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

active substance - digoxin (in terms of 100%) - 0.25 mg; auxiliary substances: sucrose (refined sugar) - 17.5 mg, potato starch - 7.93 mg, lactose (milk sugar) - 40 mg, dextrose monohydrate (glucose monohydrate) 2.5 mg, talc 1.4 mg, calcium stearate 0.42 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. Blocks the transport Na⁺/TO⁺-ATP-ase, resulting in increased content Na⁺ in the cardiomyocyte, which leads to the discovery of Ca²⁺channels and the entry of Ca²⁺ in cardiomyocytes. Excess Na* causes activation of sodium / calcium metabolism, which leads to an acceleration of Ca release²⁺ from the sarcoplasmic reticulum and an increase in the content of calcium ions, as a result of which the force of myocardial contraction increases. Increase in Ca concentration²⁺ leads to inhibition of the troponin complex, which exerts a depressing effect on the interaction of actin and myosin. The increase in strength and rate of myocardial contraction occurs by a mechanism different from the Frank-Starling mechanism (it does not depend on the degree of pre-stretching of the myocardium). The systole becomes shorter and energy-efficient.

As a result of increased myocardial contractility, the shock volume of blood and the minute volume of blood increase.

The end-systolic volume and the end-diastolic volume 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.

Due 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 atrioventricular (AV) node, which allows using for paroxysms of supraventricular tachycardia and tachyarrhythmias. With ciliary tachyarrhythmia, it slows down the heart rate, lengthens the diastole, improves intracardiac and systemic hemodynamics. Reduction of the heart rate is a result of direct and indirect effects on the regulation of the heart rate. A positive batmotropic effect is manifested in the administration of toxic and toxic doses. The direct action is to reduce the automatism of the sinus node. A greater significance in the formation of a negative chronotropic action has a change in the reflex regulation of the heart rhythm: in patients with ciliary tachyarrhythmia,blockade of conducting the weakest impulses; increase in the tone of the vagus nerve as a result of a reflex from the aortic arch receptor and carotid sinus with an increase in the minute volume of blood; decrease in pressure in the mouth of the hollow veins and right atrium (as a result of increased left ventricular myocardial contractility, more complete emptying, pulmonary artery pressure lowering and hemodynamic discharge of the right heart), elimination of the Bainbridge reflex and reflex activation of the sympathoadrenal system (in response to an increase in the minute volume of blood). It has a direct vasoconstrictive effect, which is most clearly manifested in the case when a positive inotropic effect is not realized. 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), usually prevails over direct vasoconstrictive action, resulting in a decrease in the overall peripheral vascular resistance.

Pharmacokinetics:

Absorption from the gastrointestinal tract (GIT) is variable, depends on the motility of the gastrointestinal tract, on the dosage form,from concomitant intake of food, from interaction with other medicines. Bioavailability is 60-80%.

With a normal acidity of gastric juice, an insignificant amount of detoxin is destroyed, with a hyperacid state, more of it can be destroyed. For complete absorption, sufficient exposure in the intestine is required: with a decrease in the motility of the gastrointestinal tract, the bioavailability of drugs 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 plasma. The maximum concentration of toxin in the blood plasma is reached after 1-2 hours. The connection with plasma proteins is 20-25%. The relative volume of the distribution is 5 l / kg. Metabolised in the liver. Ditoxin is excreted mainly by the kidneys (60-80% unchanged). The half-life is 30-40 hours. 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 according to the NYHA classification; tahisistolicheskaya form of flicker and atrial flutter of paroxysmal and chronic course (especially in combination with chronic heart failure (CHF)).

Contraindications:Hypersensitivity to the drug, glycoside intoxication, Wolff-Parkinson-White syndrome, atrioventricular blockade of the 2nd degree, intermittent blockade, children under 3 years of age, patients with rare hereditary diseases: fructose intolerance and glucose / galactose absorption impairment syndrome or insufficiency of sucrose / isomaltase; deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:

(comparing benefit / risk): AV block of I degree, sinus node weakness syndrome without pacemaker, probability of unstable conduction in AV node, history of Morgagni-Adams-Stokes attacks,hypertrophic obstructive cardiomyopathy, 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, amyloidosis of the heart, constrictive pericarditis, cardiac tamponade), extrasystole, marked dilatation of the heart cavities, "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 labor, the concentration of detoxin 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 benefits for 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:

Method 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 of age

The dose of the drug 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 the control of an electrocardiogram (ECG) 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.

