Sotalol

Pharmacological properties

sorhythmic is a non-selective β-adrenergic receptor 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 areas of the cardiac conduction system (III class of antiarrhythmic drugs). reduces heart rate and myocardial contractility, reduces the automatism of the sinus node, slows av-conduction. blocking β2-adrenergic receptors, increases the tone of the smooth muscles of the bronchi, blood vessels.

Pharmacokinetics After oral administration, 75–90% of sotalol hydrochloride is absorbed in the digestive tract. Due to the lack of the effect of the primary passage through the liver, the absolute bioavailability is 75–90%. Time to reach C_max in blood plasma - 2-3 hours. Distribution volume - 1.6–2.4 l / kg. Sotalol does not bind to plasma proteins. 75–90% of the applied dose is excreted by the kidneys unchanged, the rest with feces. The renal clearance is 120 ml / min. T_½ - 10–20 hours. With renal failure, it lengthens to 42 hours, which requires a reduction in the dose of the drug. The drug is excreted during hemodialysis.

Indications

Severe symptomatic ventricular arrhythmias.

Symptomatic supraventricular arrhythmias of the type of tachycardia requiring treatment:

• prevention of chronic atrial fibrillation after pacing with direct current;
• prevention of paroxysmal atrial fibrillation.

Application

When treating life-threatening ventricular arrhythmias with antiarrhythmic drugs, it is necessary to start therapy, as well as increase doses in a hospital setting with the equipment for monitoring and evaluating heart rate variability.

During treatment, control studies should be carried out at regular intervals (for example, using a standard ECG with an interval of 1 month or a long ECG every 3 months and, if necessary, an ECG under load).

Therapy should be reviewed if individual parameters worsen (for example, the duration of the QRS increases or the Q – T interval lengthens above 25%, the P – Q interval lengthens above 50%, or the 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 distributed into 2-3 doses.

The appointment of such a dose requires an assessment of the ratio of potential benefit and risk regarding the possibility of severe adverse reactions (especially proarrhythmogenic effects).

It is recommended to increase the dose with an interval of at least 2-3 days.

Atrial fibrillation. The initial dose of sotalol hydrochloride is 80 mg 2 times a day. In case of insufficient effectiveness, the daily dose can be increased to 80 mg 3 times a day. This dose should not be exceeded in case of paroxysmal atrial fibrillation.

In case of insufficient effectiveness in patients with a chronic form of atrial fibrillation, the dose can be increased to a maximum of 160 mg 2 times a day.

It is recommended to increase the dose with an interval of at least 2-3 days.

Recommended doses for renal failure. Since there is a risk of accumulation of sotalol against the background of repeated use in patients with impaired renal function, the dose of such patients should be adjusted depending on the creatinine clearance, taking into account heart rate (not less than 50 beats / min) and clinical effectiveness.

In severe renal failure, the use of sotalol hydrochloride is recommended only with regular monitoring of the ECG and the concentration of the drug in the blood plasma.

If creatinine clearance is 60 ml / min, the recommended dose should be prescribed; with creatinine clearance of 30-60 ml / min, a dose reduction of 50% is recommended; with a clearance of 10-30 ml / min, use ¼ of the recommended dose; with creatinine clearance of 10 ml / min, do not use the drug.

Elderly patients. For the treatment of elderly patients, possible impaired renal function should be considered.

Mode of application. The tablets should be swallowed without chewing, washed down with a sufficient amount of liquid (for example, 1 glass of water) before eating. The drug Soritmic should not be used with food, since the absorption of sotalol hydrochloride in the digestive tract can be reduced (in particular, milk and dairy products).

Duration of use. The duration of treatment is determined by the doctor.

Patients who have suffered myocardial infarction, or patients with severe cardiac impairment, need constant careful medical supervision during dose adjustment of antiarrhythmic drugs.

In the case of prolonged use of the drug or in patients with coronary heart disease and / or with arrhythmia, drug therapy should be discontinued gradually, since sudden withdrawal can lead to a worsening of the clinical condition.

