INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SORITMIC (SORITMIC)

Composition:

Active substance: 1 tablet contains 80 mg or 160 mg of sotalol hydrochloride;

Excipients: lactose monohydrate; corn starch; microcrystalline cellulose; povidone; sodium starch glycolate (type A); magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white, flat cylindrical tablets with bevelled edges and a score line.

Pharmacotherapeutic group. Non-selective β-adrenoreceptor blockers.

ATC code C07AA07.

Pharmacological Properties.

Pharmacodynamics.

Sotalemic – a non-selective β-adrenoblocker acting on β1- and β2-adrenergic receptors. It has pronounced antiarrhythmic activity, the mechanism of which involves prolonging the action potential duration and refractory period in all areas of the heart's conduction system (Class III antiarrhythmic drugs). It reduces heart rate and myocardial contractility, decreases the automaticity of the sinus node, and slows atrioventricular conduction. By blocking β2-adrenergic receptors, it increases the tone of bronchial and vascular smooth muscle.

Pharmacokinetics.

After oral administration, 75–90% of sotalol hydrochloride is absorbed from the gastrointestinal tract. Due to the absence of a first-pass liver effect, absolute bioavailability is 75–90%. Time to reach maximum plasma concentration – 2–3 hours. Volume of distribution – 1.6–2.4 L/kg. Sotalol does not bind to plasma proteins. 75–90% of the administered dose is excreted unchanged by the kidneys, the remainder – in feces. Renal clearance is 120 mL/min. Elimination half-life – 10–20 hours. In renal insufficiency, it is prolonged up to 42 hours, necessitating dose reduction. The drug is removed during hemodialysis.

Clinical characteristics.

Indications.

Severe symptomatic ventricular arrhythmias.

Symptomatic supraventricular arrhythmias of tachycardia type requiring treatment:

prevention of chronic atrial fibrillation after direct current cardioversion;
prevention of paroxysmal atrial fibrillation.

Contraindications.

Hypersensitivity to sotalol, sulfonamides, or any other component of the medicinal product.

NYHA (New York Heart Association) Class IV heart failure, acute and chronic heart failure of Class II–III (in decompensated stage), acute myocardial infarction, second- or third-degree atrioventricular block (if the patient does not have a functioning pacemaker), torsades de pointes ventricular tachycardia or use of drugs promoting development of this condition, sinoatrial block, sick sinus syndrome, symptomatic sinus bradycardia (< 50 beats/min), severe sinus node dysfunction, congenital or acquired long QT syndrome or use of drugs that prolong the QT interval, severe or uncontrolled chronic heart failure including right ventricular failure following pulmonary hypertension, Prinzmetal's angina, cardiogenic shock, renal failure (creatinine clearance < 10 mL/min), hypokalemia, hypomagnesemia, arterial hypotension, marked peripheral circulatory disorders, bronchial asthma and chronic obstructive pulmonary diseases, laryngeal edema, allergic rhinitis, metabolic acidosis, untreated pheochromocytoma, diabetes mellitus, cardiomegaly (without signs of heart failure), peripheral vascular occlusive diseases (complicated by gangrene, intermittent claudication, or rest pain), Raynaud’s syndrome, anesthesia with drugs causing myocardial depression, concomitant use of monoamine oxidase A (MAO-A) inhibitors, floctafénine.

For patients treated with sotalol (except in intensive pharmacological therapy), intravenous administration of calcium channel antagonists of verapamil and diltiazem types or other antiarrhythmic drugs is contraindicated.

Interaction with other medicinal products and other forms of interaction.

Do not use:

with Class I antiarrhythmic agents (disopyramide, quinidine, procainamide) and Class III antiarrhythmics (amiodarone) – potentially may increase myocardial refractoriness. Amiodarone increases the risk of bradycardia and atrioventricular (AV) conduction depression. When sotalol is used concomitantly with other β-blockers, additive Class II effects (reduction in blood pressure and heart rate) may be expected;
with medicinal products that increase QT interval duration (Class I and Class III antiarrhythmic agents, phenothiazine derivatives, tricyclic and tetracyclic antidepressants, terfenadine, astemizole, erythromycin, lithium preparations, quinolone antibiotics, halofantrine, pentamidine), neuroleptics, narcotic analgesics, antihistamines, sedatives, hypnotics, and ethanol.

Concomitant use of sotalol hydrochloride with tricyclic antidepressants, barbiturates, phenothiazines, narcotic analgesics, as well as antihypertensives, diuretics, and vasodilators may lead to excessive reduction in blood pressure.

