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

Composition:One tablet contains: active substance: digoxin 0.25 mg; Excipients: sugar-refined sugar (sucrose) 17.5 mg, milk sugar (lactose) 40.0 mg, potato starch 7.93 mg glucose (dextrose) 2.5 mg, talc 1.4 mg, calcium stearate - 0.42 mg.

Description:Tablets of white color of flat-cylindrical form with a facet.

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 on the Na + / K + -ATP-ase membrane of cardiomyocytes, which leads to an increase in the intracellular content of sodium ions and, accordingly, a decrease in potassium ions.As a result, the content of sodium ions in the cardiomyocyte increases, which leads to the discovery of calcium channels and the entry of calcium ions into the cardiomyocytes. Excess sodium ions also leads to an acceleration of the release of calcium ions from the sarcoplasmic reticulum. An increase in the content of calcium ions leads to the elimination of the action of the troponin complex, which exerts a depressing effect on the interaction of actin and myosin.

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 the sensitivity of cardiopulmonary baroreceptors.

The negative dromotropic effect is manifested in the increased refractoriness of the atrioventricular (AV) node, which allows for use in paroxysms of supraventricular tachycardias and tachyarrhythmias.

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 medicines. 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 apparent volume of 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 insignificant 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 according to the NYHA classification; tahysistolicheskaya form of flicker and flutter, atrial paroxysmal and chronic course (especially in combination with chronic heart failure).

Contraindications:Hypersensitivity to the drug, glycoside intoxication, Wolff-Parkinson-White syndrome, atrioventricular block, grade II, intermittent blockade, children under 3 years of age, patients with rare hereditary diseases: fructose intolerance and glucose / galactose absorption impairment syndrome or insufficiency sucrose / isomaltase; deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:

AV blockade of I degree, syndrome of weakness of the sinus node without a pacemaker; the probability of unstable conduction in the AV node, the indication in the anamnesis for the attacks of Morgagni-Adams-Stokes, hypertrophic obstructive cardiomyopathy, isolated mitral stenosis with a rare heart rate (HR),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), arrythmia, marked dilatation of the cavities of the heart, "pulmonary" heart.

Electrolyte disorders: hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia. Hypothyroidism, alkalosis, myocarditis, advanced age, renal and / or liver failure, obesity.

Pregnancy and lactation:Drugs foxglove come through the placenta. During delivery, the concentration of digoxin in the blood serum of the newborn and the mother is the same. Digoxin on the safety of its use in pregnancy, according to the classification of the administration of food and medicines, the United States is classified as "C" (risk in use is not excluded). Studies of the use of digoxin in pregnant women are not enough, but the benefit to the mother can justify the risk of its use.

Lactation period

Digoxin penetrates into the mother's milk. Since there is no evidence of drug-induced effects on the newborn when breastfeeding, it is recommended that breastfeeding be discontinued if therapy is needed during this period.

Dosing and Administration:

Mode of application 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.

Dose of the drug 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 is 0.75-1.25 mg divided into 2 doses, under ECG monitoring before each subsequent dose.

After reaching saturation, they switch to supportive 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, the drug 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 0.0625-0.0125 mg (1/4; 1/2 tablets). Supportive therapy

The daily dose for maintenance therapy is set individually and is 0.125-0.75 mg. Supportive therapy, as a rule, is carried out for a long time.

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 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. Impaired renal function

If the excretory function of the kidneys is impaired, the dose of digoxin should be reduced: at a creatinine clearance value of 50-80 ml / min, the average maintenance dose (SPD) is 50% of the SPD for individuals 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; ECG - reduction of the segment ST with education two-phase T wave;

from the digestive tract: anorexia, nausea, vomiting, diarrhea, abdominal pain, intestinal necrosis;

from the central nervous system: sleep disorders, headache, dizziness, neuritis, radiculitis, manic-depressive syndrome, paresthesia and syncope, in rare cases (mainly in elderly patients with atherosclerosis) - disorientation, confusion, monochromatic visual hallucinations;

from the senses: staining of visible objects in yellow-green color, flashing of "flies" before the eyes, reduced visual acuity, macro and microposs; allergic reactions are possible: skin rash, rarely - hives;

from the hematopoiesis and hemostasis system: 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, SA blockade, flicker and flutter of the atria, AV blockade, drowsiness, confusion, delirious psychosis, decreased 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, radiculitis, manic-depressive psychosis, paresthesia.

Treatment: cancellation Digoxin, the use of activated carbon (to reduce absorption), the administration of antidotes (sodium dimercaptopropanesulfonate, sodium calcium edetate (EDTA), antibodies to digoxin), symptomatic therapy. Carry out constant monitoring of the ECG.

In the 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 ions) for adults with adequate kidney function. In emergency cases, intravenous drip injection of 2% or 4% potassium chloride solution is indicated.The daily dose is 40-80 mEq K + (diluted to a concentration of 40 mEq K + per 500 ml). The recommended rate of administration should not exceed 20 mEq / h (under ECG monitoring).

When hypomagnesemia parenteral application of magnesium salts is recommended.

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

In the presence of A V blockade II-III 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, procainamide, brethil tosylate and phenytoin. Cardioversion can provoke ventricular fibrillation.

For treatment bradyarrhythmias and AV blockades shows the use of atropine. When AV blockade of II-III degree, asystole and suppression of activity of the sinus node, the mouth is shownan artificial 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 simultaneous use of spironolactone not only changes the concentration of digoxin inserum, but it can also affect the results of the digoxin concentration determination method, therefore special attention is required when evaluating the results.

