dose Total Incidence % of Pts. Who Discont. 450 mg 600 mg ≥900 mg (N=1430) (N=1337) (N=1333) (N=2127) Dizziness 4% 7% 11% 13% 2.4% Nausea and/or Vomiting 2% 6% 9% 11% 3.4% Unusual Taste 3% 5% 6% 9% 0.7% Constipation 2% 4% 5% 7% 0.5% Fatigue 2% 3% 4% 6% 1.0% Dyspnea 2% 2% 4% 5% 1.6% Proarrhythmia 2% 2% 3% 5% 4.7% Angina 2% 2% 3% 5% 0.5% Headache(s) 2% 3% 3% 5% 1.0% Blurred Vision 1% 2% 3% 4% 0.8% CHF 1% 2% 3% 4% 1.4% Ventricular Tachycardia 1% 2% 3% 3% 1.2% Dyspepsia 1% 2% 3% 3% 0.9% Palpitations 1% 2% 3% 3% 0.5% Rash 1% 1% 2% 3% 0.8% AV Block, First Degree 1% 1% 2% 3% 0.3% Diarrhea 1% 2% 2% 3% 0.6% Weakness 1% 2% 2% 2% 0.7% Dry Mouth 1% 1% 1% 2% 0.2% Syncope/Near Syncope 1% 1% 1% 2% 0.7% QRS Duration, Increased 1% 1% 2% 2% 0.5% Chest Pain 1% 1% 1% 2% 0.2% Anorexia 1% 1% 2% 2% 0.4% Abdominal Pain, Cramps 1% 1% 1% 2% 0.4% Ataxia 0% 1% 2% 2% 0.2% Insomnia 0% 1% 1% 2% 0.3% Premature Ventricular Contraction(s) 1% 1% 1% 2% 0.1% Bradycardia 1% 1% 1% 2% 0.5% Anxiety 1% 1% 1% 2% 0.6% Edema 1% 0% 1% 1% 0.2% Tremor(s) 0% 1% 1% 1% 0.3% Diaphoresis 1% 0% 1% 1% 0.3% Bundle Branch Block 0% 1% 1% 1% 0.5% Drowsiness 1% 1% 1% 1% 0.2% Atrial Fibrillation 1% 1% 1% 1% 0.4% Flatulence 0% 1% 1% 1% 0.1% Hypotension 0% 1% 1% 1% 0.4% Intraventricular Conduction Delay 0% 1% 1% 1% 0.1% Pain, Joints 0% 0% 1% 1% 0.1% In addition, the following adverse reactions were reported less frequently than 1% either in clinical trials or in marketing experience ( adverse events for marketing experience are given in italics ). Causality and relationship to propafenone therapy cannot necessarily be judged from these events. Cardiovascular System: Atrial flutter, AV dissociation, cardiac arrest, flushing, hot flashes, sick sinus syndrome, sinus pause or arrest, supraventricular tachycardia. Nervous System: Abnormal dreams, abnormal speech, abnormal vision, apnea, coma, confusion, depression, memory loss, numbness, paresthesias, psychosis/mania, seizures (0.3%), tinnitus, unusual smell sensation, vertigo. Gastrointestinal: A number of patients with liver abnormalities associated with propafenone therapy have been reported in post-marketing experience. Some appeared due to hepatocellular injury, some were cholestatic and some showed a mixed picture. Some of these reports were simply discovered through clinical chemistries, others because of clinical symptoms including fulminant hepatitis and death. One case was rechallenged with a positive outcome. Cholestasis (0.1%), elevated liver enzymes (alkaline phosphatase, serum transaminases) (0.2%), gastroenteritis, hepatitis (0.03%). Hematologic: Agranulocytosis, anemia, bruising, granulocytopenia, increased bleeding time, leukopenia, purpura, thrombocytopenia. Other: Alopecia, eye irritation, hyponatremia/inappropriate ADH secretion, impotence, increased glucose, kidney failure, positive ANA (0.7%), lupus erythematosis, muscle cramps, muscle weakness, nephrotic syndrome, pain, pruritus.

