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Active ingredients
Digoxin
Release form
Pills
Composition
1 tablet contains the active substances: digoxin - 0.25 mg excipients: colloidal silicon dioxide, magnesium stearate, gelatin, talc, corn starch, lactose monohydrate.
Pharmacological effect
Cardiac glycoside. It has a positive inotropic effect. This is due to the direct inhibitory effect on Na + / K + -ATP-ases on the membrane of cardiomyocytes, which leads to an increase in the intracellular content of sodium ions and, accordingly, a decrease in potassium ions. The increased content of sodium ions causes the activation of sodium-calcium metabolism, an increase in the content of calcium ions, as a result of which the force of contraction of the myocardium increases. As a result of an increase in myocardial contractility, the stroke volume of the blood increases. The end systolic and end diastolic volumes of the heart are reduced, which, along with an increase in myocardial tone, leads to a reduction in its size and thus to a decrease in myocardial oxygen demand. It has a negative chronotropic effect, reduces excessive sympathetic activity by increasing the sensitivity of cardiopulmonary baroreceptors. Due to the increase in the activity of the vagus nerve, it has an antiarrhythmic effect, due to the decrease in the speed of the impulses through the atrioventricular node and the lengthening of the effective refractory period. This effect is enhanced by a direct action on the atrioventricular node and sympatholytic action. The negative dromotropic effect is manifested in an increase in the refractoriness of the atrioventricular node, which allows the use of supraventricular tachycardias and tachyarrhythmias in paroxysms. In atrial tachyarrhythmias, it slows down the frequency of ventricular contractions, lengthens diastole, improves intracardiac and systemic hemodynamics. A positive bathmotropic effect is manifested in the administration of subtoxic and toxic doses. It has a direct vasoconstrictive effect, which is most clearly manifested in the absence of congestive peripheral edema. At the same time, the indirect vasodilating effect (in response to an increase in the minute volume of blood and a decrease in excessive sympathetic stimulation of vascular tone), as a rule,prevails over direct vasoconstrictor action, resulting in a decrease in the total peripheral vascular resistance (OPS).
Pharmacokinetics
Absorption from the gastrointestinal tract can be different and makes up 70-80% of the dose taken. Absorption depends on the motility of the gastrointestinal tract, the dosage form, concomitant use of the forest, on the interaction with other drugs. Bioavailability of 60-80%. With normal acidity of gastric juice, a small amount of digoxin is destroyed, with hyperacid states, more of it can be destroyed. For full absorption, sufficient exposure in the intestine is required: with a decrease in gastrointestinal motility, bioavailability is maximal, with enhanced peristalsis - minimal. The ability to accumulate in the tissues (cumulate) explains the lack of correlation at the beginning of treatment between the severity of the pharmacodynamic effect and its concentration in the blood plasma. Cmax of digoxin in blood plasma is achieved in 1-2 hours. Communication with plasma proteins is 25%. Relative Vd - 5 l / kg. Metabolized in the liver. Digoxin is excreted mainly by the kidneys (60-80% unchanged). T1 / 2 is about 40 hours. Withdrawal and T1 / 2 is determined by the function of the kidneys. The intensity of renal excretion is determined by the size of the glomerular filtration. With an insignificant chronic renal failure, a decrease in renal excretion of digoxin is compensated for by the hepatic metabolism of digoxin to inactive metabolites. In hepatic insufficiency, compensation occurs due to increased renal excretion of digoxin.
Indications
In the complex treatment of chronic heart failure II (in the presence of clinical manifestations) and III -IV functional class. tachysystolic form of atrial fibrillation and flutter of paroxysmal and chronic course (especially in combination with chronic heart failure).
