Tambocor
Tambocor Medication Information:
Tambocor medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Tambocor 50 mg
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Tambocor 100 mg
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Tambocor 150 mg
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Pharmacology
Flecainide belongs to the membrane stabilizing group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the 1C class of the modified Vaughan-Williams classification. It also possesses local anesthetic properties.
In single cell preparations from canine cardiac tissue (Purkinje fibres) flecainide decreased the rate of rise (Vmax, Phase O) of the action potential without greatly affecting its duration; the duration of the effective refractory period was lengthened and a small change was observed in the slope of Phase 4 depolarization. In ventricular muscle, some lengthening of the action potential duration has been observed.
Flecainide produces a dose-related decrease in intracardiac conduction in all parts of the heart with the greatest effect on the His-Purkinje system (H-V conduction). Effects upon atrioventricular (AV) nodal conduction time and intra-atrial conduction times, although present, are less pronounced than those on ventricular conduction velocity. Significant effects on refractory periods were observed only in the ventricle. Sinus node recovery times (corrected) following pacing and spontaneous cycle lengths are somewhat increased. This latter effect may become significant in patients with sinus node dysfunction (see Warnings).
Decreases in ejection fraction, consistent with a negative inotropic effect, have been observed after single administration of 200 to 250 mg flecainide; both increases and decreases in ejection fraction have been encountered during multidose therapy in patients at usual therapeutic doses (see Warnings).
During long-term clinical studies, some patients have developed congestive heart failure (CHF) while taking flecainide (see Warnings and Adverse Effects).
Flecainide does not usually alter heart rate, although bradycardia and tachycardia have been reported. In clinical studies, systolic and diastolic blood pressures increased slightly during therapy. A few patients have required changes in antihypertensive medication.
Following oral administration, flecainide is nearly completely absorbed with bioavailability of 90 to 95%. Peak plasma levels are attained at about 3 hours in most individuals (range, 1 to 6 hours). Food and antacids do not affect absorption. Flecainide does not undergo any consequential presystemic biotransformation.
The plasma half-life averages about 20 hours (range, 12 to 27 hours) after multiple oral doses in patients with premature ventricular complexes and normal renal function; this is similar to that in patients with CHF (mean, 19 hours), but it is moderately longer than for healthy subjects (mean, 14 hours). In patients with renal impairment the plasma half-life of flecainide is often prolonged and ranges from about 14 to 190 hours. Flecainide elimination from plasma is somewhat slower in healthy elderly subjects (t½=18 hours) than in young healthy subjects.
Steady-state plasma levels are reached within 3 to 5 days; once steady state is attained, no additional drug accumulation in plasma occurs. Therapeutic plasma concentrations of flecainide range from 0.2 to 1.0 µg/mL. The plasma levels are not directly proportional to dose. Within the usual therapeutic dose range, plasma levels deviate upwards from direct proportionality (average deviation about 10 to 15% per 100 mg).
The extent of flecainide binding to plasma proteins is about 40% and is independent of plasma drug level over the range of 0.015 to 3.4 µg/mL.
In healthy subjects, about 30% of a single oral dose (range, 10 to 50%) is excreted in urine as unchanged flecainide. The 2 major metabolites are meta-O-dealkylated flecainide (active, but about one fifth as potent) and the meta-O-dealkylated lactam of flecainide (nonactive metabolite). These 2 metabolites (primarily conjugated) account for most of the remaining portion of the dose in urine. Several minor metabolites (3% of the dose or less) are also found in urine; only 5% of an oral dose is excreted in feces. In patients, free (unconjugated) plasma levels of the 2 major metabolites are very low (less than 0.05 µg/mL).
With increasing renal impairment, the extent of unchanged drug excretion in urine is reduced. Since flecainide is also extensively metabolized, there is no simple relationship between creatinine clearance and the rate of flecainide elimination from plasma (see Dosage). When urine is very alkaline (pH 8 or higher), as may occur in rare conditions (e.g., renal tubular acidosis, strict vegetarian diet), flecainide elimination from plasma is much slower.
Hemodialysis removes only about 1% of an oral dose as unchanged flecainide.
