Brands, Medical Use, Clinical Data
- Tablet (150, 225 and 300 mg)
Brands / Synonyms
Propafenona [INN-Spanish]; Propafenone; Propafenone HCl; Propafenone hydrochloride; Propafenone-HCl; Propafenonum [INN-Latin]; Rythmol; Rythmol SR; Rythmol SR
Used to prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. Also used for the treatment of life-threatening documented ventricular arrhythmias, such as sustained ventricular tachycardia.
Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes. It is used in the treatment of atrial and ventricular arrhythmias. It works by slowing the influx of sodium ions into the cardiac muscle cells, causing a decrease in excitablity of the cells. Propafenone has local anesthetic activity approximately equal to procaine.
Mechanism of Action
The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.
Nearly completely absorbed following oral administration (90%). Systemic bioavailability ranges from 5 to 50%, due to significant first-pass metabolism. This wide range in systemic bioavailability is related to two factors: presence of food (food increases bioavailability) and dosage (bioavailability is 3.4% for a 150-mg tablet compared to 10.6% for a 300-mg tablet).
Symptoms of propafenone overdose (usually most severe within the first 3 hours) may include convulsions (rarely), heartbeat irregularities, low blood pressure, and sleepiness.
Biotrnasformation / Drug Metabolism
Metabolized primarily in the liver where it is rapidly and extensively metabolized to two active metabolites, 5-hydroxypropafenone and N-depropylpropafenone. These metabolites have antiarrhythmic activity comparable to propafenone but are present in concentrations less than 25% of propafenone concentrations.
RYTHMOL (propafenone HCl) is contraindicated in the presence of uncontrolled congestive heart failure, cardiogenic
shock, sinoatrial, atrioventricular and intraventricular disorders of impulse generation and/or conduction (e.g.,
such sinus node syndrome, atrioventricular block) in the absence of an artificial pacemaker, bradycardia, marked
hypotension, bronchospastic disorders, manifest electrolyte imbalance, and known hypersensitivity to the drug.
Quinidine: Small doses of quinidine completely inhibit the hydroxylation metabolic pathway, making all
patients, in effect, slow metabolizers (see CLINICAL PHARMACOLOGY). There is,
as yet, too little information to recommend concomitant use of propafenone and quinidine.
Local Anesthetics: Concomitant use of local anesthetics (i.e., during pacemaker implantations, surgery, or
dental use) may increase the risks of central nervous system side effects.
Digitalis: RYTHMOL (propafenone hydrochloride) produces dose-related increases in serum digoxin levels
ranging from about 35% at 450 mg/day to 85% at 900 mg/day of propafenone without affecting digoxin renal clearance.
These elevations of digoxin levels were maintained for up to 16 months during concomitant administration. Plasma
digoxin levels of patients on concomitant therapy should be measured, and digoxin dosage should ordinarily be reduced
when propafenone is started, especially if a relatively large digoxin dose is used or if plasma concentrations are
Beta-Antagonists: In a study involving healthy subjects, concomitant administration of propafenone and
propranolol has resulted in substantial increases in propranolol plasma concentration and elimination half-life with
no change in propafenone plasma levels from control values. Similar observations have been reported with metoprolol.
Propafenone appears to inhibit the hydroxylation pathway for the two beta-antagonists (just as quinidine inhibits
propafenone metabolism). Increased plasma concentrations of metoprolol could overcome its relative cardioselectivity.
In propafenone clinical trials, patients who were receiving beta-blockers concurrently did not experience an
increased incidence of side effects. While the therapeutic range for beta-blockers is wide, a reduction in dosage may
be necessary during concomitant administration with propafenone.
Warfarin: In a study of eight healthy subjects receiving propafenone and warfarin concomitantly, mean
steady-state warfarin plasma concentrations increased 39% with a corresponding increase in prothrombin times of
approximately 25%. It is therefore recommended that prothrombin times be routinely monitored and the dose of warfarin
be adjusted if necessary.
Cimetidine: Concomitant administration of propafenone and cimetidine in 12 healthy subjects resulted in a
20% increase in steady-state plasma concentrations of propafenone with no detectable changes in electrocardiographic
parameters beyond that measured on propafenone alone.
Desipramine: Concomitant administration of propafenone and desipramine may result in elevated serum
desipramine levels. Both desipramine, a tricyclic antidepressant, and propafenone are cleared by oxidative pathways
of demethylation and hydroxylation carried out by the hepatic P-450 cytochrome.
Cyclosporin: Propafenone therapy may increase levels of cyclosporin.
Theophylline: Propafenone may increase theophylline concentration during concomitant therapy with the
development of theophylline toxicity.
Rifampin: Rifampin may accelerate the metabolism and decrease the plasma levels and antiarrhythmic efficacy
Other: Limited experience with propafenone combined with calcium antagonists and diuretics has been
reported without evidence of clinically significant adverse reactions.