Overdosage with flecainide is a potentially life threatening medical emergency. No specific antidote is known. There is no known way of rapidly removing flecainide from the system, but forced acid diuresis may theoretically be helpful. Neither dialysis nor haemoperfusion is helpful and injections of anticholinergics are not recommended.
Treatment may include therapy with an inotropic agent, intravenous calcium, giving circulatory assistance (e.g. balloon pumping), mechanically assisting respiration, or temporarily inserting a transvenous pacemaker if there are severe conduction disturbances or the patient's left ventricular function is otherwise compromised.
2 years
Hypersensitivity to flecainide or to any of the excipients.
Tambocor is contra-indicated in cardiac failure and in patients with a history of myocardial infarction who have either asymptomatic ventricular ectopics or asymptomatic non-sustained ventricular tachycardia.
Flecainide is contra-indicated in the presence of cardiogenic shock.
It is also contra-indicated in patients with long standing atrial fibrillation in whom there has been no attempt to convert to sinus rhythm, and in patients with haemodynamically significant valvular heart disease.
Known Brugada syndrome.
Unless pacing rescue is available, Tambocor should not be given to patients with sinus node dysfunction, atrial conduction defects, second degree or greater atrio- ventricular block, bundle branch block or distal block.
None known
Excipients:
Microcrystalline Cellulose
Methacrylic acid-methyl methacrylate (1:2) copolymer
Macrogol 400
Talc
Capsule shell:
Gelatin
Titanium Dioxide (E171)
Iron Oxide Black (E172)
Erythrosine (E127)
Printing ink contains:
Shellac (E904)
Propylene glycol (E1520)
Iron Oxide Black (E172)
Prolonged release capsule hard.
Size 1 hard gelatin capsule with light grey cap and opaque pink body with 3M 200 printed in black ink.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/l0), common (>1/100 and <1/10), uncommon (>1/1000 and <1/100), rare (> 1/10,000 and <1/1000) and very rare (<1/10,000), not known (cannot be estimated from the available data).
Blood and lymphatic system disorders:
Uncommon: red blood cell count decreased, white blood cell count decreased and platelet count decreased
Immune system disorders:
Very rare: antinuclear antibody increased with and without systemic inflammation
Psychiatric disorders:
Rare: hallucination, depression, confusional state, anxiety, amnesia, insomnia
Nervous system disorders:
Very common: dizziness, which is usually transient
Rare: paraesthesia, ataxia, hypoaesthesia, hyperhidrosis, syncope, tremor, flushing, somnolence, headache, neuropathy peripheral, seizure, dyskinesia
Eye disorders:
Very common: visual impairment, such as diplopia and vision blurred
Very rare: corneal deposits
Ear and labyrinth disorders:
Rare: tinnitus, vertigo
Cardiac disorders:
Common: Proarrhythmia (most likely in patients with structural heart disease and/or significant left ventricular impairment).
Frequency not known (cannot be estimated from the available data). Dose-related increases in PR and QRS intervals may occur (see 4.4). Altered pacing threshold (see 4.4).
Uncommon: Patients with atrial flutter can develop a 1:1 AV conduction with increased heart rate.
Frequency not known (cannot be estimated from the available data): atrioventricular block-second-degree and atrioventricular block third degree, cardiac arrest, bradycardia, cardiac failure/ cardiac failure congestive, chest pain, hypotension, myocardial infarction, palpitations, sinus pause or arrest, and tachycardia (AT or VT) or ventricular fibrillation. Demasking of a pre-existing Brugada syndrome.
Respiratory, thoracic and mediastinal disorders:
Common: dyspnoea
Rare: pneumonitis
Frequency not known (cannot be estimated from the available data): pulmonary fibrosis, interstitial lung disease
Gastrointestinal disorders:
Uncommon: nausea, vomiting, constipation, abdominal pain, decreased appetite, diarrhoea, dyspepsia, flatulence
Hepatobiliary disorders:
Rare: hepatic enzyme increased with and without jaundice
Frequency not known (cannot be estimated from the available data): hepatic dysfunction
Skin and subcutaneous tissue disorders:
Uncommon: dermatitis allergic, including rash, alopecia
Rare: serious urticaria
Very rare: photosensitivity reaction
Musculoskeletal and connective tissue disorders:
Not known: Arthralgia and Myalgia
General disorders and administration site conditions:
Common: asthenia, fatigue, pyrexia, oedema
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
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.
Tambocor is a potent sodium channel blocking agent for the treatment of the conditions listed below:
The effect on the JT interval is insignificant at therapeutic levels.
Tambocor XL capsules are indicated for:
a) AV nodal reciprocating tachycardia, arrhythmias associated with Wolff- Parkinson-White Syndrome and similar conditions with accessory pathways.
b) Paroxysmal atrial fibrillation in patients with disabling symptoms when treatment need has been established and in the absence of left ventricular dysfunction (see 4.4, Special warnings and precautions for use).
