Digoxin, tablets 250 mcg 30 pcs

A cardiac glycoside. It has a positive inotropic effect. This is due to a direct inhibitory effect on Na⁺/K⁺-ATPase on the membrane of cardiomyocytes, which leads to an increase in intracellular sodium ions and, consequently, a decrease in potassium ions. The increased content of sodium ions causes activation of sodium-calcium metabolism, increases the content of calcium ions, resulting in increased strength of myocardial contraction.

As a result of increased contractility of the myocardium, the stroke volume of the blood increases. The final systolic and final diastolic volumes of the heart decrease, which, along with an increase in myocardial tone, leads to a reduction in myocardial size and thus decreases myocardial oxygen demand. It has a negative chronotropic effect, reduces excessive sympathetic activity by increasing the sensitivity of the cardiopulmonary baroreceptors.

With increased activity of the vagus nerve, it has antiarrhythmic effect due to the decrease of the pulse rate through the atriventricular node and the prolongation of the effective refractory period. This effect is enhanced by direct action on the atrioventricular node and sympatholytic action.

The negative dromotropic effect is manifested by an increase in refractoriness of the atrioventricular node, which allows use in paroxysms of supraventricular tachycardia and tachyarrhythmias.

In atrial fibrillation tachyarrhythmia helps to slow the rate of ventricular contractions, prolongs diastole, improves intracardiac and systemic hemodynamics.

Positive butotropic effects are evident in the administration of subtoxic and toxic doses.

It has a direct vasoconstrictor effect that is most clearly seen in the absence of congestive peripheral edema.

At the same time, the indirect vasodilatory effect (in response to increased minute blood volume and reduced excessive sympathetic stimulation of vascular tone) generally prevails over the direct vasoconstrictor effect, resulting in a decrease in total peripheral vascular resistance (TPR).

Indications

Active ingredient

Composition

How to take, the dosage

It is administered orally.

As with all cardiac glycosides, the dose needs to be adjusted with caution, individually for each patient.

If a patient was taking cardiac glycosides before being prescribed digoxin, then the dose of the drug must be reduced.

Adults

The dose of digoxin depends on the need to achieve a rapid therapeutic effect.

Moderately rapid digitalization (24-36 h) is used in emergencies

The daily dose is 0.75-1.25 mg divided into 2 doses, with ECG monitoring before each subsequent dose.

After saturation is achieved, switch to maintenance treatment.

Slow diet (5-7 days)

The daily dose is 125-500 mcg 1 time/d for 5-7 days (until saturation is achieved), after which supportive treatment is switched to.

Chronic heart failure (CHF)

In patients with CHF, digoxin should be used in low doses: up to 250 mcg/day (for patients with body weight over 85 kg up to 375 mcg/day). In elderly patients, the daily dose should be reduced to 62.5-125 mcg (1/4-1/2 tablets).

The maintenance therapy

The daily dose for maintenance therapy is set individually and is 125-750 mcg. Maintenance therapy is usually long-term.

Interaction

Concomitant administration of Digoxin with drugs that cause electrolyte imbalances, in particular hypokalemia (e.g., diuretics, glucocorticosteroids, insulin, beta-adrenomimetics, amphotericin B) increases the risk of arrhythmias and other toxic effects of Digoxin. Hypercalcemia may also lead to the development of toxic effects of Digoxin, so IV administration of calcium salts should be avoided in patients taking digoxin. In these cases, the dose of Digoxin should be reduced. Some drugs can increase the serum concentration of Digoxin, such as quinidine, slow calcium channel blockers (especially verapamil), amiodarone, spironolactone and triamterene.

Digoxin absorption in the intestine may be reduced by colestyramine, colestipol, aluminum-containing antacids, neomycin, tetracyclines. There is evidence that concomitant use of spironolactone not only changes the concentration of Digoxin in serum, but can also distort the results of determination of Digoxin concentration, so special attention is required when evaluating the results.

