Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Accord-UK Ltd (Trading style: Accord), Whiddon Valley, Barnstaple, Devon, EX32 8NS
Pharmacotherapeutic group: Antiarrhythmics, class 1c, Flecainide
ATC code: CO1BC04
Flecainide acetate is a Class IC antiarrhythmic agent used for the treatment of severe symptomatic life-threatening ventricular arrhythmias and supraventricular arrhythmias.
Electrophysiologically, flecainide is a local anaesthetic-type (Class IC) of antiarrhythmic compound. It is an amide type of local anaesthetic, being structurally related to procainamide and encainide in so far as these agents are also benzamide derivatives.
The characterisation of flecainide as a Class IC compound is based on a triad of features: marked depression of the fast sodium channel in the heart; slow onset and offset kinetics of inhibition of the sodium channel (reflecting slow attachment to and dissociation from sodium channels); and the differential effect of the drug on the action potential duration in ventricular muscle versus Purkinje fibres, having no effect in the former and markedly shortening it in the latter. This composite of properties leads to a marked depression in conduction velocity in fibres dependant on the fast-channel fibres for depolarisation but with a modest increase in the effective refractory period when tested in isolated cardiac tissues. These electrophysiological properties of flecainide may lead to prolongation of the PR-interval and QRS duration on the ECG. At very high concentrations flecainide exerts a weak depressant effect on the slow channel in the myocardium. This is accompanied by a negative inotropic effect.
Flecainide is almost completely absorbed after oral administration and does not undergo extensive first-pass metabolism. The bioavailability from flecainide acetate tablets has been reported to be about 90%. Protein binding of flecainide is within the range 32 to 58%.
Recovery of unchanged flecainide in urine of healthy subjects was approximately 42% of a 200mg oral dose, whilst the two major metabolites (Meta-O-Dealkylated and Dealkylated Lactam Metabolites) accounted for a further 14% each. The elimination half-life was 12 to 27 hours.
The therapeutic plasma concentration range is generally accepted as 200 to 1000ng per ml.
Flecanide is about 40% bound to plasma proteins. Flecainide passes the placenta and is excreted in breast milk.
Flecainide is extensively metabolised (subject to genetic polymorphism), the 2 major metabolites being m-O-dealkylated flecainide and m-O-dealkylated lactam of flecainide, both of which may have some activity.
It is excreted mainly in the urine, approximately 30% as unchanged drug and the remainder as metabolites. About 5% is excreted in the faeces. Excretion of flecainide is decreased in renal failure, liver diseases, heart failure, and in alkaline urine. Haemodialysis removes only about 1% of unchanged flecainide.
The elimination half-life of flecainide is about 20 hours.
One rabbit tribe showed teratogenicity and embryotoxicity under flecainide. This effect was neither present in other rabbit tribes nor in rats or mice. Prolongation of gestation was seen in rats under a dose of 50 mg/kg. No effects on fertility were observed. No human data concerning pregnancy and lactation are available.
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