Instructions for Soritmik tablets 80 mg blister No. 20
Composition
active ingredient: 1 tablet contains sotalol hydrochloride 80 mg or 160 mg;
Excipients: lactose monohydrate; corn starch; microcrystalline cellulose; povidone; sodium starch glycolate (type A); magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: flat-cylindrical tablets with beveled edges and a score, white or almost white in color.
Pharmacotherapeutic group
Non-selective β-adrenergic blockers.
ATX code C07A A07.
Pharmacological properties
Pharmacodynamics.
Soritmik is a non-selective β-adrenergic blocker that acts on β1- and β2-adrenergic receptors. It has a pronounced antiarrhythmic effect, the mechanism of which is to increase the duration of the action potential and the refractory period in all parts of the cardiac conduction system (class III antiarrhythmic drugs). It reduces heart rate and myocardial contractility, reduces sinus node automatism, slows down atrioventricular conduction. By blocking β2-adrenergic receptors, it increases the tone of the smooth muscles of the bronchi and blood vessels.
Pharmacokinetics.
After oral administration, 75–90% of sotalol hydrochloride is absorbed from the digestive tract. Due to the absence of the effect of first-pass metabolism, the absolute bioavailability is 75–90%. The time to reach maximum plasma concentration is 2–3 hours. The volume of distribution is 1.6–2.4 l/kg. Sotalol does not bind to plasma proteins. 75–90% of the administered dose is excreted by the kidneys unchanged, the rest with feces. Renal clearance is 120 ml/min. The half-life is 10–20 hours. In renal failure, it is prolonged to 42 hours, which requires a reduction in the dose of the drug. The drug is removed by hemodialysis.
Indication
Severe symptomatic ventricular arrhythmias.
Symptomatic supraventricular arrhythmias of the tachycardia type requiring treatment:
– prevention of chronic atrial fibrillation after direct current cardiac pacing;
– prevention of paroxysmal atrial fibrillation.
Contraindication
Hypersensitivity to sotalol, sulfonamides or other components of the drug.
NYHA (New York Heart Association) class IV heart failure, acute and chronic heart failure of the II-III degree (in the stage of decompensation), acute myocardial infarction, atrioventricular block of the II-III degree (if the patient does not have a functioning pacemaker), ventricular tachycardia of the torsades de pointes type or taking drugs that contribute to the development of this disease, sinoatrial block, sick sinus syndrome, symptomatic sinus bradycardia (< 50 beats/min), severe sinus node dysfunction, congenital or acquired long QT syndrome or taking drugs that contribute to the prolongation of the QT interval, severe or uncontrolled chronic heart failure, including right ventricular heart failure after pulmonary hypertension, Prinzmetal's angina, cardiogenic shock, renal failure (creatinine clearance < 10 ml/min), hypokalemia, hypomagnesemia, arterial hypotension, severe peripheral circulatory disorders, bronchial asthma and chronic obstructive pulmonary disease, laryngeal edema, allergic rhinitis, metabolic acidosis, untreated pheochromocytoma, diabetes mellitus, cardiomegaly (without signs of heart failure), occlusive peripheral vascular disease (complicated by gangrene, intermittent claudication or pain at rest), Raynaud's syndrome, anesthesia with drugs that cause myocardial depression, concomitant use of monoamine oxidase A (MAO-A) inhibitors, floctafenine.
For patients treated with sotalol (except for intensive medical treatment), intravenous administration of calcium antagonists such as verapamil and diltiazem or other antiarrhythmic drugs is contraindicated.
Interaction with other medicinal products and other types of interactions
Do not use:
– with antiarrhythmic drugs of class I (disopyramide, quinidine and procainamide) and class III (amiodarone) – can potentially increase myocardial refractoriness. Amiodarone increases the risk of bradycardia and inhibition of atrioventricular (AV) conduction. In the case of using sotalol together with other β-blockers, additive effects of class II (decrease in blood pressure and heart rate) can be expected;
– with drugs that increase the QT interval (class I and class III antiarrhythmic drugs, phenothiazine derivatives, tri-tetracyclic antidepressants, terfenadine, astemizole, erythromycin, lithium preparations, quinoline antibiotics, halofantrine, pentamidine), neuroleptics, narcotic analgesics, antihistamines, sedatives, hypnotics and ethanol.