Digoxin bioavailability is decreased when simultaneously prescribed with activated charcoal, astringent drugs, kaolin, sulfasalazine (binding in the lumen), metoclopramide, proserine (increase of GI motility).

The bioavailability of Digoxin is increased when concomitantly prescribed with broad-spectrum antibiotics that inhibit intestinal microflora (reduction of destruction in the gastrointestinal tract).

Beta-adrenoblockers and verapamil increase the severity of the negative chronotropic effect, reduce the strength of the inotropic effect.

Microsomal oxidation inducers (barbiturates, phenylbutazone, phenytoin, rifampicin, antiepileptics, oral contraceptives) may stimulate the metabolism of Digoxin (in case of their withdrawal digitalis intoxication is possible).

When concomitant use with digoxin the following medicines may interact, due to which the therapeutic effect is reduced or side or toxic effects of Digoxin are manifested: mineralocorticoids, glucocorticoids with significant mineralocorticoid effect, amphotericin B for injection, carboanhydrase inhibitors, adrenocorticotropic hormone (ACTH), diuretics that promote water and potassium excretion (bumetadine, ethacrynic acid, furosemide, indapamide, mannitol and thiazide derivatives), sodium phosphate.

Hypokalemia caused by the above mentioned drugs increases the risk of toxic effects of Digoxin, so if they are used simultaneously with Digoxin, constant monitoring of blood potassium concentration is required.

Concomitant administration with Hypericum preparations induces P-glycoprotein and cytochrome P450 and therefore decreases bioavailability, increases metabolism and markedly decreases plasma concentrations of Digoxin.

Concomitant administration with amiodarone increases plasma concentrations of digoxin to toxic levels. The interaction of amiodarone and digoxin inhibits the activity of the sinus and atrioventricular nodes of the heart, and also slows the conduction of the nerve impulse through the cardiac conduction system. Therefore, when amiodarone is prescribed, Digoxin should be stopped or the dose should be halved.

Aluminum salts, magnesium salts and other antacids can reduce digoxin absorption and decrease its concentration in the blood.

The concomitant use of antiarrhythmic agents, calcium salts, pancuronium, rauwolfia alkaloids, succinylcholine, and sympathomimetics with digoxin may provoke development of cardiac rhythm disturbances, therefore in these cases the patient’s heart activity and ECG should be controlled.

Caolin, pectin and other adsorbents, colestyramine, colestipol, laxatives, neomycin and sulfasalazine reduce absorption of Digoxin and thus reduce its therapeutic effect.

Slow calcium channel blockers, captopril increase concentration of Digoxin in plasma, therefore if they are used together the dose of Digoxin should be reduced in order to avoid its toxic effect.

Edrophonium (anticholinesterase agent) increases the tone of the parasympathetic nervous system, so its interaction with digoxin may cause marked bradycardia.

Erythromycin improves absorption of Digoxin in the intestine.

Digoxin reduces the anticoagulant effect of heparin, so doses of heparin should be increased when administered simultaneously with Digoxin.

Indomethacin reduces Digoxin excretion, so there is an increased risk of toxic effects of the latter.

Magnesium sulfate solution for injection is used to reduce the toxic effects of cardiac glycosides.

Phenylbutazone reduces the concentration of digoxin in blood serum.

Potassium salt preparations should not be taken if ECG conduction abnormalities have occurred under the influence of Digoxin. However, potassium salts are often prescribed together with preparations of digitalis to prevent cardiac rhythm disturbances.

Quinidine and quinine can dramatically increase the concentration of Digoxin.

Spironolactone decreases the excretion rate of Digoxin, so the dose of Digoxin should be adjusted if they are used together.

In myocardial perfusion studies with thalia (Thalia chloride) drugs, patients taking Digoxin have decreased thalia accumulation in areas of cardiac muscle lesions and the study results are distorted.

Thyroid hormones increase metabolism, so the dose of Digoxin should definitely be increased.

