Clarissa Marie Arce

Keeping hearts in rhythm for over 25 years and counting… Backed by more than 25 years of study and clinical experience1,2… Recommended First-Line Treatment for Restoring and Maintaining Sinus Rhythm Flecainide is recommended as one of the first-line treatment options for restoring and maintaining sinus rhythm in patients with atrial fibrillation with minimal or no structural heart disease (without significant left ventricular disease or coronary heart disease).1,3 Guidelines-Based Rhythm Control of Atrial Fibrillation3 Recent onset AF Urgent Yes Hemodynamic instability Elective No Patient choice Pharmacological cardioversion Severe HFrEF, significant aortic stenosis Electrical cardioversion (IB) Intravenous Amiodarone (IA) Coronary artery disease moderate HFrEF or HFmrEF/HFpEF abnormal LVH Intravenous Vernakalant (IIbB) Amiodarone (IA) No relevant structural heart disease Intravenous Flecainide (IA) Ibutilide (IIaB)* Propafenone (IA) Vernakalant (IIbB) Pill in the pocket Flecainide (IA) Propafenone (IA) AF = atrial fibrillation; HFmrEF = heart failure with mid-range ejection fraction; HFpEF = heart failure with preserved ejection fraction; HFrEF = heart failure with reduced ejection fraction; LVH = left ventricular hypertrophy *Ibutilide should not be used in patients with long QT interval Class of Recommendation Level of Evidence In patients with no history of ischemic or structural heart disease, Flecainide, Propafenone, or Vernakalant are recommended for pharmacological cardioversion of new-onset AF.3 I A Dronedarone, Flecainide, Propafenone, or Sotalol are recommended for prevention of recurrent symptomatic AF in patients with normal left ventricular function and without pathological left ventricular hypertrophy.3 I A In selected patients with recent-onset AF and no significant structural or ischemic heart disease, a single oral dose of Flecainide or Propafenone (the ‘pill in the pocket’ approach) should be considered for patient-led cardioversion, following safety assessment.3 II B Recommendation Flecainide is also recommended as a first-line treatment for supraventricular tachycardia. Despite beta blocker therapy, breakthrough arrhythmias occur in patients with catecholaminergic polymorphic ventricular tachycardia because of treatment failure, non-compliance, and sub-therapeutic dosing. Flecainide in combination with a beta blocker can suppress ventricular ectopy by as much as 76% in patients with catecholaminergic polymorphic ventricular tachycardia during exercise testing or clinical follow-up.4,5 Guidelines-Based Rhythm Control of Catecholaminergic Polymorphic Ventricular Tachycardia4,5 Recommendation Class of Recommendation Level of Evidence I B I B II C In patients with CPVT, a beta blocker is recommended.4 In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker, flecainide), left cardiac sympathetic denervation, and /or an ICD is recommended.4 Flecainide is reasonable in patients with CPVT who continue to have syncope of suspected VA despite beta blocker therapy. In patients intolerant of beta blocker therapy, flecainide is useful as monotherapy.5 CPVT = catecholaminergic polymorphic ventricular tachycardia; VT = ventricular tachycardia; ICD = implantable cardioverter-defibrillator; VA = ventricular arrhythmias Classes of Recomendation Classes of Recomendations Class I Class II Definition Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure. Class IIa Weight of evidence/opinion is in favour of usefulness/efficacy. Class IIb Usefulness/efficacy is less well established by evidence/opinion. Class III Evidence or general agreement that the given treatment or procedure is not useful/effective; and in some cases may be harmful. Levels of Evidence Level of evidence A Data derived from multiple randomized clinical trials or meta-analyses. Level of evidence B Data derived from a single randomized clinical trial or large non-randomized studies. Level of evidence C Consensus of opinion of the experts and/or small studies, retrospective studies, registries. Favorable Safety Profile and Improvement of Patient’s