Sotalol Sandoz tablets 160 mg blister No. 50

Instructions Sotalol Sandoz tablets 160 mg blister No. 50

Composition

active ingredient: sotalol;

1 tablet contains sotalol hydrochloride 40 mg or 80 mg, or 160 mg;

Excipients: corn starch, lactose monohydrate, sodium starch glycolate (type A), hydroxypropylcellulose, colloidal anhydrous silicon dioxide, magnesium stearate.

Dosage form

Pills.

Main physicochemical properties:

40 mg tablets: white, round, biconvex tablets debossed with “SOT” on one side;

80 mg tablets: white round tablets with a score on one side, convex with embossing “SOT” on the other;

160 mg tablets: white, round, biconvex tablets with a score on one side and embossed with “SOT” on the other.

Pharmacotherapeutic group

Non-selective β-adrenergic blockers. ATC code C07A A07

Pharmacological properties

Pharmacodynamics

Sotalol is a non-selective β-adrenergic blocker, acting 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 dose taken is excreted by the kidneys unchanged, the rest with feces. Renal clearance is 120 ml/min. The half-life is approximately 15 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

Ventricular arrhythmias:

prevention of recurrences of life-threatening ventricular tachyarrhythmia;

treatment of symptomatic unstable ventricular tachyarrhythmia.

Supraventricular arrhythmias:

prevention of paroxysmal atrial tachycardia, paroxysmal atrial fibrillation, paroxysmal atrioventricular (AV) nodal reciprocating tachycardia, paroxysmal AV-reciprocating tachycardia in the presence of additional conduction pathways, paroxysmal supraventricular tachycardia after surgery;

maintenance of normal sinus rhythm after conversion of atrial fibrillation or fibrillation.

Contraindication

Hypersensitivity to sotalol, sulfonamides or other components of the drug;

heart failure of the IV degree according to the NYHA classification (New York Heart Association); acute and chronic heart failure of the II-III degree (in the stage of decompensation);

acute myocardial infarction;

sick sinus syndrome, including sinoatrial block if the patient does not have a functioning pacemaker; severe sinus node dysfunction;

2nd–3rd degree AV block (if the patient does not have a functioning pacemaker);

congenital or acquired long QT syndrome or taking drugs that prolong the QT interval;

ventricular tachycardia of the torsade de pointes type or taking drugs that contribute to the development of this disease;

symptomatic sinus bradycardia (≤ 45–50 beats/min);

uncontrolled congestive heart failure, including right ventricular heart failure after pulmonary hypertension;

cardiogenic shock;

anesthesia with drugs that cause myocardial depression;

hypokalemia; hypomagnesemia;

untreated pheochromocytoma;

arterial hypotension (except that resulting from arrhythmia);

Raynaud's syndrome and severe peripheral circulatory disorders;

bronchial asthma and chronic obstructive pulmonary disease;

metabolic acidosis;

renal failure (creatinine clearance < 10 ml/min).

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 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 duration of the QT interval (class I and III antiarrhythmic drugs, phenothiazine derivatives, tri- and tetracyclic antidepressants (imipramine, maprotiline), quinoline antibiotics (e.g. sparfloxacin), terfenadine, astemizole, erythromycin, lithium preparations, probucol, haloperidol, halofantrine, pentamidine). The risk of torsade de pointes increases.

Calcium channel blockers – simultaneous use led to the development of arterial hypotension, bradycardia, conduction disturbances, and heart failure.

Tri- and tetracyclic antidepressants, neuroleptics, narcotic analgesics, antihistamines, sedatives, hypnotics, and ethanol increase central nervous system depression and increase the risk of ventricular arrhythmias.

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

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 simultaneous use with drugs that deplete catecholamine reserves (reserpine, guanethidine), an excessive decrease in the tone of the sympathetic nervous system may be observed. Patients should regularly monitor blood pressure and heart rate, 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, alpha-methyldopa, guanfacine and cardiac glycosides.

In case of simultaneous 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.

In case of simultaneous use with antihypertensive agents (diuretics, sympatholytics, clonidine, hydralazine), excessive reduction in blood pressure is possible.

Furosemide, hydrochlorothiazide, and other diuretics that deplete potassium or magnesium can trigger the development of arrhythmias due to hypokalemia.

