Flecainide acetate 50 mg

Flecainide

Flecainide is the generic name for the brand-name drug Tambocor, which is used to prevent and treat life-threatening irregular heartbeats (arrhythmias).

The medicine belongs to a class of drugs known as anti-arrhythmics. It works by slowing the electrical signals in the heart to stabilize the heart rhythm.

The Food and Drug Administration (FDA) approved flecainide in 1985. It’s manufactured as Tambocor by 3M.

Flecainide Warnings

Flecainide should only be used to treat people with a life-threatening irregular heartbeat.

The medicine contains a black-box warning because in clinical trials, flecainide raised the risk of either death or a second heart attack among trial participants who had already had a heart attack in the past two years.

There’s not enough data to say whether flecainide also poses a serious risk to people who haven’t had a heart attack in the past two years.

Flecainide contains another black-box warning because it may raise your risk of developing a new, different irregular heartbeat that can be life-threatening.

Tell your doctor if you have atrial fibrillation or atrial flutter (conditions in which the heart’s upper chambers don’t beat effectively) before taking this medicine. You may be at higher risk for developing a new irregular heartbeat.

Also, tell your doctor if you have, or have had, any of the following before taking flecainide:

  • Heart block (a condition in which electrical signals don’t pass through the heart normally)
  • A pacemaker
  • A heart attack, heart failure, or any type of heart disease
  • High or low levels of potassium in the blood
  • Liver disease
  • Kidney disease

Let your healthcare provider know if you’re on a strict vegetarian diet before taking this medicine, as the diet could lead to flecainide being cleared from your body more slowly.

Flecainide may help control your irregular heartbeat, but it won’t cure the condition. Continue to take the drug even if you feel well.

Don’t stop taking flecainide without first talking to your doctor. Your condition may worsen if you stop taking the medicine suddenly.

Be sure to let your doctor know you’re taking flecainide before having any type of surgery, including a dental procedure.

This medicine shouldn’t be given to a child unless your doctor tells you to do so.

Pregnancy and Flecainide

It’s not known whether flecainide can harm an unborn baby.

Tell your doctor if you’re pregnant, or might become pregnant, before taking this medicine.

Flecainide is passed into breast milk. Talk to your doctor about the risks and benefits of breastfeeding while taking the drug.

Tambocor

SIDE EFFECTS

In post-myocardial infarction patients with asymptomatic PVCs and non-sustained ventricular tachycardia, TAMBOCOR (flecainide) therapy was found to be associated with a 5.1% rate of death and non-fatal cardiac arrest, compared with a 2.3% rate in a matched placebo group. (See WARNINGS.)

Adverse effects reported for TAMBOCOR (flecainide) , described in detail in the Warnings section, were new or worsened arrhythmias which occurred in 1% of 108 patients with PSVT and in 7% of 117 patients with PAF; and new or exacerbated ventricular arrhythmias which occurred in 7% of 1330 patients with PVCs, non-sustained or sustained VT. In patients treated with flecainide for sustained VT, 80% (51/64) of proarrhythmic events occurred within 14 days of the onset of therapy. 198 patients with sustained VT experienced a 13% incidence of new or exacerbated ventricular arrhythmias when dosage was initiated at 200 mg/day with slow upward titration, and did not exceed 300 mg/day in most patients. In some patients, TAMBOCOR (flecainide) treatment has been associated with episodes of unresuscitatable VT or ventricular fibrillation (cardiac arrest). (See WARNINGS.) New or worsened CHF occurred in 6.3% of 1046 patients with PVCs, non-sustained or sustained VT. Of 297 patients with sustained VT, 9.1% experienced new or worsened CHF. New or worsened CHF was reported in 0.4% of 225 patients with supraventricular arrhythmias. There have also been instances of second- (0.5%) or third-degree (0.4%) AV block. Patients have developed sinus bradycardia, sinus pause, or sinus arrest, about 1.2% altogether (see WARNINGS). The frequency of most of these serious adverse events probably increases with higher trough plasma levels, especially when these trough levels exceed 1.0μg/mL.

There have been rare reports of isolated elevations of serum alkaline phosphatase and isolated elevations of serum transaminase levels. These elevations have been asymptomatic and no cause and effect relationship with TAMBOCOR (flecainide) has been established. In foreign postmarketing surveillance studies, there have been rare reports of hepatic dysfunction including reports of cholestasis and hepatic failure, and extremely rare reports of blood dyscrasias. Although no cause and effect relationship has been established, it is advisable to discontinue TAMBOCOR (flecainide) in patients who develop unexplained jaundice or signs of hepatic dysfunction or blood dyscrasias in order to eliminate TAMBOCOR (flecainide) as the possible causative agent.

Incidence figures for other adverse effects in patients with ventricular arrhythmias are based on a multicenter efficacy study, utilizing starting doses of 200 mg/day with gradual upward titration to 400 mg/day. Patients were treated for an average of 4.7 months, with some receiving up to 22 months of therapy. In this trial, 5.4% of patients discontinued due to non-cardiac adverse effects.

Table 1 Most Common Non-Cardiac Adverse Effects in Ventricular Arrhythmia Patients Treated with TAMBOCOR (flecainide) in the Multicenter Study

The following additional adverse experiences, possibly related to TAMBOCOR (flecainide) therapy and occurring in 1% to less than 3% of patients, have been reported in acute and chronic studies: Body as a Whole– malaise, fever; Cardiovascular– tachycardia, sinus pause or arrest; Gastrointestinal– vomiting, diarrhea, dyspepsia, anorexia; Skin– rash; Visual– diplopia; Nervous System– hypoesthesia, paresthesia, paresis, ataxia, flushing, increased sweating, vertigo, syncope, somnolence, tinnitus; Psychiatric– anxiety, insomnia, depression.

The following additional adverse experiences, possibly related to TAMBOCOR (flecainide) , have been reported in less than 1% of patients: Body as a Whole– swollen lips, tongue and mouth; arthralgia, bronchospasm, myalgia; Cardiovascular– angina pectoris, seconddegree and third-degree AV block, bradycardia, hypertension, hypotension; Gastrointestinal– flatulence; Urinary System– polyuria, urinary retention; Hematologic– leukopenia, granulocytopenia, thrombocytopenia; Skin– urticaria, exfoliative dermatitis, pruritis, alopecia; Visual– eye pain or irritation, photophobia, nystagmus; Nervous System– twitching, weakness, change in taste, dry mouth, convulsions, impotence, speech disorder, stupor, neuropathy; Respiratory– pneumonitis/pulmonary infiltration possibly due to chronic flecainide treatment; Psychiatric– amnesia, confusion, decreased libido, depersonalization, euphoria, morbid dreams, apathy. For patients with supraventricular arrhythmias, the most commonly reported noncardiac adverse experiences remain consistent with those known for patients treated with TAMBOCOR (flecainide) for ventricular arrhythmias. Dizziness is possibly more frequent in PAF patients.