Quality of Life Flecainide is better tolerated than Quinidine, and is associated with a lower rate of adverse events as compared to Propafenone.2 When administered following recommended guidelines, Flecainide is safe, improves quality of life, and is not associated with increased mortality.6 Proven Clinical Efficacy in Restoring and Maintaining Sinus Rhythm Flecainide significantly restores sinus rhythm.2 Clinical trial Patients in flecainide arm AF duration Formulation Reversion rate Capucci et al 22 patients ≤7d Single oral dose (300mg) 8 h → 91% 24 h → 95% Boriani et al 69 patients <8d Single oral dose (300mg) 1 h → 13% 3 h → 57% 8 h → 75% Adapted from reference 2 Flecainide effectively maintains sinus rhythm following cardioversion compared to other antiarrhythmic drugs.1 Relapse rates for different antiarrythmic drugs reported in the litrature* Mean relapse rate (range) Studies (n) No drug 69% (44-85) 10 Quinidine 59% (46-89) 11 Disopyramide 51% (46-56) 3 Propafenone 61% (54-70) 3 Flecainide 38% (19-51) 3 Sotalol 58% (51-63) 3 Amiodarone 47% (17-54) 4 *Minimum 6-months follow-up. Adapted from reference 1 Flecainide (Tambocor®) is suitable in AF patients with minimum or no structural heart disease for:1,3 On-going maintenance of sinus rhythm Cardioversion of recent-onset atrial fibrillation Out-of-hospital acute oral therapy (‘pill-in-the-pocket’ approach)* *only for carefully selected patients previously assessed in a hospital setting Recommended dosages for adults:7 Supraventricular arrhythmias: Starting dosage 100mg twice daily and most patients will be controlled at this dose. May be increased to a maximum of 300mg daily. Ventricular arrhythmias: Starting dosage 100mg twice daily. Maximum daily dose is 400mg and this is normally reserved for patients of large build or where rapid control of the arrhythmia is required. After 3-5 days, it is recommended that the dosage be progressively adjusted to the lowest level which maintains control of the arrhythmia. PRODUCT SHOT Abridged Product Information PLEASE REVIEW FULL PRODUCT INFORMATION BEFORE PRESCRIBING Flecainide acetate (TAMBOCOR) Tablet Indications: Flecainide acetate (Tambocor) tablets are indicated for: a.) Paroxysmal supraventricular tachycardias, including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia and other supraventricular tachycardias of unspecified mechanism. b.) Paroxysmal atrial fibrillation/flutter. c.) Symptomatic sustained ventricular tachycardia. d.) Premature ventricular contractions and/or non-sustained ventricular tachycardia which are causing disabling symptoms. Contraindications: 1.) In cardiac failure. 2.) Unless pacing rescue is available, Flecainide acetate (Tambocor) should not be given to patients with sinus node dysfunction, atrial conduction defects, second degree or greater atrioventricular block, bundle brunch block or distal block. 3.) Asymptomatic premature ventricular contractions and/or asymptomatic non-sustained ventricular tachycardia in patients with a history of myocardial infarction. Precautions: Electrolyte disturbances should be corrected before using Flecainide acetate (Tambocor). Patients with significant hepatic impairment. Caution in all patients with permanent pacemakers or temporary pacing electrodes, and should not be administered to patients with existing poor thresholds or non-programmable pacemakers unless suitable pacing rescue is available. Difficult to obtain ventricular thresholds less than 1 volt at initial implantation in the presence of Flecainide acetate (Tambocor). Difficulty has been experienced in defibrillating some patients. Concomitant antiarrhythmic therapy is not recommended. Adverse effects: Most commonly giddiness, dizziness and lightheadedness. Visual disturbances, such as double vision and blurring of vision, may occur. More rarely nausea and vomiting. These effects are usually transient and disappear upon continuing or reducing the dosage. Pro-arrhythmic effects have been reported in a small number of patients. A few cases of elevated liver enzymes and jaundice have been reported which were possibly