Class Ic antiarrhythmic
Brand names: Tambocor
Updated · Methodology
First line
Class IC antiarrhythmic for pharmacological cardioversion of atrial fibrillation paroxysms and sinus rhythm maintenance in patients without structural heart disease. SEC uses the "pill-in-the-pocket" strategy for infrequent episodes.
Sources
ICD-10: I48 · ICD-11: BC81.3
Second line
Treats supraventricular tachycardias including AV nodal reentrant and accessory-pathway-mediated forms. SEC requires exclusion of structural heart disease before starting.
Sources
ICD-10: I47.1 · ICD-11: BC81.Z
Flecainide blocks fast Nav1.5 sodium channels during phase 0 of the action potential and slows conduction across atria, ventricles, and the His–Purkinje system. It is used for supraventricular tachyarrhythmias, including the «pill-in-the-pocket» approach to paroxysmal atrial fibrillation in patients without structural heart disease. The 1989 CAST trial showed increased mortality in post-myocardial-infarction patients, so flecainide is contraindicated after MI and in structural heart disease. The drug can unmask a Brugada pattern and becomes proarrhythmic during ischaemia.
AEMPS summary of product characteristics (section 4.6): there are no or limited data on flecainide in pregnant women, and animal studies are insufficient with respect to reproductive toxicity. High doses of flecainide caused some fetal anomalies in New Zealand White rabbits, but not in Dutch Belted rabbits, rats or mice, and the relevance of these findings to humans has not been established. In patients taking flecainide during pregnancy, the drug crosses the placenta to the fetus. Flecainide should be used in pregnancy only if the benefits outweigh the risks.
Compatible. Hale L3. Transfers into milk (RID about 5%) with minimal clinical exposure of the infant. Infant ECG monitoring is advised during prolonged maternal therapy.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
2 pairs found. Sorted from critical to minor.
Mechanism
The enzyme CYP2D6 breaks down a large part of flecainide. Ritonavir inhibits this enzyme and, even more strongly, the CYP3A enzymes. According to the ritonavir documents, flecainide blood levels rise, and with them the risk of arrhythmias and other serious adverse reactions. The documents give no figures for this pair. The US ritonavir label only says that the area under the curve (AUC) of drugs broken down by CYP2D6 can rise up to 2-fold. Flecainide lengthens the PR and QRS intervals on the electrocardiogram in a dose-related way. Ritonavir prolongs the PR interval on its own, and rare cases of second- or third-degree atrioventricular block have been reported with it.
Symptoms
When flecainide levels rise above the therapeutic range, adverse reactions become more likely, mainly cardiac ones. The electrocardiogram (ECG) shows a wider QRS complex and longer PR and QT intervals. Atrioventricular block, a slow heart rate, ventricular tachycardia or ventricular fibrillation can develop. The person may notice palpitations, dizziness, or double or blurred vision. Low blood pressure, fainting, and new or worsening heart failure with breathlessness and swelling can occur. In severe flecainide toxicity, seizures, cardiac arrest and death have been reported.
Management
The combination is contraindicated (ritonavir prescribing information from the European Medicines Agency, , and the US Food and Drug Administration, ). These documents set no dose condition for flecainide, so the contraindication also covers the low ritonavir doses used to boost other human immunodeficiency virus (HIV) protease inhibitors. When ritonavir boosts another protease inhibitor, check that drug's prescribing information for contraindications as well (ritonavir summary of product characteristics, EMA; ritonavir label, FDA). The flecainide prescribing information also says to avoid this combination (Spanish Agency of Medicines and Medical Devices, AEMPS). If a patient has taken both drugs, flecainide blood levels can be measured. Trough levels are usually 0.2–1.0 µg/mL, and adverse reactions, especially cardiac ones, become more likely above 0.7–1.0 µg/mL (flecainide prescribing information, AEMPS). Flecainide overdose is life-threatening. There is no specific antidote, and dialysis does not help. Treatment is supportive, and temporary transvenous pacing is considered for conduction block (flecainide prescribing information, AEMPS). Flecainide has a half-life of about 20 hours, so this treatment may be needed for a long time (flecainide prescribing information, AEMPS).
