Strofantin-g

INSTRUCTION for medical use of the medicinal product STROPHANTHIN-G

Composition:

Active substance: g-strophanthin;

1 ml of solution contains ouabain (g-strophanthin) 0.25 mg;

Excipients: citric acid monohydrate; sodium hydroxide; water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: colorless clear liquid.

Pharmacotherapeutic group. Cardiotonic agents. Cardiac glycosides. ATC code C01AC01.

Pharmacological properties.

Pharmacodynamics. Strophanthin is a cardiac glycoside isolated from Strophanthus gratus and is one of the main "polar" cardiac glycosides. The drug exerts a cardiotonic effect, increasing the force and velocity of myocardial contraction (positive inotropic effect), reducing heart rate (negative chronotropic effect), and decreasing atrioventricular conduction (negative dromotropic effect). In heart failure, it increases stroke volume and cardiac output, improves ventricular emptying, and thereby enhances circulation.

The mechanism of action of strophanthin involves partial inhibition of Na⁺/K⁺-ATPase in myocardial cell membranes, resulting in reduced potassium influx into cardiomyocytes and decreased sodium efflux. It stimulates a vagotrophic effect (bradycardia) by delaying impulse conduction through the heart's conducting system. ECG changes during strophanthin administration include QT interval prolongation, ST segment depression below the isoelectric line, increased PP interval, prolonged PQ interval, and flattening or inversion of the T wave.

Pharmacokinetics. After intravenous administration, approximately 40% of the administered dose binds to plasma proteins. The time to reach maximum plasma concentration ranges from 0.5 to 2 hours. The drug undergoes minimal biotransformation. It is excreted unchanged by the kidneys in 70–90% of the dose; the remainder is excreted via bile into the intestine. The elimination half-life (T½) averages 23 hours, and the drug's effect lasts 2–3 days. In patients with chronic renal insufficiency, the T½ of the drug is prolonged.

Clinical characteristics.

Indications. Acute heart failure, chronic heart failure stage IІb–III (III–IV stage according to NYHA classification), supraventricular tachycardia, atrial fibrillation.

Contraindications. Hypersensitivity to the components of the drug. Glycoside intoxication, constrictive pericarditis, acute myocardial infarction, ventricular tachycardia, marked bradycardia, atrioventricular block of degree II and III, sinoatrial node weakness syndrome, hypercalcemia, hypokalemia, isolated mitral stenosis, hypertrophic obstructive cardiomyopathy, pericarditis, acute myocarditis, endocarditis, marked cardiac sclerosis, carotid sinus syndrome, aneurysm of the thoracic aorta, Wolff–Parkinson–White syndrome.

Interaction with other medicinal products and other forms of interaction. Sympathomimetics, methylxanthines, reserpine, tricyclic antidepressants, phosphodiesterase inhibitors (e.g., theophylline) – when used concomitantly with ouabain, increase the risk of cardiac rhythm disturbances.

Methyldopa, clonidine, spironolactone, verapamil, quinidine, amiodarone, captopril, calcium antagonists, erythromycin, tetracyclines – when used concomitantly, increase the concentration of ouabain in blood plasma.

Diuretics (especially thiazide and carbonic anhydrase inhibitors), glucocorticoids, catecholamines, insulin, calcium preparations – when used concomitantly with ouabain, increase the risk of glycoside intoxication.

Glucocorticoids and diuretics – when used concomitantly with ouabain, increase the risk of developing hypokalemia and hypomagnesemia.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers – when used concomitantly with ouabain, reduce the risk of developing hypokalemia and hypomagnesemia.

ß-adrenoblockers and antiarrhythmic drugs of class Ia, verapamil, magnesium sulfate – when used concomitantly with ouabain, more pronounced reduction in atrioventricular conduction occurs.

Special precautions. The drug has a narrow therapeutic window; therefore, individual dose selection must be performed carefully.

ECG monitoring is required during intravenous administration of the drug and for 1 hour thereafter. If frequent grouped or polytopic ventricular extrasystoles occur, administration must be stopped, and the next dose should be reduced by half.

In renal insufficiency, the dose of the drug should be slightly reduced to prevent glycoside intoxication. Hypokalemia, hypomagnesemia, and hypercalcemia increase the likelihood of relative overdose.

In cases of marked cardiac chamber dilation, cor pulmonale, alkalosis, and in elderly patients, dose adjustment is required to prevent overdose.

When first-degree atrioventricular conduction disturbance is present, administration of the drug must be accompanied by ECG monitoring.

If the patient has previously received other cardiac glycosides, a pause is required before administering ouabain, since its effect may add to that of accumulated digitalis glycosides. The duration of the pause is 5 days; however, if drugs with strong cumulative effect (digoxin) were used, the pause should be extended to 10–14 days.

