Rythmol

Rythmol - General Information

An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [PubChem]

Pharmacology of Rythmol

Rythmol 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. Rythmol has local anesthetic activity approximately equal to procaine.

Rythmol for patients

Rythmol Interactions

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 relatively high.

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 of propafenone.

Other: Limited experience with propafenone combined with calcium antagonists and diuretics has been reported without evidence of clinically significant adverse reactions.

Rythmol Contraindications

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.

Additional information about Rythmol

Rythmol Indication: 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.
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. Rythmol 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.
Drug Interactions: Aminophylline Rythmol increases the effect of theophylline
Dyphylline Rythmol increases the effect of theophylline
Oxtriphylline Rythmol increases the effect of theophylline
Theophylline Rythmol increases the effect of theophylline
Warfarin The agent increases the effect of anticoagulant
Acenocoumarol The agent increases the effect of anticoagulant
Dicumarol The agent increases the effect of anticoagulant
Anisindione The agent increases the effect of anticoagulant
Venlafaxine Rythmol increases the effect and toxicity of venlafaxine
Sertraline Fluoxetine increases the effect and toxicity of propafenone
Ritonavir Ritonavir increases the effect and toxicity of propafenone
Mexiletine Rythmol increases the effect and toxicity of mexilitine
Cyclosporine Rythmol increases the effect and toxicity of cyclosporine
Digoxin Rythmol increases the effect of digoxin
Atomoxetine Tje CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Propranolol Rythmol increases the effect of the beta-blocker
Metoprolol Rythmol increases the effect of the beta-blocker
Quinidine Quinidine increases the effect of propafenone
Quinidine barbiturate Quinidine increases the effect of propafenone
Dihydroquinidine barbiturate Quinidine increases the effect of propafenone
Rifabutin Rifampin decreases the effect of propafenone
Rifampin Rifampin decreases the effect of propafenone
Duloxetine Possible increase in the levels of this agent when used with duloxetine
Cisapride Increased risk of cardiotoxicity and arrhytmias
Mesoridazine Increased risk of cardiotoxicity and arrhytmias
Thioridazine Increased risk of cardiotoxicity and arrhytmias
Terfenadine Increased risk of cardiotoxicity and arrhytmias
Fluoxetine Fluoxetine increases the effect and toxicity of propafenone
Paroxetine Fluoxetine increases the effect and toxicity of propafenone
Food Interactions: Not Available
Generic Name: Propafenone
Synonyms: Propafenona [INN-Spanish]; Propafenone HCl; Propafenone hydrochloride; Propafenone-HCl; Propafenonum [INN-Latin]
Drug Category: Anti-Arrhythmia Agents
Drug Type: Small Molecule; Approved

Other Brand Names containing Propafenone: Rythmol; Rythmol SR;
Absorption: 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).
Toxicity (Overdose): Symptoms of propafenone overdose (usually most severe within the first 3 hours) may include convulsions (rarely), heartbeat irregularities, low blood pressure, and sleepiness.
Protein Binding: 97%
Biotransformation: 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.
Half Life: 2-10 hours
Dosage Forms of Rythmol: Tablet Oral
Chemical IUPAC Name: 1-[2-(2-hydroxy-3-propylaminopropoxy)phenyl]-3-phenylpropan-1-one
Chemical Formula: C21H27NO3
Propafenone on Wikipedia: https://en.wikipedia.org/wiki/Propafenone
Organisms Affected: Humans and other mammals