Inhalational anesthetics (hydrocarbon derivatives) and muscle relaxants increase the risk of myocardial depression and development of arterial hypotension.

Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis.

When used concomitantly with medicinal products that deplete catecholamine stores (reserpine, guanethidine), excessive reduction in sympathetic tone may occur. Patients should be monitored regularly for blood pressure and heart rate (HR), as hypotension, marked bradycardia, and loss of consciousness may occur.

The negative chronotropic and negative dromotropic effects of sotalol hydrochloride may be enhanced when used concomitantly with reserpine, clonidine, α-methyldopa, guanfacine, and cardiac glycosides.

When used concomitantly with digoxin, the risk of proarrhythmic effects increases, and the positive inotropic effect of digitalis glycosides is reduced. Both digitalis glycosides and sotalol hydrochloride slow AV conduction. If, despite adequate digitalis therapy, no improvement in severity of heart failure is observed, sotalol treatment should be discontinued.

When used concomitantly with antihypertensive agents (diuretics, sympatholytics, clonidine, hydralazine), excessive reduction in blood pressure may occur.

Furosemide, hydrochlorothiazide, and other potassium-wasting diuretics may provoke arrhythmias due to hypokalemia.

When sotalol is used concomitantly with amphotericin B, corticosteroids, serum potassium levels should be monitored.

Iodine-containing intravenous contrast media increase the risk of anaphylactic reactions.

Xanthines and sympathomimetics reduce sotalol activity.

When used concomitantly with β2-receptor agonists such as salbutamol, terbutaline, and isoprenaline, increased doses of the β2-agonist may be required.

Non-steroidal anti-inflammatory drugs (NSAIDs) and estrogens reduce the antihypertensive effect of sotalol hydrochloride; sulfasalazine increases its plasma concentration.

Calcium antagonists (verapamil and diltiazem), cardiac glycosides, and antiarrhythmic agents enhance disturbances in AV conduction, increasing the risk of development or worsening of AV block and heart failure. Concomitant use with calcium channel blockers may result in additive hypotensive effects on blood pressure.

Concomitant use of calcium ion antagonists of the nifedipine type may lead to a significant reduction in blood pressure and exacerbation of sick sinus syndrome.

Norepinephrine, MAO-B inhibitors, and abrupt discontinuation of clonidine may potentiate "rebound" hypertension. Sotalol use should be discontinued several days before gradual withdrawal of clonidine, and there should be a minimum 14-day interval between stopping treatment with MAO-B inhibitors and sotalol.

Floctafénine. β-blockers may interfere with compensatory cardiovascular responses associated with arterial hypotension or shock caused by floctafénine.

Sotalol prolongs the action of non-depolarizing muscle relaxants, the anticoagulant effect of coumarins, increases plasma concentration of lidocaine, enhances the effect of insulin, and reduces the effect of oral hypoglycemic agents (thus dose adjustment of antidiabetic medicinal products may be necessary).

Concomitant use with insulin or oral hypoglycemic agents, especially during intense physical exertion, may induce hypoglycemia and mask its symptoms.

Neuromuscular blockade caused by tubocurarine may be enhanced due to β-adrenoreceptor blockade.

The negative inotropic effect of sotalol hydrochloride and narcotic analgesics or antiarrhythmic agents may be additive.

Special precautions for use.

Particular medical supervision is required in the following cases:

Renal function impairment (dose reduction): monitoring of renal function, including creatinine determination, is necessary; serum sotalol concentration monitoring is also advisable;
Diabetes mellitus with significant fluctuations in blood glucose levels (hypoglycemic symptoms may be masked): blood glucose concentration monitoring is required, and patients should be informed that increased sweating is the main symptom of hypoglycemia during sotalol therapy;
Prolonged fasting;
Hyperthyroidism (adrenergic symptoms may be masked): when treating patients suspected of thyrotoxicosis, rapid discontinuation of sotalol should be avoided, as exacerbation of hyperthyroidism symptoms, including thyrotoxic crisis, may occur;
Peripheral perfusion disorders such as Raynaud's syndrome and intermittent claudication: complaints may occur at the beginning of treatment;
Pheochromocytoma: sotalol hydrochloride may be used only after prior α-adrenoceptor blockade;
Patient's atopic history, history of anaphylactic reactions, and undergoing desensitization therapy (anaphylactic reactions may be more severe and unresponsive to usual doses of adrenaline (epinephrine) in their treatment);
Vasospastic angina (Prinzmetal's angina), myasthenia gravis, depression (including in history);
Conditions and/or use of medicinal products that promote QT interval prolongation;
Recent myocardial infarction (increased risk of arrhythmogenic effects);
Sinoatrial node dysfunction associated with symptomatic arrhythmias (sotalol hydrochloride may cause sinus bradycardia, sinus pauses, or sinoatrial node arrest);
Congestive heart failure;
Psoriasis (exacerbation of psoriasis symptoms).