Special Instructions

In order to avoid side effects resulting from overdose, the patient should be monitored during the entire period of Digoxin treatment. Patients receiving digitalis preparations should not be prescribed calcium preparations for parenteral administration.

Dose of Digoxin should be reduced in patients with chronic pulmonary heart disease, coronary artery disease, water-electrolyte balance disorders, renal or hepatic insufficiency. Caution is also required in elderly patients, especially in the presence of one or more of the above-mentioned conditions. It should be taken into account that in these patients, even with impaired renal function, creatinine clearance (CK) values may be within normal limits, which is associated with decreased muscle mass and decreased creatinine synthesis. Since in renal failure pharmacokinetic processes are disturbed, the dose selection should be carried out under the control of Digoxin serum concentrations. If this is not feasible, the following recommendations can be used. The dose should be reduced by approximately the same percentage by which CK is reduced. If no CK is determined, it can be approximated based on the serum creatinine concentration (SCC). For men, the formula is (140 – age)/CCS. For women, multiply by 0.85.

In severe renal failure, the serum Digoxin concentration should be determined every 2 weeks, at least during the initial period of treatment.

In idiopathic subaortic stenosis (obstruction of the left ventricular exit tract by asymmetrically hypertrophied interventricular septum) the administration of Digoxin leads to an increase in the severity of obstruction. In severe mitral stenosis and normo- or bradycardia, heart failure develops due to decreased diastolic filling of the left ventricle. Digoxin, by increasing myocardial contractility of the right ventricle, causes further increase in pressure in the pulmonary artery system, which may provoke pulmonary edema and aggravate left ventricular failure. Patients with mitral stenosis are prescribed cardiac glycosides if right ventricular failure is associated, or if atrial fibrillation is present.

In patients with AV-blockade degree II, the prescription of cardiac glycosides may worsen it and lead to Morgans-Adams-Stokes attack. Administration of cardiac glycosides in AV blockade degree I requires caution, frequent ECG monitoring, and in some cases, pharmacological prophylaxis with agents improving AV conductivity.

Digoxin in Wolff-Parkinson-White syndrome, by slowing down AV conductivity, promotes impulses through additional conduction pathways to bypass AV node and, thus, provokes development of paroxysmal tachycardia. The likelihood of glycoside intoxication increases in hypokalemia, hypomagnesemia, hypercalcemia, hypernatriemia, hypothyroidism, marked heart cavity dilatation, “pulmonary” heart, myocarditis and in the elderly.

The monitoring of plasma concentrations of cardiac glycosides is used as one of the methods of controlling the content of digitalis when prescribing cardiac glycosides.

Cross-sensitivity

Allergic reactions to digoxin and other foxglove drugs rarely develop. If hypersensitivity occurs to any one foxglove drug, the other members of this group can be used because cross-sensitivity to foxglove drugs is not common.

The patient must follow the following instructions exactly:

1. Use the medication only as prescribed by the physician, do not change the dose yourself;

2. Use the medication only at the time prescribed each day;

3. If the heart rate is below 60 bpm, consult a physician immediately;

4. If the next dose of the drug is missed, it must be taken as soon as possible;

5. The dose must not be increased or doubled;

6. If the patient has not taken the drug for more than 2 days, the physician must be informed.

If the patient has not taken the medication for 2 days, this must be reported to the physician.

If vomiting, nausea, diarrhea, and rapid pulse occur, seek medical attention immediately.

Digoxin should be warned before surgery or emergency care.

The use of other drugs is undesirable without a physician’s permission.

Contraindications

With caution (the perceived benefit and potential risk must be compared): Grade I AV blockade, sinus node weakness syndrome without rhythm driver, possibility of unstable conduction across the AV node, history of Morgania-Adams-Stokes seizures; hypertrophic subaortic stenosis, isolated mitral stenosis with rare HR, cardiac asthma in patients with mitral stenosis (in the absence of tachysystolic atrial fibrillation), acute myocardial infarction, unstable angina arteriovenous shunt, hypoxia, heart failure with impaired diastolic function (restrictive cardiomyopathy, cardiac amyloidosis, constrictive pericarditis, cardiac tamponade), extrasystole, marked heart cavity dilatation, “pulmonary” heart.