When using sotalol simultaneously with amphotericin B and corticosteroids, it is necessary to monitor potassium levels.

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 (e.g. disopyramide) increase AV conduction disturbances, increase the risk of developing or worsening AV block and heart failure. When used with calcium channel blockers, an additive hypotensive effect on blood pressure is possible. Their concomitant use with sotalol should be avoided.

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 MAO-B inhibitors and sotalol should be at least 14 days.

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, and 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;

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, may occur.

peripheral perfusion disorders; complaints may occur especially at the beginning of treatment;

pheochromocytoma (see section "Contraindications"): sotalol hydrochloride can be used only after prior blockade of a-adrenoceptors;

atopic history, anaphylactic reactions in the patient's history and desensitization therapy (a more severe course of anaphylactic reactions and insensitivity to usual doses of adrenaline (epinephrine) during their treatment is possible);

vasospastic angina (Prinzmetal's angina), myasthenia gravis, depression (including a history);

sick sinus syndrome associated with symptomatic arrhythmias (sotalol hydrochloride may cause sinus bradycardia, sinus pauses or sinus arrest);

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 more severe ventricular tachycardia, ventricular fibrillation, or torsades de pointes. The risk of torsades de pointes is associated with QT prolongation, decreased heart rate, decreased serum magnesium and potassium levels, and concomitant use of sotalol with drugs that induce torsades de pointes. Torsades de pointes occurs soon after initiation of therapy or dose increase and resolves spontaneously in most patients. Although most episodes of this tachycardia resolve spontaneously or are associated with symptoms (e.g., syncope), it may progress to ventricular fibrillation. Risk factors for torsades de pointes include increased dose, presence of sustained ventricular tachycardia, female gender, excessive prolongation of the QTc interval, cardiomegaly, and congestive heart failure.

If during therapy the QTc interval exceeds 500 ms, caution is required when using it, and if it exceeds 550 ms, a dose reduction or discontinuation of the drug is required. During clinical studies, bradycardia was often observed in patients with arrhythmia who took sotalol, which increases the risk of developing torsade de pointes tachycardia. 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 at 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 torsade de pointes-type ventricular tachycardia.

Monitoring of patients taking sotalol should include monitoring of heart rate, blood pressure, ECG, and blood glucose levels in diabetic patients. In elderly patients, renal function should be monitored. Patients with renal insufficiency require adjustment of the dosage regimen.

In patients with left ventricular dysfunction who have recently had a myocardial infarction, the potential benefits and risks of using sotalol should be carefully weighed. Careful monitoring and dose titration are essential before and after initiating therapy. Sotalol should not be used in patients with left ventricular ejection fractions ≤ 40% without severe ventricular arrhythmias.

In combination treatment with class I antiarrhythmic drugs, especially quinidine-like ones, drugs that can widen the QRS complex should not be used, as the QT interval may be significantly prolonged and the risk of ventricular arrhythmia may significantly increase.

The concomitant use of sotalol with class III antiarrhythmic drugs should be avoided as this may lead to excessive prolongation of the QT interval.

Before prescribing the drug, other antiarrhythmic drugs must be discontinued.

At the end of the course of treatment, sotalol hydrochloride should be discontinued gradually, reducing the dose over 2 weeks or more, under the supervision of a physician. The frequency of taking the drug should not be changed. Treatment should not be stopped abruptly - severe arrhythmias and myocardial infarction may develop. Abrupt withdrawal of the drug 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.

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 taking sotalol; a few days before the operation, sotalol should be discontinued or an anesthetic agent with minimal negative inotropic effects should be selected.

In rare cases, the drug may cause psoriasis, worsening of its symptoms, or 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.

Patients with breathing difficulties should be prescribed the drug after careful assessment of the benefit-risk ratio.

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 drug contains lactose, so it should not be prescribed to patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

The use of sotalol hydrochloride may cause positive results in doping tests.

During treatment, alcohol should not be consumed due to the likelihood of developing orthostatic hypotension.

The medicinal product contains sodium starch glycolate. Caution should be exercised when used in patients on a controlled sodium diet.