<table width="80%" ID="i138e79ff-293c-46f0-8a5e-f69457cb38ef"> <caption>Adverse Reactions Reported for &gt;1.5% of SVT Patients</caption> <col width="40%" align="left" valign="top"/> <col width="30%" align="center" valign="top"/> <col width="30%" align="center" valign="top"/> <thead> <tr styleCode="TopRule"> <th styleCode="Rrule"/> <th styleCode="TopRule Rrule">Incidence (N=480)</th> <th styleCode="TopRule Lrule Rrule">% of Patients Who Discontinued</th> </tr> </thead> <tbody> <tr styleCode="BotRule"> <td styleCode="Lrule">Unusual taste</td> <td styleCode="Lrule">14%</td> <td styleCode="Lrule Rrule">1.3%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Nausea and/or Vomiting</td> <td styleCode="Lrule">11%</td> <td styleCode="Lrule Rrule">2.9%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dizziness</td> <td styleCode="Lrule">9%</td> <td styleCode="Lrule Rrule">1.7%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Constipation</td> <td styleCode="Lrule">8%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Headache</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule Rrule">0.8%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Fatigue</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule Rrule">1.5%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Blurred Vision</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule Rrule">0.6%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Weakness</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule Rrule">1.3%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dyspnea</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">1.0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Wide Complex Tachycardia</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">1.9%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">CHF</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.6%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Bradycardia</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Palpitations</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Tremor</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Anorexia</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Diarrhea</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.4%</td> </tr> <tr> <td styleCode="Lrule">Ataxia</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.0%</td> </tr> </tbody> </table>

<table width="80%" ID="i8ab54330-8fd4-4486-8329-d9aa17cc45cb"> <caption>Adverse Reactions Reported for &#x2265;1% of Ventricular Arrhythmia Patients</caption> <col width="40%" align="left" valign="top"/> <col width="15%" align="center" valign="top"/> <col width="15%" align="center" valign="top"/> <col width="15%" align="center" valign="top"/> <col width="15%" align="center" valign="top"/> <thead> <tr styleCode="TopRule"> <th styleCode="Rrule"/> <th styleCode="Rrule TopRule BotRule" colspan="2">Prop./Placebo Trials</th> <th styleCode="Rrule Lrule TopRule BotRule" colspan="2">Prop./Quinidine Trial</th> </tr> <tr> <th styleCode="Rrule"/> <th styleCode="Rrule BotRule">Prop.</th> <th styleCode="Rrule BotRule">Placebo</th> <th styleCode="Rrule BotRule">Prop.</th> <th styleCode="Rrule Lrule BotRule">Quinidine</th> </tr> <tr> <th styleCode="Rrule BotRule"/> <th styleCode="Rrule BotRule">(N=247)</th> <th styleCode="Rrule BotRule">(N=111)</th> <th styleCode="Rrule BotRule">(N=53)</th> <th styleCode="Rrule Lrule BotRule">(N=52)</th> </tr> </thead> <tbody> <tr styleCode="BotRule"> <td styleCode="Lrule">Unusual Taste</td> <td styleCode="Lrule">7%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">23%</td> <td styleCode="Lrule Rrule">0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dizziness</td> <td styleCode="Lrule">7%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule">15%</td> <td styleCode="Lrule Rrule">10%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">First Degree AV Block</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Headache(s)</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">8%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Constipation</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule Rrule">2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Intraventricular Conduction Delay</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule Rrule">-</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Nausea and/or Vomiting</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule Rrule">15%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Fatigue</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule Rrule">2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Palpitations</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule Rrule">-</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Blurred Vision</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule Rrule">2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dry Mouth</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule Rrule">6%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dyspnea</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule Rrule">0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Abdominal Pain/Cramps</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">8%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dyspepsia</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">8%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">CHF</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Fever</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">10%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Tinnitus</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Vision, Abnormal</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Esophagitis</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Gastroenteritis</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Anxiety</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule Rrule">-</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Anorexia</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule Rrule">2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Proarrhythmia</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Flatulence</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Angina</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Second Degree AV Block</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule Rrule">-</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Bundle Branch Block</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Loss of Balance</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">-</td> <td styleCode="Lrule Rrule">-</td> </tr> <tr> <td styleCode="Lrule">Diarrhea</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule Rrule">39%</td> </tr> </tbody> </table>