Sotalol hydrochloride may increase the severity of existing arrhythmias or cause new ones. Proarrhythmic effects may vary: from increased frequency of ventricular premature beats to development of more severe ventricular tachycardia, ventricular fibrillation, or torsades de pointes tachycardia. Risk factors increasing the likelihood of torsades de pointes include: dose, presence of sustained ventricular tachycardia, gender (higher incidence in women), excessive prolongation of QTc interval, cardiomegaly, or chronic heart failure.

If during therapy the QTc interval exceeds 500 ms, caution is required; if it exceeds 550 ms, dose reduction or discontinuation of the drug is necessary. Proarrhythmic effects are most commonly observed within the first 7 days after initiation of therapy or after dose escalation. To reduce the risk of proarrhythmia, treatment should be initiated at a dose of 80 mg twice daily, followed by gradual dose titration with simultaneous monitoring of efficacy (programmed electrical stimulation or Holter ECG monitoring) and safety (QT interval duration, heart rate, and serum electrolyte levels).

In cases of severe diarrhea or concomitant administration of medicinal products causing magnesium and/or potassium loss, monitoring of electrolyte balance and acid-base equilibrium is required.

Sotalol should not be administered to patients with hypokalemia or hypomagnesemia until these imbalances are corrected due to the risk of QT interval prolongation and development of torsades de pointes ventricular tachycardia.

Monitoring of patients receiving Soritmik should include observation of heart rate, blood pressure, ECG, and blood glucose levels in patients with diabetes mellitus. In elderly patients, renal function parameters should be monitored. Patients with renal impairment require dose regimen adjustment.

In patients who have experienced myocardial infarction or have worsening ventricular function, there is a risk of arrhythmia exacerbation (proarrhythmia).

Sotalol should not be administered to patients with left ventricular ejection fraction less than 40% unless they have severe ventricular arrhythmia.

In patients with left ventricular dysfunction who have recently experienced myocardial infarction, the potential benefits and risks of sotalol use must be carefully weighed. Close monitoring and dose titration are extremely important before and after initiation of therapy.

Before prescribing the medicinal product, other antiarrhythmic agents must be discontinued; a washout period of at least 2–3 elimination half-lives of the previous agents should be observed.

At the end of treatment, sotalol hydrochloride should be gradually discontinued under medical supervision, with dose reduction over a period of 2 weeks or longer. The dosing schedule must not be altered. Sudden withdrawal may unmask latent heart failure and may also lead to arterial hypertension.

When treating elderly patients, possible comorbidities, including renal impairment and increased sensitivity to the drug, even at usual doses, should be taken into account.

Patients who wear contact lenses should be aware that tear production may decrease during treatment.

Due to β-adrenoceptor blockade, sotalol may increase sensitivity to allergens and the severity of anaphylactic reactions; this should be considered when treating patients with severe hypersensitivity reactions (including in history) and those undergoing desensitization therapy.

If surgery is required, the anesthesiologist must be informed about sotalol use; sotalol should be discontinued several days before surgery or an anesthetic agent with minimal negative inotropic effect should be selected.

In isolated cases, the medicinal product may cause psoriasis, worsen its symptoms, or lead to a psoriasiform exanthem.

Sotalol should be used with caution in first-degree AV block due to its negative effect on conduction.

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 yield falsely elevated values.

In patients suspected of pheochromocytoma who are receiving sotalol hydrochloride, urine analysis should be performed using high-performance liquid chromatography (HPLC) with solid-phase extraction.

The medicinal product contains lactose and therefore should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Sotalol hydrochloride use may result in positive doping test results.

The medicinal product may be prescribed to patients with breathing difficulties only after careful benefit-risk assessment.

Alcohol consumption should be avoided during treatment due to the potential risk of orthostatic hypotension.

Use during pregnancy or breastfeeding.

As there is insufficient experience with the use of sotalol hydrochloride during pregnancy, the drug should be prescribed only when 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; therefore, adverse effects such as bradycardia, arterial hypotension, and hypoglycemia may be expected in the fetus or newborn. For this reason, therapy should be interrupted 48–72 hours before the expected delivery date. Newborns should be closely monitored for some time after birth (β-receptor blockade effects may occur).