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 adverse reactions such as bradycardia, hypotension and hypoglycemia can be expected in the fetus or infant. For this reason, therapy should be discontinued 48–72 hours before the estimated date of delivery. β-blockers can cause a decrease in placental blood flow, which can lead to premature birth and even intrauterine fetal death. After birth, infants should be carefully monitored for some time (possible development of β-receptor blockade).

Sotalol hydrochloride passes into breast milk, reaching concentrations 3-5 times higher than its concentration 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 hazardous activities that require increased concentration and speed of psychomotor reactions. This is especially important at the beginning of treatment, when increasing the dose, when changing the drug or when interacting with alcohol.

Method of administration and doses

When treating life-threatening ventricular arrhythmias with antiarrhythmic agents, therapy should be initiated and the dose increased in a hospital setting with equipment available to monitor and assess heart rate variability.

During treatment, control studies should be performed regularly (for example, with a standard ECG - at intervals of 1 month, a long-term ECG - every 3 months, and, if necessary, an ECG during exercise).

Therapy should be reviewed if individual parameters deteriorate, such as QRS duration increases or QT interval prolongation exceeds 25%, PQ interval prolongation exceeds 50%, or frequency and severity of arrhythmias increase.

The following dosage regimen is recommended: the initial dose is 80 mg per day as a single dose or in 2 doses (40 mg each) with an interval of 12 hours.

If the effectiveness of therapy is insufficient, the daily dose can be gradually increased with an interval of at least 3 days to achieve equilibrium concentration of sotalol in the blood plasma and monitor the duration of the QT intervals using ECG.

Individual patients may require a daily dose of 160–320 mg, divided into 2 doses.

For the prevention of supraventricular arrhythmias, the recommended dose is 320 mg/day in 2 divided doses 12 hours apart. For the prevention of supraventricular arrhythmias after cardiac surgery, the daily dose should be 240 mg in 2 divided doses.

In selected patients with life-threatening, persistent ventricular arrhythmias, 480–640 mg of sotalol per day may be prescribed. However, the use of such a dose requires careful assessment of the potential benefit versus the risk of serious adverse reactions (especially proarrhythmic effects).

Dosage in renal impairment.

Since sotalol is excreted primarily in the urine, the dose should be reduced if creatinine clearance is less than 60 ml/min, according to the table:

Creatinine clearance can be calculated using the formula:

Men:

(140 – patient’s age) × body weight (kg)

72 × serum creatinine level (mg/dL)

Women:

Creatinine clearance calculated for men × 0.85.

If the serum creatinine level is given in units of μmol/L, the result obtained must be divided by 88.4 (1 mg/dL = 88.4 μmol/L).

Dosage in liver dysfunction.

No dose adjustment is necessary.

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 (e.g. 1 glass of water), before meals. The medicine should not be taken during meals, as this may reduce the absorption of sotalol hydrochloride from the digestive tract (this applies in particular to milk and dairy products).

Duration of use.

The duration of treatment is determined by the doctor.

Patients who have had a myocardial infarction or have severe cardiac disorders require constant close medical supervision when adjusting the dose of antiarrhythmic drugs.

In patients with ischemic heart disease and/or arrhythmia, as well as in the case of long-term use of the drug, therapy should be discontinued gradually, since sudden withdrawal may lead to a deterioration in the clinical condition.

Children.

The drug should not be used in children.

Overdose

Symptoms of overdose depend on the general condition of the patient's cardiac activity (left ventricular function, cardiac arrhythmia). In case of severe heart failure, even when using the drug in the lowest doses, deterioration of cardiac function may occur.

According to clinical data, depending on the degree of intoxication, the following symptoms of overdose occurred: dizziness, fainting, weakness, asystole, symptoms of cardiogenic or hypovolemic shock, heart failure, arterioventricular block, arrhythmia, cyanosis of the nails or palms, convulsions, difficulty breathing, bronchospasm, hypoglycemia, increased fatigue, loss of consciousness, mydriasis, sometimes generalized seizures, arterial hypotension, hypoglycemia, severe bradycardia up to cardiac arrest (replacement rhythm often on ECG), prolongation of the QT interval, atypical ventricular tachycardia (torsade de pointes), symptoms of cardiovascular shock. Overdose of sotalol hydrochloride in isolated cases resulted in death.