Inhalation anesthetics (hydrocarbon derivatives) and muscle relaxants increase the risk of myocardial depression and the development of arterial hypotension.
Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis.
In case of concomitant use with drugs that deplete catecholamine reserves (reserpine, guanethidine), excessive reduction in the tone of the sympathetic nervous system is possible. Patients should regularly monitor blood pressure and heart rate (HR), as hypotension, severe bradycardia, and loss of consciousness are possible.
The negative chronotropic and negative dromotropic effects of sotalol hydrochloride may be increased by concomitant use with reserpine, clonidine, α-methyldopa, guanfacine and cardiac glycosides.
In case of concomitant use with digoxin, the likelihood of proarrhythmic effects increases, the positive inotropic effect of digitalis glycosides decreases. Both digitalis glycosides and sotalol hydrochloride slow AV conduction. If, despite adequate therapy with digitalis glycosides, there is no decrease in the severity of heart failure, sotalol should be discontinued.
When used concomitantly with antihypertensive agents (diuretics, sympatholytics, clonidine, hydralazine), excessive reduction in blood pressure is possible.
Furosemide, hydrochlorothiazide and other potassium-sparing diuretics can trigger the development of arrhythmias due to hypokalemia.
When using sotalol simultaneously with amphotericin B, corticosteroids, the patient's blood potassium level should be monitored.
Iodine-containing radiopaque agents for intravenous administration increase the risk of anaphylactic reactions.
Xanthines and sympathomimetics reduce the activity of sotalol.
When used concomitantly with β2-receptor agonists such as salbutamol, terbutaline and isoprenaline, an increase in the dose of the β2-receptor agonist may be necessary.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and estrogens weaken the hypotensive effect of sotalol hydrochloride, sulfasalazine increases its concentration in blood plasma.
Calcium antagonists (verapamil and diltiazem), cardiac glycosides and antiarrhythmics increase AV conduction disturbances, increase the risk of developing or worsening AV block and heart failure. When used together with calcium channel blockers, an additive hypotensive effect on blood pressure is possible.
Concomitant use of calcium ion antagonists such as nifedipine may lead to a significant decrease in blood pressure and exacerbation of sick sinus syndrome.
Norepinephrine, MAO-B inhibitors, and abrupt withdrawal of clonidine may potentiate rebound hypertension. Sotalol should be discontinued several days before gradual withdrawal of clonidine, and the interval between treatment with MAO-B inhibitors and sotalol should be at least 14 days.
Floctafenine: β-blockers may interfere with the compensatory cardiovascular responses associated with hypotension or shock, which may be induced by floctafenine.
Sotalol prolongs the action of non-depolarizing muscle relaxants, the anticoagulant effect of coumarins, increases the concentration of lidocaine in blood plasma, enhances the effect of insulin and reduces the effect of oral hypoglycemic agents (therefore, dose adjustment of antidiabetic drugs may be necessary).
Concomitant use with insulin or oral hypoglycemic agents, especially during heavy physical exertion, may induce hypoglycemia and mask its symptoms.
Neuromuscular blockade caused by tubocurarine may be enhanced by β-adrenergic receptor blockade.
The negative inotropic effect of sotalol hydrochloride and narcotic analgesics or antiarrhythmics may be additive.
Application features
Particularly careful medical supervision is necessary in the following cases:
– renal impairment (dose reduction): monitoring of renal function is necessary, including determination of creatinine; it is also advisable to monitor the concentration of sotalol in the blood serum;
– diabetes mellitus with significant fluctuations in blood glucose levels (in which case symptoms of hypoglycemia may be masked): it is necessary to monitor blood glucose concentrations and inform patients that the main symptom of hypoglycemia during treatment with sotalol is increased sweating;
– prolonged fasting;
– hyperthyroidism (adrenergic symptoms may be masked): when treating patients with suspected thyrotoxicosis, rapid discontinuation of sotalol should be avoided, as exacerbation of hyperthyroidism symptoms, including thyrotoxic crisis, is possible;
– peripheral perfusion disorders such as Raynaud's phenomenon and intermittent claudication: complaints may occur at the beginning of treatment;
– pheochromocytoma: sotalol hydrochloride can be used only after prior blockade of a-adrenoceptors;
– vasospastic angina (Prinzmetal's angina), myasthenia gravis, depression (including a history);
– conditions and/or use of medications that contribute to prolongation of the QT interval;
– recent myocardial infarction (increased risk of arrhythmogenic effects);
– sick sinus syndrome associated with symptomatic arrhythmias (sotalol hydrochloride may cause sinus bradycardia, sinus pauses or sinus arrest);
– congestive heart failure;
– psoriasis (worsening of psoriasis symptoms).