Sources
Verbatim lines from the interaction sections, in the language of the label
«Anti-arrítmicos de Clase III: cuando se administra flecainida en pacientes que reciben amiodarona, la dosis de flecainida deberá reducirse un 50% y monitorizar estrechamente la aparición de efectos…»AEMPS, section 4.5 · Open on CIMA
«Productos para dejar de fumar : La administración conjunta de bupropión (metabolizados por CYP2D6) con flecainida, se debe abordar con precaución y debe iniciarse con la dosis más baja del rango…»AEMPS, section 4.5 · Open on CIMA
«Antivirales : Ritonavir aumenta las concentraciones plasmáticas (aumento del riesgo de arritmias ventriculares) (evitar el uso concomitante).»AEMPS, section 4.5 · Open on CIMA
«Anti-arrítmicos de Clase IV: Se debe proceder con precaución con el uso de flecainida con bloqueantes de los canales de calcio, por ejemplo verapamilo .»AEMPS, section 4.5 · Open on CIMA
«Anti-arrítmicos de Clase IV: Se debe proceder con precaución con el uso de flecainida con bloqueantes de los canales de calcio, por ejemplo verapamilo .»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: When amiodarone is added to flecainide acetate therapy, plasma flecainide levels may increase two-fold or more in some patients, if flecainide acetate dosage is not reduced. (See…»FDA, section 7 · Open on DailyMed
«Drug Interactions: Flecainide is not extensively bound to plasma proteins. In vitro studies with several drugs which may be administered concomitantly showed that the extent of flecainide binding to…»FDA, section 7 · Open on DailyMed
«Antidepresivos : Fluoxetina, paroxetina y otros antidepresivos aumentan la concentración plasmática de flecainida; incremento del riesgo de arritmias con los tricíclicos.»AEMPS, section 4.5 · Open on CIMA
«Antiepilépticos: Datos limitados en pacientes que reciben inductores conocidos de enzimas ( fenitoína, fenobarbital, carbamazepina) indican solo un aumento del 30% de la tasa de eliminación de…»AEMPS, section 4.5 · Open on CIMA
«Pueden producirse acontecimientos adversos que amenacen la vida o incluso letales debidos a interacciones que originen un incremento de las concentraciones plasmáticas (ver sección 4.9). Flecainida…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: In a study involving healthy subjects receiving flecainide acetate and propranolol concurrently, plasma flecainide levels were increased about 20% and propranolol levels were…»FDA, section 7 · Open on DailyMed
«Anti-arrítmicos de Clase II: Debe tenerse en cuenta la posibilidad de efectos inotrópicos negativos de carácter aditivo al administrar conjuntamente a nti-arrítmicos de Clase II, es decir…»AEMPS, section 4.5 · Open on CIMA
«Pueden producirse acontecimientos adversos que amenacen la vida o incluso letales debidos a interacciones que originen un incremento de las concentraciones plasmáticas (ver sección 4.9). Flecainida…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: Flecainide is not extensively bound to plasma proteins. In vitro studies with several drugs which may be administered concomitantly showed that the extent of flecainide binding to…»FDA, section 7 · Open on DailyMed
«Antipsicóticos : Clozapina- aumento del riesgo de arritmias.»AEMPS, section 4.5 · Open on CIMA
«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: Sotalol no debe combinarse con antiarrítmicos de clase Ia, como disopiramida, quinidina, procainamida y flecainida, ni con otros medicamentos antiarrítmicos de clase III como…»AEMPS, section 4.5 · Open on CIMA
«Flecainida: Dado que la flecainida se metaboliza principalmente por CYP 2D6, al inhibir dicha isoenzima, amiodarona puede aumentar los niveles plasmáticos de flecainida; se aconseja reducir la dosis…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Antiarrhythmics quinidine, procainamide, flecainide Reserve concomitant use for patients who are unresponsive to a single agent. Antiarrhythmic metabolism inhibited by amiodarone…»FDA, section 7 · 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
«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: codeína, dextrometorfano, flecainida, mexiletina, ondansetron, tamoxifeno, el tramadol.»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
«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
«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
«Antiarrítmicos: Flecainida»AEMPS, section 4.5 · Open on CIMA
Showing 40 of 67, heaviest first
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Flecainide is evaluated for the following indications with varying evidence strength: Atrial fibrillation (evidence tier B), Supraventricular tachycardia (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Flecainide (≥ 1 in 100): Dizziness, Visual disturbances, Nausea, Fatigue, Tremor. See the Safety section for uncommon and serious reactions.
AEMPS summary of product characteristics (section 4.6): there are no or limited data on flecainide in pregnant women, and animal studies are insufficient with respect to reproductive toxicity. High doses of flecainide caused some fetal anomalies in New Zealand White rabbits, but not in Dutch Belted rabbits, rats or mice, and the relevance of these findings to humans has not been established. In patients taking flecainide during pregnancy, the drug crosses the placenta to the fetus. Flecainide should be used in pregnancy only if the benefits outweigh the risks.
Compatible. Hale L3. Transfers into milk (RID about 5%) with minimal clinical exposure of the infant. Infant ECG monitoring is advised during prolonged maternal therapy.
Flecainide is contraindicated in: Hypersensitivity to flecainide; Heart failure NYHA class III–IV; Asymptomatic ventricular ectopy or non-sustained ventricular tachycardia; History of myocardial infarction (CAST trial findings); Cardiogenic shock. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Hawthorn (Crataegus monogyna / laevigata), Isosorbide dinitrate, Isosorbide mononitrate, Ivabradine, Meldonium, Ranolazine, Digoxin, Lidocaine