<table width="80%" ID="iac958f25-6eac-474b-807b-22451e59a290"> <caption>Adverse Reactions Reported for &#x2265;1% of Ventricular Arrhythmia Patients N=2127</caption> <col width="40%" align="left" valign="top"/> <col width="12%" align="center" valign="top"/> <col width="12%" align="center" valign="top"/> <col width="12%" align="center" valign="top"/> <col width="12%" align="center" valign="top"/> <col width="12%" align="center" valign="top"/> <thead> <tr styleCode="TopRule"> <th styleCode="Rrule"/> <th styleCode="Rrule TopRule BotRule" colspan="3">Incidence by Total Daily Dose</th> <th styleCode="Rrule TopRule BotRule" rowspan="2">Total Incidence</th> <th styleCode="Lrule Rrule TopRule BotRule" rowspan="2">% of Pts. Who Discont.</th> </tr> <tr> <th styleCode="Rrule"/> <th styleCode="Rrule BotRule">450 mg</th> <th styleCode="Rrule BotRule">600 mg</th> <th styleCode="Rrule BotRule">&#x2265;900 mg</th> </tr> <tr> <th styleCode="Rrule"/> <th styleCode="Rrule">(N=1430)</th> <th styleCode="Rrule">(N=1337)</th> <th styleCode="Rrule">(N=1333)</th> <th styleCode="Rrule">(N=2127)</th> <th styleCode="Rrule Lrule"/> </tr> </thead> <tbody> <tr styleCode="BotRule"> <td styleCode="Lrule">Dizziness</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule">7%</td> <td styleCode="Lrule">11%</td> <td styleCode="Lrule">13%</td> <td styleCode="Lrule Rrule">2.4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Nausea and/or Vomiting</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule">9%</td> <td styleCode="Lrule">11%</td> <td styleCode="Lrule Rrule">3.4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Unusual Taste</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule">9%</td> <td styleCode="Lrule Rrule">0.7%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Constipation</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule">7%</td> <td styleCode="Lrule Rrule">0.5%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Fatigue</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule">6%</td> <td styleCode="Lrule Rrule">1.0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dyspnea</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule Rrule">1.6%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Proarrhythmia</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule Rrule">4.7%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Angina</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule Rrule">0.5%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Headache(s)</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule Rrule">1.0%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Blurred Vision</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule Rrule">0.8%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">CHF</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule Rrule">1.4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Ventricular Tachycardia</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule Rrule">1.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dyspepsia</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule Rrule">0.9%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Palpitations</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule Rrule">0.5%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Rash</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule Rrule">0.8%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">AV Block, First Degree</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule Rrule">0.3%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Diarrhea</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">3%</td> <td styleCode="Lrule Rrule">0.6%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Weakness</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.7%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Dry Mouth</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Syncope/Near Syncope</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.7%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">QRS Duration, Increased</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.5%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Chest Pain</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Anorexia</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Abdominal Pain, Cramps</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Ataxia</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Insomnia</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.3%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Premature Ventricular Contraction(s)</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.1%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Bradycardia</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.5%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Anxiety</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">2%</td> <td styleCode="Lrule Rrule">0.6%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Edema</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Tremor(s)</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.3%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Diaphoresis</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.3%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Bundle Branch Block</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.5%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Drowsiness</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.2%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Atrial Fibrillation</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Flatulence</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.1%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Hypotension</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.4%</td> </tr> <tr styleCode="BotRule"> <td styleCode="Lrule">Intraventricular Conduction Delay</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.1%</td> </tr> <tr> <td styleCode="Lrule">Pain, Joints</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">0%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule">1%</td> <td styleCode="Lrule Rrule">0.1%</td> </tr> </tbody> </table>