Sotalol, tablets 160 mg 20 pcs

Pharmacotherapeutic group: Non-selective beta-adrenoblocker

ATC code: C07AA

Pharmacodynamics:

Sotalol is a class II and III antiarrhythmic agent according to Vaughan-Williams classification with the properties of a non-selective beta-adrenoblocker. It is a racemic mixture consisting of D- and L-stereoisomers of sotalol. Both isomers have class III antiarrhythmic effects while the L-stereoisomer is responsible for virtually all beta-adrenoblocking actions.

Sotalol has no sympathomimetic or membrane-stabilizing activity of its own.

Like other beta-adrenoblockers, sotalol suppresses renin secretion, and this effect is pronounced both at rest and under load.

The beta-adrenoblocking action of sotalol causes a decrease in heart rate (HR) (negative chronotropic effect) and a limited decrease in heart force (negative inotropic effect). These changes in heart rate reduce myocardial oxygen demand and the amount of load on the heart.

The antiarrhythmic properties of sotalol are associated with both the ability to block beta-adrenergic receptors and the ability to prolong myocardial action potential. The main effect of sotalol is to increase the duration of effective refractory periods in the atrial ventricular and accessory pulse conduction pathways.

Pharmacokinetics:

Absorption

Bioavailability with oral administration is 90-100%.

The maximum plasma concentration is reached 25-4 h after oral administration and equilibrium concentration within 2-3 days (i.e. after 5-6 doses when taken 2 times daily).

The absorption of Sotalol is reduced by approximately 20% when combined with food compared to fasting.

In the dose range of 40 to 640 mg/day, the plasma concentration of Sotalol is proportional to the dose taken.

The pharmacokinetics of the D- and L-enantiomers of sotalol are virtually identical.

Distribution

Distribution occurs in plasma as well as in peripheral organs and tissues with a half-life of 10-20 h. Sotalol does not bind to plasma proteins. It poorly penetrates through the blood-brain barrier and its concentration in cerebrospinal fluid is only 10% of that in blood plasma.

Metabolism

Sotalol does not undergo metabolism.

Elevation

The main route of excretion from the body is excretion through the kidneys. About 80% to 90% of the administered dose is excreted unchanged by the kidneys and the rest is excreted through the intestines.

The elimination half-life of Sotalol is 10-20 hours.

Patient special groups

Patients with impaired renal function should use lower doses of the drug.

The pharmacokinetics do not change much with patient age, although impaired renal function in older patients decreases the excretion rate, which leads to increased accumulation of sotalol in the body.

Indications

Ventricular arrhythmia:

• prevention of recurrence of life-threatening ventricular tachyarrhythmia;
• treatment of symptomatic unstable ventricular tachyarrhythmia.

Transventricular arrhythmia:

• .Prevention of the development of paroxysmal atrial tachycardia paroxysmal atrial fibrillation paroxysmal atrial-ventricular nodal reciprocal tachycardia type “re-entry” paroxysmal atrial-ventricular reciprocal tachycardia involving additional pathways and paroxysmal supraventricular tachycardia after surgical intervention;
• maintenance of normal sinus rhythm after conversion of atrial fibrillation or atrial flutter.

.

Active ingredient

Sotalol

Composition

Composition per tablet 160 mg:

The active ingredient:

sotalol hydrochloride – 160.00 mg.

The excipients:

Lactose monohydrate (milk sugar) – 157.30 mg,

Corn starch – 30.40 mg,

sodium carboxymethyl starch – 15.20 mg,

povidone-K25 – 1 1.40 mg,

magnesium stearate – 3.80 mg,

colloidal silicon dioxide – 1.90 mg.

How to take, the dosage

Orally 1 to 2 hours before a meal, without chewing and with plenty of fluids. Simultaneous intake of food (especially milk and dairy products) reduces absorption of the drug.

The dose of the drug is adjusted individually, depending on the severity of the disease and on the evaluation of ECG renal function, the interaction of the drug with other drugs taken, and the patient’s response to the treatment.

The starting dose is 80 mg daily (1/2 tablet of Sotalol 80 mg 2 times daily about 12 hours apart). If the therapeutic effect is insufficient, after appropriate clinical assessment of the patient, the dose may be gradually increased to 240-320 mg daily divided into 2-3 doses.

In most patients, the therapeutic effect is achieved with a daily dose of 160-320 mg divided into 2 doses.

In life-threatening severe arrhythmias, it is possible to increase the dose to a maximum of 480-640 mg divided into 2 or 3 separate doses. However, these doses should only be used when the potential benefit exceeds the risk of side effects, especially proarrhythmogenic effects.

