Rythmol adverse reactions

Propafenone
RYTHMOL® FDA Package Insert
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
How Supplied/Storage and Handling
Labels and Packages
RYTHMOL SR® FDA Package Insert
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
How Supplied/Storage and Handling
Labels and Packages
Clinical Trials on Propafenone
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

Adverse Reactions

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions associated with RYTHMOL occur most frequently in the gastrointestinal, cardiovascular, and central nervous systems. About 20% of subjects treated with RYTHMOL have discontinued treatment because of adverse reactions.

Adverse reactions reported for > 1.5% of 474 subjects with SVT who received RYTHMOL in US clinical trials are presented in Table 1 by incidence and percent discontinuation, reported to the nearest percent.

In controlled trials in subjects with ventricular arrhythmia, the most common reactions reported for RYTHMOL and more frequent than on placebo were unusual taste, dizziness first degree AV block, intraventricular conduction delay, nausea nd/or vomiting and constipation Headache was relatively common also, but was not increased compared with placebo. Other reactions reported more frequently than on placebo or comparator and not already reported elsewhere included anxiety, angina, second-degree AV block, bundle branch block, loss of balance, congestive heart failure, and dyspepsia.

Adverse reactions reported for ≥1% of 2,127 subjects with ventricular arrhythmia who received propafenone in US clinical trials were evaluated by daily dose. The most common adverse reactions appeared dose-related (but note that most subjects 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. Other adverse reactions included rash syncope chest pain, abdominal pain, ataxia, and hypotension.

In addition, the following adverse reactions were reported less frequently than 1% either in clinical trials or in marketing experience. 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, confusion, depression memory loss, numbness paresthesias, psychosis/mania, seizures (0.3%), tinnitus, unusual smell sensation, vertigo.

Gastrointestinal: Cholestasis , elevated liver enzymes (alkaline phosphatase, serum transaminases), gastroenteritis, hepatitis .

Hematologic: Agranulocytosis, anemia, bruising, granulocytopenia, leukopenia, purpura, thrombocytopenia.

Other: Alopecia, eye irritation, impotence, increased glucose, positive ANA (0.7%), muscle cramps, muscle weakness, nephrotic syndrome, pain, pruritus.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of RYTHMOL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal: A number of patients with liver abnormalities associated with propafenone therapy have been reported in postmarketing 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.

Blood and Lymphatic System: Increased bleeding time.

Immune System: Lupus erythematosis.

Nervous System: Apnea, coma.

Renal and Urinary: Hyponatremia/inappropriate ADH secretion, kidney failure.