Instructions Amidaron tablets 0.2 g blister No. 30
Composition
active ingredient: 1 tablet contains amiodarone hydrochloride 200 mg;
Excipients: lactose monohydrate; microcrystalline cellulose; corn starch; croscarmellose sodium; povidone; magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: round tablets with a flat surface with beveled edges and a score, white or almost white in color.
Pharmacotherapeutic group
Class III antiarrhythmic drugs. ATX code C01B D01.
Pharmacological properties
Pharmacodynamics.
Antiarrhythmic properties.
The prolongation of the III phase of the action potential of cardiomyocytes is mainly due to a decrease in the current of potassium ions (class III according to the Vaughan-Williams classification).
The slowing of the heart rate occurs due to inhibition of sinus node automaticity. This effect is not blocked by atropine.
Non-competitive alpha- and beta-adrenergic action.
Slowing of sinoatrial, atrial, and nodal impulse conduction in the myocardium, which is more pronounced the faster the rhythm.
No changes in intraventricular conduction.
Increased refractory period and decreased myocardial excitability at the atrial, nodal, and ventricular levels.
Slowing of conduction and prolongation of refractory periods in accessory atrioventricular conduction pathways.
Other properties.
Reduced oxygen consumption due to a moderate decrease in peripheral vascular resistance and a decrease in heart rate.
Increased coronary blood flow due to a direct effect on the smooth muscles of myocardial vessels; maintenance of cardiac output against the background of reduced blood pressure and peripheral vascular resistance, as well as in the absence of negative inotropic effects.
Pharmacokinetics.
Amiodarone is a compound characterized by slow transport and high tissue affinity.
Its oral bioavailability, depending on the individual characteristics of the patient, can range from 30% to 80% (on average 50%). After a single dose of the drug, maximum plasma concentrations are reached within 3-7 hours. Therapeutic activity is manifested on average within 1 week of drug use (from several days to 2 weeks).
The half-life of amiodarone is long and has considerable interindividual variability (20 to 100 days). During the first days of treatment, the drug accumulates in most body tissues, especially in adipose tissue. Elimination begins after a few days, and the drug intake/excretion ratio reaches equilibrium within one or more months, depending on the patient.
Such characteristics justify the use of a loading dose to quickly achieve the level of drug uptake by tissues necessary for the manifestation of its therapeutic activity.
Some iodine is released and excreted in the urine as iodide; with a daily dose of 200 mg amiodarone, iodine excretion is 6 mg/24 hours. The remaining compound, and therefore most of the iodine, is excreted in the feces after metabolism in the liver.
Since only a small amount of the drug is eliminated in the urine, normal doses can be used in patients with renal insufficiency.
After discontinuation of the drug, its elimination continues for several months. It should be noted that residual activity of the drug may be detected for a period of time from 10 days to 1 month.
Indication
Prevention of relapses:
− ventricular tachycardia, which poses a threat to the patient's life: treatment must be initiated in a hospital setting with constant monitoring of the patient's condition;
− symptomatic ventricular tachycardia (documented) leading to incapacity;
− supraventricular tachycardia (documented) requiring treatment, and in cases where other medications are ineffective or contraindicated;
− ventricular fibrillation.
Treatment of supraventricular tachycardia: slowing or reducing atrial fibrillation or flutter.
Ischemic heart disease and/or left ventricular dysfunction.
Contraindication
Sinus bradycardia, sinoatrial heart block in the absence of an endocardial pacemaker (artificial pacemaker).
Sick sinus syndrome in the absence of an endocardial pacemaker (risk of sinus node arrest).
High-grade atrioventricular conduction disorders in the absence of an endocardial pacemaker. Thyroid dysfunction.
Known hypersensitivity to iodine, amiodarone or one of the excipients.
Combination with drugs capable of causing paroxysmal ventricular tachycardia of the torsades de pointes type:
− class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide);
− other medicines such as arsenic compounds, bepridil, cisapride, diphemanil, dolasetron (intravenously), erythromycin (intravenously), mizolastine, vincamine (intravenously), moxifloxacin, spiramycin (intravenously), toremifene, some neuroleptics.
Interaction with other medicinal products and other types of interactions
Antiarrhythmic drugs. Many antiarrhythmic drugs inhibit cardiac automaticity, conduction, and myocardial contractility.