Decreased bioavailability: Activated carbon, astringent drugs, kaolin, sulfasalazine, (binding in the lumen of the gastrointestinal tract); metoclopramide, neostigmine methylsulfate (proserin) (increased motility of the gastrointestinal tract).

Increased bioavailability: broad-spectrum antibiotics that suppress the intestinal microflora (reduction of destruction in the digestive tract).

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

Inductors of microsomal oxidation (barbiturates, phenylbutazone, phenytoin, rifampicin, antiepileptic drugs, oral contraceptives) can stimulate digoxin metabolism (when they are canceled, digitalis intoxication is possible). - - With concomitant use with digoxin below these drugs, their interaction is possible, due to which the therapeutic effect decreases or the side-effect or toxic effect of digoxin is manifested: mineral,glucocorticosteroids; amphotericin B for injection; inhibitors of carbonic anhydrase; adreno-corticotropic hormone (ACTH); diuretics that promote the release of water and potassium ions (bumetanide, ethacrynic acid, furosemide, indapamide, mannitol and thiazide derivatives); sodium phosphate.

Hypokalemia caused by these medicines increases the risk of toxic action of digoxin, therefore, when used simultaneously with digoxin, constant monitoring of the potassium concentration in the blood is required.

- Drugs of St. John's wort: the combined use reduces the bioavailability of digoxin, increasing the rate of hepatic metabolism and significantly reducing the concentration of digoxin in the blood 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 atrioventricular nodes of the heart and the conductivity of the nerve impulse along the conduction system of the heart. Therefore, by appointing amiodarone, digoxin cancellation or its dose is reduced by half;

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

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

- Kaolin, pectin and other adsorbents, colestramine, colestipol, laxatives, neomycin and sulphasalazine reduce the 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, the dose of digoxin should be reduced so that the toxic effect of the drug does not appear;

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

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

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

- Indomethacin reduces excretion of digoxin; therefore, 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 correct the dose of the drug when combined;

- Thallium [201T1] chloride - in the study of myocardial perfusion by waist preparations, digoxin reduces the degree of accumulation of thallium [201T1] in places 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:

All time of treatment by a preparation Digoxin The patient should be under the supervision of a doctor in order to avoid the development of side effects. Patients receiving digitalis preparations should not prescribe calcium preparations for parenteral administration.

It is necessary to reduce the dose of the drug Digoxin patients with chronic "pulmonary" heart, coronary insufficiency, violations of water-electrolyte balance, renal or hepatic insufficiency. Older 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 impaired renal function, the values of creatinine clearance (CC) 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, the following recommendations can be used: in general, the dose should be reduced by approximately the same percentage as the clearance creatinine.If QC was not determined, then it can be approximately calculated based on the serum creatinine concentration (CCS). For men according to the formula (140 - age) / KKS. For women, the result should be multiplied by 0.85. In severe renal failure (CC less than 15 ml / min.), 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. Patients with mitral stenosis are assigned cardiac glycosides upon adherence to right ventricular failure, or in the presence of atrial tachyarrhythmia.

In patients with AV blockade II degree appointment of cardiac glycosides may aggravate it and lead to attacks of Morgagni-Adams-Stokes. Appointment of cardiac glycosides pri'AU blockade 1stepeni requires caution, frequent ECG monitoring, and in some cases - pharmacological prevention means improving AV conductivity.

Digoxin in Wolff-Parkinson-White syndrome, slowing down AV conductivity, facilitates impulses through additional ways of bypassing AV node, and, thereby, provokes the development of paroxysmal tachycardia.

Probability of glycoside intoxication increases with hypokalemia; hypomagnesemia, hypercalcemia, hypernatremia, hypothyroidism, marked dilatation of the heart cavities, "pulmonary" heart, myocarditis and in the elderly. Monitoring of their plasma concentration is used as one of the methods of controlling digitalization in the appointment of cardiac glycosides.

Cross-sensitivity

Allergic reactions to digoxin and other digitalis preparations are rare. If there is an increased sensitivity in relation to any one medicine digitalis,other representatives of this group can be used, since the cross-sensitivity to digitalis preparations is not peculiar.

The patient must strictly follow the following instructions:

1 Use the drug only as prescribed, do not change the dose alone;

2 Every day, use the drug only at the appointed time;

3 If the heart rate is less than 60 beats per minute, you should immediately consult your doctor;

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

5 Do not increase or double the dose;

6 If the patient did not take the drug for more than 2 days, it is necessary to inform the doctor about it.

Before stopping the use of the drug, you should inform the doctor about it. When there is vomiting, nausea, diarrhea, rapid pulse, you should immediately consult a doctor.

Before surgery or when providing emergency care, the doctor should be warned about the use of Digoxin.

Without the permission of the doctor, the use of other medicinal products is undesirable. The preparation contains sucrose, lactose, potato starch, glucose in an amount corresponding to 0.006 bread units.

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

Form release / dosage:

Tablets 0.25 mg.

Packaging:

For 10 tablets in a contour mesh box made of a polyvinyl chloride film and aluminum foil.

1, 2 or 3 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:Store in a dark place at a temperature of 15 to 25 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000397

Date of registration:28.02.2011

Expiration Date:28.02.2016

The owner of the registration certificate:BINNOFARM, CJSC BINNOFARM, CJSC Russia

Manufacturer: & nbsp

BINNOFARM, CJSC Russia

Information update date: & nbsp28.02.2016

Illustrated instructions

Instructions

Digoxin (Digoxin)