Propafenone Side Effects
Brand Names: Rythmol, Rythmol SR
Please note - some side effects for Propafenone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).
Side Effects of Propafenone - for the Consumer
Propafenone
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Propafenone:
Seek medical attention right away if any of these SEVERE side effects occur when using Propafenone:Change in taste; constipation; dizziness; drowsiness; gas; lightheadedness; tiredness.
Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision; chest pain; chills; excessive thirst; fast, slow, or irregular heartbeat; fever; loss of appetite; muscle weakness; prolonged diarrhea; shortness of breath; sore throat; sweating; swelling of the hands or feet; tremor; unexplained weakness; unusual bruising or bleeding; vomiting.
Propafenone Sustained-Release Capsules
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Propafenone Sustained-Release Capsules:
Seek medical attention right away if any of these SEVERE side effects occur when using Propafenone Sustained-Release Capsules:Change in taste; constipation; dizziness; drowsiness; gas; lightheadedness; tiredness.
TopSevere allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision; chest pain; chills; excessive thirst; fast, slow, or irregular heartbeat; fever; loss of appetite; muscle weakness; prolonged diarrhea; shortness of breath; sore throat; sweating; swelling of the hands or feet; tremor; unexplained weakness; unusual bruising or bleeding; vomiting.
Propafenone Side Effects - for the Professional
Propafenone
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.
| 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.
| 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.
| 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.
TopSide Effects by Body System
General
The Cardiac Arrhythmia Suppression Trial (CAST) revealed significantly higher mortality associated with some class IC antiarrhythmic agents in patients with a recent history (more than six days but less than two years prior to study) of myocardial infarction and asymptomatic non-life-threatening ventricular arrhythmias relative to placebo (5.1% versus 2.3%). Use of propafenone in this context is potentially harmful.
The safety and tolerability of propafenone after long-term administration has been reported. After 14 months, 60% of patients discontinued therapy, but only 15% discontinued therapy due to side effects. Overall, 59% of patients experienced at least 1 side effect, and the incidence was related to dose and age > 65 years. The overall incidence of side effects was not related to structural heart disease. However, cardiovascular toxicity including arrhythmia aggravation, heart failure, and serious conduction disturbances occurred more often in those with heart disease (20% vs. 13%).
Cardiovascular
Accelerated ventricular tachycardias refractory to overdrive pacing in patients on propafenone, who had arrhythmias previously responsive to overdrive pacing, have been reported.
Cardiovascular side effects may be serious. Two to four percent of patients have experienced a proarrhythmic effect. Propafenone slows conduction throughout the myocardial conduction system with very little effect on repolarization, resulting in a prolonged PR interval and QRS complex. Cases of bradycardia, sinus pauses and arrest, accelerated reentrant tachycardia, AV block, and ventricular tachycardia, including torsades de pointes, have been reported.
Propafenone has negative inotropic activity. Preexisting congestive heart failure has been aggravated in 9% of patients and new congestive heart failure induced in 5% of patients.
Nervous system
A 68 year-old man with ocular myasthenia gravis developed generalized myasthenia with ptosis, diplopia, dysarthria, dysphagia, and limb weakness within hours after beginning propafenone 450 mg per day. It is believed that propafenone, by blocking fast sodium channels, may interfere with the generation of propagation of the motor end-plate potential.
Nervous system side effects have included dizziness in 7%, headaches in 5%, ataxia in 1% to 3%, and fatigue in less than 1% of patients. Rare cases of exacerbation of myasthenia gravis and peripheral neuropathy have been associated with the use of propafenone.
Gastrointestinal
Gastrointestinal side effects have included general gastrointestinal upset in 3%, constipation in 4%, a metallic taste in 9%, and nausea or vomiting in approximately 2% of patients.
Respiratory
Respiratory side effects have included dyspnea, wheezing, and bronchoconstriction. These side effects have not exclusively been reported in patients with preexisting reactive airways disease.
Limited data indicate that the plasma concentration of propafenone is not correlated with respiratory complaints, although caution is recommended particularly when daily doses exceed 450 mg. Propafenone is associated with a significant decrease in the average dose of methacholine required to reduce the forced expiratory volume in 1 second (FEV1) by 20% and an increase in the use of beta-agonist inhalers in patients with asthma.
A case of wheezing and decreased expiratory flow rates has been associated with propafenone in a 50-year-old woman with no history of reactive airways disease and who had previously received atenolol and metoprolol without problems.
Hematologic
Hematologic side effects have been rare. A meta-analysis of all adverse drug events associated with propafenone yielded 4 cases of agranulocytosis. The reported rate is 1 case per 10,000 prescriptions per year. Anemia, granulocytopenia, increased bleeding time, leukopenia, purpura, and thrombocytopenia have occurred.
Profound neutropenia associated with bone marrow evidence of myeloid injury has been reported in at least 4 cases. Each patient recovered completely within 7 to 30 days after drug withdrawal.
Hepatic
Propafenone associated liver injury appears to be secondary to hepatocellular injury, cholestasis, or a combination of these. In some cases an allergic reaction has been suspected, while in at least one case, an idiosyncratic toxicity of propafenone metabolites in the biliary epithelial cells was suspected. There are no known fatalities or cases in which the drug had to be discontinued due to elevated liver function tests.
Hepatic side effects been reported. The overall incidence of hepatotoxicity is estimated to be 0.1% to 0.2%.
Immunologic
Immunologic side effects including the rare development of a lupus-like syndrome have been reported in at least two cases. An elevated ANA titer has been reported in 0.7% of patients.
A 63-year-old woman with hypertension, coronary artery disease, and ventricular tachycardia developed a facial photosensitive rash, generalized erythema, and an elevated ANA titer in a homogenous and speckled pattern within 2 months after beginning propafenone 300 mg every 8 hours. The clinical and laboratory abnormalities resolved within 1 month of drug discontinuation and reappeared upon rechallenge with propafenone.
Psychiatric
A 39-year-old woman with a history of congestive heart failure and symptomatic premature ventricular depolarizations developed paresthesias, insomnia, paranoia, hallucinations, and frank psychosis within 24 hours after starting propafenone 300 mg every 12 hours. The syndrome resolved within 2 to 3 days after discontinuation of the drug and institution of haloperidol. The patient subsequently did well off of haloperidol, on an alternative antiarrhythmic agent.
A 61-year-old man with a history of sick sinus syndrome, chronic atrial fibrillation, and premature ventricular depolarizations developed amnesia and disorientation within six days after starting propafenone. His mental status deterioration resolved within six to seven hours after discontinuing therapy. Comparable adverse effects have been associated with an analogous agent, propranolol.
Psychiatric abnormalities have been limited to a case of frank psychosis and a case of global amnesia.
Ocular
Ocular side effects of blurred vision (4%), abnormal vision(2%), and eye irritation (less than 1%) have been reported.
Dermatologic
Dermatologic side effects including at least one case of acute generalized exanthematous pustulosis, which resolved within 3 days after discontinuation of propafenone, has been reported.
TopMore Propafenone resources
- propafenone Concise Consumer Information (Cerner Multum)
- propafenone Advanced Consumer (Micromedex) - Includes Dosage Information
- Propafenone Prescribing Information (FDA)
- Propafenone Professional Patient Advice (Wolters Kluwer)
- Propafenone Detailed Consumer Information (PDR)
- Propafenone Medfacts Consumer Leaflet (Wolters Kluwer)
- Rythmol Prescribing Information (FDA)
- Rythmol SR Prescribing Information (FDA)
- Rythmol SR Sustained-Release Capsules Medfacts Consumer Leaflet (Wolters Kluwer)
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