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

Excipients: lactose monohydrate 39.98 mg, sucrose (sugar) 0.505 mg, dextrose monohydrate 0.5 mg, potato starch 7.76 mg, talc 0.505 mg, stearic acid 0.5 mg.

Description:Tablets are white, flat-cylindrical with a bevel.

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. It has a positive inotropic effect. This is due to the direct inhibitory effect of Na + / K + -ATP-phase on the 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 contractility of the myocardium, the shock volume of 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 the sensitivity of cardiopulmonary baroreceptors. Owing to the increase in the activity of the vagus nerve, antiarrhythmic action is caused by a decrease in the rate of impulses through the atrioventricular node and an elongation 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 in the increased refractoriness of the atrio-ventricular (AV) node, which allows the use of supraventricular tachycardias and tachyarrhythmias in paroxysms.

Atrial tachyarrhythmia contributes to slowing the frequency of ventricular contractions, lengthens the diastole, improves intracardiac and systemic hemodynamics. A positive batmotropic effect is manifested in the administration of toxic 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 the reduction of excessive sympathetic stimulation of the vascular tone) tends to prevail over direct vasoconstrictor action, resulting in a reduction in the overall peripheral vascular resistance (OPSS).

Pharmacokinetics:Absorption from the gastrointestinal tract (GIT) - variable, is 70-80% of the dose and depends on the gastrointestinal motility, dosage form, concomitant intake of food, from interaction with other drugs. Bioavailability of 60-80%. With a normal acidity of gastric juice, an insignificant amount of digoxin breaks down, while a greater amount of digoxin can degrade under hyperacid conditions.For complete absorption, sufficient exposure in the intestine is required: with a decrease in motility of the gastrointestinal tract, bioavailability is maximal, with minimal peristalsis. The ability to accumulate in tissues (cumulate) explains the lack of correlation at the beginning of the treatment between the severity of the pharmacodynamic effect and its concentration in the blood plasma. The maximum concentration of digoxin in blood plasma is reached after 1-2 hours. The connection with plasma proteins is 25%. The relative volume of the distribution is 5 l / kg. Metabolised in the liver. Digoxin is excreted mainly by the kidneys (60-80% unchanged). The half-life is about 40 hours. The excretion and half-life is determined by the function of the kidneys. The intensity of renal excretion is determined by the magnitude of glomerular filtration: With not significant chronic renal failure, the decrease in renal excretion of digoxin is compensated for by hepatic metabolism of digoxin to inactive metabolites. 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; 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, Wolff-Parkijson-White syndrome, atrio-ventricular blockade of the 2nd degree, intermittent blockade, ventricular tachycardia and ventricular fibrillation, lactation (breastfeeding), children under 3 years of age, fructose intolerance, insufficiency sucrose / isomaltase, laccase deficiency, lactose intolerance, glucose-galactose malabsorption.

Carefully:atrioventricular blockade of the 1st degree, syndrome of weakness of the sinus node without an artificial pacemaker, the probability of unstable conduction at the atrioventricular node, history of Morgagni-Adams-Stokes attacks, hypertrophic obstructive subaortal 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 diastolic dysfunction (restrictive cardiomyopathy, cardiac amyloidosis, constrictive pericarditis, cardiac tamponade), extrasystole, marked dilatation of the cavities of the heart, "pulmonary" heart.

Water-electrolyte disorders: hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia. Hypothyroidism, alkalosis, myocarditis, advanced age, renal-hepatic insufficiency, obesity, diabetes mellitus (the composition of the drug includes sucrose and glucose (dextrose monohydrate)).

Pregnancy and lactation:Drugs foxglove come through the placenta. Digoxin on the safety of its use in pregnancy refers to the category "C" (risk in the application is not excluded). Studies in pregnant women are not sufficient, the appointment

the drug is only possible if the intended benefit to the mother exceeds the potential risk to the fetus.

Digoxin is excreted in the mother's milk.Since there is no data on the called drug effects on the newborn through breastfeeding, if necessary, its use during lactation should decide on the abolition of breastfeeding.

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 need to quickly achieve a therapeutic effect.

Moderately rapid digitalization (24-36 hours) is used in emergency cases

The daily dose of 0.75 - 1.25 mg divided into 2 doses, under ECG control before each subsequent dose.

After reaching saturation, they switch to supporting treatment.

Slow digitalization (5-7 days) The daily dose of 0.125-0.5 mg is administered once a day for 5-7 days (until reaching saturation), after which they switch to maintenance 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 with a body weight of 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 tablets).