Indications
No antiarrhythmic drug has been shown to reduce the incidence of sudden death in patients with asymptomatic ventricular arrhythmias. Most antiarrhythmic drugs have the potential to cause dangerous arrhythmias; some have been shown to be associated with an increased incidence of sudden death. In light of the above, physicians should carefully consider the risks and benefits of antiarrhythmic therapy for all patients with ventricular arrhythmias.
In patients without structural heart disease and with disabling symptoms, flecainide is indicated for the prevention of: paroxysmal supraventricular tachycardias (PSVT), including AV nodal reentrant tachycardia, AV reentrant tachycardia and other supraventricular tachycardias of unspecified mechanism; paroxysmal atrial fibrillation/flutter (PAF).
Patients treated with flecainide for supraventricular arrhythmias having impaired left ventricular function (ejection fraction<40) and/or ischemic heart disease may be at increased risk for cardiac adverse reactions. Use of flecainide in chronic atrial fibrillation has not been adequately studied and is not recommended (see Warnings).
Flecainide is also indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia (sustained VT), that in the judgment of the physician, are life-threatening.
Because of the proarrhythmic effects of flecainide, its use should be reserved for patients in whom, in the opinion of the physician, the benefits of treatment outweigh the risks. The use of flecainide is not recommended in patients with less severe ventricular arrhythmias, even if the patients are symptomatic (see Warnings). Use of flecainide for treatment of sustained ventricular tachycardia should be initiated in the hospital.
Tambocor should not be used in patients with recent myocardial infarction (see Warnings).
Precautions
Drug Interactions
Flecainide has been administered to patients receiving digitalis preparations or beta-adrenergic blocking agents without adverse effects. During multiple oral doses to healthy subjects stabilized on a maintenance dose of digoxin, a 13 to 19% increase in plasma digoxin levels occurred at 6 hours postdose.
In a study involving healthy subjects receiving flecainide and propranolol concurrently, plasma flecainide levels were increased about 20% and propranolol levels were increased about 30% compared with control values. In this study, flecainide 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 on the PR interval were less than additive. In flecainide 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 has been used in a large number of patients receiving diuretics without apparent interaction.
Interactions with antiarrhythmics, see Warnings.
Limited data in patients receiving known enzyme inducers (phenytoin, phenobarbital, carbamazepine) indicate a 30% increase in the rate of flecainide elimination.
In healthy subjects receiving cimetidine (1 g daily) for 1 week, plasma flecainide levels increased by about 30% and half-life increased by about 10%.
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.
Geriatrics
Flecainide elimination from plasma is somewhat slower in this age group (see Dosage).
Occupational Hazards
Since flecainide can cause dizziness, light-headedness, faintness and visual disturbance, patients should be cautioned about engaging in activities requiring judgment and physical co-ordination (such as driving an automobile or operating dangerous machinery) when these effects occur.
Lactation
Flecainide is excreted in human milk. Because of the drug's potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Children
The safety and effectiveness in children below the age of 18 years have not been established.
Supplied
50 mg
Each white, round, unscored tablet, imprinted with 3M on one side and TR 50 on the other side, contains: flecainide acetate 50 mg. Nonmedicinal ingredients: croscarmellose sodium, hydrogenated vegetable oil, magnesium stearate, microcrystalline cellulose and starch. Tartrazine-free. Bottles of 100.
100 mg
Each white, round, scored tablet, embossed with 3M on one side and TR 100 on the other side, contains: flecainide acetate 100 mg. Nonmedicinal ingredients: croscarmellose sodium, hydrogenated vegetable oil, magnesium stearate, microcrystalline cellulose and starch. Tartrazine-free. Bottles of 100.
Store between 15 to 30°C. Protect from light.
Contraindications
In patients with: second- or third-degree AV block, unless a pacemaker is present to sustain rhythm; bifascicular or trifascicular bundle branch block unless a pacemaker is present to sustain rhythm; cardiogenic shock; and hypersensitivity to the drug.
Warnings
Pregnancy
Flecainide has been shown to have teratogenic effects (club paws, sternebrae and vertebrae abnormalities, pale hearts with contracted ventricular septum) and an embryotoxic effect (increased resorptions) in one breed of rabbit (New Zealand White) but not in another breed of rabbit (Dutch Belted) when given in doses about 4 times (but not 3 times) the usual human dose (assuming a patient weight of 50 kg). No teratogenic effects were observed in rats and mice given doses up to 50 to 80 mg/kg/day, respectively; however, delayed sternebral and vertebral ossification was observed at the high dose in rats. There is no information about the effect on human fetuses. Flecainide should not be used during pregnancy unless as a drug of last resort in life-threatening arrhythmias.
