Digoxin tablets 0.25mg, No. 56 Reneval

As part of the complex therapy of chronic heart failure II (in the presence of clinical manifestations) and III-IV functional class;
tachysystolic form of atrial fibrillation and atrial flutter of paroxysmal and chronic course (especially in combination with chronic heart failure).

Inside. Adults. As with all cardiac glycosides, the dose should be chosen with caution, individually for each patient. If the patient took cardiac glycosides before prescribing digoxin, the dose of the drug must be reduced. The dose of digoxin depends on the need to quickly achieve a therapeutic effect.

Rapid digitalization (24Ц36 h) is used in case of emergency. The daily dose is 0.75-1.25 mg, divided into 2-3 doses (every 6-8 hours). After reaching saturation, they switch to supportive 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 saturation is reached), after which they switch to supportive treatment.

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

1 tablet contains
active substance: digoxin - 0.25 mg
excipients: colloidal silicon dioxide, magnesium stearate, gelatin, talc, corn starch, lactose monohydrate.

Hypersensitivity to the drug, glycosidic intoxication, Wolff-Parkinson-White syndrome, grade II atriventricular block, intermittent complete blockade.
With caution (comparing benefit / risk): 1st degree AV block, sick sinus syndrome without a pacemaker, the likelihood of unstable conduction through the AV node, a history of Morgagni-Adams-Stokes attacks, hypertrophic subaortic stenosis, isolated mitral stenosis with a rare heart rate , cardiac asthma in patients with mitral stenosis (in the absence of a tachysystolic form of atrial fibrillation), acute myocardial infarction, unstable angina pectoris, arteriovenous shunt, hypoxia, heart failure with impaired diastolic function (restrictive cardiomyopathy, heart amyloidosis, constrictive peri-rasaca) , pronounced dilatation of the cavities of the heart, pulmonary heart.
Electrolyte disturbances: hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia. Hypothyroidism, alkalosis, myocarditis, old age, renal-hepatic failure, obesity.

Trade name of the drug: Digoxin

International non-proprietary name - Digoxin

Dosage form - tablets

Composition
1 tablet contains
active substance: digoxin - 0.25 mg
excipients: colloidal silicon dioxide, magnesium stearate, gelatin, talc, corn starch, lactose monohydrate.

Description
Tablets white or almost white, flat-cylindrical shape with bevel and engraving 'D' on one side

Pharmacotherapeutic group:

cardiotonic agent - cardiac glycoside

ATX code: [—01јј05]

Pharmacological action
Pharmacodynamics
Digoxin is a cardiac glycoside. 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. An increased content of sodium ions causes the 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 an increase in myocardial contractility, the stroke volume of blood increases. The end systolic and end 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. It has a negative chronotropic effect, reduces excessive sympathetic activity by increasing the sensitivity of cardiopulmonary baroreceptors. Due to an increase in the activity of the vagus nerve, it has an antiarrhythmic effect due to a decrease in the speed of impulses through the atrioventricular node and a lengthening 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 an increase in the refractoriness of the atrioventricular (AV) node, which makes it possible to use supraventricular tachycardias and tachyarrhythmias in paroxysms.
With atrial fibrillation, it slows down the frequency of ventricular contractions, lengthens diastole, improves intracardiac and systemic hemodynamics.
The positive batmotropic effect is manifested in the appointment of subtoxic and toxic doses.
It has a direct vasoconstrictor effect, which is most clearly manifested in the absence of congestive peripheral edema.
At the same time, the indirect vasodilating effect (in response to an increase in the minute blood volume and a decrease in excessive sympathetic stimulation of vascular tone), as a rule, prevails over the direct vasoconstrictor effect, as a result of which the total peripheral vascular resistance (OPSR) decreases.

Pharmacokinetics
Absorption from the gastrointestinal tract (GIT) is variable, amounts to 70-80% of the dose and depends on gastrointestinal motility, dosage form, concomitant food intake, and interaction with other drugs. Bioavailability 60-80%. With normal acidity of gastric juice, a small amount of digoxin is destroyed, with hyperacid conditions, more of it can be destroyed.
For complete absorption, sufficient exposure in the intestine is required: with a decrease in gastrointestinal motility, the bioavailability is maximum, with increased peristalsis - minimum. The ability to accumulate in tissues (cumulate) explains the lack of correlation at the beginning of treatment between the severity of the pharmacodynamic effect and its concentration in the blood plasma. The maximum concentration of digoxin in the blood plasma is reached after 1-2 hours. The connection with blood plasma proteins is 25%.
The relative volume of distribution is 5 l / kg. It is metabolized in the liver. Digoxin is excreted mainly by the kidneys (60-80% unchanged). The half-life is about 40 hours. Elimination and elimination half-life is determined by renal function. The intensity of renal excretion is determined by the amount of glomerular filtration. With minor chronic renal failure, a decrease in renal excretion of digoxin is compensated for by hepatic metabolism of digoxin to inactive metabolites. In liver failure, compensation occurs due to increased renal excretion of digoxin.

Indications for use
As part of the complex therapy of chronic heart failure II (in the presence of clinical manifestations) and III-IV functional class;
tachysystolic form of atrial fibrillation and atrial flutter of paroxysmal and chronic course (especially in combination with chronic heart failure).

Contraindications
Hypersensitivity to the drug, glycosidic intoxication, Wolff-Parkinson-White syndrome, grade II atriventricular block, intermittent complete blockade.
With caution (comparing benefit / risk): 1st degree AV block, sick sinus syndrome without a pacemaker, the likelihood of unstable conduction through the AV node, a history of Morgagni-Adams-Stokes attacks, hypertrophic subaortic stenosis, isolated mitral stenosis with a rare heart rate , cardiac asthma in patients with mitral stenosis (in the absence of a tachysystolic form of atrial fibrillation), acute myocardial infarction, unstable angina pectoris, arteriovenous shunt, hypoxia, heart failure with impaired diastolic function (restrictive cardiomyopathy, heart amyloidosis, constrictive peri-rasaca) , pronounced dilatation of the cavities of the heart, pulmonary heart.
Electrolyte disturbances: hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia. Hypothyroidism, alkalosis, myocarditis, old age, renal-hepatic failure, obesity.

Pregnancy and lactation Digitalis
drugs cross the placenta. During childbirth, the concentration of digoxin in the serum of the newborn and the mother is the same. Digoxin for the safety of its use in pregnancy according to the classification of the Administration of the Food and Drug Administration of the United States belongs to category 'C': the risk of use is not excluded. Studies in pregnant women are insufficient, but the anticipated therapeutic effects of the drug may justify the risk of its use.

Lactation period
Digoxin is excreted in mother's milk. However, data on the effects of the drug on newborns are not provided.

Method of administration and dosage

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

Adults The
dose of digoxin depends on the need for a rapid therapeutic effect.

Moderately rapid digitalization (24-36 hours) is used in emergency cases.
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).
A daily dose of 0.125 - 0.5 mg is prescribed once a day for 5-7 days (until saturation is reached), after which they switch to supportive 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 weighing 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 tablet)

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

Side effects
Reported side effects are often the initial signs of overdose.
Digital intoxication:
on the part of the cardiovascular system - ventricular paroxysmal tachycardia, ventricular premature beats (often bigeminia, polytopic ventricular premature beats), nodal tachycardia, sinus bradycardia, sinoauricular (SA) block, atrial fibrillation and tachycardia on the ECG - a decrease in the ST segment with the formation of a biphasic T wave.
From the digestive tract: anorexia, nausea, vomiting, diarrhea, abdominal pain, intestinal necrosis.
From the side of the central nervous system:sleep disorders, headache, dizziness, neuritis, sciatica, manic-depressive syndrome, paresthesia and fainting, in rare cases (mainly in elderly patients suffering from atherosclerosis) disorientation, confusion, monochrome visual hallucinations.
From the senses: staining visible objects in a yellow-green color, flashing 'flies' in front of the eyes, decreased visual acuity, macro- and micropsia.
Allergic reactions are possible: skin rash, rarely hives.
On the part of the hematopoietic system and the hemostatic system: thrombocytopenic purpura, epistaxis, petechiae.
Others: hypokalemia, gynecomastia.

Overdose
Symptoms: decreased appetite, nausea, vomiting, diarrhea, abdominal pain, intestinal necrosis; ventricular paroxysmal tachycardia, ventricular premature beats (often polytopic or bigeminy), nodal tachycardia, SA blockade, atrial fibrillation and atrial flutter, AV block, drowsiness, confusion, delirious psychosis, decreased visual acuity, yellow-green staining of visible objects flies 'before the eyes, the perception of objects in a reduced or enlarged form; neuritis, sciatica, manic-depressive syndrome, paresthesia.

Treatment
Cancellation of Digoxin, administration of activated charcoal (to reduce absorption), administration of antidotes (unitiol, EDTA, antibodies to digoxin), symptomatic therapy.
Conduct continuous 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 renal 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 infusion rate should not exceed 20 mEq / h (under ECG control).
With hypomagnesemia, the appointment of magnesium salts is recommended.
In casesventricular tachyarrhythmias are indicated by slow intravenous administration of lidocaine. In patients with normal heart and kidney function, slow intravenous administration (within 2-4 minutes) of lidocaine at an initial dose of 1-2 mg / kg of body weight is usually effective, followed by a transition to drip administration at a rate of 1-2 mg / min. In patients with impaired renal and / or cardiac function, the dose should be reduced accordingly. In the presence of P-III degree AV block, lidocaine and potassium salts should not be prescribed until an artificial pacemaker is installed.
During treatment, it is necessary to monitor the content of calcium and phosphorus in the blood and daily urine.
There is experience with the use of the following drugs with a possible positive effect: beta-blockers, procainamide, bretilium, and phenytoin. Cardioversion can cause ventricular fibrillation. For the treatment of bradyarrhythmias and AV block , the use of atropine is indicated. With AV blockade of II - III degree, asystole and suppression of the activity of the sinus node, the installation of a pacemaker is indicated.

Interaction with other drugs
With the simultaneous administration of digoxin with drugs that cause electrolyte imbalance, in particular hypokalemia (for example, diuretics, glucocorticosteroids, insulin, beta-adrenergic agonists, amphotericin B), the risk of arrhythmia and the development of other toxic effects of digoxin increases. Hypercalcemia can also lead to the development of toxic effects of digoxin, so intravenous calcium salts should be avoided in patients taking digoxin. In these cases, the dose of digoxin must be reduced.
Certain drugs can increase serum digoxin levels, such as quinidine, slow calcium channel blockers (especially verapamil), amiodarone, spironolactone, and triamterene.
The absorption of digoxin in the intestine can be reduced by the action of cholestyramine, colestipol, aluminum-containing antacids, neomycin, tetracyclines. There is evidence that the simultaneous use of spironolactone not only changes the concentration of digoxin in the serum, but can also affect the results of the method for determining the concentration of digoxin, therefore, special attention is required when evaluating the results obtained.
Decreased bioavailability: activated carbon, astringent drugs, kaolin, sulfasalazine (binding in the lumen of the gastrointestinal tract); metoclopramide, proserin (increased gastrointestinal motility).
Increased bioavailability: broad-spectrum antibiotics that suppress the intestinal microflora (reduce destruction in the gastrointestinal tract).
Beta-blockers and verapamil increase the severity of the negative chronotropic effect, reduce the strength of the inotropic effect.
Microsomal oxidation inducers (barbiturates, phenylbutazone, phenytoin, rifampicin, antiepileptic, oral contraceptives) can stimulate the metabolism of digitoxin (if they are canceled, digitalis intoxication is possible).
When used simultaneously with digoxin, the following drugs may interact, as a result of which the therapeutic effect decreases or the side or toxic effect of digoxin is manifested: mineralocorticosteroids, glucocorticosteroids, which have a significant mineralocorticosteroid effect; amphotericin B for injection; carbonic anhydrase inhibitors; adrenocorticotropic hormone (ACTH); diuretic drugs that promote the release of water and potassium (bumetadine, ethacrynic acid, furosemide, indapamide, mannitol and thiazide derivatives); sodium phosphate.
Hypokalemia caused by these drugs increases the risk of the toxic effect of digoxin, therefore, when they are used simultaneously with digoxin, constant monitoring of the concentration of potassium in the blood is required.
-St. John's wort preparations (their interaction with digoxin induces P-glycoprotein and cytochrome P450, i.e. reduces bioavailability, increases metabolism and significantly reduces 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 conduction of the nerve impulse through the cardiac conduction system. Therefore, by prescribing amiodarone, digoxin is canceled or its dose is reduced by half;
- Preparations of salts of aluminum, magnesium and other antacids can reduce the absorption of digoxin and reduce its concentration in the blood;
- Simultaneous use with digoxin: antiarrhythmics, calcium salts, pancuronium, rauwolfia alkaloids, succinylcholine and sympathomimetics can provoke the development of cardiac arrhythmias, therefore, in these cases, it is necessary to monitor the patient's cardiac activity and ECG;
- Kaolin, pectin and other adsorbents, cholestyramine, colestipol, laxatives, neomycin and sulfosalazine reduce the 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, using them together, it is necessary to reduce the dose of digoxin so that the toxic effect of the drug does not appear;
- Edrophonium (anticholinesterase agent) - increases the tone of the parasympathetic nervous system, so its interaction with digoxin can cause severe bradycardia;
- Erythromycin - its action improves the absorption of digoxin in the intestine;
- Heparin - digoxin reduces the anticoagulant effect of heparin, so the dose has to be increased;
- Indomethacin reduces the release of digoxin, therefore, the danger of the toxic effects of the drug increases;
- A solution of magnesium sulfate for injection is used to reduce the toxic effects of cardiac glycosides;
- Phenylbutazone - reduces the concentration of digoxin in the blood serum;
- Preparations of potassium salts, they should not be taken if, under the influence of digoxin, conduction disturbances appear on the ECG. However, potassium salts are often prescribed together with digitalis preparations to prevent cardiac arrhythmias;
- Quinidine and quinine - these drugs can dramatically increase the concentration of digoxin;
- Spironolactone - reduces the rate of digoxin release, therefore it is necessary to adjust the dosage of the drug when used together;
- Waist chloride (TL 201) - when examining myocardial perfusion with the Waist preparations, digoxin reduces the degree of accumulation of the waist in places where the heart muscle is damaged and distorts the study data;
- Thyroid hormones - when they are prescribed, the metabolism increases, so the dose of digoxin must be increased.

Special instructions
During treatment with Digoxin, the patient should be monitored in order to avoid side effects resulting from an overdose. Patients receiving digitalis preparations should not be prescribed parenteral calcium preparations.
The dose of Digoxin should be reduced in patients with chronic pulmonary heart disease, coronary insufficiency, impaired water and 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 impaired renal function, the values ??of creatinine clearance (CC) may be within the normal range, which is associated with a decrease in muscle mass and a decrease in creatinine synthesis.
Since in renal failure pharmacokinetic processes are disturbed, the dose selection should be carried out under the control of the concentration of digoxin in the blood serum. If this is not feasible, then you can use the following recommendations. In general, the dose should be reduced by about the same percentage as the reduced creatinine clearance. If the CC was not determined, then it can be approximately calculated based on the indicator of the concentration of creatinine in the blood serum (CCC). For men according to the formula (140-age): KKS. For women, the result should be multiplied by 0.85.
In severe renal failure, the serum digoxin concentration should be measured every 2 weeks, at least during the initial period of treatment.
In idiopathic subaortic stenosis (obstruction of the outflow tract of the left ventricle with an asymmetrically hypertrophied interventricular septum), the administration of digoxin leads to an increase in the severity of the obstruction. With severe mitral stenosis and normo- or bradycardia, heart failure develops due to a decrease in diastolic filling of the left ventricle.
Digoxin, by 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 when right ventricular failure is attached, or in the presence of atrial fibrillation.
In patients with grade II AV block, the appointment of cardiac glycosides can aggravate it and lead to the development of a Morgagni-Adams-Stokes attack. Appointment of cardiac glycosides in AV blockade of the 1st stage requires caution, frequent ECG monitoring, and in some cases - pharmacological prophylaxis with drugs that improve AV conduction.
Digoxin in Wolff-Parkinson-White syndrome, slowing down AV conduction, promotes the conduction of impulses through additional conduction pathways bypassing the AV node and, thereby, provokes the development of paroxysmal tachycardia. The likelihood of glycosidic intoxication increases with hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia, hypothyroidism, severe dilatation of the heart cavities, cor pulmonale, myocarditis and in the elderly.
As one of the methods to control the content of digitalization when prescribing cardiac glycosides, monitoring of their plasma concentration is used.

Cross-sensitivity
Allergic reactions to digoxin and other digitalis drugs are rare.
If hypersensitivity appears in relation to any one digitalis drug, other representatives of this group can be used, since crosssensitivity to digitalis drugs is not characteristic

The patient is obliged to follow exactly the following instructions.
1 Use the drug only as prescribed, do not change the dose yourself;
2 Use the drug every day only 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 Do not increase or double the dose;
6 If the patient has not taken the drug for more than 2 days, it is necessary to inform the doctor about this.
Before stopping the use of the drug, you must inform the doctor about it.
If you experience vomiting, nausea, diarrhea, rapid heart rate, you should immediately consult a doctor.
Before surgery or in the provision of emergency care, it is necessary to warn about the use of digoxin.
It is undesirable to use other medicines without the permission of a doctor.

Release form
Tablets of 0.25 mg.
50 tablets in a white polypropylene bottle. Each bottle, along with instructions for use, is placed in a cardboard box.

Storage conditions
List A.
Store at a temperature of 15 to 30 ? C.
Keep out of the reach of children.

Shelf life is
3 years.
Do not use after the expiration date.

Terms of dispensing from pharmacies
Prescription.