Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-4227 NDC: 50090-4227-0 60 TABLET, COATED in a BOTTLE; Propafenone Hydrochloride Label Image
- 16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-4227 NDC: 50090-4227-0 60 TABLET, COATED in a BOTTLE
- Propafenone Hydrochloride Label Image
Overview
Propafenone Hydrochloride Tablets USP are an antiarrhythmic drug supplied in scored, film-coated tablets of 150 mg, 225 mg and 300 mg for oral administration. Propafenone has some structural similarities to beta-blocking agents. Chemically, propafenone hydrochloride is 2’-[2-hydroxy-3-(propylamino)-propoxy]-3-phenylpropiophenone hydrochloride, with a molecular weight of 377.92. The molecular formula is C 21 H 27 NO 3 •HCl. The structural formula of propafenone hydrochloride is given below: Propafenone hydrochloride occurs as colorless crystals or white crystalline powder with a very bitter taste. It is slightly soluble in water (20°C), chloroform, and ethanol. The following inactive ingredients are contained in the tablet: corn starch, croscarmellose sodium, hypromellose, maltodextrin, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, povidone, silicon dioxide colloidal, titanium dioxide, and triacetin. structure
Indications & Usage
Propafenone Hydrochloride Tablets are indicated to: • prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. • prolong the time to recurrence of paroxysmal supraventricular tachycardia (PSVT) associated with disabling symptoms in patients without structural heart disease. • treat documented ventricular arrhythmias, such as sustained ventricular tachycardia that, in the judgment of the physician, are life-threatening. Initiate treatment in the hospital. Usage Considerations: • The use of Propafenone Hydrochloride Tablets in patients with permanent atrial fibrillation (AF) or in patients exclusively with atrial flutter or PSVT has not been evaluated. Do not use Propafenone Hydrochloride Tablets 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 use of Propafenone Hydrochloride Tablets in patients with chronic atrial fibrillation has not been evaluated. • Because of the proarrhythmic effects of Propafenone Hydrochloride Tablets, its use with lesser ventricular arrhythmias is not recommended, even if patients are symptomatic, and any use of the drug should be reserved for patients in whom, in the opinion of the physician, the potential benefits outweigh the risks. • The effect of propafenone on mortality has not been determined [see Boxed Warning ] . Propafenone Hydrochloride Tablets are 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 ) • prolong the time to recurrence of paroxysmal supraventricular tachycardia (PSVT) associated with disabling symptoms in patients who do not have structural heart disease. ( 1 ) • treat documented life-threatening ventricular arrhythmias. ( 1 ) Usage Considerations: • Use in patients with permanent atrial fibrillation or with atrial flutter or 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 Hydrochloride Tablets with drugs that increase the atrioventricular nodal refractory period. ( 1 ) • Because of proarrhythmic effects, use with lesser ventricular arrhythmias is not recommended, even if patients are symptomatic. ( 1 ) • The effect of propafenone on mortality has not been determined. ( 1 )
Dosage & Administration
The dose of Propafenone Hydrochloride Tablets must be individually titrated on the basis of response and tolerance. Initiate therapy with Propafenone Hydrochloride Tablets 150 mg given every 8 hours (450 mg per day). Dosage may be increased at a minimum of 3- to 4- day intervals to 225 mg every 8 hours (675 mg per day). If additional therapeutic effect is needed, the dose of Propafenone Hydrochloride Tablets may be increased to 300 mg every 8 hours (900 mg per day). The usefulness and safety of dosages exceeding 900 mg per day have not been established. In patients with hepatic impairment or those with significant widening of the QRS complex or second- or third-degree AV block, consider reducing the dose. As with other antiarrhythmic agents, in the elderly or in ventricular arrhythmia patients with marked previous myocardial damage, the dose of Propafenone Hydrochloride Tablets should be increased more gradually during the initial phase of treatment. The combination of cytochrome P450 3A4 (CYP3A4) inhibition and either cytochrome P450 2D6 (CYP2D6) deficiency or CYP2D6 inhibition with the simultaneous administration of propafenone may significantly increase the concentration of propafenone and thereby increase the risk of proarrhythmia and other adverse events. Therefore, avoid simultaneous use of Propafenone Hydrochloride Tablets with both a CYP2D6 inhibitor and a CYP3A4 inhibitor [see Warnings and Precautions ( 5.4 ), Drug Interactions ( 7.1 )] . • Initiate therapy with 150 mg given every 8 hours. ( 2 ) • As needed, uptitrate in 3 to 4 days to 225 to 300 mg every 8 hours. ( 2 ) • Consider reducing the dose in patients with hepatic impairment, significant widening of the QRS complex, or second- or third-degree AV block. ( 2 )
