Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Accord-UK Ltd (Trading style: Accord), Whiddon Valley, Barnstaple, Devon, EX32 8NS
Initiation of flecainide therapy and dose changes should be made in hospital under ECG and plasma level monitoring.
Treatment with oral flecainide should be under direct hospital or specialist supervision for patients with:
Flecainide has been shown to increase mortality risk of post-myocardial infarction patients with asymptomatic ventricular arrhythmia. An acceleration of the ventricular rate of atrial fibrillation in case of therapy failure has been reported.
Flecainide has a selective effect that increases the refractory period of the anterograde, and especially, the retrograde pathways.
Flecainide, 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 section 4.8).
Flecainide should be avoided in patients with structural heart disease or abnormal left ventricular function (see section 4.8).
Flecainide 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.
Flecainide prolongs the QT interval and widens the QRS complex by 12-20%. The effect on the JT interval is insignificant. Nevertheless, there have been reports of prolongation of the JT interval of up to 4%. This action is less marked than that observed with the class 1a antiarrhythmic drugs however.
Flecainide should be used with caution in patients with sick sinus syndrome.
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.
Severe bradycardia or pronounced hypotension should be corrected before using flecainide.
Flecainide 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. Flecainide 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 flecainide.
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.
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 outweigh the risks. Plasma level monitoring is recommended.
Flecainide 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.
Electrolyte disturbances (e.g. hypo- and hyperkalaemia) should be corrected before using flecainide (see section 4.5 for some drugs causing electrolyte disturbances). Hypokalaemia may occur in patients who use diuretics, corticosteroids or laxatives.
The rate of flecainide elimination from plasma may be reduced in the elderly. This should be taken into consideration when making dose adjustments.
Flecainide is not recommended in children under 12 years of age, as there is insufficient evidence of its use in this age group.
For further warnings and precautions please refer to section 4.5.
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 antiarrhythmic. The following known categories of drugs may interact with flecainide.
Cardiac glycosides: Use of flecainide with other sodium channel blockers is not recommended. 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 I antiarrhythmics: Flecainide should not be administered concomitantly with other class I antiarrythmics.
Class II antiarrhythmics: The possibility of additive negative inotropic effects of Class II antiarrhythmics, i.e. beta-blockers, cardiac depressants such as verapamil, with flecainide should be recognised.
Class III antiarrhythmics: If 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 antiarrhythmics: The use of flecainide with calcium channel blockers, e.g. verapamil, is not recommended.
Life-threatening or even lethal adverse events due to interactions causing increased plasma concentrations may occur (see 4.9). Flecainide is metabolized 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. Drugs that induce Cytochrome P450 can reduce the plasma level of flecainide.
An increase of plasma levels may also result from renal impairment due to a reduced clearance of flecainide (see 4.4).
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.
Antihistamines: Increased risk of ventricular arrhythmias with mizolastine, astemizole and terfenadine (avoid concomitant use).
Antivirals: Plasma concentrations are increased by ritonavir, lopinavir and indinavir (increased risk of ventricular arrhythmias) (avoid concomitant use).
Antidepressants: Fluoxetine, Paroxetine and other antidepressants increases plasma flecainide concentration; increased risk of arrhythmias with tricyclics.
Antiepileptics: Limited data in patients receiving known enzyme inducers (phenytoin, phenobarbital, carbamazepine) indicate only a 30% increase in the rate of flecainide elimination.
Antipsychotics: Clozapine – increased risk of arrhythmias.
Antimalarials: Quinine and halofantrine increases plasma concentrations of flecainide.
Antifungals: Terbinafine may increase plasma concentrations of flecainide resulting from its inhibition of CYP2D6 activity.
Diuretics: Class effect due to hypokalaemia giving rise to cardiotoxicity.
H2 antihistamines (for the treatment of gastric ulcers): The H2 antagonist cimetidine inhibits metabolism of flecainide. In healthy subjects receiving cimetidine (1 g daily) for 1 week, the AUC of flecainide increased by about 30% and the half-life increased by about 10%.
Antismoking aids: Co-administration of bupropion (metabolised by CYP2D6) with 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: The treatment with flecainide is compatible with the use of oral anticoagulants
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 (see 5.3). 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. Flecainide should only be used in pregnancy if the benefit outweighs the risks.
Flecainide is excreted in human milk. Plasma concentrations obtained in a nursing infant are 5-10 times lower than therapeutic drug concentrations (see 5.2). Although the risk of adverse effects to the nursing infant is very small, flecainide should only be used during lactation if the benefit outweighs the risks.
Flecainide 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.
Very common: ≥1/10
Common: ≥1/100, <1/10
Uncommon: ≥1/1,000, ≤1/100
Rare: ≥1/10,000, ≤1/1000
Very rare: ≤1/10,000
Not known: Cannot be estimated from the available data
Uncommon: reductions in red and white blood cells and platelets, these changes are usually mild.
Rare: cases of increases in anti-nuclear antibodies, with and without systemic inflammatory involvement.
Common: depression, anxiety, insomnia.
Uncommon: hallucinations, confusion, amnesia.
Rare: nervousness.
Very common: dizziness, and light headedness which are usually transient. Giddiness, headache.
Common: paraesthesia, ataxia, dyskinesia, hypaesthesia, hyperhidrosis, syncope, tremor, vertigo, flushing, somnolence, tinnitus, increased sweating.
Uncommon: peripheral neuropathy, convulsions.
Very common: visual disturbances, such as double vision and blurring of vision these are usually transient and disappear upon continuing or reducing the dosage.
Very rare: corneal deposits.
Rare: tinnitus, vertigo.
Common: pro-arrhythmic effects are most likely in patients with structural heart disease and/or significant left ventricular impairment. These pro-arrhythmic effects include the increase of the frequency of premature ventricular contractions to more severe forms of ventricular tachycardia.
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): specific ECG changes (prolongation of PQ, QT, PR or QRS interval, increase in number or severity of arrhythmia), altered pacing threshold, incidences of bradycardia, sinus arrest or inducement or worsening of heart failure. In patients with atrial flutter the use of flecainide has been associated with 1:1 AV conduction following initial atrial slowing with resultant ventricular acceleration.
Frequency not known (cannot be estimated from the available data): AV block (II and III grades), bundle branch block or SA block, cardiac arrest, bradycardia, cardiac failure/ cardiac failure congestive, chest pain, hypotension, myocardial infarction, palpitations, sinus arrest, and tachycardia (AT or VT) has been reported. In these cases the therapy with flecainide should be discontinued. Demasking of a pre-existing Brugada syndrome.
Common: dyspnoea.
Uncommon: interstitial pneumonitis.
Rare: pneumonitis.
Frequency not known (cannot be estimated from the available data): pulmonary fibrosis, interstitial lung disease.
Common: nausea, vomiting, diarrhoea, constipation, abdominal pain.
Uncommon: dysgeusia, dry mouth, decreased appetite, dyspepsia, flatulence.
Rare: elevated liver enzymes with or without jaundice.
Frequency not known (cannot be estimated from the available data): hepatic dysfunction.
Uncommon: dermatitis allergic, including rash, alopecia.
Rare: serious urticaria.
Not known: photosensitivity, flushing, allergic skin reactions.
Very rare: arthralgia and myalgia.
Very rare: impotence.
Common: asthenia, fatigue, pyrexia, oedema.
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; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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