The simultaneous use of antiarrhythmic drugs belonging to different classes may provide a beneficial therapeutic effect, but treatment with such a combination is often a very delicate process that requires careful clinical and ECG monitoring. The simultaneous use of antiarrhythmic drugs that can induce the occurrence of torsades de pointes (such as disopyramide, quinidine compounds, sotalol) is contraindicated.
The simultaneous use of antiarrhythmic drugs of the same class is not recommended, except in exceptional cases, as such treatment increases the risk of cardiac side effects.
Concomitant use with drugs that have a negative inotropic effect, contribute to slowing the heart rate and/or slow atrioventricular conduction, therefore requires careful clinical and ECG monitoring.
Medicinal products that may induce torsades de pointes. This arrhythmia may be induced by certain medicinal products, whether or not they are antiarrhythmic medicinal products. Predisposing factors include hypokalaemia (see section “Potassium-lowering medicinal products”), bradycardia (see section “Medicines that slow the heart rate”) or congenital or acquired prolongation of the QT interval.
Drugs that may induce torsades de pointes include class Ia and III antiarrhythmics and some neuroleptics. For erythromycin, spiramycin and vincamicin, this interaction is only possible with intravenous formulations.
The simultaneous use of two drugs, each of which is a torsades de pointes-inducing agent, is usually contraindicated.
However, methadone and some subgroups of drugs are exceptions to this rule, namely:
− antiparasitic drugs (halofantrine, lumefantrine, pentamidine) are not recommended for use together with other drugs that contribute to the occurrence of torsades de pointes;
− neuroleptics that can induce torsades de pointes are also not recommended for use with other agents that contribute to the occurrence of torsades de pointes, but such a combination is not contraindicated.
Drugs that slow the heart rate. Many drugs can cause bradycardia. This includes class Ia antiarrhythmic drugs, beta-blockers, some class III antiarrhythmic drugs, some calcium channel blockers, digitalis drugs, pilocarpine, and anticholinesterase drugs.
Contraindicated combinations (see section "Contraindications"). Medicinal products that may induce torsades de pointes (except antiparasitic drugs, neuroleptics and methadone; see section "Non-recommended combinations").
Increased risk of developing ventricular arrhythmias, especially torsades de pointes.
Not recommended combinations.
Cyclosporine: Increased serum concentrations of cyclosporine due to impaired hepatic metabolism, with the risk of nephrotoxic effects.
Quantitative determination of serum cyclosporine concentrations, monitoring of renal function, and adjustment of cyclosporine dose are necessary during amiodarone treatment.
Fluoroquinolones: Fluoroquinolones should be avoided during treatment with amiodarone.
Diltiazem for injection. Risk of bradycardia and atrioventricular block.
If the use of this combination cannot be avoided, close clinical supervision and continuous ECG monitoring are essential.
Verapamil for injection. Risk of bradycardia and atrioventricular block.
If the use of this combination cannot be avoided, close clinical supervision and continuous ECG monitoring are essential.
Antiparasitic drugs that can induce torsades de pointes (halofantrine, lumefantrine, pentamidine). Increased risk of ventricular arrhythmias, especially torsades de pointes. If possible, one of the concomitant drugs should be discontinued. If the combination cannot be avoided, it is extremely important to perform a preliminary assessment of the QT interval and perform ECG monitoring.
Neuroleptics that can induce torsades de pointes (amisulpride, chlorpromazine, cyamemazine, droperidol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperon, pipotiazine, sertindole, sulpiride, sultopride, tiapride, zuclopenthixol). Increased risk of ventricular arrhythmias, especially torsades de pointes.
Methadone: Increased risk of ventricular arrhythmias, especially torsades de pointes.
Oral anticoagulants. Increased anticoagulant effect and increased risk of bleeding. More frequent monitoring of international normalized ratio (INR) is necessary. Dosage adjustment of oral anticoagulant may be necessary during amiodarone treatment and for 8 days after discontinuation of the drug.
Beta-blockers, except sotalol (contraindicated combination) and esmolol (combination requiring precautions for use). Disturbances of automaticity and conduction (suppression of compensatory sympathetic mechanisms). ECG and clinical monitoring are necessary.
Beta-blockers used for heart failure (bisoprolol, carvedilol, metoprolol, nebivolol). Disturbances in myocardial automatism and conduction with the risk of excessive slowing of the heart rate. Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and regular ECG monitoring is necessary.
Dabigatran: Increased plasma concentrations of dabigatran with increased risk of haemorrhagic events. Clinical monitoring and dose adjustment of dabigatran are required if necessary, but not higher than 150 mg/day.
Since amiodarone has a long half-life, interactions may occur for several months after discontinuation of amiodarone treatment.
P-glycoprotein substrates: Amiodarone is a P-glycoprotein inhibitor. Concomitant use with P-glycoprotein substrates is likely to increase their blood concentrations.
Digitalis drugs. Suppression of automatism (excessive slowing of the heart rate) and disturbances of atrioventricular conduction.
When using digoxin, an increase in digoxin levels in the blood is observed due to a decrease in digoxin clearance.
ECG and clinical monitoring, quantification of digoxin levels in the blood, and, if necessary, adjustment of the digoxin dose are necessary.
Oral diltiazem. Risk of bradycardia or atrioventricular block, especially in elderly patients. ECG and clinical monitoring required.
Some macrolides (azithromycin, clarithromycin, roxithromycin). Increased risk of ventricular arrhythmias, especially torsades de pointes.
ECG and clinical monitoring are necessary during concomitant use of these drugs.
Oral verapamil. Risk of bradycardia and atrioventricular block, especially in elderly patients. ECG and clinical monitoring required.
Esmolol. Impaired contractility, automatism and conduction (suppression of compensatory sympathetic mechanisms). ECG and clinical monitoring are required.
Potassium-depleting drugs: potassium-depleting diuretics (alone or in combination), stimulant laxatives, amphotericin B (IV), glucocorticoids (systemic), tetracosactide. Hypokalemia should be prevented (and corrected); QT interval should be closely monitored. In the event of paroxysmal ventricular tachycardia torsades de pointes, antiarrhythmic drugs should not be used (ventricular pacing should be initiated; intravenous magnesium may be administered). Increased risk of ventricular arrhythmias, especially torsades de pointes (hypokalemia is a predisposing factor). Hypokalemia should be corrected before prescribing the drug and ECG, electrolytes and clinical monitoring should be performed.
Lidocaine. Risk of increased plasma concentrations of lidocaine, with possible neurological and cardiac side effects, due to inhibition of hepatic metabolism of the drug by amiodarone. Clinical and ECG monitoring is necessary, as well as, if necessary, quantitative determination of plasma concentrations of lidocaine. If necessary, adjustment of the lidocaine dose during treatment with amiodarone and after its withdrawal.
Orlistat: Risk of decreased plasma concentrations of amiodarone and its active metabolite. Clinical monitoring and, if necessary, ECG monitoring are required.
Phenytoin (by extrapolation also fosphenytoin). Increased plasma concentrations of phenytoin with signs of overdose, especially neurological signs (inhibition of phenytoin metabolism in the liver). Clinical monitoring, quantitative determination of plasma concentrations of phenytoin, and possible dose adjustment are necessary.
Simvastatin: Increased risk of side effects (dose-dependent) such as rhabdomyolysis (inhibition of simvastatin metabolism in the liver). Given this type of interaction, the dose of simvastatin should not exceed 20 mg per day or another statin should be used.
Tacrolimus: Increased blood concentrations of tacrolimus due to inhibition of its metabolism by amiodarone. Quantitative determination of tacrolimus blood concentrations, monitoring of renal function, and adjustment of tacrolimus dose are necessary during concomitant use of amiodarone and upon its withdrawal.
Drugs that slow the heart rate. Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and ECG monitoring is necessary.
Medicinal products metabolized by cytochrome P4503A4. Concomitant use of such medicinal products with amiodarone, a CYP3A4 inhibitor, may lead to increased plasma levels of these medicinal products and increased toxicity.
− Cyclosporine: combination with amiodarone may lead to increased plasma levels of cyclosporine. Dose adjustment should be made.
− Fentanyl: combination with amiodarone may enhance the pharmacological effects of fentanyl and increase the risk of its toxicity.
− Statins: Concomitant use of amiodarone and statins metabolized by CYP3A4, such as simvastatin, atorvastatin, and lovastatin, increases the risk of muscle toxicity. When used concomitantly with amiodarone, statins not metabolized by CYP3A4 are recommended.
− Other drugs metabolized by CYP3A4: lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, colchicine.
CYP2C9 substrates: Amiodarone increases the concentrations of substances that are CYP2C9 substrates,
such as warfarin or phenytoin, due to inhibition of cytochrome P4502C9 enzymes.
Combinations that require special attention.
Pilocarpine: Risk of excessive slowing of the heart rate (additive effects of drugs that slow the heart rate).
It is recommended to avoid the use of CYP3A4 inhibitors (e.g. grapefruit juice and certain medications) during treatment with amiodarone.
Application features
Cardiac effects: Before starting the drug, an ECG should be performed and serum potassium levels should be determined.
In elderly patients, the use of the drug may increase the slowing of the heart rate.
Amiodarone induces ECG changes. These amiodarone-induced changes include prolongation of the QT interval due to prolonged repolarization, with possible appearance of a U wave. This is a sign of the therapeutic effect of the drug and not its toxicity.
The occurrence of second or third degree AV block, sinoatrial block or bifascicular block during treatment requires discontinuation of the drug. The development of first degree AV block requires increased patient monitoring.
Cases, sometimes fatal, of new arrhythmias or worsening of pre-existing and treated arrhythmias have been reported (see section 4.8).
The arrhythmogenic effect of amiodarone is weak or even lower than that observed with most antiarrhythmic drugs and usually occurs with certain drug combinations (see section "Interaction with other drugs and other types of interactions") or in the presence of electrolyte imbalance. Although amiodarone can cause QT prolongation, its ability to provoke paroxysmal ventricular tachycardia torsades de pointes is weak. ECG monitoring is recommended during treatment.
Thyroid: This medicine contains iodine, which may affect the results of some thyroid function tests (radioactive iodine binding, protein-bound iodine). However, thyroid function tests (T3, T4, TSH) may still be performed.
Amiodarone may cause thyroid dysfunction, especially in patients with a history of thyroid dysfunction. Quantitative determination of TSH is recommended for all patients before starting the drug, then regularly during treatment and for several months after drug withdrawal, as well as in case of clinical suspicion of thyroid dysfunction.
Pulmonary disorders: The appearance of dyspnea or dry cough, either isolated or associated with deterioration in general condition, should be considered as a possible sign of pulmonary toxicity of the drug, for example, the development of interstitial pneumopathy, and requires a radiological examination of the patient. The appropriateness of the use of amiodarone should be reconsidered, since interstitial pneumonitis is usually reversible with early withdrawal of amiodarone.
Liver disorders. Regular monitoring of liver function is recommended at the beginning of the drug, then periodically during treatment with amiodarone. The dose of amiodarone should be reduced or the drug should be discontinued if transaminase levels increase by more than 3 times compared to normal values. Acute liver disorders (including severe hepatocellular insufficiency or liver failure, sometimes fatal) and chronic liver disorders may develop with the use of amiodarone.
Neuromuscular disorders: Amiodarone may cause sensory, motor or mixed peripheral neuropathy and myopathy (see section 4.8).
Visual disturbances. If blurred vision or decreased visual acuity occurs, a complete ophthalmological examination, including fundoscopy, should be performed immediately. The development of optic neuropathy or neuritis caused by amiodarone requires discontinuation of the drug, since continued treatment may lead to progression of the disorders to blindness.
− beta-blockers, except sotalol (contraindicated combination) and esmolol (combination requiring precautions for use);
− verapamil and diltiazem should only be considered for the prevention of life-threatening ventricular arrhythmias.
The simultaneous use of amiodarone with the following drugs is not recommended: beta-blockers, calcium channel blockers that reduce heart rate (verapamil, diltiazem), laxatives that can cause hypokalemia.
The use of amiodarone is not recommended in combination with cyclosporine, diltiazem (for injection) and verapamil (for injection), some antiparasitic agents (halofantrine, lumefantrine and pentamidine), some neuroleptics (amisulpride, chlorpromazine, cyamemazine, droperidol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperon, pipotiazine, sertindole, sulpiride, sultopride, tiapride, zuclopenthixol) and methadone (see section "Interaction with other medicinal products and other types of interactions").
Excipient-related disorders: This medicinal product contains lactose and is therefore not recommended for use in patients with galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases).
Electrolyte disturbances, especially hypokalemia: it is important to consider situations that may be associated with hypokalemia, which may contribute to the manifestation of proarrhythmic effects of the drug.
Hypokalemia must be corrected before starting amiodarone.
The undesirable effects listed below are most often associated with excessive use of the drug; they can be avoided or minimized by careful adherence to the minimum maintenance dose.
Patients should be advised to avoid sun exposure during treatment with the drug and to use sunscreen.
The safety and efficacy of amiodarone in children have not been evaluated in controlled clinical trials.
Due to the possible increase in the defibrillation threshold and/or stimulation by implanted cardiac defibrillators or artificial pacemakers, this threshold should be checked before treatment with amiodarone and several times after starting its use, as well as each time the dose of the drug is adjusted.
Anesthesia: Before surgery, the anesthesiologist should be informed that the patient is taking amiodarone.
Long-term use of amiodarone may increase the hemodynamic risks associated with general or local anesthesia and the risk of side effects, especially bradycardia, hypotension, decreased cardiac output, and cardiac conduction disturbances. In addition, several cases of acute respiratory distress syndrome have been reported in patients receiving amiodarone in the early postoperative period. Therefore, close monitoring of such patients during mechanical ventilation is recommended.
Use during pregnancy or breastfeeding
Pregnancy: Due to its effect on the fetal thyroid gland, amiodarone is contraindicated during pregnancy unless the benefit to the mother outweighs the risk to the fetus.
Breastfeeding. Amiodarone passes into breast milk in significant quantities, so the use of the drug during breastfeeding is contraindicated.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no data on the effect of the drug on the ability to drive a car and perform work requiring increased attention. However, the possibility of developing adverse reactions from the nervous system and organs of vision should be taken into account.
Method of administration and doses
Initial treatment. The usual recommended dose of the drug is 200 mg (1 tablet) 3 times a day for 8-10 days. In some cases, higher doses (4-5 tablets per day) can be used for initial treatment, but always for a short period of time and under electrocardiographic control.
Maintenance treatment. The minimum effective dose should be used. Depending on the patient's response to the drug, the maintenance dose for adults may range from ½ tablet per day (1 tablet every 2 days) to 2 tablets per day.
Children
The safety and efficacy of amiodarone in children have not been evaluated, therefore the use of the drug in this category of patients is not recommended.
Overdose
Information on amiodarone overdose is limited.
Symptoms: There are reports of a few cases of sinus bradycardia, ventricular arrhythmias, especially torsades de pointes, and liver damage.
Treatment: Symptomatic. Given the pharmacokinetic profile of this drug, monitoring of the patient's condition, especially cardiac function, for a sufficiently long period of time is recommended. Amiodarone and its metabolites are not removed by dialysis.
Adverse reactions
On the part of the organs of vision: corneal microdeposits have occurred in almost all adults, usually within the subpupillary region, which do not require discontinuation of amiodarone. In exceptional cases, they have been associated with colored halos in bright light or with blurred vision. Corneal microdeposits are complex lipid deposits, they are always completely reversible after discontinuation of the drug.
Optic neuropathy (optic neuritis), which may progress to complete blindness, and also, according to the results of fundus examination, with swelling of the optic nerve head, which may progress to more or less severe reduction in visual acuity. The causal relationship of this adverse event to the use of amiodarone has not been established at this time. However, in the absence of other obvious causes of this adverse event, it is recommended to cancel amiodarone.
Skin and subcutaneous tissue disorders: Photosensitivity. It is recommended to avoid exposure to sunlight (and ultraviolet radiation in general) during treatment with the drug.
Skin pigmentation of a bluish or bluish-gray color, which occurs against the background of prolonged use of high daily doses of the drug and slowly disappears after discontinuation of the drug (within 10-24 months).
Erythema on the background of radiotherapy; skin rashes, usually non-specific; exfoliative dermatitis (although the causal relationship of this adverse event to the use of the drug is currently not clearly established); alopecia; urticaria.
On the part of the endocrine system: some "mismatch" in the level of thyroid hormones (increased T4 level with normal or slightly reduced T3 level), in the absence of clinical signs of thyroid dysfunction, does not require discontinuation of treatment.
Hypothyroidism causes typical symptoms: weight gain, cold intolerance, apathy, drowsiness. A significant increase in TSH levels confirms this diagnosis. Euthyroidism is usually achieved within 1-3 months after discontinuation of the drug. Drug withdrawal is not necessary: in cases where the use of amiodarone is justified, treatment with this drug can be continued in combination with thyroid hormone therapy with levothyroxine. Levothyroxine doses can be adjusted depending on TSH levels.
Hyperthyroidism is more difficult to diagnose because the symptoms are less pronounced (slight unexplained weight loss, insufficient effectiveness of antianginal and/or antiarrhythmic drugs); elderly patients have mental symptoms, even thyrotoxicosis.