In patients with impaired renal function, as well as elderly and senile patients, the drug is recommended to be administered in slightly reduced doses, starting with 0.125–0.15–0.2 mg, and subsequently not exceeding 0.25 mg per day (except in emergency conditions).

Use with special caution in patients with thyrotoxicosis and atrial extrasystoles.

Rapid intravenous administration may lead to bradyarrhythmia, ventricular tachycardia, atrioventricular block, or cardiac arrest. To prevent this effect, the daily dose should be divided into 2–3 administrations, or one of the doses should be administered intramuscularly.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding. The drug is contraindicated during pregnancy and breastfeeding.

Ability to affect reaction speed when driving or operating machinery. During treatment with this drug, patients should refrain from driving vehicles or operating machinery.

Method of Administration and Dosage

The drug should be administered intravenously to adults at a dose of 1–2 mL, diluted in 10–20 mL of 0.9% sodium chloride solution. It should be injected slowly over 5–6 minutes. Administration should be performed once or twice daily. If possible, it is preferable to administer the drug by intravenous infusion; for this, 1 mL of the drug should be diluted in 100 mL of 5% glucose solution or 0.9% sodium chloride solution. Infusion administration reduces the risk of toxic effects. An ECG monitoring must be performed 1 hour after intravenous administration. If frequent, grouped, or multifocal ventricular extrasystoles occur, administration of the drug must be discontinued and the next dose reduced by half. In patients with renal insufficiency and elderly patients, the drug should be administered in reduced doses, starting with 0.125 mg, and should not exceed 0.25 mg daily (except in emergency situations).

If necessary, the single dose may be increased by administering additional 0.1–0.15 mg (0.2–0.3 mL) at intervals of 0.5–2 hours. However, the maximum single dose should not exceed 0.25 mg, and the daily dose should not exceed 1 mg (4 mL).

Children. There is no experience with the use of the drug in children; therefore, it should not be prescribed to this age group.

Overdose. The clinical picture of overdose (glycoside intoxication) may manifest with various clinical symptoms:

Cardiovascular system: atrioventricular block and cardiac arrhythmias, including bradycardia, paroxysmal ventricular tachycardia, ventricular extrasystoles, bigeminy, multifocal ventricular tachycardia, sinoatrial block, ventricular fibrillation; in severe cases, ventricular flutter and cardiac arrest may develop;

Gastrointestinal tract: anorexia, nausea, vomiting, diarrhea, intestinal wall necrosis;

Central nervous system and sensory organs: headache, dizziness, paresthesias, neuritis, radiculitis, perception of surrounding objects in green or yellow hues, flickering "spots" before the eyes, decreased visual acuity, scotomas, macropsia and micropsia; very rarely, confusion, syncope, and manic-depressive syndrome may occur.

Treatment: discontinue the drug, administer potassium and magnesium preparations, and give unithiol parenterally. Further treatment is symptomatic; antiarrhythmic agents (lidocaine, diphenin, amiodarone) should be administered in case of ectopic arrhythmias.

Adverse Reactions

The development of adverse reactions is mainly associated with drug overdose, too rapid intravenous administration, or increased individual sensitivity of the patient to cardiac glycosides. The following clinical symptoms may occur:

Central and peripheral nervous system: headache, dizziness, confusion, increased fatigue, drowsiness, sleep disturbances, psychiatric disorders (depression, hallucinations, delirious psychosis);

Eyes: visual disturbances;

Gastrointestinal tract: decreased appetite, nausea, vomiting, diarrhea; in severe cases – mesenteric infarction;

Endocrine system: gynecomastia in males (in isolated cases);

Blood system: thrombocytopenic purpura, petechiae, nosebleeds;

Cardiovascular system: cardiac arrhythmias (bradyarrhythmia, ventricular tachycardia) and conduction disturbances (atrioventricular block);

Immune system: anaphylactic reactions, urticaria;

Other: allergic reactions, injection site reactions.

Shelf life. 5 years.

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

Keep out of reach of children.

Incompatibility. The drug is incompatible when administered in the same syringe or infusion with the following solutions: sodium bicarbonate, aminazine. Such combinations reduce the pharmacological activity of strophanthin.

Packaging. 1 ml in vials, 10 vials per pack; 10, 5×2 in blisters per pack.

Prescription status. Prescription only.

Manufacturer.

Limited Liability Company "Experimental Plant "GNCLC".

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and place of business.

8 Vorobiova Street, Kharkiv, Kharkiv Oblast, Ukraine.

(Limited Liability Company "Experimental Plant "GNCLC")

22 Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA")