Class Ic antiarrhythmic with beta-blocking activity
Brand names: Rythmol, Rytmonorm
Updated · Methodology
Second line
Propafenone is second-line antiarrhythmic for sinus rhythm maintenance in paroxysmal atrial fibrillation in patients WITHOUT structural heart disease. 2024 supports the pill-in-the-pocket strategy (450–600 mg single dose during paroxysm). Contraindicated in coronary artery disease, LV dysfunction or heart failure.
Sources
ICD-10: I48 · ICD-11: BC81.3
Blocks fast sodium channels at phase 0 of action potential (class Ic) – slows atrial, AV nodal and ventricular conduction. Active metabolite 5-hydroxypropafenone has weak beta-blocker activity. Metabolised by CYP2D6 with genetically determined variability (extensive vs poor metabolisers). Not recommended in structural heart disease (CAST 1989 – increased mortality).
Limited data. Use when necessary.
Passes into milk. Breastfeeding not recommended.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
The Rytmonorm SmPC lists grapefruit juice among substances that raise propafenone levels by inhibiting the enzymes that break it down. Propafenone is an antiarrhythmic with a narrow margin: in excess it slows cardiac conduction, can trigger new arrhythmias and causes dizziness and a metallic taste. The SmPC asks for close monitoring and dose adjustment when needed.
Source: AEMPS: Ficha técnica de Rytmonorm 150 mg comprimidos recubiertos (propafenona) (2019)
3 pairs found. Sorted from critical to minor.
Mechanism
Additive AV node slowing and QT prolongation. Bradycardia, AV block.
Symptoms
Bradycardia below 50, AV block.
Management
Avoid combination. Choose one antiarrhythmic.
Verbatim lines from the interaction sections, in the language of the label
«CYP2D6 and CYP3A4 Inhibitors: Concomitant administration of propafenone and amiodarone can affect conduction and repolarization and is not recommended.»FDA, section 7 · Open on DailyMed
«CYP2D6 and CYP3A4 Inhibitors: Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, and grapefruit…»FDA, section 7 · Open on DailyMed
«CYP2D6 and CYP3A4 Inhibitors: Small doses of quinidine completely inhibit the CYP2D6 hydroxylation metabolic pathway, making all patients, in effect, slow metabolizers [see Clinical Pharmacology (…»FDA, section 7 · Open on DailyMed
«CYP2D6 and CYP3A4 Inhibitors: Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, and grapefruit…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: • Inhibitors of CYP2D6, 1A2, and 3A4 may increase propafenone levels which may lead to cardiac arrhythmias. Simultaneous use with both a CYP3A4 and CYP2D6 inhibitor (or in patients…»FDA, section 7 · Open on DailyMed
«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…»FDA, section 7 · Open on DailyMed
«CYP2D6 and CYP3A4 Inhibitors: Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, and grapefruit…»FDA, section 7 · Open on DailyMed
«CYP2D6 and CYP3A4 Inhibitors: Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, and grapefruit…»FDA, section 7 · Open on DailyMed
«CYP2D6 and CYP3A4 Inhibitors: Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, and grapefruit…»FDA, section 7 · Open on DailyMed
«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…»FDA, section 7 · Open on DailyMed
«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…»FDA, section 7 · Open on DailyMed
«Antiarrítmicos: La coadministración con ritonavir es probable que dé como resultado un aumento de las concentraciones pl asmáticas de amiodarona, bepridil, dronedarona, encainida, flecainida…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine»FDA, section 4 · Open on DailyMed
«Antiarrítmicos de Clase-I (ej. quinidina, disopiramida; lidocaína, fenitoína; flecainida, propafenona): Pueden potenciar los efectos sobre el tiempo de conducción auriculoventricular y aumentar el…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: • CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based…»FDA, section 7 · Open on DailyMed
«Metoprolol: Se recomienda precaución cuando se administra citalopram con medicamentos que son metabolizados por esta enzima, y que tienen un estrecho margen terapéutico, p.ej., flecainida…»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: Cardiac Disorders : ranolazine, ivabradine dronedarone Other antiarrhythmics e.g. amiodarone, bepridil, disopyramide, flecainide…»FDA, section 7 · Open on DailyMed
«Otros medicamentos metabolizados por CYP2D6 : Fluoxetina es un potente inhibidor de la enzima CYP2D6, por lo que los tratamientos concomitantes con medicamentos que sean también metabolizados por…»AEMPS, section 4.5 · Open on CIMA
«CYP2D6 Inhibitors: Drugs that are strong inhibitors of CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone were shown to double metoprolol concentrations. While there is no information…»FDA, section 7 · Open on DailyMed
«Antiarrítmicos de clase I (quinidina, hidroquinidina, cibenzolina, flecainida, disopiramida, lidocaína, mexiletina, propafenona): puede potenciarse el efecto sobre el tiempo de conducción…»AEMPS, section 4.5 · Open on CIMA
