Flecainid HEXAL

Tambocor tablets 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 special precautions for use). Arrhythmias of recent onset will respond more readily.

c) Symptomatic sustained ventricular tachycardia.

d) Premature ventricular contractions and/or non-sustained ventricular tachycardia which are causing disabling symptoms, where these are resistant to other therapy or when other treatment has not been tolerated.

Tambocor tablets can be used for the maintenance of normal rhythm following conversion by other means.

Tambocor tablets are for oral administration.

Adults: Supraventricular arrhythmias: The recommended starting dosage is 50mg twice daily and most patients will be controlled at this dose. If required the dose may be increased to a maximum of 300mg daily.

Ventricular arrhythmias: The recommended starting dosage is 100mg twice daily.

The maximum daily dose is 400mg and this is normally reserved for patients of large build or where rapid control of the arrhythmia is required.

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 200-1000 ng/ml may be needed to obtain the maximum therapeutic effect. Plasma levels above 700-1000 ng/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 daily (or 50mg twice daily).

When used in such patients, frequent plasma level monitoring is strongly recommended.

It is recommended that intravenous treatment with Tambocor should be initiated in hospital. Treatment with oral Tambocor 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.

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.

Tambocor 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 atrioventricular block, bundle branch block or distal block. Tambocor is contra-indicated in case of hypertensitivity to the active substance or any of excipients.

Treatment with oral flecainide should be under direct hospital or specialist supervision for patients with:

- AV nodal reciprocating tachycardia; arrhythmias associated with WPW Syndrome and similar conditions with accessory pathways.

- Paroxysmal atrial fibrillation in patients with disabling symptoms.

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 - ie 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 nonprogrammable 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, athero-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 with 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.

Treatment for patients with other indications should continue to be initiated in hospital.

Intravenous treatment with Tambocor should be initiated in hospital.

Continuous ECG monitoring is recommended in all patients receiving bolus injection

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.

Tambocor 100 mg tablets have 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)

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.

Overdosage with flecainide is a potentially life-threatening medical emergency. Increased drug susceptibility and plasma levels exceeding therapeutic levels may also result from drug interaction (see 4.5). No specific antidote is known. There is no known way to rapidly remove flecainide from the system. Neither dialysis nor haemoperfusion is effective.

Treatment should be supportive and may include removal of unabsorbed drug from the GI tract. Further measures may include inotropic agents or cardiac stimulants such as dopamine, dobutamine or isoproterenol as well as mechanical ventilation and circulatory assistance (e.g. ballon pumping). Temporarily inserting a transvenous pacemaker in the event of conduction block should be considered. Assuming a plasma half-life of approximately 20 h, these supportive treatments may need to be continued for an extended period of time. Forced diuresis with acidification of the urine theoretically promotes drug excretion.

Pharmacotherapeutic group: 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.

Oral administration of flecainide results in extensive absorption, with bioavailability approaching 90 to 95%. Flecainide does not appear to undergo significant hepatic first-pass metabolism. In patients, 200 to 500 mg flecainide daily produced plasma concentrations within the therapeutic range of 200-1000 μg/L. 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.

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.

Not applicable.

Not applicable