Contraindications

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

NYHA grade IV heart failure, acute and chronic heart failure II – III degree (at the stage of decompensation), acute myocardial infarction, AV block II – III degree (if the patient has a functioning pacemaker installed), ventricular tachycardia according to the torsades de pointes type or taking drugs that provoke the development of this disease, sinoatrial blockade, sinus node weakness syndrome (including sinoatrial blockade, if the patient has a functioning pacemaker), symptomatic sinus bradycardia ( 50 beats / min), severe sinus node dysfunction, congenital or acquired syndrome of an extended Q – T interval or taking drugs that cause an extension of the Q – T interval, severe or uncontrolled chronic heart failure, including heart failure of the right ventricle after pulmonary hypertension, Prinzmetal angina pectoris, cardiogenic shock, renal failure (creatinine clearance 10 ml / min), hypokalemia, hypomagnesemia, arterial hypotension, severe peripheral circulatory disorders, BA and COPD, edema g ortany, allergic rhinitis, metabolic acidosis, untreated pheochromocytoma, diabetes mellitus, cardiomegaly (without signs of heart failure), peripheral vascular occlusion diseases (complicated by gangrene, intermittent claudication or pain at rest), Raynauds syndrome, anesthesia with drugs that cause myocardial depression concomitant use of MAO-A inhibitors, flactaphenin.

For patients treated with sotalol (with the exception of intensive drug treatment), intravenous administration of calcium antagonists such as verapamil and diltiazem or other antiarrhythmic drugs is contraindicated.

Side effects

On the part of the immune system: sotalol can increase sensitivity to allergens and the severity of anaphylactic reactions, hypersensitivity reactions.

Metabolic and nutritional disorders: hypoglycemia (signs of a decrease in blood glucose, in particular tachycardia, may be masked during drug therapy).This should be taken into account for patients who have a long-term fasting, patients with diabetes mellitus and with a spontaneous history of hypoglycemia. Hyperglycemia, hypothyroid state. An increase in the level of total cholesterol and TG, a decrease in the level of HDL cholesterol.

From the psyche: anxiety, confusion, mood changes, hallucinations, increased irritability, depression; sleep disturbance.

From the side of the nervous system: dizziness, drowsiness, headache, dissomnia, paresthesia, a feeling of coldness in the limbs, weakness, convulsions, tremors.

From the side of the organ of vision: visual impairment; conjunctivitis; keratoconjunctivitis, decreased secretion of tear fluid (especially when using contact lenses), dryness and pain in the eyes, inflammation of the cornea and conjunctiva, photophobia.

On the part of the hearing organ: hearing impairment.

From the cardiovascular system: chest pain, orthostatic hypotension, increased symptoms of heart failure (ankle swelling, feet, shortness of breath), bradycardia, palpitations, ECG deviations, impaired myocardial conduction, AV block, syncopal or presyncopal conditions, proarrhythmogenic effects (rhythm change or increased arrhythmia, which can lead to a significant violation of cardiac activity with possible cardiac arrest), weakening of the myocardial contractile function, manifestations of angiospasm (enhanced peripheral circulation disorders, a feeling of cold extremities, intermittent claudication, Raynauds syndrome). Arrhythmogenic effects are more often noted in patients with severe, life-threatening arrhythmias and left ventricular dysfunction; an increase in the number of angina attacks and a violation of peripheral perfusion. Considering that sotalol prolongs the Q – T interval, ventricular tachyarrhythmia (including torsades de pointes) may occur during its use, especially in cases of overdose.

Severe proarrhythmogenic effects (persistent ventricular tachycardia or ventricular flutter / fibrillation or torsades de pointes) mainly depend on the dose of the drug and occur mainly at the beginning of therapy and with an increase in dose.

From the respiratory system: rhinitis, shortness of breath, bronchospasm, laryngospasm; dyspnea (may occur in patients with obstructive pulmonary disorders); allergic bronchitis with fibrosis.

From the digestive system: taste disturbances, abdominal pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, xerostomia; constipation, dry mouth, anorexia, impaired liver function (dark urine, yellowness of the sclera or skin, cholestasis).

