Digoxin - instructions for use, dose, side effects, contraindications

Each tablet contains: active substance: digoxin 0.25 mg, excipients: potato starch, sucrose (sugar), calcium stearate, dextrose monohydrate, lactose monohydrate (sugar milk), talc.

Description:

Pills white color, flat-cylindrical shape, with a bevel, marked "R" on one side or without it.

Pharmacotherapeutic group:Cardiotonic is a cardiac glycoside.

ATX: & nbsp

C.01.A.A.05 Digoxin

C.01.A.A Glycosides of Digitalis

Pharmacodynamics:

Digoxin is a cardiac glycoside. Has a positive inotropic effect due to direct inhibitory action of sodium-potassium ATPase membranes 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 activation of sodium-calcium metabolism, an increase in the content of calcium ions, as a result of which the force of myocardial contraction increases. As a result of increased myocardial contractility, the shock volume of the blood increases. The final systolic and terminal diastolic volumes of the heart decrease, which, along with an increase in myocardial tone, leads to a reduction in its size and thus to a decrease in myocardial oxygen demand. Has a negative chronotropic effect, reduces excessive sympathetic activity by increasing sensitivity of cardiopulmonary baroreceptors. By increasing the activity of the wandering nerve has an antiarrhythmic effect due to a decrease in the rate of impulses through the atrioventricular node and an elongation of the effective refractory period. This effect occurs as a result of an indirect effect on the atrioventricular node. The negative dromotropic effect is manifested in the increased refractoriness of the atrioventricular node, which causes application with paroxysms supraventricular tachycardias and tachyarrhythmias. When ciliary

tachyarrhythmia contributes to slowing the frequency of ventricular contractions, lengthens the diastole, improves intracardiac and systemic hemodynamics. A positive batmotropic effect is manifested with the use of subtoxic and toxic doses. Has a direct vasoconstrictive effect, which is most clearly manifested in the absence of stagnant 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), usually prevails over direct vasoconstrictor action. as a result of which the overall peripheral vascular resistance is reduced.

Pharmacokinetics:

The absorption of digoxin from the gastrointestinal tract is variable, is 70-80% of the dose and depends on the motility of the gastrointestinal tract tract, dosage form, concomitant intake of food, from interaction with other medicinal

means. Bioavailability of 60-80%. At normal acidity of gastric juice, an insignificant amount of digoxin is destroyed. In hyperacid conditions, more of it can be destroyed.For complete absorption, sufficient exposure in the intestine is required: with a decrease in motility of the gastrointestinal tract, bioavailability is maximal. with increased peristalsis - minimal. The ability of digoxin to accumulate in tissues (cumulate) explains the absence of correlation at the beginning of treatment between the severity of the pharmacodynamic effect and its concentration in the blood plasma. The connection with plasma proteins is 25%. The apparent volume of distribution is 5 l / kg. Metabolised in the liver. It is excreted mainly by the kidneys (60-80% unchanged), the half-life is about 40 hours (determined by the kidney function). The intensity of renal excretion is determined by the magnitude of glomerular filtration. With insignificant chronic renal failure, the reduction in renal excretion of digoxin is compensated for by hepatic metabolism to inactive compounds. In case of hepatic failure, compensation occurs due to increased renal excretion of digoxin.

Indications:In the complex therapy of chronic heart failure II (in the presence of clinical manifestations) and III-IV functional class forthe NYHA classification; tahisystolic form of flicker and atrial flutter of paroxysmal and chronic course (especially in combination with chronic heart failure).

Contraindications:

Hypersensitivity to the components of the drug, glycoside intoxication, syndrome Wolf-Parkinson-White, atrioventricular blockade of the 2nd degree. ventricular tachycardia and ventricular fibrillation, intermittent blockade, children under 3 years; patients with rare hereditary diseases: lactose intolerance, fructose, lactase deficiency, sucrose / isomaltase or glucose-galactose malabsorption.

