Drug Interaction:
Antiarrhythmic agents include-
Group I - Moricizine, Qunidine, Procainamide, Disopyramide, Lidocaine, Phenytoin,
Tocainide, Mexiletine, Flecanide, , Propafenone
Group II- Propranolol, Esmolol, Acebutol
Group III- Bretylium, Amiodarone, Solatol
Group IV- Verapramil, Digoxin, Adenosine
Interacting drugs - summary
+ Flecainide-
Amiodrone +
Flecainide plasma levels increased
Cimetidine +
Flecainide bioavailability and total renal excretion decreased
Disopyramide +
Disopyramide has negative inotropic properties; do not use with
flecainide unless benefits outweigh risks
Propranolol + Flecanide
Flecainide and propranol levels were increased in healthy subjects
negative inotropic effects were additive,
Flecanide + Propranol
Efects on PR intervals less than aditive
Smoking
Compared to nonsmokers, smokers have a greater plasma clearance
of flecainide. An increased flecainide dose necessary
Urinary acidifiers / Urinary alkalinser +
Alerations in urinary excretion and plasma eilimination of flecainide
changes in urinary pH (acidic urine increases elimination
and decreases bioavailability; alkaline urine decreases eliminatin and
increases bioavailability
Verapramil +
Verapramil has negative inotropic properties, do not use with flecainide
unless benefits outweighs the risks
Flucainide + Digoxin
Digoxins absorption, peak concentration and bioavailability
increased
Indication:
Paraoxysmal atrial fibrilation/flutter (PAF) associated with disabling symptoms and paraoxysmal supraventricular tachycardia (PSVT)
Approved by FDA in 1985
Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Flecainide Acetate Antiarrhythmic March 1993
Antiarrhythmic agents include-
Group I - Moricizine, Qunidine, Procainamide, Disopyramide, Lidocaine, Phenytoin,
Tocainide, Mexiletine, Flecanide, , Propafenone
Group II- Propranolol, Esmolol, Acebutol
Group III- Bretylium, Amiodarone, Solatol
Group IV- Verapramil, Digoxin, Adenosine
Adverse Reaction:
Most frequent-
Dizziness, ( 18% ) lightheadedness, faintness, unsteadiness and near syncope,(10% )
dyspnea, ( 10.% ) headache (9% ) , nausea, ( 8% ) fatigue ( 7% ), palpitation, ( 6% )
chest pain,( 5 % ) asthenia, ( 4 % ) tremor ( 4% ) , constipation, ( 4% )
edema ( 3.5% ) , abdominal pain ( 3.3% ).
Other-
Fever, (3% ) swollen lips, tongue and mouth, arthalgia, bronchospasm, myalgia ( 2% )
Dermatoligic-
Rash, ( 3% ) urticaria, exfoliative dermatitis, pruritus, alopecia ( < 1% ),
GI-
Vomiting, diarrhea, dyspepsia, anorexia, faltulence, change in taste, dry mouth.( < 1% )
CNS-
Hypothesia, paresthesia, paresis, ataxia, flushing, increased sweating, vertigo, syncope,
somnolence,tinnitus,anxiety, insomnia, depression, malaise, ( 3% )
twitching, weakness, convulsions, neuropathy, speech disorder, stupor, amnesia, confusion,euphoria, depersonalization, morbid dreams, apathy. ( < 1% )
Cardiovascular-
New or worsensed arrthythmias , episodes of unresucescitable VT ot ventricular fibrillation
( cardiac arrest ), new or worsened CHF , second- degree ( 0.5% ) or third-degree ( 0.4% )
AV block, sinus bradycardia, sinus pause, or tachycardia, sinus arrest, ( 1% )
tachycardia ( 3% ) angina pectoris , bradycardia, hypertension , hypotension ( < 1% )
In post- MI patients with asymptomatic PVCs and non-sustained ventricular tachycardia,
flecanide therapy was associated with 5% rate of death and non-cardiac arrest compared with a 2% rate in a matched placebo group
Opthalmic-
Visual disturbances, including blurred vision, difficulty in focusing, spots before eyes ( 16% ) diplopia, ( 3% ) eye pain/irritation, photophobia, nystagmus ( < 1% )
Hematologic-
Leukopenia, thrombocytopenia, ( < 1% )
GU-
Impotence, decreased libido, polyuria, urinary retension ( < 1% )
Contra-Indications:
Preexisting second or third degree AV block, hypesens to the drug
Special precautions:
Non-life threatening ventricular arrhythmias, proarrhythmic effects, sick sinus syndrome, heart failure, cardiac conductionelectrolyte disturbance.
Warnings-
Survival- as with other antiarrhythmics, there is no evidence that flecanide favorably affects survival or the incidence of sudden death.
Non-life threatening ventricular arrhythmias- generally unacceptable in patients whose ventricular arrhthmias are not life threatening even if the patients are experiencing unpleasant but not life-threatening symptoms or signs.
Proarrhythmic effects- flecanide can cause new or worsened arrhythmias
Sick sinus syndrome- use only with extreme caution , the drug may cause sinus bradycardia , sinus pause, or sinus arrest. The refequency increases probably with higher trough plasma, especially when they exceed 1mcg/ml
Heart failure- flecanide has a negative inotropic effect andmay cause or worsen CHF particularly in patients with cardiomyopathy, preexisibg severe herat failure or low ejection fractions.
