Strophanthin^® K (Solution) Instructions for Use

Marketing Authorization Holder

Halychpharm, JSC (Ukraine)

ATC Code

C01AC01 (Strophanthin-G)

Dosage Form

Strophanthin® K

Solution for intravenous and intramuscular injection 250 mcg/1 ml: amp. 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular injection transparent, colorless or slightly yellowish in hue.

Excipients: ethanol 96% – 20 µl, water for injection – up to 1 ml.

1 ml – ampoules of colorless glass (10) – cardboard boxes.
1 ml – ampoules of colorless glass (10) – contour cell packs (1) – cardboard packs.

Clinical-Pharmacological Group

Cardiac glycoside

Pharmacotherapeutic Group

Cardiotonic agent – cardiac glycoside

Pharmacological Action

Strophanthin^® K is a short-acting cardiac glycoside that blocks the transport Na+/K+-ATPase, resulting in an increase in the sodium ion content in cardiomyocytes, which leads to the opening of calcium channels and the entry of calcium ions into cardiomyocytes.

The excess of sodium ions leads to accelerated release of calcium ions from the sarcoplasmic reticulum, thus the intracellular concentration of calcium ions increases, which leads to the blockade of the troponin complex, which has an inhibitory effect on the interaction of actin and myosin.

It increases the strength and speed of myocardial contraction, which occurs by a mechanism different from the Frank-Starling mechanism and does not depend on the degree of preliminary myocardial stretching; systole becomes shorter and more energy-efficient. As a result of increased myocardial contractility, stroke volume and minute blood volume increase.

It reduces end-systolic volume and end-diastolic volume of the heart, which, along with an increase in myocardial tone, leads to a reduction in its size and thus to a decrease in myocardial oxygen demand.

The negative dromotropic effect is manifested in an increase in the refractoriness of the atrioventricular node, which allows the use of the drug for paroxysms of supraventricular tachycardia and tachyarrhythmia. In atrial tachyarrhythmia, it slows the heart rate, prolongs diastole, improving intracardiac and systemic hemodynamics. The decrease in heart rate occurs as a result of direct and indirect effects on the regulation of heart rhythm.

It has a direct vasoconstrictor effect (in the case where the positive inotropic effect of cardiac glycosides is not realized – in patients with normal contractility or with excessive heart stretching); in patients with chronic heart failure, it causes an indirect vasodilatory effect, reduces venous pressure, increases diuresis: reduces edema, shortness of breath. The positive bathmotropic effect is manifested in subtoxic and toxic doses. It has a slight negative chronotropic effect. When administered intravenously (IV), the action begins after 10 minutes and reaches a maximum after 15-30 minutes.

Pharmacokinetics

The cumulative effect is practically absent.

Distribution is relatively uniform; it is concentrated to a somewhat greater extent in the tissues of the adrenal glands, pancreas, liver, and kidneys. 1% of the drug is found in the myocardium. Binding to plasma proteins is 5%.

Elimination. It is not subject to biotransformation, it is excreted by the kidneys unchanged. 85-90% of the drug is excreted within 24 hours; plasma concentration decreases by 50% after 8 hours; it is completely eliminated from the body after 1-3 days.

Indications

• As part of complex therapy for acute and chronic heart failure of functional class II (in the presence of clinical manifestations), III-IV functional class according to the NYHA classification;
• Tachysystolic form of atrial fibrillation and atrial flutter of paroxysmal and chronic course (especially in combination with chronic heart failure).

ICD codes

Dosage Regimen

Strophanthin^® K is used intravenously, intramuscularly, only in emergency situations when it is impossible to use cardiac glycosides orally. For intravenous administration, a 0.025% solution of the drug is used. It is diluted in 10-20 ml of 5% dextrose (glucose) solution or 0.9% sodium chloride solution. Administration is carried out slowly, over 5 – 6 minutes (because rapid administration can cause shock). Strophanthin K solution can also be administered by drip (in 100 ml of 5% dextrose (glucose) solution or 0.9% sodium chloride solution), since the toxic effect develops less frequently with this form of administration.

The maximum doses of Strophanthin K for adults intravenously: single – 2 ml (2 ampoules), daily – 4 ml (4 ampoules).