Contraindications
Hypersensitivity to the drug, glycosidic intoxication, wolfaparkinson-White syndrome, atriventricular block II degree, intermittent complete blockade. With caution (comparing the benefit / risk): av block i degree, sick sinus syndrome without a pacemaker, the likelihood of unstable av av node, a history of bouts of morgania-Adams-Stokeshypertrophic subaortic stenosis, isolated mitral stenosis with a rare heart rate, cardiac asthma in patients with mitral stenosis (in the absence tachysystolic atrial fibrillation), acute myocardial infarction, unstable angina, arteriovenous shunt, hypoxia, heart failure with diastolic dysfunction (restrictive cardiomyopathy, amyloidosis heart, constrictive pericarditis, cardiac tamponade), extrasystole, marked dilatation of the heart cavities, pulmonary heart. Electrolyte disorders: hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia. Hypothyroidism, alkalosis, myocarditis, old age, renal-hepatic failure, obesity. Use during pregnancy and lactation. Digitalis drugs penetrate the placenta. During labor, the concentration of digoxin in the serum of the newborn and the mother is the same. According to the classification of administration of food products and medicines of the United States, digoxin is classified as safe with its use in pregnancy: the risk in use is not excluded. Studies in pregnant women are insufficient, but the anticipated therapeutic effect of the drug may justify the risk of its use. Lactation period: Digoxin is excreted into the mother's milk. But data on the effect of the drug on the newborn are not given.
Precautionary measures
Since the cardiovascular system: ventricular paroxysmal tachycardia, ventricular premature beats (often bigeminy, polytopic ventricular extrasystoles), nodular tachycardia, sinus bradycardia, sinoauricular blockade, flicker and atrial flutter, AV block, atrophy of the atria, blockage, atrophy of the atria, blockage, atrophic atrial, blockage, atrophy of the atria, blockage, atrophic atrial, blockade, atrial fibrillation, blockage, atrophy of the atria, blockage, atrophy of the atria, blockage, atrophy of the atria, blockage, atrophy of the atria, blockage, atrophy of the atria, blockage, atrophy of the atria, blockage, atrophy, pread for aneurysm, adrenaline atrophy, preoperative atrophy On the part of the digestive system: anorexia, nausea, vomiting, diarrhea, abdominal pain, intestinal necrosis. On the part of the central nervous system: sleep disorders, headache, dizziness, optic neuritis, sciatica, manic-depressive syndrome, paresthesia and syncope, rarely (mainly in elderly patients suffering from atherosclerosis) - disorientation, confusion, monochrome visual hallucinations. On the part of the organ of vision: the staining of visible objects in yellow-green color, the flashing of the flies before the eyes, reduced visual acuity, macro- and microxia.Allergic reactions: skin rash is possible, rarely - urticaria. On the part of the hematopoietic system and hemostasis: thrombocytopenic purpura, nasal bleeding, petechiae. Other: hypokalemia, gynecomastia.
Use during pregnancy and lactation
Digitalis drugs penetrate the placental barrier. During labor, the concentration of digoxin in the serum of the newborn and the mother is the same. Digoxin for the safety of its use in pregnancy belongs to category C: the risk in the application is not excluded. Studies of pregnant women are insufficient, the purpose of the drug is possible only in the case when the intended benefits to the mother outweigh the potential risk to the fetus. Digoxin passes into breast milk. However, data on the effect of the drug on the newborn is not provided.
Dosage and administration
As with all cardiac glycosides, the dose should be selected with care, individually for each patient. If the patient took cardiac glycosides before the appointment of digoxin, in this case, the dose of the drug should be reduced. Adults The dose of digoxin depends on the need to quickly achieve a therapeutic effect. Moderately fast digitalization (24-36 h) is used in emergency cases. Daily dose of 0.75-1.25 mg, divided into 2 doses, under the control of an ECG before each subsequent dose. After reaching saturation go to maintenance treatment. Slow digitalization (5-7 days). The daily dose of 0.125-0.5 mg is prescribed 1 time per day for 5-7 days (until saturation is achieved), after which they switch to supportive treatment. Chronic heart failure (CHF) In patients with CHF, digoxin should be used in small doses: up to 0.25 mg per day (for patients weighing more than 85 kg to 0.375 mg per day) In elderly patients, the daily dose of digoxin should be reduced to 0 , 0625-0,125 mg (1/4; 1/2 pills).
Side effects
Reported side effects are often the initial signs of an overdose. Digitaliskaya intoxication on the part of the cardiovascular system - ventricular paroxysmal tachycardia, ventricular premature beats (often bigemini, polytopic ventricular premature beats), junctional tachycardia, sinus bradycardia, sinuauricular (SA) block, fibrilloflutter, AV block. on the ECG - reduction of the ST segment with the formation of a two-phase T wave. On the part of the digestive tract anorexia, nausea, vomiting, diarrhea, abdominal pain, intestinal necrosis.From the central nervous system, sleep disorders, headache, dizziness, optic neuritis, sciatica, manic-depressive syndrome, paresthesia and syncope, in rare cases (mainly in elderly patients suffering from atherosclerosis) disorientation, confusion, monochrome visual hallucinations. On the part of the senses, the staining of visible objects in yellow-green color, the flashing of "flies" before the eyes, reduced visual acuity, macro- and microxia. Allergic reactions are possible skin rash, rarely urticaria. On the part of the blood-forming organs and the hemostasis system, thrombocytopenic purpura, nasal bleeding, petechiae. Other hypokalemia, gynecomastia.
Overdose
Symptoms: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, bowel necrosis, ventricular paroxysmal tachycardia, ventricular premature beats (often politopnye or bigemini), junctional tachycardia, sinoatrial block, flicker and flutter, AV block, drowsiness, confusion, delirious psychosis, reduction of visual acuity, staining of visible objects in yellow-green color, flashing of flies before the eyes, perception of objects in a reduced or enlarged form, neuritis, sciatica, manic-depressive indrom, paresthesias. Treatment: removal of digoxin, the appointment of activated carbon (to reduce absorption), the introduction of antidotes (unithiol, EDTA, antibodies to digoxin), symptomatic therapy. Conduct continuous monitoring of ECG. 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 provided adequate renal function. In emergency cases, it is shown in / in the drip injection of 2% or 4% solution of potassium chloride. 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). When hypomagnesemia recommended the appointment of magnesium salts. In cases of ventricular tachyarrhythmias, slow i.v. administration of lidocaine is indicated. In patients with normal function of the heart and kidneys, it is usually effective to slowly administer intravenously (within 2–4 min) lidocaine at an initial dose of 1-2 mg / kg body weight, followed by a transition to drip administration at a rate of 1-2 mg / min In patients with impaired renal function and / or heart, the dose must be reduced accordingly.In the presence of AV blockade of grade II-III, lidocaine and potassium salts should not be administered until an artificial pacemaker is installed. During treatment, it is necessary to control the level of calcium and phosphorus in the blood and daily urine. There is an experience of using the following drugs with a possible positive effect: β-blockers, procainamide, bretylium and phenytoin. Cardioversion can trigger ventricular fibrillation. Atropine is indicated for the treatment of bradyarrhythmias and AV blockade. When AV block II-III degree, asystole and suppression of the activity of the sinus node shows the installation of the pacemaker.