Sotalol hydrochloride may aggravate existing arrhythmias or induce new ones. Proarrhythmic effects may range from an increase in the frequency of premature ventricular contractions to the development of more severe ventricular tachycardia, ventricular fibrillation, or torsades de pointes. Risk factors that increase the likelihood of torsades de pointes include: dose, presence of persistent ventricular tachycardia, gender (women have a higher incidence), excessive prolongation of the QTc interval, cardiomegaly, or chronic heart failure.
If during therapy the QTc interval exceeds 500 ms, caution is required when using the drug, and if it exceeds 550 ms, a dose reduction or discontinuation of the drug is required. Proarrhythmic effects are most often observed in the first 7 days after the start of therapy or when the dose is increased. To reduce the risk of proarrhythmia, it is recommended to start treatment with a dose of 80 mg 2 times a day, and then gradually titrate the dose with simultaneous monitoring of efficacy (programmed electrocardiostimulation or Holter ECG monitoring) and safety (QT interval duration, heart rate and serum electrolyte levels).
In cases of severe diarrhea or concurrent administration of drugs that cause magnesium and/or potassium loss, electrolyte and acid-base balance should be monitored.
Do not use sotalol in patients with hypokalemia or hypomagnesemia until the imbalance is corrected due to the potential risks of QT prolongation and the development of torsades de pointes-type ventricular tachycardia.
Monitoring of patients using the drug Soritmik should include monitoring of heart rate, blood pressure, ECG, blood glucose levels in patients with diabetes. In elderly patients, it is necessary to monitor kidney function. Patients with renal failure require correction of the dosage regimen.
Patients who have had a myocardial infarction or who have deteriorated ventricular function are at risk of exacerbation of arrhythmias (proarrhythmias).
Sotalol should not be used in patients with left ventricular ejection fractions less than 40% without severe ventricular arrhythmia.
In patients with left ventricular dysfunction who have recently had a myocardial infarction, the potential benefits and risks of sotalol should be carefully weighed. Careful monitoring and dose titration are essential before and after initiation of therapy.
Before prescribing the drug, other antiarrhythmic drugs must be discontinued; the break in treatment should be at least 2–3 half-lives of the latter.
At the end of the course of treatment, the use of sotalol hydrochloride should be discontinued gradually, reducing the dose over 2 weeks or more, under the supervision of a physician. The frequency of use of the drug should not be changed. Abrupt withdrawal may unmask a latent form of heart failure, in addition, arterial hypertension may develop.
When treating elderly patients, it is necessary to take into account the possible presence of concomitant pathology, in particular renal failure and hypersensitivity to the action of the drug, even with the usual dosage.
Patients who wear contact lenses should be aware that treatment may reduce tear production.
Due to the blockade of β-adrenergic receptors, sotalol may increase sensitivity to allergens and the severity of anaphylactic reactions, which must be taken into account when treating patients with severe hypersensitivity reactions (including a history) and those undergoing desensitization therapy.
If surgery is necessary, the anesthesiologist should be informed about the use of sotalol; a few days before the operation, sotalol should be discontinued or an anesthetic agent with minimal negative inotropic effect should be selected.
In rare cases, the drug may cause psoriasis, worsen its symptoms, or lead to psoriasis-like exanthema.
Sotalol should be used with caution in first-degree AV block due to negative effects on conduction.
The use of sotalol is contraindicated in severe allergic rhinitis due to increased airway obstruction.
Due to the presence of sotalol hydrochloride in urine, photometric determination of metanephrine may result in overestimated values.
In patients with suspected pheochromocytoma who are receiving sotalol hydrochloride, urinalysis should be performed using high-performance liquid chromatography (HPLC) with solid-phase extraction.
The use of sotalol hydrochloride may lead to positive results in doping tests.
Patients with breathing difficulties may be prescribed the drug after careful assessment of the benefit-risk ratio.
During treatment, alcohol should not be consumed due to the likelihood of developing orthostatic hypotension.