β-blockers may cause reduced placental blood flow, which may lead to intrauterine fetal death or premature delivery.

Sotalol hydrochloride accumulates in breast milk, reaching concentrations 3–5 times higher than those in maternal plasma. Breastfeeding during treatment with this medicinal product must be discontinued.

Ability to affect reaction speed when driving or operating machinery.

During treatment, caution is required when driving or engaging in other potentially hazardous activities requiring high concentration and rapid psychomotor reactions.

Dosage and Administration

When treating life-threatening ventricular arrhythmias with antiarrhythmic agents, initiation of therapy and dose escalation must be performed in a hospital setting with equipment available for monitoring and assessing heart rate variability.

During treatment, regular monitoring tests should be conducted (e.g., standard ECG monthly or prolonged ECG every 3 months, and, if necessary, exercise ECG).

Therapy should be re-evaluated if certain parameters worsen (e.g., QRS duration increases, 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

Initial dose: 80 mg of sotalol twice daily. If therapeutic efficacy is insufficient, the daily dose may be increased to 80 mg of sotalol hydrochloride three times daily or to 160 mg of sotalol hydrochloride twice daily.

In cases of insufficient efficacy in treating life-threatening arrhythmias, the daily dose of sotalol hydrochloride may be increased up to 480 mg and divided into 2–3 doses.

Administration of such a dose requires careful assessment of the benefit-risk ratio due to the potential for severe adverse reactions (especially proarrhythmic effects).

Dose increases are recommended at intervals of not less than 2–3 days.

Atrial fibrillation

Initial dose of sotalol hydrochloride: 80 mg twice daily. If efficacy is insufficient, the daily dose may be increased to 80 mg three times daily. This dose should not be exceeded in cases of paroxysmal atrial fibrillation.

In patients with chronic atrial fibrillation and insufficient response, the dose may be increased to a maximum of 160 mg twice daily.

Dose increases are recommended at intervals of not less than 2–3 days.

Recommended doses in renal impairment

Due to the risk of sotalol accumulation with repeated administration in patients with impaired renal function, dosage should be adjusted according to creatinine clearance, taking into account heart rate (not below 50 beats/min) and clinical efficacy.

In severe renal impairment, sotalol hydrochloride should be used only with regular ECG monitoring and serum drug concentration measurements.

If creatinine clearance > 60 mL/min: administer recommended doses.
If creatinine clearance is 30–60 mL/min: reduce dose by 50%.
If creatinine clearance is 10–30 mL/min: administer ¼ of the recommended dose.
If creatinine clearance < 10 mL/min: do not use the drug.

Elderly patients

When treating elderly patients, possible renal function impairment should be considered.

Administration method

Tablets should be taken whole, without chewing, with sufficient fluid (e.g., one glass of water), before meals. Soritmik should not be taken during meals, as gastrointestinal absorption of sotalol hydrochloride may be reduced (particularly with milk and dairy products).

Duration of treatment

Treatment duration is determined by the physician.

Patients who have suffered myocardial infarction or those with severe cardiac dysfunction require continuous careful medical supervision during antiarrhythmic dose adjustments.

In cases of long-term drug use or in patients with ischemic heart disease and/or arrhythmia, therapy should be discontinued gradually, as abrupt withdrawal may worsen the clinical condition.

Children. The drug is not intended for use in children.

Overdose.

Symptoms. Symptoms of sotalol hydrochloride overdose depend on the patient's overall cardiac status (left ventricular function, cardiac arrhythmia). In cases of severe heart failure, even at the lowest doses, cardiac function may deteriorate.

Depending on the degree of intoxication, the following overdose symptoms may occur: dizziness, fainting, weakness, asystole, symptoms of cardiogenic or hypovolemic shock, heart failure, atrioventricular block, arrhythmia, cyanosis of nails or palms, seizures, dyspnea, bronchospasm, hypoglycemia, fatigue, loss of consciousness, mydriasis, occasionally generalized seizures, arterial hypotension, hypoglycemia, marked bradycardia up to cardiac arrest (escape rhythm on ECG), QT interval prolongation, chronic heart failure, atypical ventricular tachycardia (torsades de pointes), symptoms of cardiovascular shock. Sotalol hydrochloride overdose has, in isolated cases, resulted in fatal outcomes.

Treatment. Administration of the drug must be discontinued immediately. Gastric lavage and supportive therapy for vital functions are indicated. Treatment is symptomatic.