Electrolyte disorders: hypokalemia, hypomagnesemia, hypercalcemia, hypernatriemia. Hypothyroidism, alkalosis, myocarditis, old age, renal and renal insufficiency obesity.

Side effects

The side effects noted are often initial signs of overdose.

Digital intoxication symptoms

Cardiovascular symptoms: Ventricular paroxysmal tachycardia, ventricular extrasystole (often bigemia, polytopic ventricular extrasystole), nodal tachycardia, sinus bradycardia, sinoauricular block, atrial fibrillation and flutter, AV blockade, on ECG – ST segment decrease with formation of biphasic T tooth.

Digestive system disorders: anorexia, nausea, vomiting, diarrhea, abdominal pain, intestinal necrosis.

CNS disorders: sleep disturbances, headache, dizziness, neuritis, radiculitis, manic-depressive syndrome, paresthesia and fainting, rarely (mainly in elderly patients with atherosclerosis) – disorientation, confusion, monochrome visual hallucinations.

Visually: staining of visible objects in yellow-green color, flickering of “flies” before eyes, decreased visual acuity, macro- and microopsia.

Allergic reactions: skin rash is possible, urticaria is rare.

Hematopoietic and hemostatic system disorders: thrombocytopenic purpura, nasal bleeding, petechiae.

Others: hypokalemia, gynecomastia.

Overdose

Symptoms: decreased appetite, nausea, vomiting, diarrhea, abdominal pain, bowel necrosis, ventricular paroxysmal tachycardia, ventricular extrasystole (often polytopic or bigemia), nodal tachycardia, sinoatrial block, atrial fibrillation and flutter, AV blockade, drowsiness, confusion, delirium psychosis, decreased visual acuity, yellow-green coloring of visible objects, flickering of “flies” before the eyes, perception of objects in reduced or enlarged form, neuritis, radiculitis, manic-depressive syndrome, paresthesias.

Treatment: withdrawal of digoxin, administration of activated charcoal (to reduce absorption), administration of antidotes (unitiol, EDTA, antibodies to digoxin), symptomatic therapy. Constant ECG monitoring is performed.

In cases of hypokalemia, potassium salts are widely used: 0.5-1 g of potassium chloride is dissolved in water and taken several times a day to a total dose of 3-6 g (40-80 mEq of potassium) for adults on condition of adequate renal function. In emergency cases, IV drip administration of 2% or 4% potassium chloride solution is indicated. The daily dose is 40-80 mEq of potassium (diluted to a concentration of 40 mEq of potassium per 500 ml). The recommended rate of administration should not exceed 20 mEq/h (under ECG control). In case of hypomagnesemia, administration of magnesium salts is recommended.

In cases of ventricular tachyarrhythmia, slow IV infusion of lidocaine is indicated. In patients with normal heart and renal function, slow IV administration (over 2-4 minutes) of lidocaine at an initial dose of 1-2 mg/kg body weight, followed by drip infusion at a rate of 1-2 mg/min is usually effective. In patients with impaired renal and/or cardiac function, the dose should be reduced accordingly.

In the presence of grade II-III AV blockade, lidocaine and potassium salts should not be administered until an artificial pacemaker is installed.

Calcium and phosphorus levels in blood and daily urine should be monitored during treatment.

The following medications with possible beneficial effects have been experienced: β-adrenoblockers, procainamide, bretylium, and phenytoin. Cardioversion can induce ventricular fibrillation. Atropine is indicated for treatment of bradyarrhythmias and AV-blockade. In grade II-III AV-blockade, asystole, and sinus node suppression, a pacemaker is indicated.