If intravenous administration is not possible, the drug is used intramuscularly. To reduce sharp pain during intramuscular injection, 5 ml of a 2% procaine solution is first injected, and then, through the same needle, the required dose of Strophanthin K, diluted in 1 ml of a 2% procaine solution, is administered. For intramuscular administration, the doses are increased by 1.5 times.

For children daily doses, which are also saturation doses when using a 0.025% solution of Strophanthin K; for newborns – 0.06-0.07 ml/kg; up to 3 years – 0.04-0.05 ml/kg; from 4 to 6 years – 0.4-0.5 ml/kg; from 7 to 14 years – 0.5-1 ml. The maintenance dose is 1/2-1/3 of the saturation dose.

Adverse Reactions

From the gastrointestinal tract decreased appetite, nausea, vomiting, diarrhea.

From the cardiovascular system bradycardia, extrasystole, atrioventricular block, ventricular paroxysmal tachycardia, ventricular fibrillation.

From the central nervous system headache, dizziness, sleep disturbances, fatigue, impaired color perception, depression, drowsiness, psychoses, confusion.

Other allergic reactions, urticaria, petechiae, thrombocytopenia, thrombocytopenic purpura, nosebleeds, gynecomastia. With the intramuscular method of administration, pain at the injection site.

Contraindications

• Glycoside intoxication;
• Wolff-Parkinson-White syndrome;
• Second-degree atrioventricular block;
• Intermittent atrioventricular or sinoatrial complete block;
• Hypersensitivity to the drug.

With caution (weighing benefit/risk): first-degree atrioventricular block, sick sinus syndrome without an artificial pacemaker, the likelihood of unstable conduction through the atrioventricular node, history of Morgagni-Adams-Stokes attacks, hypertrophic obstructive cardiomyopathy, isolated mitral stenosis with a low heart rate, cardiac asthma in patients with mitral stenosis (in the absence of tachysystolic form of atrial fibrillation), acute myocardial infarction, unstable angina, arteriovenous shunt, hypoxia, constrictive pericarditis, heart failure with impaired diastolic function (restrictive cardiomyopathy, cardiac amyloidosis, constrictive pericarditis, cardiac tamponade), ventricular extrasystole, severe dilation of the heart chambers, cor pulmonale. Atrial extrasystole due to the possibility of its transition to atrial fibrillation.

Electrolyte disturbances: hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia. Hypothyroidism, alkalosis, myocarditis, old age, renal-hepatic failure, thyrotoxicosis.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and breastfeeding due to the lack of data on safety of use.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

There are no age restrictions for use.

Geriatric Use

Use with caution in elderly persons.

Special Precautions

Use with particular caution in patients with thyrotoxicosis and atrial extrasystole.

Given the low therapeutic index, careful medical supervision and individual dose selection are necessary during treatment.

If renal excretory function is impaired, the dose should be reduced (prevention of glycoside intoxication).

The likelihood of overdose increases with hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia, severe dilation of the heart chambers, cor pulmonale, alkalosis, and in elderly patients. Particular caution and electrocardiographic monitoring are required in case of impaired atrioventricular conduction.

In pronounced mitral stenosis with normo- or bradycardia, chronic heart failure develops due to reduced diastolic filling of the left ventricle. Strophanthin^® K, by increasing the contractility of the right ventricular myocardium, causes a further increase in pressure in the pulmonary artery system, which can provoke pulmonary edema or worsen left ventricular failure. In patients with mitral stenosis, cardiac glycosides are prescribed when right ventricular failure is associated or in the presence of atrial tachyarrhythmia. Strophanthin^® K, in Wolff-Parkinson-White syndrome, by reducing atrioventricular conduction, promotes the conduction of impulses through accessory pathways – bypassing the atrioventricular node, provoking the development of paroxysmal tachycardia. One of the methods for controlling digitalization is monitoring the plasma concentration of cardiac glycosides.

With rapid intravenous administration, the development of bradyarrhythmia, ventricular tachycardia, atrioventricular block, and cardiac arrest is possible. At the peak of action, extrasystole may appear, sometimes in the form of bigeminy. To prevent this effect, the dose can be divided into 2-3 intravenous administrations or the first of the doses is administered intramuscularly. If the patient has previously been prescribed other cardiac glycosides, it is necessary to take a break before intravenous administration of Strophanthin K (5-24 days – depending on the severity of the cumulative properties of the previous drug).