Cardiac conduction- flecainde slows cardiac conduction in most patients to produce dose-related increases in PR, QRS, and QT intervals.
Electrolyte disturbances- hypokalemia or hyperkalemia may alter the effects of class I antiarrhythmiac drugs. Correct preexisting hypokalemia or hyperkalemia before administration
Effects on pace maker thresholds- flecanide increases endocardial pacing thresholds and may suppress ventricular escape rhythms
Urinary pH- alters flecainde elimination, alkalinization (as may occur in rare conditions such as tubular acidosis or strict vegetarian diet ) decreases and acidification increases , flecanide excretion.
Hepatic funtion impairment- since flecanide elimination from plasma can be markedly slower in patients with significant hepatic impairment do not use in such patients unless the potential benefits outweigh the risks.
Elderly- patients up to age 80 andabove have been safely treated with usual doses.
Pregnancy- use during pregnancy only if potential benefits outweigh potential hazards to the fetus.
Lactation- becauseof the drugs potential for serious adverse efects in infants detremine whether to discontinue nursing or discontinue the drug taking into consideration the importance of the drug to the mother.
Children- safety asnd efficacy for use in children have not been established
Dosages/ Overdosage Etc:
Approved by FDA in 1985
Indications-
Paraoxysmal atrial fibrilation/flutter (PAF) associated with disabling symptoms and paraoxysmal supraventricular tachycardia (PSVT)
Dosage-
PSVT and PAF- recommended dosage- 50mg every 12 hours.
Doses may be increased in increments of 50mg twice daily every 4 days until efficacy is acheived.
Overdosage- Symptoms
Treatment
Animal studies suggest that the following events
1.Removal of unabsorbed drug from the GI tract(charcoal occur with overdosage- lenghtening of PR interval, instillation appears to be effective in lowering flecainide increase in the QRS duration, QT interval and plasma concentrations, even after an interval of 90 amplitude of the Twave, reduction in herat rate and minutes from ingestion of flecainide) myocardial contratility, conductiondisturbances,
2. Inotropic agents or catdiac stimulants such as dopamine hypotension, death from resiratory failure or asystole dobutamine,orisoproterenol, mechanical ventilation, circulatory assists such as aortic ballon pumping, transvenous pacing innthe event of conduction block
3. Because of the drugs long plasma half-life (12 to 27 hrs) and the possibility of nonlinear elimination kinetics at very high doses , thesesupportive treatments may need to be continued for extended periods of time.
4 Since flacainide elimination is much slower when urine is very alkaline (pH > 8) theoritically acidification of urine to promote drug excretion may be beneficial in overdose cases with very alkaine urine.
5. There is no evidence that acidification from normal urinary pH increases excretion
6. Hemodialysis is not effective
Missed dose-
1. If you miss a dose of this medicine, and remember within 6 hours of take it as soon as possible unless the dose is less than 4 hours.
2. However, if you do not remember until later, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Patient Information:
FLECAINIDE-
1. Take as prescribed
2. Serious heart disturbances can result from missing doses
3. Serious side effects can result from increasing or decreasing doses without supervision
4. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to flecanide .lidocaine, tocainamide or anesthetics. Also tell your doctor if your are allergic to any other substances such as foods, preservatives or dyes.
5. Pregnancy- no studied i pregna women. Before taking flecainamide make sure your doctor knows if you are pregnant or if you become pregnant.
6.Breast feeding- flecanide has not shown tocause problems in nursing babies
7.Children- no specific information available comparing flecainide in children with use with other age groups
8. Elderly- flecainide may be more likely to cause irregular heart beat in elderly people.
9.Other medcines- Tell your doctor if you are taking any of the following- Other medicines for heart rhythm problems - both wanted and unwanted effects on the heart may increase
10. Other medical problems- presence of other medical problems may afect the use of this medicine- Congestive heart failure or - flecainde may make this condition worse
Kidney disease or Liver disease -effects of flecainde may be increased because of slower removal from the body
11. Dosing- Follwyours nstructin and do not change the dose uless your doctor tels you to do so.
12. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double dose
13. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.
14. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.
Pharmacology/ Pharmacokinetics:
Pharmacology:
Flecainide has local anesthetic activity and belongs to the membrane stabilizing group of antiarrhythmic agent. It has electrophysiologic effects charcacterised by the IC class of antiarrhythmics
Pharmacokinetics:
Oral absorption is nearly complete. Peak plasma levels are attained at about 3 hours. Food or antacids do affect absorption. The plasma half-life averages 20 hours after multiple oral doses. Steady state levels are approached in 3 to 5 days; once at steady state no accumulation occurs during chronic therapy.
Interaction with Food:
Food do not affect absorption.
Pregnancy and lactation:
Pregnancy:
Use during pregnancy only if needed.
Lactation:
Excercise caution and decide whether to discontinue the drug or discontinue nursing depending on the importance on the drug to the mother.
Children-
Safety asnd efficacy for use in children have not been established