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»AEMPS, section 4.5 · Open on CIMA
«Posibilidad de que afecte a la exposición de otros medicamentos: Se recomienda precaución cuando se administre conjuntamente con medicamentos activados o metabolizados por el CYP2D6, en especial…»AEMPS, section 4.5 · Open on CIMA
«El tratamiento concomitante con medicamentos con índices terapéuticos estrechos metabolizados predominantemente por la CYP2D6 se debe iniciar en el extremo inferior del intervalo de dosis del…»AEMPS, section 4.5 · Open on CIMA
«Potential for Clozapine to Affect Other Drugs: Concomitant use of clozapine with other drugs metabolized by CYP2D6 can increase levels of these CYP2D6 substrates. Use caution when coadministering…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Interactions: Other antiarrhythmics: e.g., amiodarone disopyramide flecainide mexiletine propafenone quinidine ↑ antiarrhythmics Clinical monitoring is…»FDA, section 7 · Open on DailyMed
«Medicamentos que pueden estar afectados por darunavir potenciado con ritonavir: Un ensayo clínico que asocia medicamentos metabolizados por los citocromos CYP2C9, CYP2C19 y CYP2D6 demostró un aumento…»AEMPS, section 4.5 · Open on CIMA
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«Se recomienda precaución si se administra duloxetina con medicamentos metabolizados predominantemente por el CYP2D6 (risperidona, antidepresivos tricíclicos (ADTs) como nortriptilina, amitriptilina e…»AEMPS, section 4.5 · Open on CIMA
«Escitalopram es un inhibidor de la enzima CYP2D6. Se recomienda precaución cuando escitalopram se administre conjuntamente con otros medicamentos que son metabolizados principalmente por esta enzima…»AEMPS, section 4.5 · Open on CIMA
«Sustratos de CYP2D6: Beta-bloqueantes (metoprolol, propafenona, timolol)»AEMPS, section 4.5 · Open on CIMA
«Metoprolol es un sustrato del CYP2D6. Los fármacos que inhiben el CYP2D6 pueden tener un efecto en la concentración plasmática de metoprolol. Ejemplos de fármacos que inhiben CYP2D6 son quinidina…»AEMPS, section 4.5 · Open on CIMA
«Se recomienda precaución si mirabegrón se administra de forma concomitante con medicamentos que tienen un estrecho margen terapéutico y que sean metabolizados de forma significativa por el CYP2D6…»AEMPS, section 4.5 · Open on CIMA
«CYP2D6 Inhibitors: Use caution when nebivolol tablets are co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.) [see Clinical Pharmacology ( 12.5 )] .»FDA, section 7 · Open on DailyMed
«Fluvoxamina e inhibidores del CYP1A2: Pirfenidona debe utilizarse con precaución en pacientes tratados con otros inhibidores moderados de CYP1A2 (p.ej. amiodarona o propafenona).»AEMPS, section 4.5 · Open on CIMA
«Los datos disponibles sugieren que la ranolazina es un inhibidor débil del CYP2D6. La administración de ranolazina 750 mg dos veces al día aumentó 1,8 veces las concentraciones plasmáticas de…»AEMPS, section 4.5 · Open on CIMA
«Fármacos que prolongan el intervalo QT: Como ocurre con otros antipsicóticos, se recomienda precaución cuando se recete risperidona con medicamentos que se sabe que prolongan el intervalo QT, tales…»AEMPS, section 4.5 · Open on CIMA
«Drug-Drug Interactions: In vivo studies have shown that terbinafine is an inhibitor of the CYP450 2D6 isozyme. Drugs predominantly metabolized by the CYP450 2D6 isozyme include the following drug…»FDA, section 7 · Open on DailyMed
«Fluoxetina y paroxetina: Inhibidores del CYP2D6, tales como los inhibidores selectivos de la recaptación de serotonina, fluoxetina y paroxetina, o los antiarrítmicos quinidina o propafenona, pueden…»AEMPS, section 4.5 · Open on CIMA
«CYP2D6 Inhibitors and Poor Metabolizers: Interactions of carvedilol with potent inhibitors of CYP2D6 isoenzyme (such as quinidine, fluoxetine, paroxetine, and propafenone) have not been studied, but…»FDA, section 7 · Open on DailyMed
«amiodarona, flecainida, prazosin, propafenona, quinidina, espironolactona, eritromicina, tetraciclina, gentamicina, itraconazol, quinina, trimetoprima, alprazolam, difenoxilato con atropina…»AEMPS, section 4.5 · Open on CIMA
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Propafenone is evaluated for the following indications with varying evidence strength: Atrial fibrillation (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Propafenone (≥ 1 in 100): Metallic taste, Nausea, Dizziness, Bradycardia, QRS widening. See the Safety section for uncommon and serious reactions.
Limited data. Use when necessary.
Passes into milk. Breastfeeding not recommended.
Propafenone is contraindicated in: Structural heart disease (CAD, post-MI, LV dysfunction, HF); Second/third-degree AV block without pacemaker; Sick sinus syndrome; Severe hepatic impairment; Myasthenia gravis. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Quinidine, Ranolazine, Amiodarone, Ubidecarenone (coenzyme Q10), Disopyramide, Hawthorn (Crataegus monogyna / laevigata), Ivabradine, Digoxin