On the part of the skin: erythema, skin rash, urticaria, pruritus, exanthema, increased sweating, hyperemia of the skin; alopecia; psoriasis-like exanthema, the appearance / progression of psoriasis symptoms.

From the musculoskeletal system: muscle spasm or myasthenia gravis, back pain, arthralgia, muscle pain.

From the reproductive system: impaired potency.

Common disorders: fever, fatigue, cyanosis of the limbs, asthenia, withdrawal syndrome.

Laboratory indicators: thrombocytopenia, agranulocytosis, leukopenia, the formation of antinuclear antibodies, changes in enzyme activity, bilirubin level.

special instructions

Particularly careful medical supervision is necessary in such cases:

• impaired renal function (dose reduction): regular monitoring of renal function, including determination of creatinine level, is necessary; it is also advisable to control the concentration of sotalol in blood plasma;
• patients with diabetes mellitus with significant fluctuations in blood glucose levels (while the 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): in the treatment of patients with suspected thyrotoxicosis, the rapid discontinuation of sotalol should be avoided, since exacerbation of symptoms of hyperthyroidism, in particular thyrotoxic crisis, is possible;
• peripheral perfusion disorders, such as Raynauds syndrome and intermittent claudication: complaints may occur at the beginning of treatment;
• patients with pheochromocytoma: sotalol hydrochloride can be used only after preliminary blockade of α-adrenergic receptors;
• patients with an atopic history, history of anaphylactic reactions and patients receiving desensitizing therapy (a possibly more severe course of anaphylactic reactions and insensitivity to the usual doses of adrenaline (epinephrine) in their treatment);
• patients with vasospastic angina (Prinzmetal angina), myasthenia gravis, depression (including a history)
• in the presence of conditions and / or the use of drugs, causing lengthening of the Q – T interval;
• patients who have recently suffered myocardial infarction (increased risk of arrhythmogenic effects);
• patients with sinus node dysfunction syndrome associated with symptomatic arrhythmias (sotalol hydrochloride may cause sinus bradycardia, sinus pauses, or sinus stop);
• patients with congestive heart failure;
• patients with psoriasis (increased symptoms of psoriasis).

Sotalol hydrochloride may increase the severity of existing arrhythmias or cause new ones. Proarrhythmogenic effects can be varied: from an increase in the frequency of premature ventricular contractions to the development of more severe ventricular tachycardia, ventricular fibrillation, or pirouette tachycardia. Risk factors that increase the likelihood of pirouette tachycardia are: dose, the presence of persistent ventricular tachycardia, gender (the frequency of occurrence is higher in women), an excessive increase in the duration of the Q – Tc interval, cardiomegaly, or chronic heart failure.

If during the treatment, the duration of the Q – Tc interval exceeds 500 ms, caution is required during use, and if it exceeds 550 ms, a dose reduction or cessation of drug use is necessary. Proarrhythmogenic effects are most often observed in the first 7 days after the start of therapy or with an increase in dose. 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 effectiveness (programmed pacemaker or ECG monitoring according to Holter) and safety (Q-T interval duration, heart rate and plasma electrolyte levels )

In cases of severe diarrhea or competitive administration of drugs that cause loss of magnesium and / or potassium, it is necessary to monitor the electrolyte balance and acid-base balance.

Do not use sotalol in patients with hypokalemia or hypomagnesemia before correcting the imbalance due to the likelihood of risks of lengthening the Q – T interval and the development of ventricular tachycardia according to the torsades de pointes type.

Monitoring of patients using the drug Soritmic should include monitoring of heart rate, blood pressure, ECG, blood glucose in patients with diabetes mellitus. In elderly patients, it is necessary to monitor renal function indicators. Patients with renal failure need to adjust the dosage regimen.

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

Sotalol should not be used in patients with left ventricular ejection fractions of 40% without severe ventricular arrhythmias.

In patients with left ventricular dysfunction who have recently suffered myocardial infarction, the possible benefits and risks of using sotalol must be carefully weighed. Careful monitoring and dose titration are extremely important before and after starting therapy.