Read the entire FDA prescribing information for Tambocor (Flecainide)

Identification

Are you a new drug developer? Contact us to learn more about our customized products and solutions. Stay in the know! As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages. #DrugBankUpdates Name Flecainide Accession Number DB01195 (APRD00129) Type Small Molecule Groups Approved, Withdrawn Description

Flecainide is a Class I anti-arrhythmic agent like encainide and propafenone.7 Flecainide’s development began in 1966 and was first synthesized in 1972 as an attempt to generate new anesthetics.10 It is used to prevent supraventricular and ventricular arrhythmias, as well as paroxysmal atrial fibrillation and flutter.12,13

Flecainide was granted FDA approval on 31 October 1985.11

Structure 3D Download Similar Structures

Structure for Flecainide (DB01195)

× Close Synonyms External IDs CCRIS 313 Product Ingredients

Ingredient UNII CAS InChI Key
Flecainide acetate M8U465Q1WQ 54143-56-5 RKXNZRPQSOPPRN-UHFFFAOYSA-N

Product Images Prescription Products

Name Dosage Strength Route Labeller Marketing Start Marketing End
Unlock Additional Data
Flecainide acetate Tablet 50 mg/1 Oral County Line Pharmaceuticals, LLC 2016-11-04 2019-10-01 US
Flecainide Acetate Tablet 150 mg/1 Oral Mylan Pharmaceuticals 2011-08-02 2011-11-30 US
Flecainide Acetate Tablet 100 mg/1 Oral Mylan Pharmaceuticals 2011-08-02 2012-03-31 US
Flecainide acetate Tablet 150 mg/1 Oral County Line Pharmaceuticals, LLC 2016-11-04 2019-10-01 US
Flecainide Acetate Tablet 50 mg/1 Oral Mylan Pharmaceuticals 2011-08-02 2011-11-30 US
Flecainide acetate Tablet 100 mg/1 Oral County Line Pharmaceuticals, LLC 2016-11-04 2019-10-01 US
Tambocor Tablet 100 mg/1 Oral Graceway Pharmaceuticals 2007-04-01 2013-04-30 US
Tambocor Tablet 50 mg/1 Oral Physicians Total Care, Inc. 2004-05-18 2011-06-30 US
Tambocor Tablet 100 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1966-12-31 Not applicable Canada
Tambocor Tablet 150000 ug/1 Oral 3M Company 1985-10-31 2006-12-29 US

Additional Data Available

  • Application Number Application Number

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  • Product Code Product Code

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Generic Prescription Products

Name Dosage Strength Route Labeller Marketing Start Marketing End
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Apo-flecainide Tablet Oral Apotex Corporation 2006-05-08 Not applicable Canada
Apo-flecainide Tablet Oral Apotex Corporation 2006-05-08 Not applicable Canada
Auro-flecainide Tablet Oral Auro Pharma Inc 2017-02-27 Not applicable Canada
Auro-flecainide Tablet Oral Auro Pharma Inc 2017-02-27 Not applicable Canada
Flecainide Acetate Tablet 100 mg/1 Oral Amneal Pharmaceuticals of New York Llc 2009-12-01 Not applicable US
Flecainide Acetate Tablet 150 mg/1 Oral Rising Health, Llc 2015-07-08 Not applicable US
Flecainide Acetate Tablet 100 mg/1 Oral A-S Medication Solutions 2017-11-03 2017-12-31 US
Flecainide Acetate Tablet 50 mg/1 Oral West-Ward Pharmaceuticals Corp. 2003-01-14 Not applicable US
Flecainide Acetate Tablet 50 mg/1 Oral Aurobindo Pharma Limited 2017-11-03 Not applicable US
Flecainide Acetate Tablet 100 mg/1 Oral Barr Laboratories 2002-11-19 2017-07-31 US

Additional Data Available

  • Application Number Application Number

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  • Product Code Product Code

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International/Other Brands Almarytm / Apocard Categories UNII K94FTS1806 CAS number 54143-55-4 Weight Average: 414.3427
Monoisotopic: 414.137811746 Chemical Formula C17H20F6N2O3 InChI Key DJBNUMBKLMJRSA-UHFFFAOYSA-N InChI InChI=1S/C17H20F6N2O3/c18-16(19,20)9-27-12-4-5-14(28-10-17(21,22)23)13(7-12)15(26)25-8-11-3-1-2-6-24-11/h4-5,7,11,24H,1-3,6,8-10H2,(H,25,26) IUPAC Name N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide SMILES FC(F)(F)COC1=CC(C(=O)NCC2CCCCN2)=C(OCC(F)(F)F)C=C1

Pharmacology

Indication

In New Zealand and America, flecainide is indicated to prevent supraventricular arrhythmias and ventricular arrhythmias.12 In the United States, it is also indicated to prevent paroxysmal atrial fibrillation and flutter.9,13

Associated Conditions

  • Atrial Fibrillation (AF)
  • Ventricular Tachycardia (VT)
  • Severe Atrioventricular nodal reentrant tachycardia
  • Severe Paroxysmal atrial fibrillation
  • Severe Paroxysmal supraventricular tachycardia
  • Severe Supraventricular Tachycardias
  • Severe Sustained ventricular tachycardia
  • Severe ventricular arrhythmias

Pharmacodynamics

Flecainide inhibits the action of sodium and potassium ion channels in the heart, raising the threshold for depolarization and correcting arrhythmias.10 Flecainide has a long duration of action, allowing for once daily dosing.12 The therapeutic index is narrow.8 Patients should not take this medication if there is already structural heart disease or left ventricular systolic dysfunction.12

Mechanism of action

Flecainide blocks fast inward sodium channels and slowly unbinds during diastole, prolonging the refractory period of the heart.10 This blockade also shortens the duration of action potentials through the Purkinjie fibers.10 Flecainide also prevents delayed rectifier potassium channels from opening, lengthening the action potential through ventricular and atrial muscle fibers.10 Finally, flecainide also blocks ryanodine receptor opening, reducing calcium release from sarcoplasmic reticulum, which reduces depolarization of cells.10

Target Actions Organism
ASodium channel protein type 5 subunit alpha inhibitor Humans
ASodium channel protein type 4 subunit alpha inhibitor Humans
UPotassium voltage-gated channel subfamily H member 2 inhibitor Humans
URyanodine receptor 2 inhibitor Humans

Unlock Additional Data Additional Data Available Adverse Effects

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Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more Additional Data Available Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more Absorption

Oral flecainide has a Tmax of 3-4h and a bioavialability of 90%.6,10 Taking flecainide with food or aluminum hydroxide antacids do not significantly affect the absorption of flecainide.6,12,13

Volume of distribution

The average volume of distribution in 8 male subjects is 5.0-13.4L/kg.6

Protein binding

Flecainide is 40% bound to protein in serum, mainly to alpha-1-acid glycoprotein and minorly to serum albumin.6,13