Because of the drug’s class III antiarrhythmic effects, the possibility of QT interval prolongation should be monitored and the doses should be adjusted if necessary.

Particular patient groups

In patients with cardiomyopathy or chronic heart failure (CHF) with arterial hypertension angina pectoris after myocardial infarction, initiation of therapy in a hospital setting is recommended. The initial dose is 160 mg/day in 1 or 2 doses. After a week, the dose may be increased by 80 mg/day at weekly intervals, if necessary.

The rate of dose increase depends on patient tolerability, which is assessed particularly by the degree of induced bradycardia and the therapeutic response to therapy.

Owing to a relatively long half-life in most patients, Sotalol is effective once daily. The dose interval is 160-320 mg/day.

Patients with impaired renal function

Patients with impaired renal function have a risk of cumulation; therefore, they should have their creatinine clearance (CK) and HR (at least 60 BPM) monitored.

Because sotalol is mainly excreted by the kidneys and its half-life is prolonged, the dosing regimen (time between doses) should be changed when the CK is less than 60 mL/min according to the table below:

The creatinine clearance for men is calculated using the formula: ((140-age) x weight(kg)) / (72 x serum creatinine concentration (mg/dL)); for women, the result obtained is multiplied by 085. If the laboratory analyzer gives serum creatinine concentration in units of μmol/l, divide the result by 884 (1 mg/dl = 884 μmol/l).

In severe renal dysfunction (CK 10-29 ml/min), regular ECG and serum drug concentrations should be monitored.

Patient use in patients with hepatic impairment

Dose adjustment is not required.

The duration of therapy is determined by the physician.

If you forget to take the tablet on time, do not double the dose next time.

Interaction

Antiarrhythmic agents

The concomitant use of Sotalol with antiarrhythmic agents of class IA (disopyramide quinidine procainamide) and class III (e.g. amiodarone dronedarone) may cause prolongation of the QT interval.

Digoxin

The use of sotalol has no significant effect on the serum concentration of digoxin. Arrhythmogenic effects developed more frequently in patients using sotalol and digoxin concomitantly; however, this may be due to chronic heart failure, which is a risk factor for arrhythmogenic effects in patients receiving digoxin.

Slow calcium channel blockers (CMBs)

The concomitant use of beta-adrenoblockers and CMBs can lead to arterial hypotension, bradycardia, impaired conduction, and heart failure.

The concomitant use of beta-adrenoblockers with myocardial suppressors (e.g., verapamil and diltiazem) should be avoided due to the additive effect of these agents on AV conduction and ventricular function. Intravenous administration of these drugs should be avoided with Sotalol (except in emergency medicine).

Potassium-containing diuretics (e.g., furosemide hydrochlorothiazide)

The use of this type of diuretics can lead to hypokalemia or hypomagnesemia, which increases the chance of pirouette-type polymorphic ventricular tachycardia.

Drugs that prolong the QT interval

Sotalol should be used with extreme caution when taking QT prolonging agents such as antiarrhythmic agents of class I phenothiazine derivatives tricyclic antidepressants H1 antihistamines (terfenadine and astemizole) and some quinolone antibiotics.

Catecholamine-lowering drugs

The concomitant use of catecholamine depleting drugs (e.g., reserpine and guanethidine) with beta-adrenoblockers leads to excessive suppression of the resting tone of the sympathetic nervous system.

Patients should be closely monitored because of possible signs of markedly decreased BP and/or marked bradycardia, which may lead to fainting.

Insulin or oral hypoglycemic agents

Hypoglycemia may develop in which case doses of hypoglycemic agents need to be adjusted. Sotalol may mask the symptoms of hypoglycemia.

Beta2-adrenomimetics

Concomitant use with sotalol may require higher doses of beta2-adrenomimetics such as salbutamol terbutaline and isoprenaline.

Norepinephrine and MAO inhibitors

The simultaneous use of norepinephrine (noradrenaline) or MAO inhibitors may cause arterial hypertension.

Clonidine

Beta-adrenoblockers may potentiate arterial withdrawal hypertension after stopping clonidine. Therefore, beta-adrenoblockers should be withdrawn gradually several days before discontinuing clonidine. Discontinuation of clonidine should also be done gradually and only a few days after discontinuation of sotalol.

Floktafenin

In case of shock or arterial hypotension due to floktafenin, β-adrenoblockers cause decreased compensatory cardiovascular responses.