Before prescribing a drug, it is necessary to cancel other antiarrhythmic drugs; a break in treatment should be at least 2-3 T_½ the latter.

At the end of the course of treatment, the use of sotalol hydrochloride must be stopped gradually, reducing the dose for 2 weeks or more, under the supervision of a doctor. The frequency of use of the drug cannot be changed. Sudden cancellation can unmask the latent form of heart failure, in addition, hypertension can develop.

In the treatment of 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 under normal dosage.

Patients who use contact lenses should take into account that tear fluid production may be reduced during treatment.

Due to the blockade of β-adrenergic receptors, sotalol may increase sensitivity to allergens and the severity of anaphylactic reactions, which should be considered when treating patients with severe hypersensitivity reactions (including a history) and patients undergoing desensitizing therapy.

If surgery is necessary, the anesthetist should be advised of the use of sotalol; a few days before the operation, it is necessary to stop the use of sotalol or to choose an anesthesia drug with minimal negative inotropic effect.

In isolated cases, the drug can cause psoriasis, an increase in the severity of its symptoms or lead to psoriasis-like exanthema.

Sotalol should be used with caution in AV blockade of the first degree due to the negative effect on conductivity.

The use of sotalol is contraindicated in severe allergic rhinitis due to increased airway obstruction.

Due to the presence of sotalol hydrochloride in the urine, the photometric determination of methanephrine can lead to overestimated values.

In patients with suspected pheochromocytoma receiving sotalol hydrochloride, urinalysis should be performed using high performance liquid chromatography 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 can lead to positive doping test results.

Patients with shortness of breath can be prescribed a drug, provided that a careful assessment of the ratio of benefit and risk is provided.

During treatment, you should not drink alcohol due to the likelihood of developing orthostatic hypotension.

Use during pregnancy and lactation. Since there is insufficient experience with the use of sotalol hydrochloride during pregnancy, the drug can 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 the tissues of the fetus; therefore, adverse reactions such as bradycardia, arterial hypotension, and hypoglycemia can be expected in the fetus or baby. For this reason, therapy must be interrupted 48–72 hours before the calculated date of birth. After birth, babies need to be carefully monitored for a while (development of β-receptor blockade is possible).

Blockers of β-adrenergic receptors can cause a decrease in placental blood flow, which can lead to fetal death of the fetus, premature birth.

Sotalol hydrochloride accumulates in breast milk, reaching concentrations 3-5 times higher than the concentration in the blood plasma of the mother. Breastfeeding during drug treatment should be discontinued.

Children. Do not use the drug in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. During treatment, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

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 the use of sotalol together with other β-adrenoreceptor blockers, additive effects of class II can be expected (decrease in blood pressure and heart rate);
• with drugs that increase the duration of the Q – T interval (class I and III antiarrhythmic drugs, phenothiazine derivatives, tri- and tetracyclic antidepressants, terfenadine, astemizole, erythromycin, lithium drugs, quinoline antibiotics, halofantrine, pentamidine drugs, neuroleptamidets, , antihistamines, sedatives, hypnotics and ethanol.

The combined use of sotalol hydrochloride with tricyclic antidepressants, barbiturates, phenothiazine and narcotic analgesics, as well as antihypertensive drugs, diuretics and vasodilators can lead to an excessive decrease in blood pressure.

Means for inhalation anesthesia (hydrocarbon derivatives) and muscle relaxants increase the risk of inhibition of myocardial function and the development of arterial hypotension.

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

In the case of combined use with drugs that deplete the reserves of catecholamines (reserpine, guanitidine), an excessive decrease in the tone of the sympathetic nervous system is possible. In patients, it is necessary to regularly monitor blood pressure and heart rate, since arterial hypotension, severe bradycardia, and loss of consciousness are possible.

The negative chronotropic and negative dromotropic effects of sotalol hydrochloride may increase with simultaneous use with reserpine, clonidine, α-methyldopa, guanfacin and cardiac glycosides.