related to treatment with Flecainide acetate (Tambocor). During long-term therapy, a few cases of peripheral neuropathy, paresthesia and ataxia have been reported. Extremely rare cases of corneal deposits, pulmonary fibrosis, interstitial lung disease and pneumonitis have also been reported. Drug interactions: Use of flecainide with other sodium channel blockers is not recommended. Treatment with Tambocor is compatible with use of oral anti-coagulants. Flecainide can cause the plasma digoxin level to rise by about 15%. The possibility of additive negative inotrophic effects of beta blockers and other cardiac depressants with flecainide should be recognized. Enzyme inducers (phenytoin, phenobarbital, carbamazepine) indicate only 30% increase in the rate of flecainide elimination. In healthy subjects receiving cimetidine (1g daily) for one week, plasma flecainide levels increased by about 30% and the half life increased by 10%. Flecainide in the presence of amiodarone, the usual flecainide dosage should be reduced by 50% and the patient monitored closely for adverse effects. Plasma level monitoring is strongly recommended in these circumstances. Available forms: 100mg Tablet – packs of 90’s tablets. (Blister). Dosage regimens: Adults: Ventricular arrhythmias: the recommended starting dosage is 100mg twice daily. The maximum daily dose is 400mg and this is normally reserved for patients of large build or where rapid control of arrhythmia is required. After 3-5 days, it is recommended that the dosage be progressively adjusted to the lowest level which maintains control of arrhythmia. It may be possible to reduce dosage during long-term treatment. Supraventricular arrhythmias: the recommended starting dosage is 50mg twice daily and most patients will be controlled at this dose. If required, the dose may be increased to a maximum of 300mg daily. Children: Flecainide acetate (Tambocor) is not recommended in children under 12, as there is no evidence of its use in this age group. Elderly patients: The rate of flecainide elimination from plasma may be reduced in elderly people. An initial dose of one tablet twice daily will usually be adequate, and it may well be possible to reduce this dose for maintenance therapy after one week. Dosage in impaired renal function: In patients with significant renal impairment (creatinine clearance of 35ml/min/1.73sq.m. or less), the maximum initial dosage should be 100mg daily. When used in such patients, frequent plasma level monitoring is strongly recommended. Route of administration: Oral Special patient groups: Flecainide acetate (Tambocor) is not recommended in children under 12. Elderly patients, the rate of flecainide elimination from plasma may be reduced. Impaired renal function, frequent plasma level monitoring is strongly recommended when used in such patients. Pregnancy and Lactation. Manufactured By: 3M Healthcare Limited Derby Road, Loughborough, Leicestershire, LE11 5SF, United Kingdom For: iNova Pharmaceuticals (Aust) Pty Ltd. 9-15 Chilvers Road, Thornleigh, NSW 2120 Australia Imported and Distributed by: Metro Drug Inc. Compound Mañalac Ave., Bagumbayan, Taguig City Philippines 1632 References: 1. Aliot E, et al. Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. Europace (2011), doi:10.1093/europace/euq382. 2. Andrikopoulos GK, Pastromas S, Tzeis S. Flecainide: Current status and perspectives in arrhythmia management. World Journal of Cardiology (2015), doi:org/10.4330/wjc.v7.i2.76. 3. Kirchhof P, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal (2016), doi:10.1093/eurheartj/ehw210. 4. Al-Khatib SM, et al. 2017 AHA/ACC/HRS Guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Heart Rhythm (2017), doi:10.1016/j.hrthm-. Win-Kuang S, et al. 2017 ACC/AHA/HRS Guideline for the evaluation and management of patients with syncope. Journal of the American College of Cardiology (2017), doi:10.1016/j.jacc-. Provenier F, Droogmans S. Atrial fibrillation and flecainide - safety, effectiveness, and quality of life outcomes. European Cardiology Review (2010), doi:-/ecr-. Tambocor Product Information.