Warnings & Precautions
• May cause new or worsened arrhythmias. Evaluate patients via ECG prior to and during therapy. ( 5.1 ) • Propafenone Hydrochloride Tablets may unmask Brugada or Brugada-like Syndrome. ( 4 , 5.2 ) • Avoid use with other drugs that prolong the QT interval. ( 5.3 ) • Avoid simultaneous use of propafenone with both a cytochrome P450 2D6 (CYP2D6) inhibitor and a 3A4 inhibitor (CYP3A4). ( 5.4 ) • May provoke overt heart failure. ( 5.5 ) • May cause dose-related first-degree AV block or other conduction disturbances. Only use in patients with conduction disorders who have pacemakers. ( 5.6 ) • May affect artificial pacemakers. Monitor pacemaker function. ( 5.7 ) • Agranulocytosis: Patients should report signs of infection. ( 5.8 ) • May exacerbate myasthenia gravis. ( 5.11 ) 5.1 Proarrhythmic Effects Propafenone has caused new or worsened arrhythmias. Such proarrhythmic effects include sudden death and life-threatening ventricular arrhythmias such as ventricular fibrillation, ventricular tachycardia, asystole, and torsade de pointes. It may also worsen premature ventricular contractions or supraventricular arrhythmias, and it may prolong the QT interval. It is therefore essential that each patient given propafenone hydrochloride tablets be evaluated electrocardiographically prior to and during therapy to determine whether the response to propafenone hydrochloride tablets supports continued treatment. Because propafenone prolongs the QRS interval in the electrocardiogram, changes in the QT interval are difficult to interpret [see Clinical Pharmacology ( 12.2 )]. In a U.S. uncontrolled, open-label, multicenter trial in subjects with symptomatic supraventricular tachycardia (SVT), 1.9% (9/474) of these subjects experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) during the trial. However, in 4 of the 9 subjects, the ventricular tachycardia was of atrial origin. Six of the 9 subjects that developed ventricular arrhythmias did so within 14 days of onset of therapy. About 2.3% (11/474) of all subjects had a recurrence of SVT during the trial which could have been a change in the subjects’ arrhythmia behavior or could represent a proarrhythmic event. Case reports in patients treated with propafenone for atrial fibrillation/flutter have included increased premature ventricular contractions (PVCs), VT, VF, torsade de pointes, asystole, and death. Overall in clinical trials with propafenone hydrochloride tablets (which included subjects treated for ventricular arrhythmias, atrial fibrillation/flutter, and PSVT), 4.7% of all subjects had new or worsened ventricular arrhythmia possibly representing a proarrhythmic event (0.7% was an increase in PVCs; 4.0% a worsening or new appearance of VT or VF). Of the subjects 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 subjects with less serious or benign arrhythmias, which include subjects 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 trial [see Boxed Warning: Mortality ] suggests that an increased risk of proarrythmia is present throughout treatment. In a trial of sustained-release propafenone, there were too few deaths to assess the long-term risk to patients. There were 5 deaths; 3 in the pooled group for sustained-release propafenone (0.8%), and 2 in the placebo group (1.6%). In the overall database of 8 trials of sustained-release propafenone and immediate-release propafenone, the mortality rate was 2.5% per year on propafenone and 4.0% per year on placebo. Concurrent use of propafenone with other antiarrhythmic agents has not been well studied. 5.2 Unmasking Brugada Syndrome Brugada Syndrome may be unmasked after exposure to propafenone hydrochloride tablets. Perform an ECG after initiation of propafenone hydrochloride tablets, and discontinue the drug if changes are suggestive of Brugada Syndrome [see Contraindications ( 4 )] . 5.3 Use with Drugs that Prolong the QT Interval and Antiarrhythmic Agents The use of propafenone hydrochloride tablets in conjunction with other drugs that prolong the QT interval has not been extensively studied. Such drugs may include many antiarrhythmics, some phenothiazines, tricyclic antidepressants, and oral macrolides. Withhold Class IA and III antiarrhythmic agents for at least 5 half-lives prior to dosing with propafenone hydrochloride tablets. Avoid the use of propafenone with Class IA and III antiarrhythmic agents (including quinidine and amiodarone). There is only limited experience with the concomitant use of Class IB or IC antiarrhythmics. 