As indicated, administer atropine 1–2 mg intravenously by infusion (bolus administration possible); sympathomimetics according to body weight and response: dopamine, dobutamine, isoprenaline, orciprenaline, and epinephrine; glucagon has been shown to be effective: initially 1–10 mg intravenously, then 2–2.5 mg/hour as continuous infusion.

In cases of bradycardia: atropine, other anticholinergic drugs, β-adrenergic agonists, or transvenous cardiac pacing are indicated; in heart block (second- or third-degree): isoprenaline or transvenous cardiac pacing; in heart failure: cardiac glycosides, diuretics, glucagon; in hypotension (depending on associated factors): epinephrine is more appropriate than isoprenaline or norepinephrine, in addition to atropine and digitalis glycosides, if necessary; in bronchospasm: β2-adrenergic agonists by aerosol or aminophylline; in hypoglycemia: intravenous glucose; in torsades de pointes: epinephrine, magnesium sulfate, transvenous cardiac pacing, or direct current cardioversion.

Since sotalol hydrochloride is a competitive antagonist of isoprenaline, high doses of isoprenaline may neutralize many effects of excessive doses of Soritmik. However, when using isoprenaline, one must be prepared for complications that high doses may cause.

The drug can be removed by hemodialysis.

Adverse Reactions.

Immune system disorders: Sotalol may increase sensitivity to allergens and the severity of anaphylactic reactions, hypersensitivity reactions.

Metabolism and nutrition disorders: Hypoglycemia (signs of low blood sugar, such as tachycardia, may be masked during treatment with the drug). This should be considered in patients undergoing prolonged fasting, patients with diabetes mellitus, and those with a history of spontaneous hypoglycemia. Hyperglycemia, hypothyroid state. Increase in total cholesterol and triglycerides, decrease in high-density lipoprotein cholesterol.

Psychiatric disorders: Anxiety, confusion, mood changes, hallucinations, increased excitability, depression; sleep disturbances.

Nervous system disorders: Dizziness, drowsiness, headache, dysomnia, paresthesia, cold sensation in the extremities, weakness, cramps, tremor.

Eye disorders: Visual disturbances; conjunctivitis; keratoconjunctivitis, decreased tear secretion (especially when using contact lenses), dryness and eye pain, corneal and conjunctival inflammation, photophobia.

Ear disorders: Hearing disturbances.

Cardiovascular system disorders: Chest pain, orthostatic hypotension, worsening of heart failure symptoms (ankle and foot edema, shortness of breath), bradycardia, palpitations, ECG abnormalities, myocardial conduction disturbances, atrioventricular block, syncope or presyncope, proarrhythmic effects (rhythm changes or worsening of arrhythmia, which may lead to significant impairment of cardiac function with possible cardiac arrest), reduced myocardial contractile function, signs of angiospasm (worsening of peripheral circulation, cold extremities sensation, intermittent claudication, Raynaud’s syndrome). Proarrhythmic effects are more commonly observed in patients with severe, life-threatening arrhythmias and left ventricular dysfunction; increased frequency of angina attacks and impaired peripheral perfusion. Since sotalol prolongs the QT interval, ventricular tachyarrhythmias (including torsades de pointes) may occur during its use, especially in cases of overdose.

Severe proarrhythmic effects (persistent ventricular tachycardia or ventricular flutter/fibrillation, or torsades de pointes) are predominantly dose-dependent and usually occur at the beginning of therapy or during dose escalation.

Respiratory system disorders: Rhinitis, dyspnea, bronchospasm, laryngospasm; dyspnea (may occur in patients with obstructive lung disorders); allergic bronchitis with fibrosis.

Gastrointestinal disorders: Taste disturbances, abdominal pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, xerostomia; constipation, dry mouth, anorexia, liver function abnormalities (dark urine, jaundice of sclera or skin, cholestasis).

Skin disorders: Erythema, skin rashes, urticaria, pruritus, exanthema, increased sweating, skin hyperemia; alopecia; psoriasiform exanthema, onset/worsening of psoriasis symptoms.

Musculoskeletal system disorders: Muscle spasms or myasthenia, back pain, arthralgia, muscle pain.

Reproductive system disorders: Impotence.

General disorders: Fever, fatigue, cyanosis of extremities, asthenia, withdrawal syndrome.

Laboratory findings: Thrombocytopenia, agranulocytosis, leukopenia, formation of antinuclear antibodies, changes in enzyme activity and bilirubin levels.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 10 tablets per blister; 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and place of business.

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua

Sorimic