Arrhythmias of recent onset will respond more readily. Tambocor XL capsules can be used for the maintenance of normal rhythm following conversion by other means.
Tambocor XL capsules are for oral administration.
Tambocor is a Class 1 anti-arrhythmic (local anaesthetic) agent. ATC code: C01BC04.
Tambocor slows conduction through the heart, having its greatest effect on His Bundle conduction. It also acts selectively to increase anterograde and particularly retrograde accessory pathway refractoriness. Its actions may be reflected in the ECG by prolongation of the PR interval and widening of the QRS complex. The effect on the JT interval is insignificant.
Tambocor XL capsules contain polymer-coated microgranules, allowing controlled release of the active substance. Each microgranule constitutes a controlled release form of flecainide acetate, allowing prolongation of the absorption time without modifying the elimination parameters.
Absorption of flecainide acetate via the oral route is greater than 80% of the dose administered
After administration of one XL capsule, plasma flecainide concentrations gradually increase after a lag time of 2 to 3 hours to reach a peak between the 21st and 25th hour and remain at plateau levels until after the 30th hour.
Absorption of flecainide acetate from capsules is not modified by food.
Steady-state is reached after five days of treatment with minimal fluctuations, and 50% flattening of plasma concentration peaks compared to the tablet form.
Flecainide acetate is widely and rapidly distributed in the tissues. The mean volume of distribution is 8.31 l/kg. Protein binding is low (about 40%).
Flecainide acetate is essentially eliminated in the urine: 25% of the dose is eliminated after 24 hours in the unchanged form. Haemodialysis does not appear to be an effective way to eliminate flecainide acetate. Flecainide acetate is also eliminated by metabolism, especially via the cytochrome 2D6 pathway. The apparent plasma elimination half-life is about 12 to 27 hours, it is not modified with the XL capsule form.
No enzyme induction or inhibition phenomena have been observed after prolonged dosing.
July 2017
Tambocortm XL 200mg capsules
Meda Pharmaceuticals Ltd
Skyway House
Parsonage Road
Takeley
Bishop's Stortford
CM22 6PU
United Kingdom
Do not store above 25°C. Store in original package.
UPVC/PVDC/Aluminium blister packs containing 15, 30 or 60 capsules.
PL 15142/0076
Pregnancy
There is no evidence as to drug safety in human pregnancy. In New Zealand White rabbits high doses of flecainide caused some foetal abnormalities, but these effects were not seen in Dutch Belted rabbits or rats. The relevance of these findings to humans has not been established. Data have shown that flecainide crosses the placenta to the foetus in patients taking flecainide during pregnancy.
Lactation
Flecainide is excreted in human milk and appears in concentrations which reflect those in maternal blood. The risk of adverse effects to the nursing infant is very small.
Each capsule contains flecainide acetate 200mg
For excipients see 6.1
Arrhythmias of recent onset will respond more readily. Tambocor XL capsules can be used for the maintenance of normal rhythm following conversion by other means.
Tambocor XL capsules are for oral administration.
4.2 Posology and method of administrationThe controlled-release form of flecainide acetate is administered as a once-daily dose. Tambocor XL should not be used for control of arrhythmias in acute situations. Treatment should be initiated with either Intravenous or oral Tambocor IR formulations then switched to Tambocor XL.
Adults: Supraventricular arrhythmias: The recommended starting dosage is 50mg twice daily (IR formulation) and most patients will be controlled at this dose. If required the dose may be increased to a maximum of 300mg (IR formulation) daily.
Those patients controlled on 200mg (IR) daily may be switched to one 200mg XL capsule once daily. After 3-5 days it is recommended that the dosage be progressively adjusted to the lowest level which maintains control of the arrhythmia. It may be possible to reduce dosage during long-term treatment.
Children: Tambocor is not recommended in children under 12, as there is insufficient evidence of its use in this age group.
Elderly Patients: The rate of flecainide elimination from plasma may be reduced in elderly people. This should be taken into consideration when making dose adjustments.
Plasma levels: Based on PVC suppression, it appears that plasma levels of 200 - 1000ng/ml may be needed to obtain the maximum therapeutic effect. Plasma levels above 700 - 1000ng/ml are associated with increased likelihood of adverse experiences.
Renal impairment: In patients with significant renal impairment (creatinine clearance of 35ml/min/1.73 sq.m. or less) the maximum initial dosage should be 100mg IR daily. When used in such patients, frequent plasma level monitoring is strongly recommended.
It is recommended that intravenous treatment with Tambocor should be administered in hospital.
Treatment with Tambocor XL should be under direct hospital or specialist supervision for patients with:
a) AV nodal reciprocating tachycardia; arrhythmias associated with Wolff- Parkinson-White Syndrome and similar conditions with accessory pathways.
b) Paroxysmal atrial fibrillation in patients with disabling symptoms.
Treatment for patients with other indications should continue to be initiated in hospital.
4.3 ContraindicationsHypersensitivity to flecainide or to any of the excipients.
Tambocor is contra-indicated in cardiac failure and in patients with a history of myocardial infarction who have either asymptomatic ventricular ectopics or asymptomatic non-sustained ventricular tachycardia.
Flecainide is contra-indicated in the presence of cardiogenic shock.
It is also contra-indicated in patients with long standing atrial fibrillation in whom there has been no attempt to convert to sinus rhythm, and in patients with haemodynamically significant valvular heart disease.
Known Brugada syndrome.
Unless pacing rescue is available, Tambocor should not be given to patients with sinus node dysfunction, atrial conduction defects, second degree or greater atrio- ventricular block, bundle branch block or distal block.
4.4 Special warnings and precautions for useElectrolyte disturbances (e.g. hypo- and hyperkalaemia) should be corrected before using )..
Since flecainide elimination from the plasma can be markedly slower in patients with significant hepatic impairment, flecainide should not be used in such patients unless the potential benefits clearly outweigh the risks. Plasma level monitoring is strongly recommended in these circumstances.
Tambocor is known to increase endocardial pacing thresholds - i.e. to decrease endocardial pacing sensitivity. This effect is reversible and is more marked on the acute pacing threshold than on the chronic. Tambocor should thus be used with caution in all patients with permanent pacemakers or temporary pacing electrodes, and should not be administered to patients with existing poor thresholds or non- programmable pacemakers unless suitable pacing rescue is available.
Generally a doubling of either pulse width or voltage is sufficient to regain capture, but it may be difficult to obtain ventricular thresholds less than 1 Volt at initial implantation in the presence of Tambocor.
The minor negative inotropic effect of flecainide may assume importance in patients predisposed to cardiac failure. Difficulty has been experienced in defibrillating some patients. Most of the cases reported had pre-existing heart disease with cardiac enlargement, a history of myocardial infarction, arterio-sclerotic heart disease and cardiac failure.
Tambocor has been shown to increase mortality risk of post-myocardial infarction patients with asymptomatic ventricular arrhythmia.
Tambocor, like other antiarrhythmics, may cause proarrhythmic effects, i.e. it may cause the appearance of a more severe type of arrhythmia, increase the frequency of an existing arrhythmia or the severity of the symptoms (see 4.8).
Tambocor should be used with caution in patients with impaired renal function (creatinine clearance ≤ 35 ml/min/1.73 m2) and therapeutic drug monitoring is recommended.
The rate of flecainide elimination from plasma may be reduced in the elderly. This should be taken into consideration when making dose adjustments.
Tambocor is not recommended in children under 12 years of age, as there is insufficient evidence of its use in this age group. Severe bradycardia or pronounced hypotension should be corrected before using flecainide.
Tambocor should be avoided in patients structural organic heart disease or abnormal left ventricular function.
Tambocor should be used with caution in patients with acute onset of atrial fibrillation following cardiac surgery.
Tambocor prolongs the QT interval and widens the QRS complex by 12-20 %. The effect on the JT interval is insignificant.
A Brugada syndrome may be unmasked due to flecainide therapy. In the case of development of ECG changes during treatment with flecainide that may indicate Brugada syndrome, consideration to discontinue the treatment should be made.
In a large scale, placebo-controlled clinical trial in post-myocardial infarction patients with asymptomatic ventricular arrhythmia, oral flecainide was associated with a 2.2 fold higher incidence of mortality or non-fatal cardiac arrest as compared with its matching placebo. In that same study, an even higher incidence of mortality was observed in flecainide-treated patients with more than one myocardial infarction. Comparable placebo-controlled clinical trials have not been done to determine if flecainide is associated with higher risk of mortality in other patient groups.
Dairy products (milk, infant formula and possibly yoghurt) may reduce the absorption of flecainide in children and infants. Flecainide is not approved for use in children below the age of 12 years, however flecainide toxicity has been reported during treatment with flecainide in children who reduced their intake of milk, and in infants who were switched from milk formula to dextrose feedings.
Flecainide as a narrow therapeutic index drug requires caution and close monitoring when switching a patient to a different formulation.
(Interaction).
Tambocor XL 200mg capsules has no or negligible influence on the ability to drive and use machines. However, driving ability, operation of machinery and work without a secure fit may be affected by adverse reactions such as dizziness and visual disturbances (if present)
The controlled-release form of flecainide acetate is administered as a once-daily dose. Tambocor XL should not be used for control of arrhythmias in acute situations. Treatment should be initiated with either Intravenous or oral Tambocor IR formulations then switched to Tambocor XL.