Use during pregnancy or breastfeeding
Since there is insufficient experience with the use of sotalol hydrochloride during pregnancy, the drug should only be prescribed if the expected benefit to the mother outweighs the potential risk to the fetus.
Sotalol hydrochloride crosses the placenta and reaches pharmacologically effective concentrations in fetal tissues, so the fetus or infant may experience adverse reactions such as bradycardia, hypotension, and hypoglycemia. For this reason, therapy should be discontinued 48–72 hours before the estimated date of delivery. Infants should be closely monitored for some time after birth (possible development of β-receptor blockade).
β-blockers can cause a decrease in placental blood flow, which can lead to intrauterine fetal death and premature birth.
Sotalol hydrochloride accumulates in breast milk, reaching concentrations 3-5 times higher than in maternal plasma. Breastfeeding should be discontinued during treatment with the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
Method of administration and doses
When treating life-threatening ventricular arrhythmias with antiarrhythmic agents, therapy should be initiated and doses increased in a hospital setting with equipment available to monitor and assess heart rate variability.
During treatment, regular monitoring should be performed (e.g., with a standard ECG at 1-month intervals or a long-term ECG every 3 months and, if necessary, an exercise ECG).
Therapy should be reviewed if individual parameters deteriorate (e.g., QRS duration increases or QT interval prolongs by more than 25%, PQ interval prolongs by more than 50%, or frequency and severity of arrhythmias increase).
Severe symptomatic ventricular arrhythmias
The initial dose is 80 mg of sotalol 2 times a day. If the effectiveness of therapy is insufficient, the daily dose can be increased to 80 mg of sotalol hydrochloride 3 times a day or to 160 mg of sotalol hydrochloride 2 times a day.
In case of insufficient effectiveness in the treatment of arrhythmias that threaten the patient's life, the daily dose of sotalol hydrochloride can be increased to 480 mg and divided into 2–3 doses.
The appointment of such a dose requires an assessment of the potential benefit-risk ratio regarding the possibility of severe adverse reactions (especially proarrhythmic effects).
It is recommended to increase the dose at intervals of at least 2–3 days.
Atrial fibrillation
The initial dose of sotalol hydrochloride is 80 mg twice daily. In case of insufficient efficacy, the daily dose can be increased to 80 mg three times daily. This dose should not be exceeded in case of paroxysmal atrial fibrillation.
In case of insufficient efficacy in patients with chronic atrial fibrillation, the dose may be increased to a maximum of 160 mg twice daily.
It is recommended to increase the dose at intervals of at least 2–3 days.
Recommended doses for renal failure
Since there is a risk of accumulation of sotalol with repeated administration in patients with impaired renal function, the dose in such patients should be adjusted depending on creatinine clearance, taking into account heart rate (not lower than 50 beats/min) and clinical efficacy.
In severe renal failure, the use of sotalol hydrochloride is recommended only with regular monitoring of ECG and serum drug concentration.
If creatinine clearance > 60 ml/min – the recommended doses should be administered; with creatinine clearance 30–60 ml/min – a 50% dose reduction is recommended; with clearance 10–30 ml/min – use ¼ of the recommended dose; with creatinine clearance < 10 ml/min – do not use the drug.
Elderly patients
When treating elderly patients, possible renal impairment should be considered.
Method of application
The tablets should be taken without chewing, with sufficient liquid (for example, 1 glass of water) before meals. The drug Soritmik should not be used during meals, as the absorption of sotalol hydrochloride from the digestive tract may be reduced (in particular, this applies to milk and dairy products).
Duration of use. The duration of treatment is determined by the doctor.
In case of prolonged use of the drug or in patients with ischemic heart disease and/or arrhythmia, drug therapy should be discontinued gradually, as abrupt withdrawal may lead to worsening of the clinical condition.
Children. The medicine should not be used in children.
Overdose
Symptoms: Symptoms of sotalol hydrochloride overdose depend on the general condition of the patient's cardiac activity (left ventricular function, cardiac arrhythmias). In case of severe heart failure, even at the lowest doses, deterioration of cardiac function is possible.
Depending on the degree of intoxication, the following symptoms of overdose may occur: dizziness, fainting, weakness, asystole, symptoms of cardiogenic or hypovolemic shock, heart failure, atrioventricular block, arrhythmia, cyanosis of the nails or palms, convulsions, difficulty breathing, bronchospasm, hypoglycemia, fatigue, loss of consciousness, mydriasis, sometimes generalized seizures, arterial hypotension, hypoglycemia, severe bradycardia up to cardiac arrest (replacement rhythm on the ECG), prolongation of the QT interval, chronic heart failure, atypical ventricular tachycardia (torsades de pointes), symptoms of cardiovascular shock. Overdose with sotalol hydrochloride in isolated cases resulted in death.