In the case of combined use with digoxin, the likelihood of proarrhythmogenic effects increases, the positive inotropic effect of digitalis glycosides decreases. Both digitalis glycosides and sotalol hydrochloride slow down AV conduction. If, despite adequate digitalis glycoside therapy, there is no decrease in the severity of heart failure, the use of sotalol should be discontinued.

With concomitant use with antihypertensive drugs (diuretics, sympatholytics, clonidine, hydralazine), an excessive decrease in blood pressure is possible.

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

With the simultaneous use of sotalol with amphotericin B, corticosteroids should monitor the level of potassium in the patients blood.

Iodine-containing radiopaque substances for iv administration increase the risk of anaphylactic reactions.

Xanthines and sympathomimetics decrease sotalol activity.

With simultaneous use with β agonists₂receptors, such as salbutamol, terbutaline and isoprenaline, it may be necessary to increase the dose of β agonist₂receptors.

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 antiarrhythmic drugs increase the violation of AV conduction, increase the risk of developing or increasing the severity of AV block and heart failure. When combined with calcium channel blockers, an additive hypotensive effect on blood pressure is possible.

The simultaneous use of calcium ion antagonists such as nifedipine can lead to a significant decrease in blood pressure, an increase in the syndrome of weakness of the sinus node.

Norepinephrine, MAO-B inhibitors, and the sudden cessation of clonidine may potentiate rebound hypertension. The use of sotalol must be stopped a few days before the gradual completion of clonidine administration, and the break in treatment with MAO-B inhibitors and sotalol should be at least 14 days.

Floktafenin. Β-adrenoreceptor blockers can interfere with compensatory cardiovascular reactions associated with arterial hypotension or shock, and can be caused by flactaphenin.

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

The simultaneous use with insulin or oral hypoglycemic agents, especially during severe physical exertion, can induce hypoglycemia and mask its symptoms.

Neuromuscular blockade caused by tubocurarine can be enhanced by blocking β-adrenergic receptors.

The negative inotropic effect of sotalol hydrochloride and narcotic analgesics or antiarrhythmic drugs can be additive.

Overdose

Symptoms symptoms of an overdose of sotalol hydrochloride depend on the general condition of the patients cardiac activity (left ventricular function, cardiac arrhythmia). in the case of severe heart failure, even at the lowest doses, a deterioration in heart function is possible.

Depending on the degree of intoxication, overdose symptoms may occur such as dizziness, fainting, weakness, asystole, symptoms of cardiogenic or hypovolemic shock, heart failure, AV block, arrhythmia, cyanosis of the nails or palms, convulsions, shortness of breath, bronchospasm, hypoglycemia, fatigue, loss of consciousness, mydriasis, sometimes generalized attacks, arterial hypotension, hypoglycemia, severe bradycardia up to cardiac arrest (slowed rhythm on the ECG), lengthening of the Q – T interval, chronic heart failure, atypical ventricular tachycardia (torsades de pointes), symptoms of cardiovascular shock. An overdose of sotalol hydrochloride in isolated cases was fatal.

Treatment. It is necessary to stop the use of the drug; gastric lavage is indicated, the maintenance of vital functions of the body. Therapy is symptomatic.

According to indications, administer atropine 1–2 mg iv in the form of 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: first 1–10 mg iv, then 2–2.5 mg / 1 h as a continuous infusion.

In case of bradycardia, atropine, other anticholinergic drugs, β-adrenergic agonists or transvenous pacemaking are indicated; with heart block (II or III degree) - isoproterenol or transvenous pacemaking; with heart failure - cardiac glycosides, diuretics, glucagon; with arterial hypotension (depending on the associated factors) - if necessary, in addition to atropine and digitalis glycosides, it is more advisable to use epinephrine than isoproterenol or norepinephrine; with bronchospasm - stimulants β₂-adrenoreceptors in the form of an aerosol or aminophylline; with hypoglycemia - iv administration of glucose; with pirouette tachycardia - epinephrine, magnesium sulfate, transvenous cardiac pacing, pacing with direct current.

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 Soritmic, but in the case of isoproterenol, you must be prepared for the complications associated with high doses.

The drug is excreted by hemodialysis.

Storage conditions

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