Adults: Supraventricular arrhythmias: The recommended starting dosage is 50mg twice daily (IR formulation) and most patients will be controlled at this dose. If required the dose may be increased to a maximum of 300mg (IR formulation) daily.
Those patients controlled on 200mg (IR) daily may be switched to one 200mg XL capsule once daily. After 3-5 days it is recommended that the dosage be progressively adjusted to the lowest level which maintains control of the arrhythmia. It may be possible to reduce dosage during long-term treatment.
Children: Tambocor is not recommended in children under 12, as there is insufficient evidence of its use in this age group.
Elderly Patients: The rate of flecainide elimination from plasma may be reduced in elderly people. This should be taken into consideration when making dose adjustments.
Plasma levels: Based on PVC suppression, it appears that plasma levels of 200 - 1000ng/ml may be needed to obtain the maximum therapeutic effect. Plasma levels above 700 - 1000ng/ml are associated with increased likelihood of adverse experiences.
Renal impairment: In patients with significant renal impairment (creatinine clearance of 35ml/min/1.73 sq.m. or less) the maximum initial dosage should be 100mg IR daily. When used in such patients, frequent plasma level monitoring is strongly recommended.
It is recommended that intravenous treatment with Tambocor should be administered in hospital.
Treatment with Tambocor XL should be under direct hospital or specialist supervision for patients with:
a) AV nodal reciprocating tachycardia; arrhythmias associated with Wolff- Parkinson-White Syndrome and similar conditions with accessory pathways.
b) Paroxysmal atrial fibrillation in patients with disabling symptoms.
Treatment for patients with other indications should continue to be initiated in hospital.
Not applicable.
28th April 2005
Flecainide is a class I anti-arrhythmic and interactions are possible with other anti- arrhythmic drugs where additive effects may occur or where drugs interfere with the metabolism of flecainide. Flecainide should not be administered concomitantly with other class I antiarrythmics. The following known categories of drugs may interact with flecainide:
Cardiac glycosides: Flecainide can cause the plasma digoxin level to rise by about 15%, which is unlikely to be of clinical significance for patients with plasma levels in the therapeutic range. It is recommended that the digoxin plasma level in digitalised patients should be measured not less than six hours after any digoxin dose, before or after administration of flecainide.
Class II anti-arrhythmics: the possibility of additive negative inotropic effects of beta- blockers and other cardiac depressants with flecainide should be recognised.
Class III anti-arrhythmics: when flecainide is given in the presence of amiodarone, the usual flecainide dosage should be reduced by 50% and the patient monitored closely for adverse effects. Plasma level monitoring is strongly recommended in these circumstances.
Class IV anti-arrhythmics: use of flecainide with other sodium channel blockers is not recommended.
Anti-depressants: fluoxetine increases plasma flecainide concentration, increased risk of arrhythmias with tricyclics, manufacturer of reboxetine advises caution.
Life-threatening or even lethal adverse events due to interactions causing increased plasma concentrations may occur (see 4.9). Flecainide is metabolised by CYP2D6 to a large extent, and concurrent use of drugs inhibiting (e.g. antidepressants, neuroleptics, propranolol, ritonavir, some antihistamines) or inducing (e.g. phenytoin, phenobarbital, carbamazepine) this iso-enzyme can increase or decrease plasma concentrations of flecainide, respectively (see below).
An increase of plasma levels may also result from renal impairment due to a reduced clearance of flecainide
Hypokalaemia but also hyperkalaemia or other electrolyte disturbances should be corrected before administration of flecainide. Hypokalaemia may result from the concomitant use of diuretics, corticosteroids or laxatives.
Anti-epileptics: limited data in patients receiving known enzyme inducers (phenytoin, phenobarbital, carbamazepine) indicate only a 30% increase in the rate of flecainide elimination.
Anti-psychotics: clozapine - increased risk of arrhythmias.
Anti-histamines: increased risk of ventricular arrhythmias with mizolastine and terfenadine (avoid concomitant use).
Anti-malarials: quinine increases plasma concentration of flecainide.
Antivirals: plasma concentration increased by ritonavir, lopinavir and indinavir (increased risk of ventricular arrhythmias, avoid concomitant use).
Diuretics: Class effect due to hypokalaemia giving rise to cardiac toxicity.
H2 antihistamines (for the treatment of gastric ulcers): cimetidine inhibits metabolism of flecainide. In healthy subjects receiving cimetidine (1g daily) for one week, plasma flecainide levels increased by about 30% and the half-life increased by about 10%.
Anti-smoking aids: Co-administration of bupropion with drugs that are metabolized by CYP2D6 isoenzyme including flecainide, should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication. If bupropion is added to the treatment regimen of a patient already receiving flecainide, the need to decrease the dose of the original medication should be considered.
Anticoagulants:Treatment with Tambocor is compatible with use of oral anti- coagulants.
