Brands, Medical Use, Clinical Data
Drug Category
Dosage Forms
Brands / Synonyms
Flecaine; Flecainida [Inn-Spanish]; Flecainide; Flecainide acetate; Flecainidum [Inn-Latin]; Tambocor; Tambocor
Indications
For the prevention of paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia and other supraventricular tachycardias of unspecified mechanism associated with disablin.
Pharmacology
Flecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics.
Mechanism of Action
Flecainide acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers.
Absorption
Nearly complete following oral administration.
Toxicity
Oral LD50 is 50-498 mg/kg in rat. Symptoms of overdose include nausea and vomiting, convulsions, hypotension, bradycardia, syncope, extreme widening of the QRS complex, widening of the QT interval, widening of the PR interval, ventricular tachycardia, AV nodal block, asystole, bundle branch block, cardiac failure, and cardiac arrest.
Biotrnasformation / Drug Metabolism
Hepatic. Flecainide does not undergo any consequential presystemic biotransformation. The two major urinary metabolites are meta-O-dealkylated flecainide (active, but about one-fifth as potent) and the meta-O-dealkylated lactam of flecainide (non-active metabolite).
Contraindications
TAMBOCOR is contraindicated in patients with pre-existing second- or third-degree AV block, or with right bundle
branch block when associated with a left hemiblock (bifascicular block), unless a pacemaker is present to sustain the
cardiac rhythm should complete heart block occur. TAMBOCOR is also contraindicated in the presence of cardiogenic
shock or known hypersensitivity to the drug.
Drug Interactions
Drug Interactions. TAMBOCOR has been administered to patients receiving digitalis
preparations or beta-adrenergic blocking agents without adverse effects. During administration of multiple
oral doses of TAMBOCOR to healthy subjects stabilized on a maintenance dose of digoxin, a 13%-19% increase in
plasma digoxin levels occurred at six hours postdose.
In a study involving healthy subjects receiving TAMBOCOR and propranolol concurrently, plasma flecainide
levels were increased about 20% and propranolol levels were increased about 30% compared to control values. In
this formal interaction study, TAMBOCOR and propranolol were each found to have negative inotropic effects;
when the drugs were administered together, the effects were additive. The effects of concomitant administration of
TAMBOCOR and propranolol on the PR interval were less than additive. In TAMBOCOR clinical trials, patients who
were receiving beta blockers concurrently did not experience an increased incidence of side effects.
Nevertheless, the possibility of additive negative inotropic effects of beta blockers and flecainide should be
recognized.
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 human plasma proteins is either unchanged
or only slightly less. Consequently, interactions with other drugs which are highly protein bound (e.g.,
anticoagulants ) would not be expected. TAMBOCOR has been used in a large number of patients receiving
diuretics without apparent interaction. Limited data in patients receiving known enzyme inducers (
phenytoin, phenobarbital, carbamazepine ) indicate only a 30% increase in the rate of flecainide elimination.
In healthy subjects receiving cimetidine (1 gm daily) for one week, plasma flecainide levels increased by
about 30% and half-life increased by about 10%.
When amiodarone is added to flecainide therapy, plasma flecainide levels may increase two-fold or more in
some patients, if flecainide dosage is not reduced.
Drugs that inhibit cytochrome P450IID6, such as quinidine , might increase the plasma concentrations of
flecainide in patients that are on chronic flecainide therapy; especially if these patients are extensive
metabolizers.
There has been little experience with the coadministration of TAMBOCOR and either disopyramide or
verapamil. Because both of these drugs have negative inotropic properties and the effects of coadministration
with TAMBOCOR are unknown, neither disopyramide nor verapamil should be administered concurrently with
TAMBOCOR unless, in the judgment of the physician, the benefits of this combination outweigh the risks. There has
been too little experience with the coadministration of TAMBOCOR with nifedipine or diltiazem to
recommend concomitant use.
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