Metabolism

Flecainide is mainly metabolized to meta-O-dealkylated flecainide or the meta-O-dealkylated lactam of flecainide.6 Meta-O-dealkylated flecainide has 20% the activity of flecainide.6 Both of these metabolites are generally detected as glucuronide or sulfate conjugates.6 Flecainide’s metabolism involves the action of CYP2D6 and CYP1A2.13,10

  • Flecainide Meta-O-dealkylated flecainide
  • Flecainide Meta-o-dealkylated lactam

Route of elimination

Approximately 86% of a single oral dose is eliminated in the urine, with 42% as unchanged flecainide and 14% as meta-O-dealkylated flecainide, a similar amount of the meta-O-dealkylated lactam of flecainide, approximately 3% as an unidentified acid metabolite, and 6,12,13 5% is eliminated in the feces.6,13

Half life

In healthy subjects, intravenous flecainide has an average half life of 13 hours for a single dose and 16 hours for multiple oral doses.6,12,13 In patients with a ventricular premature complex, flecainide has a half life of 20 hours.6,13 The half life of meta-O-dealkylated flecainide, a major metabolite of flecainide, is 12.6h.6

Clearance

The average clearance of intravenous flecainide is 4.6-12.1mL/min/kg in 8 male subjects.6 For oral flecainide, the clearance was 4-20mL/min/kg.6

Toxicity

The oral LD50 in rats is 1346mg/kg and in mice is 170mg/kg.14 The subcutaneous LD50 in rats is 215mg/kg and in mice is 188mg/kg.14 The oral TDLO in women is 20mg/kg and in men is 40mg/kg/2W.14

Patients experiencing an overdose may present with ECG abnormalities such as a lengthened PR interval, increased QRS duration, prolonged QT interval, increased amplitude of the T wave, reduced myocardial rate and contractility, hypotension, or death.12,13 Treat patients with symptomatic and supportive treatment which may involve administration of inotropic agents, assisted respiration, circulatory assistance, and acidification of the urine.12,13 Hemodialysis is not expected to be useful in the removal of flecainide from serum.6,13

Affected organisms

  • Humans and other mammals

Pathways

Pathway Category
Flecainide Action Pathway Drug action

Pharmacogenomic Effects/ADRs Not Available

Interactions

Drug Interactions This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

  • All Drugs
  • Approved
  • Vet approved
  • Nutraceutical
  • Illicit
  • Withdrawn
  • Investigational
  • Experimental
Drug Interaction
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(R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Flecainide.
(S)-Warfarin The metabolism of (S)-Warfarin can be decreased when combined with Flecainide.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine The metabolism of Flecainide can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
4-Methoxyamphetamine The metabolism of Flecainide can be decreased when combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Flecainide.
6-O-benzylguanine The metabolism of 6-O-benzylguanine can be decreased when combined with Flecainide.
8-azaguanine The metabolism of 8-azaguanine can be decreased when combined with Flecainide.
8-chlorotheophylline The metabolism of 8-chlorotheophylline can be decreased when combined with Flecainide.
9-Deazaguanine The metabolism of 9-Deazaguanine can be decreased when combined with Flecainide.
9-Methylguanine The metabolism of 9-Methylguanine can be decreased when combined with Flecainide.

Additional Data Available

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  • Severity Severity

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  • Evidence Level Evidence Level

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  • Action Action

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Food Interactions

  • Take without regard to meals.

Synthesis Reference

Bmitt, E.H. and Brown, W.R.; U.S. Patent 3,900,481; August 19,1975; assigned to Riker Laboratories, Inc.

US3900481A General References External Links Human Metabolome Database HMDB0015326 KEGG Drug D07962 KEGG Compound C07001 PubChem Compound 3356 PubChem Substance 46508078 ChemSpider 3239 BindingDB 50131434 ChEBI 75984 ChEMBL CHEMBL652 Therapeutic Targets Database DAP000518 PharmGKB PA449646 Guide to Pharmacology GtP Drug Page RxList RxList Drug Page Drugs.com Drugs.com Drug Page Wikipedia Flecainide ATC Codes C01BC04 — Flecainide

  • C01BC — Antiarrhythmics, class Ic
  • C01B — ANTIARRHYTHMICS, CLASS I AND III
  • C01 — CARDIAC THERAPY
  • C — CARDIOVASCULAR SYSTEM

AHFS Codes

  • 24:04.04.12 — Class IC Antiarrythmics

MSDS (77.1 KB)

Clinical Trials

Clinical Trials

Phase Status Purpose Conditions Count
2 Completed Supportive Care Pain 1
2 Completed Treatment Arrhythmia / Arrhythmia of ventricular origin / Cardiovascular Heart Disease / Heart Diseases 1
2 Completed Treatment Failed First Radiofrequency Ablation Procedure / Paroxysmal Atrial Fibrillation (PAF) 1
2 Completed Treatment Narcolepsy 1
2 Recruiting Treatment Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) 1
2 Recruiting Treatment Paroxysmal Atrial Fibrillation (PAF) 1
2 Terminated Basic Science Blood Pressures / Ventricular Premature Complexes 1
2, 3 Withdrawn Treatment Atrial Fibrillation (AF) / Recurrences 1
3 Completed Prevention Arrhythmia of ventricular origin / Cardiovascular Heart Disease / Coronary Heart Disease (CHD) / Death, Sudden,Cardiac / Heart Arrest / Heart Diseases / Myocardial Infarction / Myocardial Ischemia 1
3 Completed Treatment Arrhythmia / Atrial Fibrillation (AF) / Cardiovascular Heart Disease / Heart Diseases 1
3 Completed Treatment Paroxysmal Atrial Fibrillation (PAF) 1
3 Recruiting Treatment Fetal Atrial Flutter Without Hydrops / Fetal Supraventricular Tachycardia With Hydrops / Fetal Supraventricular Tachycardia Without Hydrops 1
3 Suspended Treatment Atrial Fibrillation (AF) 1
4 Completed Not Available Paroxysmal Atrial Fibrillation (PAF) 1
4 Completed Treatment Atrial Fibrillation (AF) 2
4 Completed Treatment Atrial Fibrillation (AF) / Brugada Syndrome / Ventricular Tachycardia (VT) 1
4 Recruiting Treatment Atrial Fibrillation (AF) 2
4 Recruiting Treatment Carvedilol / Outflow Tract / Ventricular Premature Complexes 1
4 Recruiting Treatment Paroxysmal Atrial Fibrillation (PAF) 1
4 Terminated Treatment Atrial Fibrillation (AF) 1
4 Unknown Status Not Available Ventricular Premature Complexes / Ventricular Tachycardia (VT) 1
4 Unknown Status Diagnostic Atrial Fibrillation (AF) 1
4 Withdrawn Treatment Atrial Fibrillation (AF) 1
Not Available Active Not Recruiting Treatment Atrial Fibrillation (AF) 1
Not Available Active Not Recruiting Treatment Atrial Fibrillation (AF) / Quality of Life 1
Not Available Completed Not Available Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) / Brugada Syndrome 1
Not Available Completed Treatment Atrial Fibrillation (AF) 3
Not Available Completed Treatment Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) 1
Not Available Completed Treatment Heart Failure / Recurrent Atrial Fibrillation 1
Not Available Not Yet Recruiting Not Available Tachycardia, Supraventricular 1
Not Available Recruiting Treatment Ventricular premature beats 1
Not Available Unknown Status Treatment Paroxysmal Atrial Fibrillation (PAF) 1
Not Available Unknown Status Treatment Persistent Atrial Fibrillation 1

Pharmacoeconomics

Manufacturers Not Available Packagers

  • 3M Health Care
  • Alphapharm Party Ltd.
  • Amneal Pharmaceuticals
  • AQ Pharmaceuticals Inc.
  • Barr Pharmaceuticals
  • Graceway Pharmaceuticals
  • Kaiser Foundation Hospital
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Ohm Laboratories Inc.
  • Par Pharmaceuticals
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Ranbaxy Laboratories
  • Roxane Labs
  • Southwood Pharmaceuticals

Dosage forms

Form Route Strength
Tablet Oral
Tablet Oral 100 mg/1
Tablet Oral 150 mg/1
Tablet Oral 50 mg/1
Tablet Oral 100 mg
Tablet Oral 100000 ug/1
Tablet Oral 150000 ug/1
Tablet Oral 50 mg
Tablet Oral 50000 ug/1

Prices

Unit description Cost Unit
Tambocor 150 mg tablet 5.75USD tablet
Tambocor 100 mg tablet 4.27USD tablet
Flecainide acetate 150 mg tablet 3.83USD tablet
Flecainide acetate 100 mg tablet 2.95USD tablet
Tambocor 50 mg tablet 2.72USD tablet
Flecainide acetate 50 mg tablet 1.95USD tablet
Tambocor 100 mg Tablet 1.19USD tablet
Apo-Flecainide 100 mg Tablet 0.83USD tablet
Tambocor 50 mg Tablet 0.6USD tablet
Apo-Flecainide 50 mg Tablet 0.41USD tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only. Patents Not Available

Properties

State Solid Experimental Properties Predicted Properties

Property Value Source
Water Solubility 0.0324 mg/mL ALOGPS
logP 2.98 ALOGPS
logP 3.19 ChemAxon
logS -4.1 ALOGPS
pKa (Strongest Acidic) 13.68 ChemAxon
pKa (Strongest Basic) 9.62 ChemAxon
Physiological Charge 1 ChemAxon
Hydrogen Acceptor Count 4 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 59.59 Å2 ChemAxon
Rotatable Bond Count 9 ChemAxon
Refractivity 88.4 m3·mol-1 ChemAxon
Polarizability 35.92 Å3 ChemAxon
Number of Rings 2 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five Yes ChemAxon
Ghose Filter Yes ChemAxon
Veber’s Rule No ChemAxon
MDDR-like Rule No ChemAxon

Predicted ADMET features

Property Value Probability
Human Intestinal Absorption + 0.9856
Blood Brain Barrier + 0.8605
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.7773
P-glycoprotein inhibitor I Inhibitor 0.5307
P-glycoprotein inhibitor II Non-inhibitor 0.7716
Renal organic cation transporter Non-inhibitor 0.6687
CYP450 2C9 substrate Non-substrate 0.8921
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Non-substrate 0.5957
CYP450 1A2 substrate Inhibitor 0.9106
CYP450 2C9 inhibitor Non-inhibitor 0.6853
CYP450 2D6 inhibitor Non-inhibitor 0.6556
CYP450 2C19 inhibitor Inhibitor 0.5307
CYP450 3A4 inhibitor Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5538
Ames test Non AMES toxic 0.672
Carcinogenicity Non-carcinogens 0.8821
Biodegradation Not ready biodegradable 0.9968
Rat acute toxicity 2.5680 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9409
hERG inhibition (predictor II) Inhibitor 0.8474

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST) Not Available Spectra

Taxonomy

Description This compound belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring. Kingdom Organic compounds Super Class Benzenoids Class Benzene and substituted derivatives Sub Class Benzoic acids and derivatives Direct Parent Benzamides Alternative Parents Phenoxy compounds / Phenol ethers / Benzoyl derivatives / Alkyl aryl ethers / Piperidines / Secondary carboxylic acid amides / Amino acids and derivatives / Dialkylamines / Azacyclic compounds / Organopnictogen compoundsOrganofluorides / Organic oxides / Hydrocarbon derivatives / Alkyl fluorides show 4 more Substituents Benzamide / Phenoxy compound / Benzoyl / Phenol ether / Alkyl aryl ether / Piperidine / Amino acid or derivatives / Carboxamide group / Secondary carboxylic acid amide / Carboxylic acid derivativeSecondary aliphatic amine / Ether / Azacycle / Organoheterocyclic compound / Secondary amine / Organohalogen compound / Alkyl halide / Alkyl fluoride / Organic nitrogen compound / Hydrocarbon derivative / Organic oxide / Organopnictogen compound / Organofluoride / Organonitrogen compound / Organooxygen compound / Amine / Organic oxygen compound / Aromatic heteromonocyclic compound show 18 more Molecular Framework Aromatic heteromonocyclic compounds External Descriptors piperidines, organofluorine compound, aromatic ether, monocarboxylic acid amide (CHEBI:75984)

Targets

Binding Properties

×

Property Measurement pH Temperature (°C)
IC 50 (nM) 6500 N/A N/A 17506538

Details Binding Properties1. Sodium channel protein type 5 subunit alpha Kind Protein Organism Humans Pharmacological action Yes Actions Inhibitor General Function Voltage-gated sodium channel activity involved in sa node cell action potential Specific Function This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr… Gene Name SCN5A Uniprot ID Q14524 Uniprot Name Sodium channel protein type 5 subunit alpha Molecular Weight 226937.475 Da Kind Protein Organism Humans Pharmacological action Yes Actions Inhibitor General Function Voltage-gated sodium channel activity Specific Function This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr… Gene Name SCN4A Uniprot ID P35499 Uniprot Name Sodium channel protein type 4 subunit alpha Molecular Weight 208059.175 Da

  1. Desaphy JF, De Luca A, Didonna MP, George AL Jr, Camerino Conte D: Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block. J Physiol. 2004 Jan 15;554(Pt 2):321-34. Epub 2003 Nov 7.

× Details Binding Properties3. Potassium voltage-gated channel subfamily H member 2 Kind Protein Organism Humans Pharmacological action Unknown Actions Inhibitor General Function Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization Specific Function Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the … Gene Name KCNH2 Uniprot ID Q12809 Uniprot Name Potassium voltage-gated channel subfamily H member 2 Molecular Weight 126653.52 Da Kind Protein Organism Humans Pharmacological action Unknown Actions Inhibitor General Function Suramin binding Specific Function Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activa… Gene Name RYR2 Uniprot ID Q92736 Uniprot Name Ryanodine receptor 2 Molecular Weight 564562.71 Da

Enzymes

Kind Protein Organism Humans Pharmacological action Unknown Actions Substrate Inhibitor General Function Steroid hydroxylase activity Specific Function Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic… Gene Name CYP2D6 Uniprot ID P10635 Uniprot Name Cytochrome P450 2D6 Molecular Weight 55768.94 Da Kind Protein Organism Humans Pharmacological action Unknown Actions Substrate General Function Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen Specific Function Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un… Gene Name CYP1A2 Uniprot ID P05177 Uniprot Name Cytochrome P450 1A2 Molecular Weight 58293.76 Da Kind Protein Organism Humans Pharmacological action Unknown Actions Inhibitor Curator comments Enzyme inhibition data based on findings of 1 in vitro study. General Function Steroid hydroxylase activity Specific Function Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un… Gene Name CYP2C9 Uniprot ID P11712 Uniprot Name Cytochrome P450 2C9 Molecular Weight 55627.365 Da

  1. Walker DK, Alabaster CT, Congrave GS, Hargreaves MB, Hyland R, Jones BC, Reed LJ, Smith DA: Significance of metabolism in the disposition and action of the antidysrhythmic drug, dofetilide. In vitro studies and correlation with in vivo data. Drug Metab Dispos. 1996 Apr;24(4):447-55.

Carriers

Kind Protein group Organism Humans Pharmacological action Unknown Actions Binder General Function Not Available Specific Function Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in…

Components:
Name UniProt ID
Alpha-1-acid glycoprotein 1 P02763
Alpha-1-acid glycoprotein 2 P19652

Details2. Serum albumin Kind Protein Organism Humans Pharmacological action Unknown Actions Binder General Function Toxic substance binding Specific Function Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid… Gene Name ALB Uniprot ID P02768 Uniprot Name Serum albumin Molecular Weight 69365.94 Da

Transporters

Kind Protein Organism Humans Pharmacological action Unknown Actions Substrate General Function Xenobiotic-transporting atpase activity Specific Function Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. Gene Name ABCB1 Uniprot ID P08183 Uniprot Name Multidrug resistance protein 1 Molecular Weight 141477.255 Da Kind Protein Organism Humans Pharmacological action Unknown Actions Substrate Inhibitor General Function Monovalent cation:proton antiporter activity Specific Function Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat… Gene Name SLC47A1 Uniprot ID Q96FL8 Uniprot Name Multidrug and toxin extrusion protein 1 Molecular Weight 61921.585 Da ×Unlock Data

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Drug created on June 13, 2005 07:24 / Updated on February 02, 2020 04:03

Flecainide: Antiarrhythmic Medications

What you need to know about Flecainide

When should it be used?

Flecainide comes in tablets and is usually taken twice a day. Take with food or milk if it causes stomach upset.

This medication is usually started in the hospital, where your response to it can be closely monitored by your doctor.

Your prescription label tells you how much to take at each dose — follow these instructions carefully and ask your doctor or pharmacist to explain any part that you do not understand.

This medication works best when there is a constant level in your body. Therefore, it is important that you take it every 12 hours. Try to take your doses at the same times each day. NEVER skip doses or take less or more of the medication than your doctor prescribes. Even if you feel well, NEVER stop taking this medication without consulting your doctor.

Ask your pharmacist any questions you have about refilling your prescription.

What special instructions should I follow while using this drug?

  • Tell your healthcare provider about ALL medications and over-the-counter medications, vitamins and supplements you take.
  • Tell your doctor if you had a recent heart attack or if you have kidney or liver disease, a pacemaker or congestive heart failure.
  • Keep all appointments with your doctor and the lab so your doctor knows how the medication is working.
  • Do not drive a car or operate machinery until you know how this drug affects you. Flecainide can cause dizziness, headaches, fatigue and tremor.
  • Always have enough of this medication on hand. Check your supply before vacations, holidays and other times when you may not be able to get more.
  • Ask your doctor or pharmacist for advice about drinking alcoholic beverages. Alcohol can make the dizziness caused by the medication worse.
  • Do not take this medication if you are pregnant, think you might be pregnant or are breastfeeding.
  • Before any surgical or dental procedure or emergency treatment, tell the doctor or dentist that you are taking this medication.

What should I do if I forget to take a dose?

Take the missed dose if you remember it within six hours. If you do not remember it until six or more hours after the scheduled time, skip the missed dose and take your next regular dose. Do not take a double dose.

What are the common side effects?

Call your doctor if the following symptoms are persistent or severe:

  • Nausea, vomiting or diarrhea.
  • Heartburn, gas.
  • Loss of appetite.
  • Tremors.
  • Blurred vision or seeing “spots”.
  • Headache.
  • Nervousness or confusion.
  • Changes in sleep habits.
  • Weakness, muscle aches.
  • Sweating.
  • Bad taste in the mouth.
  • Decreased sex drive or impotence.
  • Numbness or swelling of hands or feet.
  • Ringing in the ears.
  • Swollen lips or tongue.
  • Dizziness, faintness.
    Get up slowly from sitting or lying positions. Also, be careful while doing activities that require you to be alert.

How should I store this drug?

  • Keep flecainide in the container it came in.
  • Store tablets at room temperature.
  • Store it away from heat and direct sunlight.
  • Do not keep flecainide in the bathroom.
  • Keep flecainide out of the reach of children.
  • Never share your medication with anyone.

Never take outdated medications. Some medication prescription labels list an expiration date. If such a date is not on your medication label, or if you are unsure how old a medication is, call your pharmacy.

Call your doctor right away if you have any of these symptoms:

  • Chest pain
  • Irregular heartbeat, fast heartbeat
  • Fainting or feeling faint more often
  • Yellow eyes or skin
  • Feel very tired
  • Memory loss
  • Depression
  • Skin rash
  • Fever of 100°F (38°C) or higher
  • Sore throat
  • Trouble breathing, urinating, walking or talking
  • Other symptoms that cause concern

This is a summary of information to help you understand and safely take your medication. Ask your doctor and/or pharmacist formore information about your medications and other information you may need based on your own healthcare needs.

This information is not intended to replace the medical advice of your doctor or healthcare provider. Please consult your healthcare provider for advice about a specific medical condition.

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GENERIC NAME: FLECAINIDE – ORAL (fleck-UH-nide)

BRAND NAME(S): Tambocor

Warning | Medication Uses | How To Use | Side Effects | Precautions | Drug Interactions | Overdose | Notes | Missed Dose | Storage

WARNING: Though this medication often gives great benefits to people with irregular heartbeat, it may infrequently cause a serious new irregular heartbeat. Therefore, when starting treatment with this drug, your doctor may recommend that you stay in the hospital for proper monitoring. Flecainide should not be used to treat a certain type of irregular heartbeat (persistent atrial fibrillation/flutter). Talk with your doctor about the benefits and risks of taking this medication for your condition.

USES: This medication is used to treat certain types of serious (possibly fatal) irregular heartbeat (such as persistent ventricular tachycardia and paroxysmal supraventricular tachycardia). It is used to restore normal heart rhythm and maintain a regular, steady heartbeat. It is also used to prevent certain types of irregular heartbeat from returning (such as atrial fibrillation). Flecainide is known as an anti-arrhythmic drug. It works by blocking certain electrical signals in the heart that can cause an irregular heartbeat. Treating an irregular heartbeat can decrease the risk for blood clots, and this effect can reduce your risk of heart attack or stroke.Older adults should discuss the risks and benefits of this medication with their doctor or pharmacist, as well as other effective and possibly safer treatments.

HOW TO USE: Take this medication by mouth with or without food, usually twice daily or as directed by your doctor.Dosage is based on your age, kidney and liver function, medical condition, other medications you may be taking, and response to treatment.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: See also Warning section.Dizziness, vision problems (such as blurred vision, problems focusing, seeing spots), shortness of breath, headache, nausea, shaking, tiredness, or weakness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor immediately if any of these unlikely but serious side effects occur: new or worsening symptoms of heart failure (such as ankle/leg swelling, increased tiredness, increased shortness of breath when lying down).Seek immediate medical attention if any of these rare but serious side effects occur: faster/more irregular heartbeat, severe dizziness, fainting.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Intrahepatic Cholestatic Hepatitis after Ajmaline and Flecainide Application in a Patient with
Ventricular Tachycardia and Cyp2d6 Polymorphism

Case Report

Intrahepatic cholestatic hepatitis is a rare but therapy-limiting side effect of antiarrhythmic drugs, in literature only few reports are related to the subscription of ajmaline . As potential causes for development of intrahepatic cholestatic hepatitis drug-triggered autoimmune reactions as well as direct toxic effects are recently discussed. However, the mechanism of this severe hepatic side effect remains unclear.

Here we present a 53-year-old male who was admitted to our emergency department with sudden-onset palpitation and dizziness without angina or dyspnoea. The initial ECG and the vital parameters revealed a hemodynamic stable ventricular tachycardia (VT) with 210 bpm. Tachycardia showed a right bundle branch block and left anterior hemiblock with a superior axis. The laboratory testing showed a slightly elevated troponin I (0,41 μg/l ) and mild cholestasis (γGT 202 U/l ) without hepatitis. A pre-hopsital i.v. application of 300 mg amiodarone and 5 mg metoprolole by the emergency physician was effectless, whereas an application of 30 mg ajmaline i.v. induced a conversion to normofrequent sinus rhythm.

At the second day after admission the patient was referred to coronary angiography and right ventricular electrophysiological examination. A coronary heart disease could be excluded; no tachycardia could be induced during electrophysiological testing. The echocardiography showed a mild to moderate impaired left ventricular function with a global hypokinesis (LV-EF 40-45%). At the third day after admission a VT-storm occurred, which was successfully terminated several times (13 times) with i.v. bolus application of 30 mg ajmaline for each VT. Therefore we conducted an emergency left ventricle electrophysiological examination, which revealed a flecainide-sensitive idiopathic focal ventricular tachycardia located in the inferolateral wall (Figure 1). Subsequently we performed a successful catheterassisted endocardial ablation by use of 3D-mapping. After the procedure we started oral flecainide (300 mg/d) for long-termtherapy as relapse prevention, as the patient’s hemodynamics was impaired due to VT-storm. Hereafter no recurrence of ventricular tachycardia was observed. A post-procedural magnetic resonance tomography of the heart showed a marked late-enhancement in projection to the ablation region with a LV ejection fraction of 42%. After all, as a secondary prophylactic step and a safety procedure concerning a relapse of VT we implanted an ICDsystem (day 14 after admission).

Figure 1: ECG during electrophysiological examination of the left ventricle at day 3 after admission. Ventricular tachycardia similar to the ECG at admission could be induced. Prompt termination by intravenous application of flecainide followed by sinus tachycardia.

Seven days after discharge the patient complained of pruritus, jaundice, fatigue and pain in the right upper abdomen for the duration of three days. Laboratory testing revealed the constellation of cholestatic hepatitis with strikingly elevated cholestatic enzymes ( γ-glutamyl transferase (γGT) 2037 U/l , Alkaline phosphatase (AP) 394 U/l ) and bilirubinaemia (3,7 mg/dl , accompanied by a significant eosinophilia (0,7/nl l ,. Infective (viral hepatitis A, B, C) and autoimmune (IgM, IgG, ANA, AMA-M2) causes of hepatitis were excluded. Ultrasound examination of the abdomen showed slightly hyperechoic parenchyma of the liver, whereas intra- and extrahepatic bile ducts were normal.

In consideration of the predominantly elevated cholestatic enzymes, the eosinophilia and the patients’ history we suspected drug-induced cholestatic hepatitis due to ajmaline or flecainide. Consistent with this diagnosis, evaluation of CIOMS/RUCAMScale (9 points) classified our case as “highly probable” for an adverse drug reaction. We reduced the dosage of oral flecainide medication (150 mg/d) and observed the patient in our outpatient clinic. Over the course of time the liver enzymes decreased continuously and normalized within 2 months (Figure 2).

Figure 2: Time course of hepatic enzymes during 12 weeks. 18 days of hospital stay. Last laboratory examination concerning liver enzymes at day 10 after admission. Peak level of all hepatic enzymes at day 25. γGT = γ-glutamyl transferase, AP = Alkaline phosphatase, GPT = Glutamate-pyruvate-transaminase (Syn: ALT = Alanin-aminotransferase), GOT = Glutamate-oxalacetate-transferase (Syn: AST = Aspartate-aminotransferase).

Pharmacogenetic genotyping of Cytochrome P450 2D6 (CYP2D6) revealed a heterozygous genotype with a defective CYP2D6 allele (CYP2D6*5) resulting in a decreased enzyme activity accordingly to an “intermediate metabolizer”.

Ajmaline and flecainide are well-known antiarrhythmic drugs and indicated for emergency treatment of supraventricular and ventricular tachycardia. These antiarrhythmic drugs are metabolized in the liver via the cytochrome P450 enzyme CYP2D6 . The polymorphism of this enzyme results in poor, intermediate, efficient or ultrarapid metabolizers of CYP2D6 drugs. About 5-10% of the European Caucasian population are poor metabolizers and nearly 10-17% are intermediate metabolizers .

Drug-induced cholestasis may occur under conditions of increased drug concentrations or genetic alterations such as CYP2D6 polymorphism. In accordance to the few reported cases of ajmaline-induced cholestatic hepatitis , our patient had a similar clinical course characterized by a latency of nearly 3 weeks until occurrence of symptoms and liver enzyme activation. Previously, Mellor et al. supposed that the mechanism of ajmaline-induced cholestatic hepatitis may relate to CYP2D6 polymorphism. Recently, to the best of our knowledge and in comparison to previous reports we demonstrate for the first time that a CYP2D6 polymorphism leads to intrahepatic cholestatic hepatitis due to antiarrhythmic medication, probably related to ajmaline.

Despite metabolization by CYP2D6, the long-term medication with flecainide was necessary to avoid a relapse of potential lifethreatening ventricular tachycardia, so that we did not interrupt this therapeutic strategy. Nevertheless we reduced the flecainidedose adjusted to the reduced enzyme-activity. Compared to ajmaline, flecainide is supposed to have minor clinical significance regarding CYP2D6 metabolism . Consistent with this assumption a continuation of flecainide therapy did not hinder recovery of the cholestatic hepatitis, even though a prolongation cannot be excluded.

Our case demonstrates that a continuation of dosage-reduced flecainide is reasonable in an intermediate metabolizer of CYP2D6 while subsiding cholestatic hepatitis. As mentioned above our patient had a mild cholestasis at admission, which is associated with a higher risk for development of drug-induced cholestasis .

Furthermore, genotype testing of CYP2D6 is not routinely implemented in the clinical setting for risk stratification concerning the development of severe hepatic side effects following treatment by antiarrhythmic drugs. In consideration of the clinical situation the evaluation of CYP2D6 polymorphism in patients at higher risk for liver side effects and medication with antiarrhythmic agents, which are metabolized by this enzyme could be helpful for prevention of adverse drug reactions. This algorithm needs to be proven in further studies. Nevertheless a strict clinical and laboratory observation of these patients in an outpatient manner is necessary.

  1. Larrey D, Pessayre D, Duhamel G, Casier A, Degott C, et al. (1986) Prolonged cholestasis after ajmaline-induced acute hepatitis. J Hepatol 2: 81-87.
  2. Mellor G, Fellows I, Williams I (2013) ‘Intrahepatic cholestatic hepatitis following diagnostic ajmaline challenge’. Europace 15: 314.
  3. Padda MS, Sanchez M, Akhtar AJ, Boyer JL (2011) Drug-induced cholestasis. Hepatology 53: 1377-1387.
  4. Lucena MI, García-Cortés M, Cueto R, Lopez-Duran J, Andrade RJ (2008) Assessment of drug-induced liver injury in clinical practice. Fundam Clin Pharmacol 22: 141-158.
  5. Bertilsson L, Dahl ML, Dalén P, Al-Shurbaji A (2002) Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol 53: 111-122.
  6. Anzenbacher P, Anzenbacherová E (2001) Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci 58: 737-747.
  7. Zhou SF (2009) Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet 48: 689-723.
  8. Eichelbaum M, Gross AS (1990) The genetic polymorphism of debrisoquine/sparteine metabolism–clinical aspects. Pharmacol Ther 46: 377-394.
  9. Andrade RJ, Camargo R, Lucena MI, González-Grande R (2004) Causality assessment in drug-induced hepatotoxicity. Expert Opin Drug Saf 3: 329-344.

Anti-arrhythmics

Anti-arrhythmics help to control or slow irregular heart rhythms such as atrial fibrillation, supraventricular tachycardia (SVT) or ventricular tachycardia (VT).

Types of anti-arrhythmics currently used outside of hospital:

  • beta blockers
  • calcium channel blockers
  • digoxin
  • amiodarone e.g. Aratac, Cordarone X
  • flecainide e.g. Tambocor
  • propafenone e.g. Rytmonorm

How do anti-arrhythmics work?

These medications work in different and sometimes multiple ways. They supress any irregularity of the heart rhythm by affecting the electrical activity of heart cells.

What’s the catch?

Amiodarone – Although unwanted side effects are not common this medication can cause issues with your liver, thyroid or lungs. Some people can also become sensitive to sunlight.

Flecainide – Generally people do not experience side effects with this medication. However after taking if for the first time some users may experience nausea, dizziness or blurred vision.

Propafenone – If you have asthma or obstructive airways disease, take care when taking this medication as it may affect your lungs. Take it with, or just after food, and swallow it whole. Do not chew or crush.

What checks do I need?

Amiodarone – You will require regular blood tests to check liver and thyroid function.

Flecainide and propafenone – You may have some blood tests to check on liver and renal function but no regular checks are thought to be necessary.

What should I look out for?

Amiodarone – Avoid eating grapefruit or drinking grapefruit juice as they may interfere with this medication.

Flecainide – All drugs may cause unwanted side effects. However, many people have none or only minor unwanted side effects. Call your doctor or get medical help if you are concerned.

Propafenone – You may feel sleepy after taking this medication. If this happens, do not drive or use tools or machines.

Related treatments and conditions

Atrial fibrillationArrhythmia

Search for another heart medication

Flecainide Side Effects

Medically reviewed by Drugs.com. Last updated on Dec 24, 2018.

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Interactions
  • More

In Summary

More frequently reported side effects include: cardiac arrest. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to flecainide: oral tablet

Warning

Oral route (Tablet)

Excessive mortality or nonfatal cardiac arrest rate was seen in patients with asymptomatic non-life-threatening ventricular arrhythmias and with myocardial infarction for more than six days but less than two years previously who received flecainide, compared with patients assigned to a carefully matched placebo in the Cardiac Arrhythmia Suppression Trial (CAST). Consider the risks of Class IC agents (including flecainide) and the lack of evidence of improved survival, which is generally unacceptable in a patient without life-threatening ventricular arrhythmias, even if the patient is experiencing unpleasant, but not life-threatening, symptoms or signs. Flecainide is not recommended for use in patients with chronic atrial fibrillation. Case reports of ventricular proarrhythmic effects in patients treated with flecainide for atrial fibrillation/flutter have included increased premature ventricular contractions, ventricular tachycardia, ventricular fibrillation, and death.

Along with its needed effects, flecainide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking flecainide:

More common

  • Difficult or labored breathing
  • dizziness, fainting, or lightheadedness
  • fast, irregular, pounding, or racing heartbeat or pulse
  • shortness of breath
  • tightness in the chest
  • wheezing

Less common

  • Burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
  • chest pain
  • fainting
  • feeling of warmth
  • fever
  • increased sweating
  • partial or slight paralysis
  • redness of the face, neck, arms, and occasionally, upper chest
  • shakiness and unsteady walk
  • shakiness in the legs, arms, hands, or feet
  • swelling of the feet or lower legs
  • trembling or shaking of the hands or feet
  • unsteadiness, trembling, or other problems with muscle control or coordination

Rare

  • Arm, back, or jaw pain
  • black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • blurred vision
  • chest discomfort
  • chest tightness or heaviness
  • chills
  • confusion
  • convulsions
  • cough
  • decrease in the frequency of urination
  • decrease in urine volume
  • difficulty in passing urine (dribbling)
  • difficulty with breathing
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • frequent urination
  • general feeling of discomfort or illness
  • headache
  • increased volume of pale, dilute urine
  • nausea
  • nervousness
  • noisy breathing
  • painful or difficult urination
  • pinpoint red spots on the skin
  • pounding in the ears
  • sensation of pins and needles
  • slow or fast heartbeat
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • stabbing pain
  • sweating
  • swollen glands
  • thickening of bronchial secretions
  • troubled breathing
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • yellow eyes or skin

Some side effects of flecainide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Blurred vision or seeing spots

Less common

  • Abdominal or stomach pain
  • acid or sour stomach
  • anxiety or mental depression
  • belching
  • constipation
  • continuing ringing or buzzing or other unexplained noise in the ears
  • depression
  • diarrhea
  • feeling of constant movement of self or surroundings
  • general feeling of discomfort or illness
  • hearing loss
  • heartburn
  • indigestion
  • lack or loss of strength
  • loss of appetite
  • sensation of spinning
  • sleepiness or unusual drowsiness
  • sleeplessness
  • skin rash
  • stomach discomfort, upset, or pain
  • trouble with sleeping
  • unable to sleep
  • weight loss

Rare

  • Bloated
  • change in color vision
  • change in taste
  • cracks in the skin
  • decreased awareness or responsiveness
  • decreased interest in sexual intercourse
  • difficulty seeing at night
  • difficulty with moving
  • dry mouth
  • excess air or gas in the stomach or intestines
  • eye pain or irritation
  • false or unusual sense of well-being
  • feeling of unreality
  • full feeling
  • hair loss or thinning of the hair
  • hives or welts
  • inability to have or keep an erection
  • increased sensitivity of the eyes to sunlight
  • itching skin
  • joint pain
  • lack of feeling or emotion
  • loss in sexual ability, desire, drive, or performance
  • loss of heat from the body
  • loss of memory
  • muscle aching or cramping
  • muscle pain or stiffness
  • passing gas
  • problems with memory
  • red, swollen skin
  • scaly skin
  • sense of detachment from self or body
  • severe sleepiness
  • swollen joints
  • swollen lips, mouth, or tongue
  • uncaring uncontrolled eye movements

For Healthcare Professionals

Applies to flecainide: oral tablet

General

The Cardiac Arrhythmia Suppression Trial (CAST) revealed significantly higher mortality associated with flecainide in patients with a recent history (more than six days but less than two years prior to study) of myocardial infarction (MI) and non-life-threatening ventricular ectopy relative to placebo (5.1% versus 2.3%). The risk of death relative to placebo in patients with a recent history of Q-wave MI and non-Q-wave MI is 8.7 and 1.7, respectively. Use of flecainide in this context is potentially harmful.

Side effects are more likely when plasma flecainide concentrations are greater than 1.0 mcg/mL.

Cardiovascular

Risk factors for a proarrhythmic effect include underlying congenital or structural heart disease.

A case of “pseudoinfarction” has been reported in which flecainide induced a transient right bundle branch block with a focal block in the septal fibers of the left bundle branch system. An electrocardiogram (ECG) also revealed ST segment elevations and a Q-wave pattern, consistent with septal infarction. The patient did not have a myocardial infarction by enzyme studies, and the ECG abnormalities resolved after discontinuation of flecainide.

One patient with a history of ischemic congestive heart failure, myocardial infarction (MI), and ventricular arrhythmias developed profound cardiogenic shock without evidence of MI or a new or worsened ventricular arrhythmia. The associated serum flecainide concentration was 1.8 mcg/mL.

Cardiovascular side effects including arrhythmias are the most serious side effects. Flecainide may cause or exacerbate arrhythmias in 1% of patients with preexisting paroxysmal supraventricular tachycardia and in 7% of patients with paroxysmal atrial fibrillation. Flecainide may also exacerbate arrhythmias in 7% to 13% of patients with preexisting sustained or nonsustained ventricular arrhythmias.

Flecainide-induced arrhythmias include sinus bradycardia or arrest in 2%, bundle branch blocks in 1%, increased premature ventricular depolarizations in 1%, ventricular tachycardia or fibrillation in 0.5%, and sudden death in 0.2% of patients. New ventricular arrhythmias have been reported in 3.4% of patients.

Flecainide may cause prolongation of the PR, QRS, and corrected QT intervals. Most of the QT interval prolongation is attributable to widening of the QRS complex rather than prolongation of the JT interval. Rare cases of torsades de pointes have been reported.

Exacerbation of congestive heart failure is rare and only occurs in about 0.5% and 9% of patients with preexisting supraventricular arrhythmias and ventricular arrhythmias, respectively. Hypotension is almost exclusively associated with intravenous administration of flecainide.

Nervous system

Flecainide may exacerbate myasthenia gravis.

At least 6 cases of flecainide-induced peripheral neuropathy (sensory loss) have been reported and it appears to develop after prolonged use ( 2 to 10 years). Following discontinuation of flecainide therapy, symptoms (e.g., lower-extremity weakness and/or paresthesias, gait disturbance) resolved over 3 to 6 months. However, in some cases the neuropathy did not resolve after discontinuation of flecainide.

Nervous system side effects, such as dizziness and visual disturbances (including blurred vision, decreased acuity, and scotomata) occur in 13% to 28% of patients who are taking flecainide doses of 400 mg per day. Transient headaches, asthenia, feelings of a thick tongue or lips, fatigue, paresthesias, and tremors have been reported in 2% to 10% of patients.

Gastrointestinal

Gastrointestinal side effects include abdominal pain, nausea, and constipation in 1% to 4% of patients. Diarrhea occurs rarely.

Musculoskeletal

Musculoskeletal side effects including weakness has been reported and may be more likely in patients with underlying muscular disorders.

A 33-year-old woman with atrial fibrillation, mitral valve prolapse, and a congenital muscle fiber disproportion myopathy developed muscle weakness which partially resolved after flecainide dosage reduction and completely resolved after substitution of flecainide with other antiarrhythmic agents.

Ocular

High performance liquid chromatographic analysis of excised corneal deposits in one patient revealed opacities with the same chromatographic characteristics of flecainide.

Ocular side effects are limited to rare cases of corneal deposits.

Genitourinary

Genitourinary side effects including complaints of impotence are reported in 4% of patients. A case of urinary retention associated with flecainide has been reported.

Class I antiarrhythmic agents such as flecainide have local anesthetic and anticholinergic properties which may rarely cause urinary retention.

Respiratory

A case of reversible flecainide-induced pneumonitis was reported in a 61-year-old man with a remote history of pulmonary tuberculosis. A complete infectious disease work-up was negative. Serial bronchial-alveolar lavages and chest radiographs were consistent with a drug-induced process.

Respiratory side effects are extremely rare.

Hematologic

One patient developed leukopenia after 5 months of flecainide therapy. The leukopenia resolved after drug discontinuation and did not recur when flecainide was reinstituted. The leukopenia may have been due to a concurrent viral infection.

Hematologic side effects are extremely rare.

Hepatic

Hepatic side effects including enzyme concentration elevations have been reported in rare cases.

Psychiatric

Psychiatric side effects including paranoid psychosis was reported in a 62-year-old patient receiving flecainide for the treatment of malignant neuropathic pain.

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

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Related treatment guides

  • Atrial Fibrillation
  • Atrial Flutter
  • Paroxysmal Supraventricular Tachycardia
  • Supraventricular Tachycardia
  • Ventricular Tachycardia
  • Wolff-Parkinson-White Syndrome

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