5.4 Drug Interactions: Simultaneous Use with Inhibitors of Cytochrome P450 Isoenzymes 2D6 and 3A4 Propafenone is metabolized by CYP2D6, CYP3A4, and CYP1A2 isoenzymes. Approximately 6% of Caucasians in the U.S. population are naturally deficient in CYP2D6 activity and other demographic groups are deficient to a somewhat lesser extent. Drugs that inhibit these CYP pathways (such as desipramine, paroxetine, ritonavir, sertraline for CYP2D6; ketoconazole, erythromycin, saquinavir, and grapefruit juice for CYP3A4; and amiodarone and tobacco smoke for CYP1A2) can be expected to cause increased plasma levels of propafenone. Increased exposure to propafenone may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity. Because of its metabolism, the combination of CYP3A4 inhibition and either CYP2D6 deficiency or CYP2D6 inhibition in users of propafenone is potentially hazardous. Therefore, avoid simultaneous use of propafenone hydrochloride tablets with both a CYP2D6 inhibitor and a CYP3A4 inhibitor. 5.5 Use in Patients with a History of Heart Failure Propafenone exerts a negative inotropic activity on the myocardium as well as beta-blockade effects and may provoke overt heart failure. In clinical trial experience with propafenone hydrochloride tablets, new or worsened congestive heart failure (CHF) has been reported in 3.7% of subjects with ventricular arrhythmia; of those 0.9% were considered probably or definitely related to propafenone hydrochloride. Of the subjects with CHF probably related to propafenone, 80% had pre-existing heart failure and 85% had coronary artery disease. CHF attributable to propafenone hydrochloride developed rarely (less than 0.2%) in subjects with ventricular arrhythmia who had no previous history of CHF. CHF occurred in 1.9% of subjects studied with PAF or PSVT. In a U.S. trial of sustained-release propafenone in subjects with symptomatic AF, heart failure was reported in 4 (1.0%) subjects receiving sustained-release propafenone (all doses) compared to 1 (0.8%) subject receiving placebo. 5.6 Conduction Disturbances Propafenone slows atrioventricular conduction and may also cause dose-related first degree AV block. Average PR interval prolongation and increases in QRS duration are also dose-related. Do not give propafenone to patients with atrioventricular and intraventricular conduction defects in the absence of a pacemaker [see Contraindications ( 4 ), Clinical Pharmacology ( 12.2 )] . The incidence of first-degree, second-degree, and third-degree AV block observed in 2,127 subjects with ventricular arrhythmia 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 hydrochloride. Bundle branch block (1.2%) and intraventricular conduction delay (1.1%) have been reported in subjects 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. In a U.S. trial in 523 subjects with a history of symptomatic AF treated with sustained-release propafenone, sinus bradycardia (rate less than 50 beats/min) was reported with the same frequency with sustained-release propafenone and placebo. 5.7 Effects on Pacemaker Threshold Propafenone may alter both pacing and sensing thresholds of implanted pacemakers and defibrillators. During and after therapy, monitor and re-program these devices accordingly. 5.8 Agranulocytosis Agranulocytosis has been reported in patients receiving propafenone. Generally, the agranulocytosis occurred within the first 2 months of propafenone therapy, and upon discontinuation of therapy the white count usually normalized by 14 days. Unexplained fever or decrease in white cell count, particularly during the initial 3 months of therapy, warrant consideration of possible agranulocytosis or granulocytopenia. Instruct patients to report promptly any signs of infection such as fever, sore throat, or chills. 5.9 Use in Patients with Hepatic Dysfunction Propafenone is highly metabolized by the liver. Severe liver dysfunction increases the bioavailability of propafenone to approximately 70% compared with 3% to 40% in patients with normal liver function. In 8 subjects with moderate to severe liver disease, the mean half-life was approximately 9 hours. Increased bioavailability of propafenone in these patients may result in excessive accumulation. Carefully monitor patients with impaired hepatic function for excessive pharmacological effects [see Overdosage ( 10 )] . 5.10 Use in Patients with Renal Dysfunction Approximately 50% of propafenone metabolites are excreted in the urine following administration of propafenone hydrochloride tablets. In patients with impaired renal function, monitor for signs of overdosage [see Overdosage ( 10 )] . 5.11 Use in Patients with Myasthenia Gravis Exacerbation of myasthenia gravis has been reported during propafenone therapy. 5.12 Elevated ANA Titers Positive ANA titers have been reported in patients receiving propafenone. They have been reversible upon cessation of treatment and may disappear even in the face of continued propafenone therapy. These laboratory findings were usually not associated with clinical symptoms, but there is one published case of drug-induced lupus erythematosis (positive rechallenge); it resolved completely upon discontinuation of therapy. Carefully evaluate patients who develop an abnormal ANA test and, if persistent or worsening elevation of ANA titers is detected, consider discontinuing therapy.