Treatment. It is necessary to stop using the drug; gastric lavage and support of vital body functions are indicated. Therapy is symptomatic.
If indicated, administer atropine 1–2 mg intravenously as an infusion (bolus administration is possible); sympathomimetics, depending on body weight and the effect obtained: dopamine, dobutamine, isoprenaline, orciprenaline and epinephrine; effective use of glucagon: initially 1–10 mg intravenously, then 2–2.5 mg per hour as a continuous infusion.
In case of bradycardia, atropine, other anticholinergic drugs, b-adrenoceptor agonists or transvenous electrocardiostimulation are indicated; in case of heart block (II or III degree) - isoproterenol or transvenous electrocardiostimulation; in case of heart failure - cardiac glycosides, diuretics, glucagon; in case of hypotension (depending on associated factors) - if necessary, in addition to atropine and digitalis glycosides, it is more appropriate to use epinephrine than isoproterenol or noradrenaline; in case of bronchospasm - b2-adrenoceptor stimulators in the form of an aerosol or aminophylline; in case of hypoglycemia - intravenous glucose administration; in case of "pirouette" tachycardia - epinephrine, magnesium sulfate, transvenous electrocardiostimulation, direct current cardiac pacing.
Since sotalol hydrochloride is a competitive antagonist of isoproterenol, high doses of isoproterenol can neutralize many of the effects of excessive doses of the drug Soritmik, but when using isoproterenol, one must be prepared for the complications that high doses can cause.
The drug is removed by hemodialysis.
Adverse reactions
On the part of the immune system: sotalol may increase sensitivity to allergens and the severity of anaphylactic reactions, hypersensitivity reactions.
Metabolic and nutritional disorders: hypoglycemia (signs of low blood sugar (in particular, tachycardia) may be masked against the background of drug therapy). This should be taken into account in patients who observe prolonged fasting, patients with diabetes mellitus and with a history of spontaneous hypoglycemia. Hyperglycemia, hypothyroidism. Increase in total cholesterol and triglycerides, decrease in high-density lipoprotein cholesterol.
Psychiatric: anxiety, confusion, mood changes, hallucinations, increased excitability, depression; sleep disturbances.
Nervous system: dizziness, drowsiness, headache, dyssomnia, paresthesia, feeling of coldness in the extremities, weakness, convulsions, tremor.
On the part of the organs of vision: visual impairment; conjunctivitis; keratoconjunctivitis, decreased tear secretion (especially when using contact lenses), dryness and pain in the eyes, inflammation of the cornea and conjunctiva, photophobia.
On the part of the auditory organs: hearing impairment.
Severe proarrhythmic effects (sustained ventricular tachycardia or ventricular flutter/fibrillation or torsades de pointes) are mainly dose-dependent and occur mainly at the beginning of therapy and with dose increases.
Respiratory system: rhinitis, difficulty breathing, bronchospasm, laryngospasm; dyspnea (may occur in patients with obstructive pulmonary disorders); allergic bronchitis with fibrosis.
Gastrointestinal: taste disturbance, abdominal pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, xerostomia; constipation, dry mouth, anorexia, liver dysfunction (dark urine, yellowing of the sclera or skin, cholestasis).
Skin: erythema, skin rash, urticaria, itching, exanthema, increased sweating, skin hyperemia; alopecia; psoriatic exanthema, appearance/progression of psoriasis symptoms.
Musculoskeletal system: muscle spasm or myasthenia gravis, back pain, arthralgia, muscle pain.
From the reproductive system: impaired potency.
General disorders: fever, fatigue, cyanosis of the extremities, asthenia, withdrawal syndrome.
Laboratory indicators: thrombocytopenia, agranulocytosis, leukopenia, formation of antinuclear antibodies, changes in enzyme activity, bilirubin levels.
Expiration date
5 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
10 tablets in a blister; 2 blisters in a pack.
Vacation category
According to the recipe.
Producer
JSC "KYIV VITAMIN FACTORY".
Location of the manufacturer and address of its place of business.
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua
