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

Excipients: silicon dioxide colloid 0.50 mg, magnesium stearate 1.00 mg, gelatin 1.50 mg, talc 1.50 mg, corn starch 20.00 mg, lactose monohydrate 75.25 mg.

Description:

White or almost white, round, flat tablets with a bevel and with an engraving "D" on one side.

Pharmacotherapeutic group:cardiotonic - 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 the 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 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 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). Half-life is about 40h. 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; tahisystolic form of flicker and atrial flutter of paroxysmal and chronic course (especially in combination with chronic heart failure).

Contraindications:

Hypersensitivity to the drug, glycoside intoxication, Wolff-Parkinson-White syndrome, second-degree atrioventricular blockade, intermittent complete blockade.

Carefully:

With caution (comparing benefit / risk): AV blockade of I degree, sinus node weakness syndrome without pacemaker, probability of unstable AV assembly, history of Morgagni-Edams-Stokes attacks, hypertrophic subaortic stenosis, isolated mitral stenosis with 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 diarrhea (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-hepatic insufficiency, 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 by classification of the administration of food and medicines USA belongs to the category "C": the risk in the application is not excluded. Studies in pregnant women are not enough, but the predicted therapeutic effect of the drug may justify the risk of its use.

Lactation period

Digoxin is excreted in the mother's milk. But the data on the effect of the drug on the newborn are not given.

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 with lefre administration of digoxin took cardiac glycosides, 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 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 supportive treatment.

Slow digitalization (5-7 days). The 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.

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; Yg pills)

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.

Side effects:

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

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:

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 syndrome, paresthesia.

Treatment

The elimination of digoxin, 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, 2% or 4% potassium chloride solution is injected intravenously. 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 availability AV blockades II-H 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 an experience of using the following drugs with a possible positive effect: beta-adrenoblockers, procainamide, brethilia, and phenytoin. Cardioversion can provoke ventricular fibrillation.

For treatment bradyarrhythmias and AV blockades 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 simultaneous administration of digoxin with drugs that cause electrolyte imbalance, in particular hypokalemia (eg, diuretics, glucocorticosteroids, insulin, beta-adrenomimetics, amphotericin B), the risk of arrhythmia and the development of other toxic effects digoxin. 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 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 required when evaluating the results obtained.

Decreased bioavailability: Activated carbon, binders JIC, kaolin, sulfasalazine, (binding in the lumen of the gastrointestinal tract); metoclopramide, 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, oral contraceptives) can stimulate digitoxin metabolism (when they are canceled, digitalis intoxication is possible). 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 (bukmetadin, 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 (interaction of them and digoxin induces P-glycoprotein and cytochrome P450, i.e., decreases bioavailability, increases metabolism and markedly decreases the concentration of digoxin 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 atrioventricular 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;

- Kaolin, pectin and other adsorbents, colestramine, colestipol, laxatives, neomycin and sulfosalazine 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, it is necessary to reduce the dose of digoxin, so that the toxic effect of the drug does not appear;

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

- Waist chloride (TL 201) - in the study of myocardial perfusion with waist preparations, digoxin Reduces the degree of accumulation of the waist in the areas of involvement of the heart muscle and distorts the 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 an overdose.Patients receiving digitalis preparations should not prescribe calcium preparations for parenteral administration.

Digoxin dose should be reduced in patients with chronic pulmonary heart disease, coronary insufficiency, water-electrolyte balance disorders, kidney or liver failure: 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, 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 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 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 diastolic filling of the left ventricle.

Digoxin, increasing myocardial contractility of the right ventricle, 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 P 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 I st requires caution, frequent monitoring of the ECG, and in some cases - pharmacological prophylaxis with agents that improve 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. 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 the content of 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 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

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

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

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

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

- Do not increase or double the dose;

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

Before discontinuing the use of the drug, it is necessary to 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 about the use of digoxin.

Without the permission of the doctor, the use of other medicinal products is undesirable.

Form release / dosage:

Tablets of 0.25 mg.

Packaging:For 50 tablets in a white polypropylene bottle. Each vial with the instruction for use is placed in a cardboard box.

Storage conditions:

At a temperature not higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014167 / 01

Date of registration:20.03.2009

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER OJSC Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp23.01.2016

Illustrated instructions

Instructions

Digoxin (Digoxin)