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

Impaired renal function

If there is a violation of the excretory function of the kidneys, it is necessary to reduce the dose of Digoxin: with a creatinine clearance value of 50 to 80 ml / min, the average maintenance dose (SPD) is 50% of the SPD for patients with normal renal function; with SC less than 10 ml / min - 25% of the usual dose.

Side effects:

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

from the cardiovascular system - ventricular paroxysmal tachycardia, ventricular extrasystole (often bigemia, polytopic ventricular extrasystole), nodular tachycardia, sinus bradycardia, sinoauric (SA) blockade, flicker and flutter of the atria, AV blockade; on ECG - trough-like depression segment

that ST.

From the side of the digestive tract: anorexia, nausea, vomiting, diarrhea, abdominal pain, necrosis of the intestine.

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

From the sense organs: staining of visible objects in a yellow-green color, flashing of "flies" before the 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:

Treatment

The elimination of digoxip, the appointment of activated charcoal (to reduce absorption), administration of antidotes (unitiol, EDTA, antibodies to digoxin), symptomatic therapy. Carry out constant monitoring of the 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 up to a total dose of 3-6 g (40-80 mEq K⁺) for adults subject to adequate kidney function.In case of emergency, intravenous injection of 2% or 4% solution of potassium chloride. The daily dose is 40-80 mEq K⁺ (diluted to a concentration of 40 mEq K⁺ for 500 ml). The recommended rate of administration should not exceed 20 meq / h (under ECG monitoring). When hypomagnesemia is recommended the appointment of magnesium salts.

In the cases ventricular tachyarrhythmia shows a slow intravenous injection of lidocaine. In patients with normal cardiac and renal function, it is usually effective to slowly slow iv injection (within 2-4 min) of lidocaine at an initial dose of 1-2 mg / kg of body weight, followed by a drop-over injection at a rate of 1-2 mg / min. In patients with impaired renal and / or cardiac function, the dose should be appropriately reduced.

When presence of A V blockade 11-111 degree should not be appointed lidocaine and potassium salts until an artificial pacemaker is installed. During treatment, it is necessary to monitor the calcium and phosphorus in the blood and daily urine.

There is experience in using the following drugs with a possible positive effect: beta-adrenoblockers, nrocainamide, brethil and phenytoin.Cardioversion can provoke ventricular fibrillation.

For treatment Bradyarrhythmia and A V blockade shows the use of atropine. When AV blockade II - III degree, asystole and suppression of activity of the sinus node shows the installation of the pacemaker.

Interaction:

With the simultaneous appointment of digoxin with drugs that cause electrolyte imbalance, in particular hypokalemia (eg, diuretics, glucocorticosteroids, insulin, beta-adrenomimetics, amphotericin B), the risk of arrhythmias and other toxic effects of digoxin increases. Hypercalcemia can also lead to the development of toxic effects of digoxin, therefore, intravenous calcium salts should be avoided for patients taking digoxin. In these cases, the dose of digoxin should 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.

The absorption of digoxin in the intestine can be reduced by the action of colestyramine, colestipol, aluminum-containing antacids, neomycin, and tetracyclines.There is evidence that the simultaneous use of spironolactone not only changes the concentration of digoxin in the blood serum, but it can also affect the results of the digoxin concentration determination method, therefore special attention is needed when evaluating the results.

With simultaneous use with digoxin below these drugs, their interaction is possible, due to which the therapeutic act or there is a side effect or toxic effect of digoxin: mineralocorticosteroids, glucocorticosteroids, which have a significant mineral corticosteroid effect; amphotericin B for injection; inhibitors of carbonic anhydrase; adrenocorticotropic hormone (ACTH); diuretic drugs that promote the release of water and potassium (bumetanide, ethacrynic acid, furosemide, indapamide, manpitol and thiazide derivatives); sodium phosphate.

Hypokalemia caused by these drugs increases the risk of toxic action of digoxin, so when used simultaneously with digoxin requires constant monitoring of the concentration of potassium in the blood.

- Preparations of St. John's wort (their interaction with digoxin induces P-glycoprotein and cytochrome P450, i.e., decreases bioavailability, increases metabolism and markedly decreases digoxin concentration in plasma);

- Amiodarone (increases the concentration of digoxin in the blood plasma to a toxic level). The interaction of amiodarone and digoxin inhibits the activity of the sinus and atriovetricular nodes of the heart and the conductivity of the nerve impulse along the conduction system of the heart. Therefore, by appointing amiodarone, digoxin abolish or reduce its dose by half;

- Drugs of salts of aluminum, magnesium and other antacid agents can reduce absorption of digoxin and reduce its concentration in the blood;