Tricyclic antidepressants barbiturates phenothiazine derivatives narcotics and hypotensive agents diuretics and vasodilators

Combined use with sotalol may cause a sharp decrease in BP.

Tubocurarine

The use of agents for inhalation anesthesia, including tubocurarine, while taking sotalol increases the risk of myocardial depression and arterial hypotension.

Cytochrome P450 isoenzymes

No interaction of sotalol with drugs that are metabolized by cytochrome P450 isoenzymes is expected.

Amphotericin B gluco- and mineralocorticosteroids (when used systemically) some laxatives

Possible occurrence of hypokalemia. Potassium control is necessary when concomitant use with sotalol.

Special Instructions

Patient monitoring

The treatment with Sotalol should be monitored with HR monitoring of the BP ECG.

The initiation of Sotalol therapy or changes in dosage should be accompanied by appropriate medical evaluation, including ECG monitoring with QT interval assessment, renal function monitoring, electrolyte measurement, and adjunctive therapy.

The patient should be trained on how to estimate HR and should be advised to consult a physician if the HR is less than 60 bpm.

In elderly patients with increasing bradycardia (less than 60 bpm) arterial hypotension (systolic BP less than 100 mm Hg) AV block bronchospasm ventricular arrhythmia severe liver or renal dysfunction should reduce the drug dose or discontinue therapy.

Cancellation of the drug

After withdrawal of beta-adrenoblockers, patients have increased sensitivity to catecholamines. After abrupt discontinuation of therapy, individual cases of exacerbation of angina arrhythmia and, in some cases, development of myocardial infarction have been registered. Therefore, if it is necessary to withdraw Sotalol, the dose should be reduced gradually especially in patients with coronary heart disease after myocardial infarction with arterial hypertension. Treatment should not be abruptly interrupted because of the risk of severe arrhythmias and myocardial infarction.

The careful monitoring of the patient especially with coronary heart disease is recommended. If possible, the dose should be reduced gradually over one or two weeks. If necessary, substitution therapy is recommended. Abrupt termination of the drug use may provoke “hidden” coronary insufficiency and development of arterial hypertension.

Proarrhythmogenic action

The most dangerous side effect of antiarrhythmic drugs is aggravation of existing arrhythmias or provocation of new arrhythmias. Drugs that prolong the QT interval may provoke pirouette-type polymorphic ventricular tachycardia. The occurrence of these arrhythmias is associated with a prolongation of the QT interval decrease in heart rate decrease in serum potassium and magnesium with high plasma concentration of sotalol as well as the simultaneous use of other drugs that prolong the QT interval. These complications occur more frequently in women.

Polymorphic pirouette-type ventricular tachycardia usually occurs early after initiation of therapy or with dose escalation and resolves spontaneously in most patients. However, dose titration reduces the risk of proarrhythmia. Other risk factors for polymorphic pirouette ventricular tachycardia include significant prolongation of QT interval in association with cardiomegaly or chronic heart failure.

Patients with sustained ventricular tachycardia and chronic heart failure have the highest risk of serious arrhythmias (7%).

Sotalol should be used with extreme caution if the QT interval is longer than 480 ms and the drug dose should be reduced. If QT interval duration exceeds 550 ms, therapy should be discontinued.

Sotalol can only be used after previous antiarrhythmic therapy with close monitoring and at least 2-3 half-lives of the previously prescribed antiarrhythmic drug (see section “Interaction with other drugs”).

Changes on ECG

Excessive prolongation of the QT interval (more than 550 ms) may be a sign of drug toxicity.

Electrolyte disturbances

Sotalol should not be used in patients with hypokalemia or hypomagnesemia until the existing disturbances are corrected as these conditions can prolong the QT interval and increase the possibility of polymorphic ventricular pirouette tachycardia. These electrolyte abnormalities should be corrected before starting Sotalol.

Water-electrolyte balance and acid-base status should be controlled in patients with severe or prolonged diarrhea and in patients receiving medications causing reduction of magnesium and/or potassium in the body.

Chronic heart failure (CHF)

Beta adrenoreceptor blockade may additionally decrease myocardial contractility and provoke exacerbation of CHF symptoms. Caution should be exercised when using Sotalol in patients with CHF receiving standard therapy (angiotensin converting enzyme inhibitors, diuretics, cardiac glycosides, etc.). In patients with left ventricular dysfunction, a lower initial dose of sotalol should be used at the beginning of therapy and the dose should be adjusted further to the clinical situation.

Myocardial infarction

The positive ratio of expected benefit to possible risk of sotalol use in patients after sustained myocardial infarction with left ventricular dysfunction has not been proven. Careful patient monitoring and dose titration are critical during initiation and continuation of therapy. Sotalol should not be used in patients with a left ventricular ejection fraction < 40% without serious ventricular arrhythmias.

Anaphylactoid reactions

When using beta-adrenoblockers, patients with a history of anaphylactic reactions to various allergens may experience more serious allergic reactions if contact with the antigen is repeated. Such patients may not respond to the usual doses of epinephrine (adrenaline) used to treat the allergic reaction. Therefore, the drug Sotalol should be used with extreme caution in case of indications in the anamnesis of allergic reactions and also during desensitization therapy.

Diabetes mellitus

Sotalol should be used with caution in patients with diabetes mellitus or a history of spontaneous hypoglycemia because use of beta-adrenoblockers may mask the signs of acute hypoglycemia (e.g., tachycardia).

Thyrotoxicosis

The use of beta-adrenoblockers may mask some clinical signs of hyperthyroidism (e.g., tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it can exacerbate the symptoms of the disease. Patients with suspected thyrotoxicosis require close monitoring to avoid the development of thyrotoxicosis, including thyrotoxic crisis, when withdrawing the drug.

Pheochromocytoma

When using Sotalol in patients with pheochromocytoma, alpha-adrenoblockers should be used concomitantly.

Psoriasis

Beta-adrenoblockers may worsen the course of psoriasis.

Smoking

The effectiveness of beta-adrenoblockers is lower in smokers than in non-smokers.

Disordered renal function

Because sotalol is primarily excreted by the kidneys in patients with impaired renal function, dosage adjustment is required.

Laboratory studies

The drug should be discontinued before determining blood and urine catecholamine normetanephrine and vanillylmindalic acid; antinuclear antibody titers.

Other

Patients who wear contact lenses should be aware that sotalol therapy may decrease tear fluid production.

It is recommended that therapy be discontinued if depression develops due to taking beta-adrenoblockers.

As with other beta-adrenoblockers, Sotalol should be used with caution in patients who have had surgery.

Alcohol should be avoided during therapy.

Sotalol should be used with caution in elderly patients.

Effects on driving:

Cautious driving and other potentially hazardous activities requiring increased concentration and quick psychomotor reactions (risk of headache and fatigue) should be observed.

Contraindications

– Hypersensitivity to sotalol to other components of the drug and to other sulfonamide derivatives;

– Signs of sinus node weakness syndrome including sinoauricular (sinoatrial) block unless there is a functioning artificial pacemaker;

– grade II or III atrioventricular (AV) block;

– congenital or acquired prolonged QT interval syndrome or use of medications that may prolong the QT interval (see “Interaction with Other Drugs”).

– Bidirectional spindle ventricular tachycardia (polymorphic pirouette ventricular tachycardia) or use of medications associated with this disorder (see “Interaction with Other Medications”).

– symptomatic sinus bradycardia (HR less than 50 bpm);

– uncontrolled chronic heart failure (CHF) including right ventricular CHF due to pulmonary hypertension;

– cardiogenic shock;

– general anesthesia causing suppression of myocardial function;

– arterial hypotension (systolic blood pressure (BP) less than 90 mm Hg).

– hypotension (systolic blood pressure (BP less than 90 mm Hg).

– severe peripheral circulatory disorders, including Raynaud’s syndrome;

– A history of bronchial asthma or chronic obstructive pulmonary disease (COPD);

– metabolic acidosis;

– renal impairment (creatinine clearance < 10 ml/min);

– pheochromocytoma (without concomitant use of alpha-adrenoblockers);

– period of breastfeeding;

– age less than 18 years (efficacy and safety not established);

– lactose intolerance lactase deficiency and glucose-galactose malabsorption syndrome.

With caution:

Caution should be exercised when using Sotalol in patients who have recently had a myocardial infarction (not earlier than 2 weeks after a myocardial infarction) diabetes mellitus psoriasis impaired renal function (CK more than 10 ml/min) atrioventricular (AV) blockade grade I chronic heart failure in disorders of water-electrolyte balance: hypomagnesemia hypokalemia; with prolongation of QT interval in elderly age with surgical interventions allergic reactions in anamnesis (increased sensitivity to allergens may increase the course of arterial hypertension and decreased therapeutic response to adrenaline) and against desensitizing therapy with obliterating diseases of peripheral blood vessels bronchospasm (in anamnesis).

Side effects

According to the World Health Organization, adverse effects are classified according to their frequency of development as follows: frequently (>1/100 < 1/10) infrequently (>1/1000 < 1/100) rarely (>1/10000 < 1/1000) and very rarely (< 1/10000) including individual reports; frequency is unknown – according to available data it was impossible to determine the frequency of occurrence.

Psychiatric disorders: often – feelings of anxiety sleep disturbance (drowsiness or insomnia) mood changes depression state of depression.

Nervous system disorders: frequent – headache dizziness light hallucinations asthenia paresthesia in the extremities syncopal condition; frequency unknown – tremor.

Visual disorders: frequent – visual disturbances; very rare – decreased tear production; frequency unknown – inflammation of the cornea and conjunctiva (should be considered when wearing contact lenses).

Hearing and labyrinth disorders: often – hearing impairment.

Heart disorders: often – bradycardia palpitations palpitations heart rhythm disturbance dyspnea pain chest pain AV block worsening symptoms of heart failure proarrhythmia polymorphic ventricular tachycardia type “pirouette”; frequency is unknown – worsening attacks of angina pectoris.

Vascular disorders: frequently – decreased BP peripheral edema; frequency unknown – syncope cold extremities Raynaud’s disease short-term exacerbation of intermittent claudication.

Respiratory system disorders of the thorax and mediastinum: infrequent – bronchospasm (especially with impaired pulmonary ventilation).

Gastro-intestinal disorders: frequently – change in taste sensation dyspepsia (nausea, vomiting) diarrhea constipation dry mucous membrane of the mouth abdominal pain flatulence.

Skin and subcutaneous tissue disorders: frequency unknown – skin rash skin itching skin redness psoriasiform dermatosis alopecia urticaria.

Muscular and connective tissue disorders: common – muscle weakness cramps.

Gender and mammary gland disorders: often – decreased potency.

General disorders and disorders at the site of administration: often – increased fatigue asthenia fever.

Laboratory and instrumental findings: frequency unknown – increased antinuclear antibody titers may be observed overestimated in urine photometric analysis for methanephrine (O-methyladrenaline).

Metabolic and nutritional disorders: frequency is unknown – hypoglycemia (most likely in patients with diabetes or when strictly following the diet).

Overdose

Symptoms: BP decrease bradycardia bronchospasm hypoglycemia loss of consciousness generalized seizures QT interval prolongation ventricular tachycardia (including polymorphic ventricular tachycardia type “pirouette”); in severe cases – symptoms of cardiogenic shock asystole sometimes with fatal outcome.

Treatment: gastric lavage hemodialysis use of activated charcoal.

Symptomatic therapy:

Bradycardia: atropine – 1-2 times intravenous stream; glucagon – first as a brief intravenous infusion in a dose of 02 mg/kg body weight then in a dose of 05 mg/kg body weight intravenous infusion for 12 hours.

Degree II-III atrioventricular block: placement of a temporary artificial pacemaker is possible.

A marked BP decrease: epinephrine (adrenaline) is effective.

Bronchospasm: aminophylline or beta2-adrenoreceptor sympathomimetics (inhaled).

Polymorphic pirouette-type ventricular tachycardia: cardioversion placement of a temporary artificial pacemaker (if necessary) epinephrine (adrenaline) and/or magnesium sulfate.

Pregnancy use

Pregnancy

There have been no adequately controlled studies in pregnant women. In animal studies, the use of Sotalol did not cause teratogenic or other damaging effects on the fetus.

The use of Sotalol during pregnancy, especially in the first trimester, is possible only for vital indications when the benefit to the mother outweighs the possible risk of fetal/infant adverse events.

Sotalol penetrates the placenta and is detected in the amniotic fluid. Beta-adrenoblockers decrease placental blood flow which can lead to intrauterine fetal death, premature delivery and immature fetal birth. In addition, adverse events (particularly hypoglycemia and bradycardia) may occur in the fetus and the newborn. If the drug is used during pregnancy, it should be discontinued 48-72 hours before the expected delivery date because of the possibility of bradycardia, arterial hypotension, hypokalemia and respiratory depression in neonates. There is an increased risk of heart and lung complications in newborns in the postpartum period. Careful monitoring of neonates is necessary for 48-72 h after delivery.

Breastfeeding

Sotalol penetrates into the breast milk and reaches effective concentrations there. Breast-feeding should be discontinued if it is necessary to use the drug during lactation.

Similarities

Sotagexal, Sotalol, Sotalol Canon