Boxed Warning
MORTALITY • In the National Heart, Lung, and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind trial in subjects with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than 6 days but less than 2 years previously, an increased rate of death or reversed cardiac arrest rate (7.7%; 56/730) was seen in subjects treated with encainide or flecainide (Class IC antiarrhythmics) compared with that seen in subjects assigned to placebo (3.0%; 22/725). The average duration of treatment with encainide or flecainide in this trial was 10 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 IC antiarrhythmic to have a significant proarrhythmic 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. WARNING: MORTALITY See full prescribing information for complete boxed warning. • An increased rate of death or reversed cardiac arrest rate was seen in subjects treated with encainide or flecainide (Class IC antiarrhythmics) compared with that seen in patients assigned to placebo. At present, it is prudent to consider any IC antiarrhythmic to have a significant risk of provoking proarrhythmic events in subjects 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.
Contraindications
Propafenone hydrochloride tablets are contraindicated in the following circumstances: • Heart failure • Cardiogenic shock • Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation or conduction (e.g., sick sinus node syndrome, AV block) in the absence of an artificial pacemaker • Known Brugada Syndrome • Bradycardia • Marked hypotension • Bronchospastic disorders or severe obstructive pulmonary disease • Marked electrolyte imbalance • Heart failure ( 4 ) • Cardiogenic shock ( 4 ) • Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation or conduction in the absence of pacemaker ( 4 ) • Known Brugada Syndrome ( 4 ) • Bradycardia ( 4 ) • Marked hypotension ( 4 ) • Bronchospastic disorders and severe obstructive pulmonary disease ( 4 ) • Marked electrolyte imbalance ( 4 )
Adverse Reactions
The most commonly reported adverse events with propafenone (greater than 5%) included: unusual taste, nausea and/or vomiting, dizziness, constipation, headache, fatigue, first-degree AV block, and intraventricular conduction delay. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-800-308-6755 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. Adverse reactions associated with propafenone hydrochloride tablets occur most frequently in the gastrointestinal, cardiovascular, and central nervous systems. About 20% of subjects treated with propafenone hydrochloride tablets have discontinued treatment because of adverse reactions. Adverse reactions reported for greater than 1.5% of 474 subjects with SVT who received propafenone hydrochloride tablets in U.S. clinical trials are presented in Table 1 by incidence and percent discontinuation, reported to the nearest percent. Table 1. Adverse Reactions Reported for >1.5% of Subjects with Supraventricular Tachycardia Adverse Reaction Incidence (n = 480) % of Subjects 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% In controlled trials in subjects with ventricular arrhythmia, the most common reactions reported for propafenone hydrochloride tablets and more frequent than on placebo 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 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 greater than or equal to 1% of 2,127 subjects with ventricular arrhythmia who received propafenone in U.S. 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 propafenone hydrochloride tablets. 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.