- Simultaneous use with digoxin: antiarrhythmics, calcium salts, pancuronium, rauwolfia alkaloids, succinylcholine and sympathomimetics can trigger the development of cardiac rhythm disturbances, therefore in these cases it is necessary to monitor the cardiac activity and the patient's ECG;

- Coalin, pectin and other adsorbents, colestramine, colestipol, laxatives, neomycin and sulfasalazine reduce absorption of digoxin and thereby reduce its therapeutic effect;

- Blocks of "slow" calcium channels, captopril - Increase the concentration of digoxin in the blood plasma, therefore, applying them together, it is necessary to reduce the dose of digoxin, so that the toxic effect of the drug does not appear;

- Edrophonia chloride (anticholinesterase) - increases the tone of the parasympathetic nervous system, so its interaction with digoxin can cause pronounced bradycardia;

- Erythromycin - its action improves the absorption of digoxin in the intestine;

- Heparin - digoxin reduces the anticoagulant effect of heparin, so the dose must be increased;

- Indomethacin decreases secretion of digoxin, so the risk of toxic effects of the drug increases;

- A magnesium sulfate solution for injection is used to reduce the toxic effects of cardiac glycosides;

- Phenylbutazone - reduces the concentration of digoxin in the blood serum;

- Drugs of potassium salts, they can not be taken, if under the influence of digoxin appeared conduction disorders on the ECG. However, potassium salts are often prescribed together with digitalis preparations to prevent cardiac rhythm disturbances;

- Quinidine and quinine - these drugs can dramatically increase the concentration of digoxin;

- Spironolactone - reduces the rate of secretion of digoxin, so it is necessary to adjust the dosage of the drug when combined;

-Thallium chloride (TL 201) - in the study of myocardial perfusion with thallium preparations, digoxin reduces the degree of thallium accumulation in the sites of cardiac muscle damage and distorts research data;

- Hormones of the thyroid gland - when their appointment increases metabolism, so the dose of digoxin should be increased.

Special instructions:During the treatment with digoxin, the patient should be monitored in order to avoid side effects resulting from overdose. Patients receiving digitalis preparations should not prescribe calcium preparations for parenteral administration. It is necessary to reduce the dose of digoxin to patients with chronic pulmonary heart disease, coronary insufficiency. disturbances of water-electrolyte balance, renal or hepatic insufficiency: 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 these patients, even with renal dysfunction, the values of creatinine clearance (CK) may be within normal limits, which is associated with a decrease in muscle mass and a decrease in the synthesis of creatinine. Since in renal failure pharmacokinetic processes are violated, the dose selection should be carried out under the control of serum digoxin concentration. If this is not feasible, then the following recommendations can be used. In general, the dose should be reduced by approximately the same percentage as the creatinine clearance is reduced. If QC was not determined, then it can be approximately calculated based on the serum creatinine concentration (CCS).

For men but the formula (140-age): CCS. 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 by an 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 left ventricular failure. For patients with mitral stenosis, cardiac glycosides are prescribed for right ventricular failure, or in the presence of atrial tachyarrhythmia. In patients with AV blockade of degree 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 AV blockade of I st requires caution, regular ECG monitoring, and in some cases - pharmacological prophylaxis with means that improve AV conduction. Digoxin with Wolff-Parkinson-White syndrome, slowing AV conduction. contributes to impulses through additional ways of bypassing the AV node and, thereby, provokes the development of paroxysmal tachycardia.The probability of occurrence of glycosidic intoxication increases with hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia, hypothyroidism, marked dilatation of the heart cavities, pulmonary heart, myocarditis and in elderly patients. As one of the methods of controlling the content of digitalization in the appointment of cardiac glycosides, their plasma concentrations are monitored. One tablet contains 0.005 XE, which should be considered when used in patients with diabetes mellitus.

Effect on the ability to drive transp. cf. and fur:During the period of drug treatment, care must be taken when driving vehicles and occupations

Other potentially hazardous activities requiring increased concentration and speed

psychomotor reactions.

Form release / dosage:

Tablets 250 mcg.

Packaging:

When manufacturing at OJSC "Pharmstandard-Tomskkhimpharm":

10 tablets in a planar cell package; 3 or 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

When produced at OJSC Pharmstandard-Leksredstva:

For 10 or 15 tablets in a planar cell package; 3 or 5 contour cell packs but 10 tablets, 1 or 2 contour packs of 15 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:4 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002052 / 01

Date of registration:01.08.2008

The owner of the registration certificate:PHARMSTANDART-TOMSKHIMFARM, OJSC PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-FORESTRY, OJSC Russia

PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Information update date: & nbsp26.01.2016

Illustrated instructions

Instructions

Digoxin (Digoxin)