Labor and Delivery: It is not known whether the use of flecainide during labor or delivery has immediate or delayed adverse effects on the mother or fetus, affects the duration of labor or delivery, or increases the possibility of forceps delivery or other obstetrical intervention.
Adverse Effects
Gastrointestinal
dyspepsia, flatulence, gastrointestinal hemorrhage.
Nervous System
anxiety, twitching, convulsions, nystagmus, stupor, dysphonia, speech disorder, coma, amnesia, confusion, depersonalization, hallucination, paranoid reaction, euphoria, apathy.
Laboratory Abnormalities
hyperglycemia, increased nonprotein in nitrogen, increased serum alkaline phosphatase, increased serum ALT and AST. Patients with elevations of liver function tests have been asymptomatic and no cause and effect relationship with flecainide has been established.
Adverse reactions leading to discontinuation of therapy occurred in 18.5% of the patients. The two most common were noncardiac adverse reactions 9.0% and new or worsened arrhythmias 6.8%.
Special Senses
deafness, parosmia, loss of taste, taste perversion.
Skin
dermatitis, hypertrichosis, photosensitivity reaction, skin discoloration.
Body as a Whole
impotence, decreased libido, gynecomastia, malaise.
Urinary System
renal failure, hematuria.
Respiratory
bronchospasm, laryngismus.
Cardiovascular
bradycardia, ECG abnormality, hypertension, hypotension, heart disorder, myocardial infarction, peripheral ischemia, pulmonary edema.
Overdose
Symptoms
Animal studies suggest the following events might occur with overdosage: lengthening of the PR interval; increase in the QRS duration, QT interval and amplitude of the T-wave; a reduction in myocardial rate and contractility; conduction disturbances; hypotension; and death from respiratory failure or asystole.
Treatment
No specific antidote has been identified for the treatment of flecainide overdosage. Treatment of overdosage should be supportive and may include the following: removal of unabsorbed drug from the gastrointestinal tract, administration of inotropic agents or cardiac stimulants such as dopamine, dobutamine or isoproterenol; mechanically assisted respiration; circulatory assists such as intra-aortic balloon pumping; and transvenous pacing in the event of conduction block. Because of the long plasma half-life of flecainide (range from 12 to 27 hours in patients), and the possibility of markedly nonlinear elimination kinetics at very high doses, these supportive treatments may need to be continued for extended periods of time.
Hemodialysis is not an effective means of removing flecainide from the body.
Since flecainide elimination is much slower when urine is very alkaline (pH 8 or higher), acidification of urine to promote drug excretion may, theoretically, be beneficial in overdose cases with very alkaline urine. There is no evidence that acidification from normal urinary pH increases excretion.
Dosage
Plasma Level Monitoring
Therapeutic trough plasma flecainide levels were found to range between 0.2 and 1.0 µg/mL. The probability of adverse experiences, especially cardiac, may increase with higher trough plasma levels, especially when these exceed 0.7 µg/mL. Periodic monitoring of trough plasma levels may be useful in patient management. Because elimination of flecainide from plasma may be markedly slower in patients with severe chronic renal failure or severe hepatic disease, plasma level monitoring is required in these patients. Plasma level monitoring is recommended in patients with congestive heart failure, moderate renal disease, and the elderly.
Based on theoretical considerations, rather than experimental data, the following suggestion is made: when transferring patients from another antiarrhythmic drug to flecainide or from flecainide to another antiarrhythmic, allow at least 2 to 4 plasma half-lives to elapse for the drug being discontinued before starting the alternative at the usual dosage. In patients where withdrawal of a previous antiarrhythmic agent is likely to produce life-threatening arrhythmias, the physician should consider hospitalizing the patient.
If flecainide is given in the presence of amiodarone (see Warnings) the usual dose of flecainide should be reduced by 50% and the patient should be monitored closely for adverse reactions. Plasma level monitoring is strongly recommended to guide dosage with such combination therapy.
