QuickView for Propafenone (compound)

Summary
General Info

PubChem

PubChem Compound 184821

Name:	Propafenone
PubChem Compound ID:	184821
Description:	An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated.
Molecular formula:	C₂₁H₂₈ClNO₃
Molecular weight:	377.905 g/mol
Synonyms:	107381-35-1

DrugBank

Identification

Name:	Propafenone
Name (isomeric):	DB01182
Drug Type:	small molecule
Description:	An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated.
Synonyms:	Propafenona [INN-Spanish]; Propafenone hydrochloride; Propafenonum [INN-Latin]; Propafenone HCl; Propafenone-HCl
Brand:	Rythmol SR, Rythmol
Category:	Anti-Arrhythmia Agents
CAS number:	54063-53-5

Pharmacology

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.
Pharmacology:	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 an... show more » 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. show less «
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 excit... show more » 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. show less «
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).
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.
Route of elimination:	Naloxone is metabolized in the liver primarily by glucuronide conjugation with naloxone-3-glucuronide as the major metabolite. After an oral or intravenous dose, about 25 to 40% of the drug is excreted as metabolites in urine within 6 hours.
Half Life:	2-10 hours
Toxicity:	Symptoms of propafenone overdose (usually most severe within the first 3 hours) may include convulsions (rarely), heartbeat irregularities, low blood pressure, and sleepiness.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Grapefruit and grapefruit juice should be avoided throughout treatment. Grapefruit can increase serum levels of this product.

Always take at the same time in regard to meals.

Drug interaction:

Terbinafine	Terbinafine may reduce the metabolism and clearance of Propafenone. Consider alternate therapy or monitor for therapeutic/adverse effects of Propafenone if Terbinafine is initiated, discontinued or dose changed.
Duloxetine	Possible increase in the levels of this agent when used with duloxetine
Anisindione	Propafenone may increase the anticoagulant effect of anisindione.
Metoprolol	Propafenone may increase the effect of beta-blocker, metoprolol.
Fluoxetine	Additive QTc-prolongation may occur increasing the risk of serious life-threatening arrhythmias. Fluoxetine may also increase the serum concentration of propafenone. Use caution during concomitant therapy and monitor for QTc-prolongation.

Terbinafine	Terbinafine may reduce the metabolism and clearance of Propafenone. Consider alternate therapy or monitor for therapeutic/adverse effects of Propafenone if Terbinafine is initiated, discontinued or dose changed.
Duloxetine	Possible increase in the levels of this agent when used with duloxetine
Anisindione	Propafenone may increase the anticoagulant effect of anisindione.
Metoprolol	Propafenone may increase the effect of beta-blocker, metoprolol.
Fluoxetine	Additive QTc-prolongation may occur increasing the risk of serious life-threatening arrhythmias. Fluoxetine may also increase the serum concentration of propafenone. Use caution during concomitant therapy and monitor for QTc-prolongation.
Mexiletine	Propafenone may increase the effect and toxicity of mexilitine.
Thiopental	Thiopental may increase the metabolism and clearance of Propafenone. Monitor for decreased therapeutic effect of Propafenone if Thiopental is initiated.
Acenocoumarol	Propafenone may increase the anticoagulant effect of acenocoumarol.
Theophylline	Propafenone increases the effect of theophylline
Dyphylline	Propafenone increases the effect of theophylline
Tizanidine	Propafenone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Sertraline	Fluoxetine increases the effect and toxicity of propafenone
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Rifampin	Rifampin decreases the effect of propafenone
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias.
Propranolol	Propafenone may increase the effect of the beta-blocker, propranolol.
Dicumarol	Propafenone may increase the anticoagulant effect of dicumarol.
Oxtriphylline	Propafenone increases the effect of theophylline
Rifabutin	Rifampin decreases the effect of propafenone
Digoxin	Propafenone increases the effect of digoxin
Warfarin	Propafenone may increase the anticoagulant effect of warfarin.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Dihydroquinidine barbiturate	Quinidine increases the effect of propafenone
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Aminophylline	Propafenone increases the effect of theophylline
Quinidine barbiturate	Quinidine increases the effect of propafenone
Tipranavir	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Propafenone. Concomitant therapy is contraindicated.
Cyclosporine	Propafenone increases the effect and toxicity of cyclosporine
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Quinidine	Quinidine increases the effect of propafenone
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Paroxetine	Paroxetine may increase the effect and toxicity of propafenone.
Venlafaxine	Propafenone increases the effect and toxicity of venlafaxine
Trimipramine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Terfenadine	Increased risk of cardiotoxicity and arrhythmias.
Ritonavir	Ritonavir increases the effect and toxicity of propafenone
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

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Targets

Sodium channel protein type 5 subunit alpha

Potassium voltage-gated channel subfamily H member 2

Enzymes

Transporters

Multidrug resistance protein 1