Treatment: it is necessary to stop using the drug; gastric lavage is indicated, support of vital body functions, symptomatic therapy. According to indications, 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) in addition to atropine and digitalis glycosides, if necessary, it is more expedient to use epinephrine rather 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 cardiostimulation.

Because sotalol hydrochloride is a competitive antagonist of isoproterenol, high doses of isoproterenol can neutralize many of the effects of excessive doses of sotalol, but when using isoproterenol, one must be prepared for the complications that high doses can cause.

The drug can be removed by hemodialysis.

Side effects

The frequency of adverse reactions is classified as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency unknown (cannot be estimated due to lack of data).

Immune system: hypersensitivity reactions; sotalol may increase sensitivity to allergens and the severity of anaphylactic 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, diabetics and patients with a history of spontaneous hypoglycemia). Hyperglycemia, hypothyroidism. Increased levels of total cholesterol and triglycerides, decreased levels of high-density lipoprotein cholesterol.

From the nervous system: often - dizziness, drowsiness, headache, dyssomnia, paresthesia, feeling of coldness in the extremities, weakness, convulsions, tremor.

On the part of the organs of vision: often - visual impairment; infrequently - conjunctivitis; very rarely - 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: often - hearing impairment.

From the cardiovascular system: often - chest pain, orthostatic and arterial hypotension, dyspnea, edema, increased symptoms of heart failure (swelling of the ankles, feet, shortness of breath), arrhythmia, bradycardia, palpitations, ECG abnormalities, myocardial conduction disorders, atrioventricular block, syncopal or presyncopal states, proarrhythmic effects (changes in rhythm or increased arrhythmia, which can lead to significant cardiac dysfunction with possible cardiac arrest), weakening of myocardial contractile function, manifestations of angiospasm (increased peripheral circulatory disorders, feeling of cold extremities, intermittent claudication, Raynaud's syndrome). Arrhythmogenic effects are more often observed in patients with severe, life-threatening arrhythmias and left ventricular dysfunction; very rarely - an increase in the number of angina attacks and peripheral perfusion disorders. Given that sotalol prolongs the QT interval, ventricular tachyarrhythmias (including torsade de pointes) may occur with its use, especially in cases of overdose.

Severe proarrhythmic effects (sustained ventricular tachycardia, ventricular flutter/fibrillation or torsade de pointes) are dose-dependent and occur mainly at the beginning of therapy and with dose increases.

From the respiratory system: often - rhinitis, difficulty breathing, bronchospasm, laryngospasm; infrequently - dyspnea: may occur in patients with obstructive lung disorders; very rarely - allergic bronchitis with fibrosis.

On the part of the digestive tract: often - taste disturbance, abdominal pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, xerostomia; rarely - constipation, dry mouth, anorexia, liver dysfunction (dark urine, yellowing of the sclera or skin, cholestasis).

Skin: often - erythema, skin rash, urticaria, itching, exanthema, frequency unknown - increased sweating, skin hyperemia; frequency unknown - alopecia; very rarely - psoriatic exanthema, appearance/progression of psoriasis symptoms.

Musculoskeletal system: muscle spasm or myasthenia gravis, back pain, arthralgia, muscle pain.

Reproductive system: erectile dysfunction.

General disorders: often - fever, fatigue, cyanosis of the extremities, asthenia, withdrawal syndrome.

Laboratory indicators: frequency unknown - thrombocytopenia, agranulocytosis, leukopenia, formation of antinuclear antibodies, changes in enzyme activity, bilirubin levels.

Expiration date

5 years.

Storage conditions

No special storage conditions are required.

Keep out of reach of children.

Packaging

40 mg tablets: 10 tablets in a blister; 5 (10 × 5) blisters or 25 tablets in a blister; 2 (25 × 2) blisters in a cardboard box.

Tablets of 80 mg and 160 mg: 10 tablets in a blister; 5 (10 × 5) blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

For all dosages: Salutas Pharma GmbH (full cycle production).

For a dose of 160 mg: Lek S. A. (primary and secondary packaging, batch release).

Address

Otto-von-Güricke-Allee 1, 39179, Barleben, Germany.

Domaniewska Street 50 C, Warsaw, 02-672, Poland.