A significant decrease in high-sensitivity TSH levels confirms this diagnosis. In such cases, amiodarone should be discontinued, which is usually sufficient to achieve clinical normalization within 3-4 weeks. Since severe cases of this adverse event can be fatal, appropriate therapy should be initiated immediately.
When thyrotoxicosis is the cause of the problem (either directly or through its effects on the fragile myocardial equilibrium), the variability in the efficacy of synthetic antithyroid drugs makes it necessary to recommend the use of high doses of corticosteroids (1 mg/kg) for a sufficiently long period of time (3 months). Cases of hyperthyroidism have been reported within several months of amiodarone withdrawal.
Very rare cases of SIDS (syndrome of inappropriate antidiuretic hormone secretion), especially if the drug is used concomitantly with drugs that can induce hyponatremia.
Respiratory, thoracic and mediastinal disorders: Cases of diffuse interstitial or alveolar pneumopathy and bronchiolitis obliterans with pneumonia, sometimes fatal, have been reported. The appearance of dyspnea on exertion or dry cough, either isolated or associated with deterioration in general health (increased fatigue, weight loss and a slight increase in body temperature), requires X-ray examination and, if necessary, discontinuation of the drug, since these lung diseases can lead to pulmonary fibrosis.
Early withdrawal of amiodarone, with or without corticosteroid therapy, results in gradual resolution of symptoms. Clinical signs usually resolve within 3–4 weeks; improvement in radiographic and pulmonary function is slower (over several months).
There are several known cases of pleurisy, usually associated with interstitial pneumopathy.
Bronchospasm in patients with acute respiratory failure, especially in patients with bronchial asthma. Acute respiratory distress syndrome, in some cases fatal, sometimes in the early postoperative period after surgery (possibly due to interaction with high doses of oxygen).
Nervous system: tremor or other extrapyramidal symptoms; sleep disorders, including nightmares; sensory, motor or mixed peripheral neuropathy; myopathy. Sensory, motor or mixed peripheral neuropathy and myopathy may develop after several months of treatment, but sometimes they occur after several years. These side effects are usually reversible after discontinuation of the drug. However, recovery may be incomplete, very slow and may occur only several months after discontinuation of the drug.
Cerebellar ataxia; benign intracranial hypertension; headache. In the event of isolated cases of headache, an examination should be performed to determine their possible cause.
Hepatobiliary tract: there are reports of cases of liver damage (these cases were diagnosed by elevated serum transaminase levels); usually moderate and isolated elevations of transaminase levels (1.5-3 times higher than normal), which disappeared after reducing the dose of the drug or even spontaneously; acute liver damage with elevated blood transaminase levels and/or jaundice, including liver failure, sometimes fatal, requiring drug withdrawal; chronic liver damage requiring long-term treatment. Histological changes correspond to the picture of pseudoalcoholic hepatitis or cirrhosis of the liver. Since clinical and laboratory signs are not clearly expressed (variable hepatomegaly, increased blood transaminase levels 1.5-5 times higher than normal), regular monitoring of liver function is indicated.
In the event of an increase in blood transaminase levels, even moderate, occurring after use of the drug for more than 6 months, there is a possibility of developing chronic liver damage. These clinical and biological changes usually disappear after discontinuation of the drug. Several cases of irreversible effects have been recorded.
Cardiovascular system: bradycardia (usually moderate and dose-dependent); myocardial conduction disorders (sinoatrial block, AV block of varying degrees); severe bradycardia and, in exceptional cases, sinus node failure (against the background of sinus node dysfunction, in elderly patients); emergence or worsening of existing arrhythmia, sometimes accompanied by cardiac arrest; paroxysmal ventricular tachycardia torsades de pointes; vasculitis.
Gastrointestinal: minor digestive disorders (nausea, vomiting, dysgeusia), which usually occur at the beginning of treatment with the drug and disappear after reducing its dose.
On the part of the mammary glands and reproductive system: epididymitis (the causal relationship of this side effect with the use of this medicinal product has not been clearly established at this time); impotence.
From the blood and lymphatic system: hemolytic and aplastic anemia, thrombocytopenia.
On the part of the immune system: possible cases of angioedema.
Investigations: rare cases of hyponatremia (may indicate the development of SNSAH); kidney damage with moderate increase in creatinine levels.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyiv Vitamin Plant".
Location of the manufacturer and its business address
04073, Ukraine, Kyiv, Kopylivska St., 38.