Effect on the ability to drive vehicles and mechanisms

During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions (driving a car, etc.).

Overdose

Symptoms

From the cardiovascular system arrhythmias, including bradycardia, atrioventricular block, ventricular paroxysmal tachycardia, ventricular fibrillation, ventricular extrasystole (bigeminy, polytopic), nodal tachycardia, sinoatrial block, atrial fibrillation and flutter.

From the gastrointestinal tract anorexia, nausea, vomiting, diarrhea.

From the central nervous system and sensory organs headache, increased fatigue, dizziness, rarely – coloring of surrounding objects in green and yellow, sensation of flickering spots before the eyes, decreased visual acuity, scotoma, macro- and micropsia; very rarely – confusion, syncope.

Treatment withdrawal of the drug or reduction of subsequent doses and increase in the time intervals between drug administrations, administration of antidotes (sodium dimercaptopropanesulfonate), symptomatic therapy (antiarrhythmic drugs – lidocaine, phenytoin, amiodarone; potassium preparations; m-cholinoblockers – atropine sulfate). As antiarrhythmic agents – class I drugs (lidocaine, phenytoin). For hypokalemia – IV administration of potassium chloride (6-8 g/day based on 1-1.5 g per 0.5 l of 5% dextrose (glucose) solution and 6-8 units of insulin; administered by drip, over 3 hours). For severe bradycardia, atrioventricular block – m-cholinoblockers. It is dangerous to administer beta-adrenomimetics, due to the possible enhancement of the arrhythmogenic effect of cardiac glycosides. For complete transverse block with Morgagni-Adams-Stokes attacks – temporary electrocardiostimulation.

Drug Interactions

When Strophanthin K is used together with barbiturates (phenobarbital, etc.), the cardiotonic effect of the glycoside decreases. Simultaneous use of Strophanthin K with sympathomimetics, methylxanthines, reserpine and tricyclic antidepressants increases the risk of arrhythmias. The concentration of Strophanthin K in plasma increases with simultaneous use of quinidine, methyldopa, amiodarone, captopril, calcium antagonists, erythromycin and tetracycline. Against the background of magnesium sulfate, the possibility of slowing conduction and occurrence of atrioventricular heart block increases. Diuretics (to a greater extent thiazides and carbonic anhydrase inhibitors), corticotropin preparation (adrenocorticotropic hormone), glucocorticosteroids, insulin, calcium preparations, laxatives, carbenoxolone, amphotericin B, benzylpenicillin, salicylates increase the risk of glycoside intoxication. Beta-blockers, antiarrhythmic agents, verapamil can not only enhance the severity of the decrease in atrioventricular conduction (negative dromotropic action), but also potentiate the negative chronotropic action of the drug Strophanthin^® K (slowing of heart rate). Inducers of liver microsomal enzymes (phenytoin, rifampicin, phenobarbital, phenylbutazone), as well as neomycin and cytotoxic agents reduce the concentration of Strophanthin K in plasma. Glycoside intoxication can be caused, due to the development of hypokalemia, by carbonic anhydrase inhibitor, mineralocorticoids, therefore, with their simultaneous use with cardiac glycosides, it is necessary to regularly determine the potassium content in plasma. Potassium salt preparations should not be used if conduction disturbances appear on the electrocardiogram under the influence of cardiac glycosides, however, potassium salts are often prescribed together with digitalis preparations to prevent heart rhythm disturbances.

Anticholinesterase drugs enhance bradycardia when used simultaneously with cardiac glycosides; edetic acid reduces the effectiveness and toxicity of cardiac glycosides; trifosadenine should not be used together with cardiac glycosides; hypervitaminosis caused by vitamin D enhances the effect of cardiac glycosides due to the development of hypercalcemia; there is evidence of a decrease in the renal excretion of cardiac glycosides under the influence of paracetamol. Glucocorticosteroids and diuretics increase the risk of hypokalemia and hypomagnesemia, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers – reduce it.

Storage Conditions

Store at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.