Chemical Properties
White or almost white, very hygroscopic, crystalline powder.
Uses
Class I antiarrhythmic.
Definition
ChEBI: An acetate salt obtained by combining flecainide with one molar equivalent of acetic acid. An antiarrhythmic agent used to prevent and treat tachyarrhythmia (abnormal fast rhythm of the heart).
Brand name
Tambocor
(3M Pharmaceuticals).
Biological Activity
Open Na + channel blocker that inhibits fast Na + current in cardiac muscle in a use and concentration-dependent manner. Orally-active class Ic antiarrhythmic agent.
Description
Flecainide acetate (54143-56-5) is an open Na+?channel blocker that inhibits fast Na+?current in cardiac muscle in a use- and concentration-dependent manner.1?Orally-active class Ic antiarrhythmic agent2,3. Inhibits hERG potassium channels at clinically relevant concentrations.4
General Description
Flecainide acetate, N-(2-piperidinylmethyl)-2,5-bis (2,2,2-trifluoroethoxy)benzamide monoacetate(Tambocor), is a class IC antiarrhythmic drug withlocal anesthetic activity; it is a chemical derivative of benzamide.The drug undergoes biotransformation, forming ameta-O-dealkylated compound, whose antiarrhythmic propertiesare half as potent as those of the parent drug, and ameta-O-dealkylated lactam of flecainide with little pharmacologicalactivity. Flecainide acetate is given orally to suppresschronic ventricular ectopy and ventricular tachycardia.It has some limitations because of CNS side effects.
Biochem/physiol Actions
Class IC antiarrhythmic agent; sodium channel blocker
Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: concentration increased by
amiodarone - halve dose of flecainide; increased
myocardial depression with other anti-arrhythmics.
Antidepressants: concentration increased by
fluoxetine; increased risk of ventricular arrhythmias
with tricyclics.
Antihistamines: increased risk of ventricular
arrhythmias with mizolastine - avoid.
Antihypertensives: increased myocardial depression
and bradycardia with beta-blockers; increased
myocardial depression and asystole with verapamil.
Antimalarials: concentration increased by quinine;
avoid with artemether/lumefantrine.
Antimuscarinics: increased risk of ventricular
arrhythmias with tolterodine.
Antipsychotics: increased risk of ventricular
arrhythmias with antipsychotics that prolong the
QT interval and phenothiazines; increased risk of
arrhythmias with clozapine.
Antivirals: concentration possibly increased by
fosamprenavir, indinavir, lopinavir, ritonavir and
saquinavir, increased risk of ventricular arrhythmias
- avoid; use telaprevir with caution.
Diuretics: increased cardiac toxicity if hypokalaemia
occurs.
Metabolism
Flecainide is extensively metabolised (subject to genetic
polymorphism), the 2 major metabolites being m-Odealkylated flecainide and m-O-dealkylated lactam of
flecainide, both of which may have some activity. Its
metabolism appears to involve the cytochrome P450
isoenzyme CYP2D6, which shows genetic polymorphism.Flecainide is excreted mainly in the urine, approximately
30% as unchanged drug and the remainder as metabolites.
About 5% is excreted in the faeces. Haemodialysis
removes only about 1% of unchanged flecainide.
storage
Desiccate at +4°C
References
1) Rouet and Ducouret (1994), Use- and concentration-dependent effects of flecainide in guinea pig right ventricular muscle; J. Cardiovasc. Pharmacol.,?24?177
2) Singh?et al. (1984),?The electrophysiology and pharmacology of verapamil, flecainide, and amiodarone: correlations with clinical effects and antiarrhythmic actions; Ann. N.Y. Acad. Sci.,?432?210
3) Banitt?et al.?(1977),?Anti-arrhythmics. 2. Synthesis and antiarrhythmic activity of N-(piperidylalkyl)trifluoroethoxybenzamides; J. Med. Chem.,?20?821
4) Melgari?et al.?(2015),?Molecular basis of hERG potassium channel blockade by the class Ic antiarrhythmic flecainide; J. Mol. Cell. Cardiol.,?86?42
