Propafenone Hydrochloride
Generic: PROPAFENONE HYDROCHLORIDE
Basic Information
Manufacturer
Strides Pharma Science Limited
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
3fc0800c-c063-48f8-ab4e-9aa9a4c3841f
Indications & Usage
1 INDICATIONS AND USAGE Propafenone HCl Extended Release Capsules, USP are indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease.
Usage Considerations: The use of propafenone ER capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated.
Do not use propafenone ER capsules to control ventricular rate during AF.
Some patients with atrial flutter treated with propafenone have developed 1:1 conduction, producing an increase in ventricular rate.
Concomitant treatment with drugs that increase the functional atrioventricular (AV) nodal refractory period is recommended.
The effect of propafenone on mortality has not been determined [see BOXED WARNING].
Propafenone HCl Extended Release Capsules, USP is an antiarrhythmic indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease.
(1) Usage Considerations: Use in patients with permanent atrial fibrillation or with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated.
Do not use to control ventricular rate during atrial fibrillation.
(1) In patients with atrial fibrillation and atrial flutter, use propafenone ER capsules with drugs that increase the atrioventricular nodal refractory period.
(1) The effect of propafenone on mortality has not been determined.
(1)
Usage Considerations: The use of propafenone ER capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated.
Do not use propafenone ER capsules to control ventricular rate during AF.
Some patients with atrial flutter treated with propafenone have developed 1:1 conduction, producing an increase in ventricular rate.
Concomitant treatment with drugs that increase the functional atrioventricular (AV) nodal refractory period is recommended.
The effect of propafenone on mortality has not been determined [see BOXED WARNING].
Propafenone HCl Extended Release Capsules, USP is an antiarrhythmic indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease.
(1) Usage Considerations: Use in patients with permanent atrial fibrillation or with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated.
Do not use to control ventricular rate during atrial fibrillation.
(1) In patients with atrial fibrillation and atrial flutter, use propafenone ER capsules with drugs that increase the atrioventricular nodal refractory period.
(1) The effect of propafenone on mortality has not been determined.
(1)
Adverse Reactions
6 ADVERSE REACTIONS The most commonly reported adverse events with propafenone (greater than 5% and greater than placebo) excluding those not reasonably associated with the use of the drug included the following: dizziness, palpitations, chest pain, dyspnea, taste disturbance, nausea, fatigue, anxiety, constipation, upper respiratory tract infection, edema, and influenza.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Strides Pharma Inc 1-877-244-9825 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
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.
The data described below reflect exposure to propafenone ER capsules 225 mg twice daily in 126 patients, to propafenone ER capsules 325 mg twice daily in 135 patients, to propafenone ER capsules 425 mg twice daily in 136 patients, and to placebo in 126 patients for up to 39 weeks (mean: 20 weeks) in a placebo‑controlled trial (RAFT) conducted in the U.S.
The most commonly reported adverse events with propafenone (greater than 5% and greater than placebo) excluding those not reasonably associated with the use of the drug or because they were associated with the condition being treated, were dizziness, palpitations, chest pain, dyspnea, taste disturbance, nausea, fatigue, anxiety, constipation, upper respiratory tract infection, edema, and influenza.
The frequency of discontinuation due to adverse events was 17%, and the rate was highest during the first 14 days of treatment.
Cardiac-related adverse events occurring in greater than or equal to 2% of the patients in any of the RAFT propafenone ER capsules treatment groups and more common with propafenone than with placebo, excluding those that are common in the population and those not plausibly related to drug therapy, included the following: angina pectoris, atrial flutter, AV block first-degree, bradycardia, congestive cardiac failure, cardiac murmur, edema, dyspnea, rales, wheezing, and cardioactive drug level above therapeutic.
Propafenone prolongs the PR and QRS intervals in patients with atrial and ventricular arrhythmias.
Prolongation of the QRS interval makes it difficult to interpret the effect of propafenone on the QT interval [ see CLINICAL PHARMACOLOGY (12.2 )].
Non-cardiac related adverse events occurring in greater than or equal to 2% of the patients in any of the RAFT propafenone ER capsules treatment groups and more common with propafenone than with placebo, excluding those that are common in the population and those not plausibly related to drug therapy, included the following: blurred vision, constipation, diarrhea, dry mouth, flatulence, nausea, vomiting, fatigue, weakness, upper respiratory tract infection, blood alkaline phosphatase increased, hematuria, muscle weakness, dizziness (excluding vertigo), headache, taste disturbance, tremor, somnolence, anxiety, depression, ecchymosis.
No clinically important differences in incidence of adverse reactions were noted by age or gender.
Too few non-Caucasian patients were enrolled to assess adverse events according to race.
Adverse events occurring in 2% or more of the patients in any of the ERAFT [see CLINICAL STUDIES ( 14 )] propafenone ER capsules treatment groups and not listed above include the following: bundle branch block left, bundle branch block right, conduction disorders, sinus bradycardia, and hypotension.