Interaction with other drugs
With the simultaneous appointment of Digoxin with drugs that cause electrolyte imbalance, in particular hypokalemia (eg, diuretics, glucocorticosteroids, insulin, β-adrenomimetics, amphotericin B), the risk of arrhythmias and the development of other toxic effects of Digoxin increases. Hypercalcemia can also lead to the development of the toxic effects of Digoxin, therefore, it is necessary to avoid the introduction of calcium salts in patients receiving digoxin. In these cases, the dose of digoxin must be reduced. Some drugs can increase the concentration of digoxin in the serum, for example, quinidine, blockers of slow calcium channels (especially verapamil), amiodarone, spironolactone and triamterene. Digoxin absorption in the intestine can be reduced by the action of colestyramine, colestipol, aluminum-containing antacids, neomycin, tetracyclines. There is evidence that the simultaneous use of spironolactone not only changes the concentration of digoxin in the serum, but can also distort the results of determining the concentration of digoxin, therefore, special attention is required when evaluating the results obtained. A decrease in the bioavailability of Digoxin is observed with simultaneous administration with activated carbon, astringent drugs, kaolin, sulfasalazine (binding in the lumen of the gastrointestinal tract), metoclopramide, prozerin (increased gastrointestinal motility). An increase in the bioavailability of Digoxin is observed with simultaneous administration with broad-spectrum antibiotics that suppress the intestinal microflora (reduction of destruction in the gastrointestinal tract).β-blockers and verapamil increase the severity of the negative chronotropic effect, reduce the strength of the inotropic effect. Inducers of microsomal oxidation (barbiturates, phenylbutazone, phenytoin, rifampicin, antiepileptic, oral contraceptives) can stimulate Digoxin metabolism (if they are canceled, digitalis intoxication is possible). In an application with digoxin below said drugs may their interaction, due to which decreases the therapeutic effect or manifested side or toxic effect Digoxin: mineralocorticoids, corticosteroids, with significant mineralocorticoid effects, Amphotericin B for injection, carbonic anhydrase inhibitors, adrenocorticotropic hormone (ACTH), diuretic drugs that promote the release of water and potassium (bumetadine, ethacrynic acid, furosemide, indapamide, mannitol and thiazide derivatives), sodium phosphate. Hypokalemia caused by the above mentioned drugs increases the risk of digoxin's toxic effects, therefore, when used simultaneously with Digoxin, constant monitoring of the potassium concentration in the blood is required. With simultaneous administration with Hypericum preparations, P-glycoprotein and P450 cytochrome are induced and, consequently, bioavailability decreases, metabolism increases and plasma concentration of digoxin decreases markedly. With simultaneous appointment with amiodarone, the concentration of digoxin in the blood plasma increases to a toxic level. The interaction of amiodarone and digoxin inhibits the activity of the sinus and atrioventricular nodes of the heart, and also slows down the conduction of the nerve impulse along the cardiac conduction system. Therefore, when prescribing amiodarone, it is necessary to cancel Digoxin or reduce the dose by half. Preparations of aluminum salts, magnesium and other antacid agents can reduce the absorption of digoxin and reduce its concentration in the blood. Simultaneous use of antiarrhythmic drugs with digoxin, calcium salts, pancuronium, rauwolfia alkaloids, succinylcholine and sympathomimetics can provoke the development of cardiac arrhythmias, therefore in these cases it is necessary to monitor the patient's heart activity and ECG.Kaolin, pectin and other adsorbents, Kolestiramine, Kolestipol, laxatives, neomycin and sulfasalazine reduce digoxin absorption and thereby reduce its therapeutic effect. Blockers of slow calcium channels, captopril - increase the concentration of digoxin in the blood plasma, therefore, when used together, it is necessary to reduce the dose of digoxin in order to avoid the toxic effect of the latter. Edrofonium (anticholinesterase agent) increases the tone of the parasympathetic nervous system, so its interaction with digoxin can cause pronounced bradycardia. Erythromycin improves digoxin absorption in the intestine. Digoxin reduces the anticoagulant effect of heparin; therefore, the dose of heparin should be increased while it is administered with Digoxin. Indomethacin reduces the release of Digoxin, therefore the risk of toxic effects of the latter increases. Magnesium sulfate solution for injection is used to reduce the toxic effects of cardiac glycosides. Phenylbutazone reduces the concentration of digoxin in the serum. Preparations of potassium salts cannot be taken if under the influence of Digoxin conduction disturbances on the ECG have appeared. However, potassium salts are often prescribed together with digitalis preparations to prevent heart rhythm disturbances. Quinidine and quinine can dramatically increase the concentration of digoxin. Spironolactone reduces the rate of excretion of Digoxin, therefore, when used together, it is necessary to adjust the dose of Digoxin. In the study of myocardial perfusion with waist preparations (Waist Chloride) in patients taking Digoxin, the degree of waist accumulation at the sites of damage to the heart muscle decreases and the results of the study are distorted. Thyroid hormones increase metabolism, so the dose of Digoxin should always be increased.
special instructions
In order to avoid the side effects resulting from an overdose, the patient should be monitored during the entire period of treatment with digoxin. Patients receiving digitalis should not be given calcium supplements for parenteral administration. It is necessary to reduce the dose of digoxin in patients with chronic pulmonary heart, coronary insufficiency, impaired water and electrolyte balance, renal or hepatic insufficiency.Elderly patients also require careful selection of the dose, especially if they have one or several of the above-mentioned conditions. It should be borne in mind that in these patients, even with impaired renal function, the value of creatinine clearance (CK) may be within the normal range, which is associated with a decrease in muscle mass and a decrease in creatinine synthesis. Since the pharmacokinetic processes are disturbed in case of renal failure, the dose selection should be carried out under the control of the concentration of digoxin in the blood serum. If this is not feasible, then you can use the following recommendations. The dose should be reduced by approximately the same percent as the QC is reduced. If QC is not determined, then it can be approximately calculated on the basis of serum creatinine concentration (CCS). For men, according to the formula (140-age) / KKS. For women, the result obtained should be multiplied by 0.85. In severe renal insufficiency, the concentration of digoxin in the serum should be determined every 2 weeks, at least in the initial period of treatment. In idiopathic subaortic stenosis (obstruction of the left ventricular outflow tract by an asymmetrically hypertrophied interventricular septum), the administration of Digoxin leads to an increase in the severity of the obstruction. In severe mitral stenosis and norm- or bradycardia, heart failure develops due to a decrease in the diastolic filling of the left ventricle. Digoxin, increasing the contractility of the myocardium of the right ventricle, causes a further increase in pressure in the pulmonary artery system, which can provoke pulmonary edema and aggravate left ventricular failure. Cardiac glycosides are prescribed to patients with mitral stenosis when joining right ventricular failure, or in the presence of atrial fibrillation. In patients with AV block II degree, the appointment of cardiac glycosides can aggravate it and lead to the development of a Morgagni-Adams-Stokes attack. The purpose of cardiac glycosides in AV block I degree requires caution, frequent ECG monitoring, and in some cases, pharmacological prophylaxis with means that improve AV conduction. Digoxin in Wolf-Parkinson-White syndrome, slowing AV conduction, contributes to the conduction of impulses through additional paths bypassing the AV node and, thus, provokes the development of paroxysmal tachycardia.The likelihood of glycoside intoxication increases with hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia, hypothyroidism, severe dilatation of the heart cavities, pulmonary heart, myocarditis, and in the elderly. As one of the methods to control the content of digitalization in the appointment of cardiac glycosides, their plasma concentration monitoring is used. Cross-sensitivity: Allergic reactions to digoxin and other digitalis preparations are rare. If hypersensitivity appears in relation to a single digitalis drug, other representatives of this group can be used, since cross-sensitivity to digitalis preparations is not peculiar. The patient must comply with the following instructions: 1. Use the drug only as prescribed by the doctor, do not change the dose yourself; 2. Every day, use the drug only at the appointed time; 3. If the heart rate is below 60 beats / min, you should immediately consult with your doctor; 4. If you miss the next dose of the drug, you need to take it immediately, when you can; 5. Do not increase or double the dose; 6. If the patient has not taken the drug for more than 2 days, you must inform the doctor about this. Before discontinuing the drug, you must inform your doctor. When vomiting, nausea, diarrhea, rapid pulse, you should immediately consult a doctor. Before surgery or in the provision of emergency care, you must warn about the use of Digoxin. Without the permission of the physician is not desirable to use other medicines.