Instructions for use Flecainide Sandoz tablets 50 mg blister No. 30
Composition
active ingredient: flecainide acetate;
1 tablet contains flecainide acetate 50 mg or 100 mg;
Excipients: pregelatinized corn starch, microcrystalline cellulose, corn starch, croscarmellose sodium, magnesium stearate.
Dosage form
50 mg tablets: white, round, biconvex tablets, uncoated, embossed with “C” on one side and the identifying letters “FI” on the other side.
Pharmacotherapeutic group
Class IC antiarrhythmics. Flecainide. ATC code C01B C04.
Pharmacological properties
Pharmacodynamics
Flecainide acetate is a class IA antiarrhythmic indicated for the treatment of life-threatening symptomatic ventricular arrhythmias and high-severity supraventricular arrhythmias.
Flecainide is an antiarrhythmic local anesthetic (class IC) with electrophysiological properties. It is an amide-type local anesthetic, structurally similar to procainamide and encainide, as these substances are also benzamide derivatives.
Flecainide, as a class IS compound, has three main properties: pronounced inhibition of fast sodium channels of the heart; slow onset of action and shifted kinetic characteristics of sodium channel inhibition (which is a consequence of slow binding and dissociation from sodium channels); differentiated effect of the drug on the duration of change of the bioelectric potential of ventricular muscles and Purkinje fibers, namely: no effect on the former and a significant reduction in the duration of change for the latter. This combination of properties provides a significant decrease in the conductivity of fibers, the depolarization of which depends on fast sodium channels, with a moderate increase in the effective refractory period, as evidenced by the results of studies using isolated heart tissues. The indicated electrophysiological properties of flecainide acetate are due to the possibility of prolonging the PR interval and the QRS complex on the ECG. At very high concentrations, flecainide causes weak inhibition of slow channels of the myocardium. This effect is associated with a negative inotropic effect.
Pharmacokinetics
Flecainide SANDOZ® is almost completely absorbed after oral administration and does not undergo active first-pass metabolism. According to available information, the bioavailability of flecainide in the acetate form is approximately 90%. The therapeutic plasma concentration range is generally considered to be 200 to 1000 ng/ml. With intravenous administration, the average time to maximum serum concentration is 0.67 hours, and the average bioavailability is 98%, compared with 1 hour and 78%, respectively, when the drug is administered as a solution for oral administration and 4 hours and 81%, respectively, when administered as tablets. Approximately 40% of flecainide binds to plasma proteins.
Flecainide SANDOZ® crosses the placenta and is excreted in breast milk.
Flecainide SANDOZ® undergoes active metabolic transformation (dependent on genetic polymorphism), the two main metabolites are meta-O-dealkylated flecainide and meta-O-dealkylated flecainide lactam, both metabolites are relatively active. Metabolic transformation occurs with the participation of an isoenzyme of the cytochrome P450 system, namely the isoenzyme CYP2D6, and is associated with genetic polymorphism.
Flecainide SANDOZ® is excreted mainly in the urine, approximately 30% of the dose is excreted unchanged, the rest in the form of metabolites. Approximately 5% is excreted in the feces. The level of flecainide excretion is reduced in renal failure, liver disease, heart failure and alkaline urine. During hemodialysis, only 1% of flecainide is excreted unchanged. The half-life of flecainide is approximately 20 hours.
Indication
AV nodal sustained tachycardia; arrhythmias associated with Wolff-Parkinson-White syndrome and similar disorders caused by the presence of additional conduction pathways - in case of ineffectiveness of other types of treatment; symptomatic paroxysmal ventricular arrhythmia of high severity, threatening the patient's life, in the absence of response to other types of therapy. Also used in case of intolerance or impossibility of other forms of therapy$ paroxysmal atrial arrhythmia (atrial fibrillation, atrial flutter, atrial tachycardia) in patients with adverse symptoms after conversion, provided that there is an undoubted need for therapy, which is confirmed by the severity of clinical symptoms, if other types of treatment are ineffective.
Before starting use, the presence of organic heart disease and/or impaired left ventricular ejection fraction should be excluded, as this increases the risk of unwanted exacerbation of arrhythmia.
Contraindication
Hypersensitivity reaction to flecainide or any of the excipients of the drug; heart failure, history of myocardial infarction, with asymptomatic ventricular ectopy or asymptomatic unstable ventricular tachycardia; cardiogenic shock; long-term atrial fibrillation, in the therapy of which sinus rhythm conversion was not attempted, as well as valvular heart disease with significant hemodynamic abnormalities; reduced or impaired ventricular function, in the presence of cardiogenic shock, severe bradycardia (less than 50 beats per minute), severe hypotension; use in combination with class I antiarrhythmic drugs (sodium channel blockers); Brugada syndrome; If pacing is not possible, flecainide should not be used in the treatment of patients with impaired sinus node function, impaired atrial conduction, second-degree or higher atrioventricular block, bundle branch block or distal block; asymptomatic ventricular arrhythmia or mild symptoms of ventricular arrhythmia.
Interaction with other medicinal products and other types of interactions
Class I antiarrhythmics. Flecainide Sandoz should not be used concomitantly with class I antiarrhythmics.
Class II antiarrhythmics: The possibility of an increase in the undesirable inotropic effects of class II antiarrhythmics, such as beta-blockers, should be considered when used concomitantly with flecainide.
Class III antiarrhythmics. When flecainide is used concomitantly with amiodarone, the usual dose of flecainide should be halved and the patient should be closely monitored for adverse events. Plasma concentrations should also be monitored.
Class IV antiarrhythmics: Concomitant use of flecainide with calcium channel blockers, such as verapamil, should be undertaken with caution.
Possible life-threatening adverse events associated with drug interactions that cause an increase in the concentration of the substance in the blood plasma. The metabolic transformation of flecainide is provided, for the most part, by CYP2D6 isoenzymes, and with simultaneous use with drugs that inhibit (e.g., antidepressants, neuroleptics, propranolol, ritonavir, some antihistamines) or increase the activity (e.g., phenytoin, phenobarbital, carbamazepine) of this isoenzyme, an increase or decrease in the concentration of flecainide in the blood plasma is observed, respectively.
An increase in the concentration of flecainide in blood plasma may also be due to impaired renal function, due to a decrease in flecainide clearance.
Hypokalemia, as well as hyperkalemia, or other electrolyte disturbances should be corrected before initiating flecainide. Hypokalemia may result from concomitant use of diuretics, corticosteroids, or laxatives.
Antihistamines: The risk of ventricular arrhythmia is increased when administered with mizolastine and terfenadine. Concomitant use should be avoided.
Antiviral agents: Plasma concentrations of the substance increase with concomitant use with ritonavir, lopinavir and indinavir (increased risk of ventricular arrhythmia) (simultaneous use should be avoided).
Antidepressants: Fluoxetine, paroxetine and other antidepressants increase plasma concentrations of flecainide; concomitant use with tricyclic antidepressants increases the risk of ventricular arrhythmia.
Antiepileptics: Limited data obtained when patients took the drug together with enzyme activators (phenytoin, phenobarbital, carbamazepine) indicate a 30% increase in the rate of excretion of flecainide.
Neuroleptics. Clozapine – increased risk of arrhythmia.
Antimalarials: Quinine increases plasma concentrations of flecainide.
Antifungal agents: Terbinafine may increase plasma concentrations of flecainide due to inhibition of CYP2D6 isoenzyme activity.
Diuretics: class effect of drugs, hypokalemia, resulting in increased cardiotoxic effects.
H2 antihistamines (for the treatment of stomach ulcers). The H2 receptor antagonist, cimetidine, inhibits the metabolic transformation of flecainide. In healthy volunteers treated with cimetidine (1 g daily) for 1 week, the AUC of flecainide increased by approximately 30% and the half-life increased by approximately 10%.
Cardiac glycosides. When using flecainide, an increase in plasma digoxin levels by 15% is possible, which is unlikely to be of clinical significance if the plasma concentration of patients is within the therapeutic range. It is recommended that the plasma digoxin level be determined in patients receiving digitalis drugs at least 6 hours after receiving digoxin, regardless of the dose, before or after taking flecainide.
Anticoagulants: Flecainide can be used concomitantly with oral anticoagulants.