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 0.0625-0.125 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 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 50-80 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 the formation of a two-phase prong T;

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, flickering "flies" in front of the eyes and 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: elimination of digoxin, the appointment of activated charcoal (to reduce absorption), administration of antidotes (sodium dimercaptopropanesulfonate, sodium calcium edetate (EDTA), antibodies to digoxin), symptomatic therapy. Carry out constant monitoring of the ECG. In the cases hypokalemia Potassium salts are widely used: 0.5-1 g of potassium chloride are dissolved in water and taken several times a day up 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⁺ for 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 AV blockades 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 content of calcium and phosphorus in 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 bradyarisms and AV blockades shows the use of atropine. When AV blockade II-III degree, asystole and inhibition of sinus node activity shows the installation of an artificial pacemaker.

Interaction:

With the simultaneous administration 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 is increased. Hypercalcemia can also lead to the development of toxic effects of digoxin, therefore, intravenous calcium salts should be avoided for patients receiving 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 colestiramine, 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.

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). Run-adrenoblockers 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, antiepileptics, oral contraceptives) can stimulate digoxin metabolism (when they are canceled, digitalis intoxication is possible).

With simultaneous use with Digoxin below mentioned drugs possible their interaction, due to which decreases therapeutic effect or a side effect or toxic effect of digoxin: mineral, glucocorticosteroids; amphotericin B for injection; inhibitors of carbonic anhydrase; adrenocorticotropic hormone; 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 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: 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;

- Preparations of salts of aluminum, magnesium and other agents used as stacid, 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 sulfasalazine reduce absorption of digoxin and thereby reduce its therapeutic effect;

- Blockers 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 a pronounced bradycardia;

- Erythromycin - improves absorption of digoxin in the intestine;

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

- Indomethacin reduces the excretion of digoxin, so the risk of toxic effects of the drug increases;

- Magnesium sulfate solution for injection used to reduce the toxic effects of cardiac glycosides;

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

- Preparations of potassium salts: they can not be taken, if under the influence of digoxin appeared conduction abnormalities 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 [20ITI] chloride - in the study of myocardial perfusion with waist preparations, digoxin reduces the degree of accumulation of thallium [20IDI] in places of involvement of the heart muscle and distorts the research data;

- Thyroid hormones - at their appointment the metabolism is amplified, therefore the dose of digoxin necessarily should be increased.

Special instructions:

During the treatment with Digoxin, the patient should be monitored in order to avoid side effects resulting from an 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, 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 renal dysfunction, CC values 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.The dose should be reduced by approximately the same percentage, by how much the QC is reduced. If KK was not determined, then it can be approximately calculated based on the serum creatinine concentration (CCS). For men according to 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, in the initial period of treatment.

With idiopathic subaortic 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 of the second degree, the appointment of cardiac glycosides can aggravate it and lead to the development of the attack of Morgagni-Adams-Stokes. The appointment of cardiac glycosides for AV blockade of the first degree requires caution, frequent monitoring of the ECG, and in some cases - pharmacological prophylaxis with agents that improve AV conductivity. Digoxin with 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.

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 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 of digitalis, other representatives of this group can be used, since the cross-sensitivity to digitalis preparations is not peculiar.

The patient must follow the instructions exactly

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

2. Apply the drug every day at the appointed time;

3. If the heart rate is below 60 beats per minute, you should immediately consult a doctor;

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

5. You can not increase or doubleamdose;

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

7. Before discontinuing the use of the drug, it is necessary to inform the doctor about it;

8. If there is vomiting, nausea, diarrhea, rapid pulse, you should immediately consult a doctor;

9. Before surgical operations or when providing emergency care, it is necessary to warn about the use of Digoxin;

10.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 service mechanisms requiring increased concentration of attention and speed of psychomotor reactions are not enough, but care should be taken.

Form release / dosage:

Tablets of 0.25 mg.

Packaging:10 tablets are placed in a contour mesh package made of a polyvinylchloride film and aluminum foil. 3 contour mesh packages together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, dark place at a temperature of 15 to 25 ° C. Keep out of the reach of children.

Shelf life:

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

Terms of leave from pharmacies:On prescription

Registration number:P N001170 / 02

Date of registration:20.04.2009

The owner of the registration certificate:MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC MOSHIMFARM PREPARATES them.N.А.Semashko, OJSC Russia

Manufacturer: & nbsp

MOSHIMFARM PREPARATES them. NA Semashko OJSC Russia

Information update date: & nbsp23.01.2016

Illustrated instructions

Instructions

Digoxin (Digoxin)