Other adverse events reported with propafenone clinical trials not already listed elsewhere in the prescribing information include the following adverse events by body system and preferred term.
Blood and Lymphatic System Anemia, lymphadenopathy, spleen disorder, thrombocytopenia.
Cardiac Unstable angina, atrial hypertrophy, cardiac arrest, coronary artery disease, extrasystoles, myocardial infarction, nodal arrhythmia, palpitations, pericarditis, sinoatrial block, sinus arrest, sinus arrhythmia, supraventricular extrasystoles, ventricular extrasystoles, ventricular hypertrophy.
Ear and Labyrinth Hearing impaired, tinnitus, vertigo.
Eye Eye hemorrhage, eye inflammation, eyelid ptosis, miosis, retinal disorder, visual acuity reduced.
Gastrointestinal Abdominal distension, abdominal pain, duodenitis, dyspepsia, dysphagia, eructation, gastritis, gastroesophageal reflux disease, gingival bleeding, glossitis, glossodynia, gum pain, halitosis, intestinal obstruction, melena, mouth ulceration, pancreatitis, peptic ulcer, rectal bleeding, sore throat.
General Disorders and Administration Site Conditions Chest pain, feeling hot, hemorrhage, malaise, pain, pyrexia.
Hepatobiliary Hepatomegaly.
Investigations Abnormal heart sounds, abnormal pulse, carotid bruit, decreased blood chloride, decreased blood pressure, decreased blood sodium, decreased hemoglobin, decreased neutrophil count, decreased platelet count, decreased prothrombin level, decreased red blood cell count, decreased weight, glycosuria present, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood bilirubin, increased blood cholesterol, increased blood creatinine, increased blood glucose, increased blood lactate dehydrogenase, increased blood pressure, increased blood prolactin, increased blood triglycerides, increased blood urea, increased blood uric acid, increased eosinophil count, increased gamma-glutamyltransferase, increased monocyte count, increased prostatic specific antigen, increased prothrombin level, increased weight, increased white blood cell count, ketonuria present, proteinuria present.
Metabolism and Nutrition Anorexia, dehydration, diabetes mellitus, gout, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypokalemia.
Musculoskeletal, Connective Tissue and Bone Arthritis, bursitis, collagen‑vascular disease, costochondritis, joint disorder, muscle cramps, muscle spasms, myalgia, neck pain, pain in jaw, sciatica, tendonitis.
Nervous System Amnesia, ataxia, balance impaired, brain damage, cerebrovascular accident, dementia, gait abnormal, hypertonia, hypothesia, insomnia, paralysis, paresthesia, peripheral neuropathy, speech disorder, syncope, tongue hypoesthesia.
Psychiatric Decreased libido, emotional disturbance, mental disorder, neurosis, nightmare, sleep disorder.
Renal and Urinary Dysuria, nocturia, oliguria, pyuria, renal failure, urinary casts, urinary frequency, urinary incontinence, urinary retention, urine abnormal.
Reproductive System and Breast Breast pain, impotence, prostatism.
Respiratory, Thoracic, and Mediastinal Atelectasis, breath sounds decreased, chronic obstructive airways disease, cough, epistaxis, hemoptysis, lung disorder, pleural effusion, pulmonary congestion, rales, respiratory failure, rhinitis, throat tightness.
Skin and Subcutaneous Tissue Alopecia, dermatitis, dry skin, erythema, nail abnormality, petechiae, pruritus, sweating increased, urticaria.
Vascular Arterial embolism limb, deep limb venous thrombosis, flushing, hematoma, hypertension, hypertensive crisis, hypotension, labile blood pressure, pallor, peripheral coldness, peripheral vascular disease, thrombosis.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Strides Pharma Inc 1-877-244-9825 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
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.
The data described below reflect exposure to propafenone ER capsules 225 mg twice daily in 126 patients, to propafenone ER capsules 325 mg twice daily in 135 patients, to propafenone ER capsules 425 mg twice daily in 136 patients, and to placebo in 126 patients for up to 39 weeks (mean: 20 weeks) in a placebo‑controlled trial (RAFT) conducted in the U.S.
The most commonly reported adverse events with propafenone (greater than 5% and greater than placebo) excluding those not reasonably associated with the use of the drug or because they were associated with the condition being treated, were dizziness, palpitations, chest pain, dyspnea, taste disturbance, nausea, fatigue, anxiety, constipation, upper respiratory tract infection, edema, and influenza.
The frequency of discontinuation due to adverse events was 17%, and the rate was highest during the first 14 days of treatment.
Cardiac-related adverse events occurring in greater than or equal to 2% of the patients in any of the RAFT propafenone ER capsules treatment groups and more common with propafenone than with placebo, excluding those that are common in the population and those not plausibly related to drug therapy, included the following: angina pectoris, atrial flutter, AV block first-degree, bradycardia, congestive cardiac failure, cardiac murmur, edema, dyspnea, rales, wheezing, and cardioactive drug level above therapeutic.
