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 Pts. 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.
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