Carefully:

Comparing benefit / risk: atrioventricular blockade of the 1st degree, syndrome of weakness of the sinus node without a pacemaker, the probability of unstable conduction at the atrioventricular node, indications in an anamnesis for the seizures of Morgagni-Adams-Stokes. hypertrophic obstructive subaortic stenosis, isolated mitral stenosis with a rare heart rate, cardiac asthma in patients with mitral stenosis (in the absence of tachycystolic form of atrial fibrillation), acute myocardial infarction,unstable angina, arteriovenous shunt, hypoxia, heart failure with violation of diastolic function (restrictive cardiomyopathy, amyloidosis of the heart, constrictive pericarditis, cardiac tamponade), extrasystole, marked dilatation of the heart cavities, "pulmonary" heart; water-electrolyte disorders: hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia; hypothyroidism, alkalosis, myocarditis, advanced age, renal and / or hepatic impairment, obesity.

Pregnancy and lactation:

Drugs foxglove come through the placenta. There was a negative effect on the fetus in animal experiments. Controlled studies in pregnant women have not been conducted, but the potential benefit to the mother may justify the use of digoxin despite the possible risk to the fetus.

Lactation period

Digoxin is excreted in breast milk. Since there is no evidence of drug-induced effects on infants during breastfeeding, it is recommended to stop breastfeeding if necessary during this period.

Dosing and Administration:

Inside.

As with all cardiac glycosides, the dose should be selected with caution, individually for each patient. If the patient before the appointment of digoxin took cardiac glycosides, in this case, the dose of the drug should be reduced.

Adults and children over 10 years of age - the dose of digoxin depends on the required rate of achievement of the therapeutic effect:

- moderately rapid digitalization (24-36 h), used in emergency cases: a daily dose of 0.75-1.25 mg divided into 2 doses, under ECG monitoring before each subsequent dose. After reaching saturation, they switch to maintenance treatment;

- slow digitalization (5-7 days): a daily dose of 0.125-0.5 mg is prescribed once a day for 5-7 days (until reaching saturation), after which they switch to maintenance treatment; maintenance therapy: the daily dose is set individually and is 0.125-0.75 mg (maintenance therapy, as a rule, is carried out for a long time).

Have patients with chronic heart failure digoxin should be used in small doses: up to 0.25 mg per day (for patients with a body weight of more than 85 kg - up to 0.375 mg per day).

Have elderly patients The daily dose of digoxin should be reduced to 0.0625-0.125 mg (1 / 4-1 / 2 tablets).

Children between the ages of 3 and 10: the saturating dose for children is 0.05-0.08 mg / kg / day; this dose is prescribed within 3-5 days with moderately rapid digitalization or for 6-7 days with slow digitalization. The maintenance dose for children is 0.01-0.025 mg / kg / day.

Patients with impaired renal function it is necessary to reduce the dose of digoxin: at a creatinine clearance value of 50-80 ml / min, the average maintenance dose is 50% of the average maintenance dose for patients with normal renal function, with creatinine clearance less than 10 ml / min - 25%.

Side effects:

The reported side effects are often the initial signs of an overdose.

Glycoside intoxication:

from the cardiovascular system: paroxysmal ventricular tachycardia, ventricular extrasystole (bigemini, polytopic ventricular extrasystole), nodular tachycardia, sinus bradycardia, sinoauric blockade, atrial fibrillation and flutter, atrioventricular block; ECG - reduction of the segment ST with the formation of a two-phase tooth T.

From the digestive tract: anorexia, nausea, vomiting, diarrhea, abdominal pain, bowel necrosis.

From the central nervous system: sleep disorders, headache, dizziness, neuritis, sciatica, manic-depressive syndrome, paresthesia and fainting, disorientation and confusion (mainly in elderly patients with atherosclerosis), single-color visual hallucinations.

From the sense organs: staining of visible objects in yellow-green color, flashing of flies before eyes, reduced visual acuity, macro- and microposs.

Allergic reactions are possible: skin rash, rarely hives.

On the part of the organs of hematopoiesis and the system of hemostasis: thrombocytopenic purpura, nosebleeds, petechiae.

Other: hypokalemia, gynecomastia.

Overdose:

Symptoms: decreased appetite, nausea, vomiting, diarrhea, abdominal pain, intestinal necrosis; ventricular paroxysmal tachycardia, ventricular extrasystole (often polytopic or bigemia), nodular tachycardia, sinouauric blockade, atrial fibrillation and flutter, atrioventricular blockade, drowsiness, confusion, delirious psychosis, decreased visual acuity, staining of visible objects in yellow-green color, flickering " flies "before the eyes,perception of objects in a reduced or enlarged form; Neuritis, radiculitis, manic-depressive syndrome,

paresthesia.

Treatment: the elimination of digoxin, the reception of activated charcoal (to reduce absorption), the administration of antidotes (dimercaptropropanesulfonate sodium, sodium edetate (EDTA), symptomatic therapy. Spend constant

ECG monitoring.

Interaction:

With the simultaneous use of digoxin and drugs that cause electrolyte imbalance, in particular, hypokalemia (mineral and glucocorticosteroids, insulin, beta-adrenomimetics, amphotericin B, inhibitors of carbonic anhydrase, corticotropin, diuretic drugs that promote the excretion of liquid and potassium (bumetanide, ethacrynic acid, furosemide, indapamide, mannitol and thiazide derivatives), sodium phosphate), the risk of arrhythmias and the development of other toxic effects of digoxin is increased, so constant monitoring of the potassium content in the blood is required. Hypercalcemia can also lead to the development of toxic effects of digoxin, therefore intravenous administration should be avoided calcium salts patients receiving digoxin, and in cases of combined use, the dose of digoxin should be reduced. Preparations potassium salts It can not be used if under the influence of digoxin there are conduction disturbances on the ECG. However, potassium salts are often prescribed together with cardiac glycosides for prevention of heart rhythm disturbances. Some drugs can increase the concentration of digoxin in the blood serum (quinidine, blockers of "slow" calcium channels (especially verapamsh), captopril, amiodarone, spironolactone and triamterene) Therefore, when combined, the dose of digoxin should be reduced so that the toxic effect of the drug does not appear.

Amiodarone increases the concentration of digoxin in the blood plasma to a toxic value. The interaction of amiodarone and digoxin inhibits the activity of the sinus and atrioventricular nodes of the heart and the conductivity of the nerve impulse along the conduction system of the heart, therefore, amiodarone, digoxin cancel or reduce its dose by half.

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

Spironolactone reduces the rate of excretion of digoxin, therefore, when combined use, adjust the dose of the drug; In addition, the simultaneous use of spironolactone may influence the results of the digoxin concentration determination method, therefore special attention is required when evaluating the results obtained.

The absorption of digoxin in the intestine can be reduced by the action of tetracycline, aluminum-containing, magnesium-containing and other antacids.

Pectin and other adsorbents, colestramine, colestipol, laxatives, neomycin reduce absorption of digoxin and thereby reduce its therapeutic effect. Decrease the bioavailability of digoxin: activated carbon, astringent medicines, kaolin, sulfasalazine (binding in the lumen of the gastrointestinal tract);

metoclopramide, neostigmine methylsulfate (proserin) (increased motility of the gastrointestinal tract).

Increase bioavailability of digoxin: broad-spectrum antibiotics, suppressing the intestinal microflora (reduction of destruction in the gastrointestinal tract).

Erythromycin improves the absorption of digoxin in the intestine. Inductors of microsomal oxidation (barbiturates, phenylbutazone, phenytoin, rifampicin, antiepileptic

means, oral contraceptives) can stimulate the metabolism of digoxin (when they are canceled, digitalis intoxication is possible). Phenylbutazone reduces the concentration of digoxin in the blood serum.

Preparations of St. John's Wort induce P-glycoprotein and cytochrome P450, which reduces bioavailability, increases metabolism and markedly reduces the concentration of digoxin in the blood plasma. Simultaneous use with digoxin antiarrhythmics, calcium salts, pancuronium bromide, rauwolfia alkaloids, suxamethonium and sympathomimetics can provoke the development of cardiac arrhythmia, therefore in these cases it is necessary to monitor the cardiac activity and the patient's ECG.

Edrophonia chloride (cholinesterase inhibitor) increases the tone parasympathetic nervous system, so its interaction with digoxin can cause a pronounced bradycardia. Digoxin reduces anticoagulant effect heparin, so the dose should be increased.

Indomethacin reduces the excretion of digoxin,therefore the risk of toxic effect of the drug increases.

Quinidine and quinine can dramatically increase the concentration of digoxin. In the study of myocardial perfusion with thallium preparations digoxin reduces the degree of accumulation of thallium in the places of damage to the heart muscle and distorts the research data.

Application iodine-containing thyroid hormones increases the metabolism, so the dose of digoxin should be increased.

Special instructions:During the entire treatment with digoxin, the patient should be under the supervision of a physician in order to avoid side effects arising from overdose. It is necessary to reduce the dose of digoxin to patients with chronic pulmonary heart disease, coronary insufficiency, violations of water-electrolyte balance, kidney or liver failure. Elderly patients also require careful dose selection, especially if they have one or more of the above conditions. It should be borne in mind that in such patients, even with impaired renal function, the values of creatinine clearance may be within normal limits, which is associated with a decrease in muscle mass and a decrease in the synthesis of creatinine.

Since renal insufficiency is impaired pharmacokinetic processes, the selection of a dose should be carried out under the control of the concentration of digoxin in the blood serum. If this is not feasible, you can use the following recommendations: the dose should be reduced by approximately the same percentage as the decrease in creatinine clearance. If creatinine clearance is not determined, then it can be approximately calculated based on the serum creatinine concentration (CK), according to the Cockcroft-Gault formula. For men: (140 - age [in years]) - weight [in kg] / (72 - CCS [mg / dL]). For women, the result should be multiplied by 0.85.

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

With idiopathic subaortal stenosis (obstruction of the left ventricular outflow tract asymmetrically hypertrophic interventricular septum) the appointment of digoxin leads to an increase in the severity of obstruction.

With severe mitral stenosis and normo- or bradycardia, heart failure develops as a result of a decrease in the diastolic filling of the left ventricle. Digoxin, 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 aggravate the left ventricular failure.

Patients with mitral stenosis are assigned cardiac glycosides upon adherence right ventricular failure, or in the presence of ciliary tachyarrhythmias. In patients with atrioventricular blockade of grade II, the appointment of cardiac glycosides may aggravate it and lead to the development of the attack of Morgagni-Adams-Stokes. The appointment of cardiac glycosides with atrioventricular blockade of the first degree requires caution, regular ECG monitoring. and in some cases - pharmacological prophylaxis with agents that improve atrioventricular conductivity. Digoxin with Wolff-Parkinson-White syndrome, slowing the atrioventricular conduction, promotes impulses through additional ways of bypassing the atrioventricular node and thereby provokes the development of paroxysmal tachycardia. The likelihood of the occurrence of glycosidic intoxication increases with hypokalemia. hypomagnesemia,

hypercalcemia, hypernatremia, hypothyroidism, marked dilatation of the heart cavities, "pulmonary" heart, myocarditis and in elderly patients.

Monitoring of their plasma concentration is used as one of the methods of controlling digitalization in the appointment of cardiac glycosides. Allergic reactions to digoxin and other cardiac glycosides rarely develop. If hypersensitivity occurs to any one cardiac glycoside, other members of this group can be used, since cross-over-hypersensitivity to cardiac glycosides is not inherent.

The patient must strictly follow the following instructions:

- apply the drug only as prescribed, do not change the dose alone;

- every day apply the drug only at the appointed time;

- if the heart rate is below 60 bpm, you should immediately consult a doctor;

- if you missed taking the next dose of the drug, it must be taken at the first opportunity, after which you continue the course according to the established scheme.

- Do not increase or double the dose;

- if the patient has not taken the drug for more than two days, this should be reported to the doctor;

- before discontinuing the use of the drug, you must inform the doctor about it;

- when there is vomiting, nausea, diarrhea, rapid pulse, you should immediately consult a doctor;

- Before surgical operations or when providing emergency care, it is necessary to warn the doctor about the use of the drug;

- without the permission of a doctor, the use of other drugs is undesirable.

Effect on the ability to drive transp. cf. and fur:Studies on the effect of digoxin on the ability to drive vehicles and serve mechanisms that require a high concentration of attention and speed of psychomotor reactions are not enough, but caution should be exercised.

Form release / dosage:

Tablets 0.25 mg.

Packaging:

For 10, 14 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil or paper packaging.

By 3, 5, 10 contour cell packs of 10 tablets or 4 contour packs of 14 tablets with instructions for use are placed in a pack of cardboard.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000051

Date of registration:24.11.2010

Manufacturer: & nbsp

UPDATE, PFC CJSC Russia

Information update date: & nbsp01.02.2016

Illustrated instructions

Instructions

Digoxin (Digoxin)