Propafenone prolongs the PR and QRS intervals in patients with atrial and ventricular arrhythmias.
Prolongation of the QRS interval makes it difficult to interpret the effect of propafenone on the QT interval [ see CLINICAL PHARMACOLOGY (12.2 )].
Non-cardiac related adverse events occurring in greater than or equal to 2% of the patients in any of the RAFT propafenone ER capsules treatment groups and more common with propafenone than with placebo, excluding those that are common in the population and those not plausibly related to drug therapy, included the following: blurred vision, constipation, diarrhea, dry mouth, flatulence, nausea, vomiting, fatigue, weakness, upper respiratory tract infection, blood alkaline phosphatase increased, hematuria, muscle weakness, dizziness (excluding vertigo), headache, taste disturbance, tremor, somnolence, anxiety, depression, ecchymosis.
No clinically important differences in incidence of adverse reactions were noted by age or gender.
Too few non-Caucasian patients were enrolled to assess adverse events according to race.
Adverse events occurring in 2% or more of the patients in any of the ERAFT [see CLINICAL STUDIES ( 14 )] propafenone ER capsules treatment groups and not listed above include the following: bundle branch block left, bundle branch block right, conduction disorders, sinus bradycardia, and hypotension.
Other adverse events reported with propafenone clinical trials not already listed elsewhere in the prescribing information include the following adverse events by body system and preferred term.
Blood and Lymphatic System Anemia, lymphadenopathy, spleen disorder, thrombocytopenia.
Cardiac Unstable angina, atrial hypertrophy, cardiac arrest, coronary artery disease, extrasystoles, myocardial infarction, nodal arrhythmia, palpitations, pericarditis, sinoatrial block, sinus arrest, sinus arrhythmia, supraventricular extrasystoles, ventricular extrasystoles, ventricular hypertrophy.
Ear and Labyrinth Hearing impaired, tinnitus, vertigo.
Eye Eye hemorrhage, eye inflammation, eyelid ptosis, miosis, retinal disorder, visual acuity reduced.
Gastrointestinal Abdominal distension, abdominal pain, duodenitis, dyspepsia, dysphagia, eructation, gastritis, gastroesophageal reflux disease, gingival bleeding, glossitis, glossodynia, gum pain, halitosis, intestinal obstruction, melena, mouth ulceration, pancreatitis, peptic ulcer, rectal bleeding, sore throat.
General Disorders and Administration Site Conditions Chest pain, feeling hot, hemorrhage, malaise, pain, pyrexia.
Hepatobiliary Hepatomegaly.
Investigations Abnormal heart sounds, abnormal pulse, carotid bruit, decreased blood chloride, decreased blood pressure, decreased blood sodium, decreased hemoglobin, decreased neutrophil count, decreased platelet count, decreased prothrombin level, decreased red blood cell count, decreased weight, glycosuria present, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood bilirubin, increased blood cholesterol, increased blood creatinine, increased blood glucose, increased blood lactate dehydrogenase, increased blood pressure, increased blood prolactin, increased blood triglycerides, increased blood urea, increased blood uric acid, increased eosinophil count, increased gamma-glutamyltransferase, increased monocyte count, increased prostatic specific antigen, increased prothrombin level, increased weight, increased white blood cell count, ketonuria present, proteinuria present.
Metabolism and Nutrition Anorexia, dehydration, diabetes mellitus, gout, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypokalemia.
Musculoskeletal, Connective Tissue and Bone Arthritis, bursitis, collagen‑vascular disease, costochondritis, joint disorder, muscle cramps, muscle spasms, myalgia, neck pain, pain in jaw, sciatica, tendonitis.
Nervous System Amnesia, ataxia, balance impaired, brain damage, cerebrovascular accident, dementia, gait abnormal, hypertonia, hypothesia, insomnia, paralysis, paresthesia, peripheral neuropathy, speech disorder, syncope, tongue hypoesthesia.
Psychiatric Decreased libido, emotional disturbance, mental disorder, neurosis, nightmare, sleep disorder.
Renal and Urinary Dysuria, nocturia, oliguria, pyuria, renal failure, urinary casts, urinary frequency, urinary incontinence, urinary retention, urine abnormal.
Reproductive System and Breast Breast pain, impotence, prostatism.
Respiratory, Thoracic, and Mediastinal Atelectasis, breath sounds decreased, chronic obstructive airways disease, cough, epistaxis, hemoptysis, lung disorder, pleural effusion, pulmonary congestion, rales, respiratory failure, rhinitis, throat tightness.
Skin and Subcutaneous Tissue Alopecia, dermatitis, dry skin, erythema, nail abnormality, petechiae, pruritus, sweating increased, urticaria.
Vascular Arterial embolism limb, deep limb venous thrombosis, flushing, hematoma, hypertension, hypertensive crisis, hypotension, labile blood pressure, pallor, peripheral coldness, peripheral vascular disease, thrombosis.