Application features
Flecainide SANDOZ® for oral use should be prescribed only in a hospital setting or under the direct supervision of a specialist for the treatment of patients with:
AV nodal sustained tachycardia, arrhythmia associated with Wolff-Parkinson-White syndrome and similar disorders associated with the presence of additional conduction pathways; paroxysmal atrial fibrillation, in the presence of adverse symptoms.
The use of the drug for other indications should be initiated in a hospital setting.
Flecainide has been shown to increase the risk of mortality in patients with asymptomatic ventricular arrhythmia after myocardial infarction.
Flecainide SANDOZ®, like other antiarrhythmic agents, may contribute to the enhancement of arrhythmia, i.e. may cause a more severe arrhythmia, an increase in the frequency of arrhythmia episodes or an increase in the intensity of undesirable symptoms.
The use of flecainide should be avoided in the treatment of patients with organic heart disease or left ventricular ejection fraction disorders.
Flecainide should be used with caution in the treatment of patients with acute development of atrial fibrillation after cardiac surgery.
Flecainide causes prolongation of the QT interval and QRS complex width by 12–20%. The effect on the QT interval is insignificant.
Brugada syndrome may occur when a patient is receiving flecainide. If ECG changes are detected that may indicate the presence of Brugada syndrome, discontinuation of flecainide therapy should be considered.
Since the elimination of flecainide from the plasma of patients with severe hepatic impairment may be significantly slower, flecainide should not be used in the treatment of such patients unless the potential benefit outweighs the potential risks. Monitoring of plasma concentrations is recommended.
Flecainide Sandoz should be used with caution in patients with impaired renal function (creatinine clearance 35 ml/min/1.73 m2 or less); therapeutic monitoring is recommended.
The rate of elimination of flecainide from the plasma of elderly patients may be reduced. This should be borne in mind when adjusting the dosage regimen.
Electrolyte imbalances (e.g. hypokalemia and hyperkalemia) should be corrected before initiating therapy with flecainide.
Severe bradycardia or significant hypotension should be corrected before initiating therapy with flecainide.
Flecainide Sandoz is known to increase the threshold of endocardial sensitivity to pacemaker signals, i.e. the sensitivity of the endocardium to pacing is reduced. This effect is reversible and affects the threshold of acute sensitivity more than chronic sensitivity. Therefore, flecainide should be used with caution in the treatment of patients with permanent or temporary pacemakers and should not be used in the treatment of patients with a high threshold of sensitivity to pacing and in the case of the use of an unprogrammed pacemaker in the absence of adequate resuscitation equipment.
Typically, doubling the frequency or amplitude of the stimulating pulse (voltage) is sufficient to normalize the heart's function, but in the initial stages after implantation, when the patient is receiving flecainide, it is very difficult to ensure a ventricular sensitivity threshold below 1 volt.
Difficulties with defibrillation have been observed. In most of these cases, patients had a history of heart disease with increased heart size, myocardial infarction, arteriosclerotic heart disease, and heart failure.
There are reports of cases of an increase in the rate of ventricular contraction in atrial fibrillation in the absence of a therapeutic effect. Flecainide Sandoz® has a selective effect, increasing the refractory period of anterograde and, especially, retrograde conduction from the sinus node to the ventricles of the heart. This effect is manifested on the ECG of most patients as a prolongation of the corrected QT interval, so the effect on the QT interval is insignificant. However, there are reports of cases of prolongation of the QT interval by 4%. However, this effect is less pronounced than with the use of class 1a antiarrhythmic drugs.
Application in pediatric practice
Flecainide SANDOZ® is not recommended for use in children under 12 years of age due to the lack of adequate data on safety and efficacy.
Dairy products (milk, baby food, and possibly yogurt) may reduce the absorption of flecainide in children and neonates. Toxicity has been reported with flecainide administered to children with reduced milk intake and in neonates whose milk-based infant formula was replaced with a glucose-containing formula.
Ability to influence reaction speed when driving vehicles or other mechanisms
It is recommended to refrain from driving vehicles or working with other mechanisms, given the possibility of dizziness and visual disturbances.
Use during pregnancy or breastfeeding
Flecainide SANDOZ® crosses the placenta and reaches the fetus when administered during pregnancy. Therefore, it should not be used during pregnancy unless the expected benefit outweighs the potential risk.
Use during lactation
Flecainide SANDOZ® passes into breast milk. The concentration in the blood plasma of a breastfed child is 5-10 times lower than the therapeutic level. If treatment is necessary, breastfeeding should be discontinued.
Method of administration and doses
The drug is administered orally. To eliminate the effect of food on the absorption of the drug substance, Flecainide SANDOZ® should be taken on an empty stomach or one hour before a meal. The Flecainide SANDOZ® 100 mg tablet can be divided into two equal parts.
Initiation of therapy with flecainide acetate and changes in the dosage regimen should be carried out under medical supervision with ECG monitoring and control of the concentration of the substance in the blood plasma. Some patients require hospitalization at this time, in particular patients with life-threatening ventricular arrhythmia. The decision on the need for hospitalization is made by a specialist. In patients with organic heart disease, especially with a history of myocardial infarction, therapy with flecainide should be started only in cases where other antiarrhythmic drugs, with the exception of class IC drugs (especially amiodarone), are ineffective or intolerable, and provided that non-drug treatment (surgery, amputation, implantation of a defibrillator) is not indicated. During therapy, constant ECG monitoring and control of the concentration of the substance in the blood plasma are necessary.
Adults and children aged 13 and over
Supraventricular arrhythmia: The recommended starting dose is 50 mg twice daily. For most patients, this dose provides control of undesirable symptoms. If necessary, the dose may be increased to a maximum of 300 mg daily.
Ventricular arrhythmia: the recommended initial dose is 100 mg twice daily. The maximum daily dose is 400 mg, but this dose is used only in the treatment of patients with large physique or when it is necessary to quickly ensure control of the arrhythmia. After 3-5 days, it is recommended to gradually adjust the dose to the minimum sufficient level that provides control of the arrhythmia. With prolonged use of the drug, a further reduction in the dose of the drug is possible.
Use in the treatment of elderly patients
In the treatment of elderly patients, the drug is used in an initial daily dose not exceeding 100 mg (1 tablet of 50 mg twice a day), since the rate of elimination of flecainide from the blood plasma of elderly people may be reduced. This should also be taken into account when adjusting the dose. The maximum dose for elderly patients should not exceed 300 mg (150 mg twice a day).
Plasma level
According to the indicators of elimination of ventricular extrasystoles, to ensure the maximum therapeutic effect, the content of the substance in the blood plasma should be 200 - 1000 ng/ml. The concentration in the blood plasma above 700 - 1000 ng/ml is associated with an increased likelihood of adverse events.
Kidney dysfunction
In the treatment of patients with severe renal impairment (creatinine clearance 35 ml/min/1.73 m2 or less), the initial dose should not exceed 100 mg/day (or 50 mg twice daily). When using the drug in the treatment of such patients, monitoring of the concentration of the substance in the blood plasma is strongly recommended. Depending on the effect and tolerability, the dose can be gradually and carefully increased. After 6-7 days, the dosage regimen should be adjusted, taking into account the effectiveness and tolerability of therapy. In some patients with severe renal impairment, the clearance of flecainide is very slow, resulting in an increase in the half-life (60-70 hours).
Liver dysfunction
When using the drug in the treatment of patients with impaired liver function, careful monitoring is necessary, the initial dose should not exceed 100 mg/day (50 mg twice a day).
In the treatment of patients with an implanted pacemaker, the drug should be used with caution; the daily dose should not exceed 100 mg, which is divided into 2 doses.
When using the drug simultaneously with cimetidine or amiodarone, careful monitoring is necessary. In the treatment of some patients, the dose should be reduced, the daily dose should not exceed 100 mg, which is divided into 2 doses. It is necessary to monitor the condition of patients during both initial and maintenance therapy.
When using Flecainide SANDOZ® in the treatment of patients requiring dose limitation, frequent ECG monitoring should be performed (in addition to monitoring of flecainide plasma concentrations). Dose adjustments are made at intervals of 6 to 8 days. To monitor the individual dosing regimen, ECG examinations of such patients should be performed 2 and 3 weeks after the start of therapy.
Children
Flecainide SANDOZ® is not recommended for use in children under 13 years of age due to a lack of adequate data on safety and efficacy.
Overdose
Overdose with Flecainide SANDOS® is life-threatening and requires immediate medical attention. Hypersensitivity to the drug and an increase in plasma concentrations above therapeutic levels may also occur due to interactions with other drugs. There is no known specific antidote. There is no known method for rapidly removing Flecainide SANDOS® from the body. Dialysis or hemoperfusion is ineffective.
Supportive therapy is necessary, possibly removing unabsorbed material from the gastrointestinal tract. Inotropic agents or cardiac stimulants such as dopamine, dobutamine or isoproterenol may be used in the future, as well as mechanical ventilation and measures to support the circulation (e.g. pump for auxiliary circulation). The use of a temporary transvenous pacemaker should be considered in case of conduction block. Since the plasma half-life is approximately 20 hours, these supportive measures should be continued for a long time.
Forced diuresis with urine oxidation, theoretically, promotes the excretion of the substance.
Adverse reactions
Like other antiarrhythmic agents, flecainide may promote arrhythmias. Symptoms of an existing arrhythmia may be exacerbated or a new episode may develop. The risk of proarrhythmic effects is greatest in patients with organic heart disease and/or significant left ventricular dysfunction.
The most common adverse events are second- or third-degree AV block, bradycardia, heart failure, chest pain, myocardial infarction, hypotension, sinus node arrest, tachycardia (atrial and ventricular tachycardia), and palpitations.
Common adverse reactions such as dizziness and visual disturbances are observed in approximately 15% of patients receiving therapy. These adverse reactions are usually transient and disappear with continued therapy or dose reduction. The list of adverse reactions is based on experience from clinical trials and information obtained during post-marketing surveillance.
Adverse reactions are classified by system organ class and frequency. The frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), frequency unknown (cannot be estimated from the available data).
From the side of the hematopoietic and lymphatic systems
Uncommon: decreased red blood cell count, decreased white blood cell count, and decreased platelet count.
On the part of the immune system
Rare: increased antinuclear antibodies, associated or not associated with systemic inflammation.
From the psyche
Rare: hallucinations, depression, confusion, anxiety, amnesia, insomnia.
From the nervous system
Very common: dizziness, which, as usual, passes quickly.
Rare: paresthesia, ataxia, hypoesthesia, hyperhidrosis, syncope, tremor, hot flashes, drowsiness, headache, peripheral neuropathy, convulsions, dyskinesia.
From the organs of vision
Very common: visual disturbances such as diplopia and blurred vision.
Rare: corneal precipitate.
On the part of the organs of hearing and balance
Rare: tinnitus, dizziness of the vertigo type.
From the side of the cardiovascular system
Common: proarrhythmic effect (most likely in patients with organic heart disease).
Uncommon: In patients with atrial fibrillation, 1:1 AV conduction may develop with increased heart rate.
Frequency unknown: Possible dose-dependent increase in PR and QRS intervals.
Changing the sensitivity threshold to the pacemaker signal.
Second or third degree atrioventricular (AV) block, cardiac arrest, bradycardia, heart failure/congestive heart failure, chest pain, hypotension, myocardial infarction, palpitations, sinus node arrest, tachycardia (atrial and ventricular), or atrial fibrillation. Manifestation of symptoms of existing Brugada syndrome.
Respiratory system
Common: dyspnea.
Rare: pneumonitis.
Frequency unknown: pulmonary fibrosis, interstitial lung disease.
From the digestive system
Uncommon: nausea, vomiting, constipation, abdominal pain, decreased appetite, diarrhea, dyspepsia, flatulence.
Hepatobiliary system
Rare: increased liver enzymes, with or without jaundice.
Frequency unknown: hepatic dysfunction.
Skin and subcutaneous tissue disorders
Uncommon: allergic dermatitis, including rash, alopecia.
Rare: photosensitivity reaction.
Systemic and injection site disorders
Common: asthenia, fatigue, fever, edema.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
Blister containing 10 tablets, 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Salutas Pharma GmbH.
Location of the manufacturer and its business address
Otto-von-Güricke-Allee 1, 39179, Barleben, Germany
