Flecainide 50 mg/100 mg/150 mg/200 mg Capsules

Treatment with FLECAINIDE CR FORRESTER should be initiated in a hospital for control of the following dysrhythmias:

• Sustained ventricular tachydysrhythmia.
• AV nodal reciprocating tachycardia: Wolff-Parkinson-White syndrome and similar conditions with accessory pathway and anterograde or retrograde conduction.
• Paroxysmal atrial fibrillation in patients with disabling symptoms.
• Dysrhythmias of recent onset will respond more readily.

FLECAINIDE CR FORRESTER is indicated in premature ventricular contractions and/or non-sustained ventricular tachycardia which are causing disabling symptoms. FLECAINIDE CR FORRESTER can be used for the maintenance of normal rhythm following conversion by other means.

Posology

Adults: FLECAINIDE CR FORRESTER is to be administered as a once daily dosage.

1. Documented supraventricular tachycardia:
   The recommended starting dosage is 100 mg per day. A dose increase should be considered only after a period of 4 to 5 days. The optimal dose is 200 mg per day; the maximum dose is 300 mg per day.
2. Documented ventricular tachycardia:
   The usual dosage is 200 mg per day. A dose increase should only be considered after a period of 4 to 5 days. The maximum dosage is 300 mg per day.
3. High risk patients:
   High risk patients include the elderly, patients with a history or symptoms suggestive of heart failure, severe renal insufficiency (creatinine less than or equal to 30 mL/min/m2). The initial dose must not exceed 100 mg per 24 hours. The dose ranges from 50 to 100 mg/24 hours depending on the patientu2019s state. The dosage of FLECAINIDE CR FORRESTER can be increased or decreased by increments of 50 mg per day, bearing in mind that a minimum of 4 to 5 days is necessary to establish new steady-state plasma levels after each dosage change. Patients should be monitored by clinical examination and by electrocardiogram.

Note: If a patient is switched from a tablet formulation of flecainide acetate to FLECAINIDE CR FORRESTER, the dose should be based on the total daily dose (e.g. 2 x 100 mg tablets to FLECAINIDE 200 CR FORRESTER).

Method of administration
Oral.

FLECAINIDE CR FORRESTER must never be used in:

• Patients who are hypersensitive to flecainide acetate or to any of the inactive ingredients of FLECAINIDE CR FORRESTER (see section 6.1)
• Myocardial infarction (old or acute).
• Heart failure, regardless of the type of dysrhythmia.
• Complete left bundle branch block, bi-fascicular block, 2nd and 3rd degree atrioventricular block, sinus node dysfunction and atrial disease, in the absence of pacing.
• Patients with long-standing atrial fibrillation and haemodynamically significant valvular heart disease.

FLECAINIDE CR FORRESTER is generally not recommended in combination with class I antidysrhythmics.

Flecainide as in FLECAINIDE CR FORRESTER was tested in a multicentre randomised double-blind trial (CAST trial) in patients with asymptomatic, non-life-threatening ventricular dysrhythmia with a history of myocardial infarction more than 6 days and less than 2 years before inclusion. The incidence of mortality and nonfatal cardiac arrests was higher with flecainide than in the placebo control group. No controlled trial has demonstrated a beneficial effect of flecainide as in FLECAINIDE CR FORRESTER in terms of survival or sudden death.

FLECAINIDE CR FORRESTER has a narrow therapeutic index and requires caution and close monitoring when switching a patient to a different formulation.

Electrocardiographic changes: FLECAINIDE CR FORRESTER must be administered cautiously in patients with pre-existing conduction disorders. FLECAINIDE CR FORRESTER should be stopped if atrioventricular block, permanent complete branch block or sinoatrial block occur during treatment. The dosage should be decreased in the case of widening of QRS complexes by more than 25 % of baseline values. In the case of modification of the dosage of FLECAINIDE CR FORRESTER or concomitant treatment able to affect cardiac conduction, patients, especially those with pre-existing conduction disorders, should be closely monitored by electrocardiogram.

Increases in endocardial pacing: FLECAINIDE CR FORRESTER is known to increase endocardial pacing thresholds i.e. to decrease endocardial pacing sensitivity. This effect is reversible and is clearer on the acute pacing threshold than on the chronic. FLECAINIDE CR FORRESTER should therefore 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. Usually, 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 FLECAINIDE CR FORRESTER.

History of heart failure: FLECAINIDE CR FORRESTER must be prescribed under strict surveillance of cardiac function in patients with a history or symptoms suggestive of heart failure, due to its negative inotropic properties. Most of the cases reported had pre-existing heart disease with cardiac enlargement, a history of myocardial infarction, arteriosclerotic heart disease and cardiac failure. FLECAINIDE CR FORRESTER has been shown to increase mortality risk of post-myocardial infarction patients with asymptomatic ventricular dysrhythmia. FLECAINIDE CR FORRESTER should be avoided in patients with structural heart disease or abnormal left ventricular function.

Severe bradycardia or pronounced hypotension should be corrected before using FLECAINIDE CR FORRESTER. FLECAINIDE CR FORRESTER should be used with caution in patients with acute onset of atrial fibrillation following cardiac surgery. FLECAINIDE CR FORRESTER prolongs the QT interval and widens the QRS complex by 12 u2013 20 %. The effect on the JT interval is insignificant. A Brugada syndrome may be unmasked due to FLECAINIDE CR FORRESTER therapy. In the case of development of electrocardiogram changes during treatment with FLECAINIDE CR FORRESTER that may indicate Brugada syndrome, discontinuation of the treatment should be considered.

Pro-dysrhythmic effects: FLECAINIDE CR FORRESTER can induce a more severe form of dysrhythmia, increase the frequency of a pre-existing dysrhythmia or worsen the severity of symptoms (see section 4.8). Spontaneous variations of the dysrhythmia specific to the patient may be difficult to distinguish from deterioration induced by administration of the medicine. Treatment of FLECAINIDE CR FORRESTER should be stopped in the case of more numerous or polymorphous ventricular premature complexes.

Renal insufficiency, elderly: FLECAINIDE CR FORRESTER should be used with caution in patients with impaired renal function (creatinine clearance u2264 35 mL/min/1,73 m2) and therapeutic drug monitoring is recommended. In patients with renal insufficiency and/or elderly subjects, the rate of elimination of FLECAINIDE CR FORRESTER can be decreased, resulting in a risk of plasma and tissue accumulation of flecainide, which can be responsible for adverse effects. This risk justifies dosage adjustment.

Hepatic impairment: Flecainide elimination from the plasma can be slower in patients with significant hepatic impairment, therefore FLECAINIDE CR FORRESTER should be used with extreme caution in such patients. Monitoring of plasma levels is recommended.

Electrolyte disorders: Hypokalaemia, hyperkalaemia or hypomagnesaemia can potentiate the pro-dysrhythmic effects of FLECAINIDE CR FORRESTER and must therefore be corrected before the administration of FLECAINIDE CR FORRESTER.

Elderly patients: The rate of elimination from plasma may be reduced in the elderly and doses of FLECAINIDE CR FORRESTER may need to be adjusted accordingly. The occurrence of cardiac arrest and symptomatic conduction disturbances is higher in the elderly.

Paediatric population: FLECAINIDE CR FORRESTER is not recommended in children under 18 years of age, as there is insufficient evidence of its use in this age group.

Class I antidysrhythmics: FLECAINIDE CR FORRESTER should not be administered concomitantly with other class I antidysrhythmics due to the risk of cardiac side effects (e.g. automatism, conduction, prodysrhythmic effects, inotropism).

Cardiac glycosides: FLECAINIDE CR FORRESTER may cause plasma digoxin levels to rise by about 15 %. It is recommended that digoxin plasma levels in digitalised patients are measured not less than 6 hours after any digoxin dose, before or after taking FLECAINIDE CR FORRESTER.

Class II antidysrhythmics: The possibility of additive negative inotropic effects of beta-blockers and other cardiac depressants with FLECAINIDE CR FORRESTER should be recognised.

Class III antidysrhythmics: If FLECAINIDE CR FORRESTER is given in the presence of amiodarone the usual dosage of FLECAINIDE CR FORRESTER should be reduced by 50 % and the patient monitored closely for adverse effects. Plasma level monitoring is strongly recommended in these circumstances.

Class IV antidysrhythmics: The use of FLECAINIDE CR FORRESTER with other sodium channel blockers is not recommended.

Antidepressants: Fluoxetine increases plasma levels of FLECAINIDE CR FORRESTER, and there is an increased risk of dysrhythmias with tricyclics.

Inhibitors or inducers of isoenzyme CYP2D6: Life-threatening or even lethal adverse events due to interactions causing increased plasma concentrations may occur. FLECAINIDE CR FORRESTER is metabolised by CYP2D6 to a large extent, and concurrent use of medicines inhibiting (e.g. antidepressants, neuroleptics, propranolol, ritonavir, antihistamines) or inducing (e.g. phenytoin, phenobarbital, carbamazepine) this iso-enzyme can increase or decrease plasma concentrations of flecainide, respectively.

Electrolyte disturbances: Hypokalaemia but also hyperkalaemia or other electrolyte disturbances should be corrected before administration of FLECAINIDE CR FORRESTER. Hypokalaemia may result from the concomitant use of diuretics, corticosteroids or laxatives.

Antipsychotics: Clozapine increases the risk of dysrhythmias.

Antimalarials: Quinine increases the plasma concentration of FLECAINIDE CR FORRESTER.

Antihistamines: There is an increased risk of ventricular dysrhythmias with mizolastine and terfenadine, therefore concomitant use with FLECAINIDE CR FORRESTER should be avoided.

Diuretics: There is a class effect due to hypokalaemia giving rise to cardiotoxicity.

Cimetidine: Co-administration with FLECAINIDE CR FORRESTER results in an increase in plasma flecainide levels. Cimetidine inhibits metabolism of flecainide acetate. In healthy subjects receiving cimetidine (1 g daily) for one week, plasma flecainide levels increased by about 30 % and the half-life increased by about 10 %. Reduction of FLECAINIDE CR FORRESTER dosage of up to 50 % is advisable.

Antismoking aids: Co-administration of bupropion with FLECAINIDE CR FORRESTER should be used with caution and should be initiated at the lower end of the dose range of the concomitant medicine. If bupropion is added to the treatment regimen of a patient already receiving FLECAINIDE CR FORRESTER, the need to decrease the dose of FLECAINIDE CR FORRESTER should be considered.

Anticoagulants: The treatment with FLECAINIDE CR FORRESTER is compatible with the use of oral anticoagulants. An increase of plasma level may also result from renal impairment due to a reduced clearance of FLECAINIDE CR FORRESTER.

Pregnancy
Safety in pregnancy has not been established. FLECAINIDE CR FORRESTER should not be administered in the case of suspected pregnancy or during the first trimester of pregnancy.

Breastfeeding
Safety in breastfeeding has not been established.

Fertility
No data are available.

FLECAINIDE CR FORRESTER may cause dizziness, visual disturbances and light-headedness. Caution is advised before driving a vehicle or operating machinery until the effects of FLECAINIDE CR FORRESTER are known.

System Organ Class Frequency Side effects

Blood and lymphatic system disorders Less frequent Decreased red blood cell count, decreased white blood cell count, decreased platelet count

Immune system Less frequent Antinuclear antibody disorders increased, with and without systemic inflammation

Psychiatric disorders Less frequent Hallucination, depression, confusional state, anxiety, amnesia, insomnia

Nervous system disorders Frequent Less frequent Giddiness, dizziness, light-headedness (usually transient), peripheral neuropathy, paraesthesia, ataxia, hypoesthesia, hyperhidrosis, syncope, tremor, flushing, somnolence, headache, convulsions, seizure, dyskinesia

Eye disorders Frequent Less frequent Visual impairment, diplopia, blurred vision, corneal deposits

Ear and labyrinth disorders Less frequent Tinnitus, vertigo

Cardiac disorders Frequent Pro-dysrhythmic effects (most likely in patients with structural heart disease and/or significant left ventricular impairment), patients with atrial flutter can develop a 1:1 AV conduction with increased heart rate. Dose-related increases in PR and QRS intervals, altered pacing threshold, atrioventricular block - second degree and atrioventricular block - third degree, cardiac arrest, bradycardia, cardiac failure / congestive cardiac failure, chest pain, hypotension, myocardial infarction, palpitations, sinus pause or arrest, tachycardia (AT or VT) or ventricular fibrillation. Demasking of a pre-existing Brugada syndrome

Respiratory, thoracic and mediastinal disorders Frequent Less frequent Dyspnoea, interstitial lung disease or pneumonitis, pulmonary fibrosis

Gastrointestinal disorders Less frequent Nausea, vomiting, constipation, abdominal pain, decreased appetite, diarrhoea, dyspepsia, flatulence

Hepato-biliary disorders Less frequent Frequency unknown Increased hepatic enzymes, jaundice, hepatic dysfunction

Skin and subcutaneous tissue disorders Less frequent Photosensitivity, allergic dermatitis, including rash, alopecia, serious urticaria

Musculoskeletal, and connective tissue disorders Frequency unknown Arthralgia, myalgia

General disorders and administration site conditions Frequent Asthenia, fatigue, pyrexia, oedema

Reporting of suspected adverse reactions: Reporting of suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

Overdosage with FLECAINIDE CR FORRESTER is a potentially life-threatening medical emergency. Increased medicine susceptibility and plasma levels exceeding therapeutic levels may also result from medicine interaction (see section 4.5). Overdose with FLECAINIDE CR FORRESTER requires monitoring in hospital in a specialised unit. Treatment is essentially symptomatic. It is marked by electrocardiographic changes, particularly widening of the QRS complex and development of cardiogenic shock. It can be accompanied by neurosensory, neuropsychiatric and cardiac symptoms. No specific antidote is known. There is also no known method of rapidly removing FLECAINIDE CR FORRESTER 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 should be supportive and may include removal of unabsorbed medicine from the GI tract. Treatment may include therapy with an inotropic medicine, 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. Assuming a plasma half-life of approximately 20 h, these supportive treatments may need to be continued for an extended period of time.