Drug Interactions
• Inhibitors of CYP2D6, 1A2, and 3A4 increase propafenone exposure. ( 7.1 ) • Propafenone may increase digoxin or warfarin levels. ( 7.2 , 7.3 ) • Orlistat may reduce propafenone exposure. Taper orlistat withdrawal. ( 7.4 ) • Lidocaine may increase central nervous system side effects. ( 7.6 ) 7.1 CYP2D6 and CYP3A4 Inhibitors Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, grapefruit juice) can be expected to cause increased plasma levels of propafenone. The combination of CYP3A4 inhibition and either CYP2D6 deficiency or CYP2D6 inhibition with administration of propafenone may increase the risk of adverse reactions, including proarrhythmia. Therefore, simultaneous use of propafenone hydrochloride tablets with both a CYP2D6 inhibitor and a CYP3A4 inhibitor should be avoided [see Warnings and Precautions ( 5.4 ), Dosage and Administration ( 2 )] . Amiodarone Concomitant administration of propafenone and amiodarone can affect conduction and repolarization and is not recommended. Cimetidine Concomitant administration of propafenone immediate-release tablets and cimetidine in 12 healthy subjects resulted in a 20% increase in steady-state plasma concentrations of propafenone. Fluoxetine Concomitant administration of propafenone and fluoxetine in extensive metabolizers increased the S-propafenone C max and AUC by 39% and 50%, respectively, and the R-propafenone C max and AUC by 71% and 50%, respectively. Quinidine Small doses of quinidine completely inhibit the CYP2D6 hydroxylation metabolic pathway, making all patients, in effect, slow metabolizers [see Clinical Pharmacology ( 12.3 )] . Concomitant administration of quinidine (50 mg 3 times daily) with 150 mg immediate-release propafenone 3 times daily decreased the clearance of propafenone by 60% in extensive metabolizers, making them slow metabolizers. Steady-state plasma concentrations more than doubled for propafenone and decreased 50% for 5-OH-propafenone. A 100-mg dose of quinidine tripled steady-state concentrations of propafenone. Avoid concomitant use of propafenone and quinidine. Rifampin Concomitant administration of rifampin and propafenone in extensive metabolizers decreased the plasma concentrations of propafenone by 67% with a corresponding decrease of 5-OH-propafenone by 65%. The concentrations of norpropafenone increased by 30%. In slow metabolizers, there was a 50% decrease in propafenone plasma concentrations and an increase in the AUC and C max of norpropafenone by 74% and 20%, respectively. Urinary excretion of propafenone and its metabolites decreased significantly. Similar results were noted in elderly patients: Both the AUC and C max of propafenone decreased by 84%, with a corresponding decrease in AUC and C max of 5-OH-propafenone by 69% and 57%, respectively. 7.2 Digoxin Concomitant use of propafenone and digoxin increased steady-state serum digoxin exposure (AUC) in patients by 60% to 270% and decreased the clearance of digoxin by 31% to 67%. Monitor plasma digoxin levels of patients receiving propafenone and adjust digoxin dosage as needed. 7.3 Warfarin The concomitant administration of propafenone and warfarin increased warfarin plasma concentrations at steady state by 39% in healthy volunteers and prolonged the prothrombin time (PT) in patients taking warfarin. Adjust the warfarin dose as needed by monitoring INR (international normalized ratio). 7.4 Orlistat Orlistat may limit the fraction of propafenone available for absorption. In postmarketing reports, abrupt cessation of orlistat in patients stabilized on propafenone has resulted in severe adverse events including convulsions, atrioventricular block, and acute circulatory failure. 7.5 Beta-Antagonists Concomitant use of propafenone and propranolol in healthy subjects increased propranolol plasma concentrations at steady state by 113%. In 4 patients, administration of metoprolol with propafenone increased the metoprolol plasma concentrations at steady state by 100% to 400%. The pharmacokinetics of propafenone was not affected by the coadministration of either propranolol or metoprolol. In clinical trials using propafenone immediate-release tablets, subjects who were receiving beta-blockers concurrently did not experience an increased incidence of side effects. 7.6 Lidocaine No significant effects on the pharmacokinetics of propafenone or lidocaine have been seen following their concomitant use in patients. However, concomitant use of propafenone and lidocaine has been reported to increase the risks of central nervous system side effects of lidocaine.
Similar Drugs
Related medications based on brand, generic name, substance, active ingredients.