Digoxin

General characteristics. Structure:

Active ingredient: 0,25 mg of digoxin in 1 tablet.

Excipients: refined sugar (sucrose), sugar milk (lactose), potato starch, glucose (dextrose), talc, calcium stearate.

Pharmacological properties:

Pharmacodynamics. Digoxin - cardiac glycoside. Has positive inotropic effect. It is caused to straight lines inhibiting effects on Na+/K+-ATF-azu of a membrane of cardiomyocytes that leads to increase in intracellular maintenance of ions of sodium and, respectively, decrease in potassium ions. Therefore the maintenance of ions of sodium increases in a cardiomyocyte that leads to opening of calcium channels and entry of calcium ions into cardiomyocytes. Surplus of ions of sodium leads also to acceleration of allocation of calcium ions from a sarcoplasmic reticulum. Increase in maintenance of calcium ions leads to elimination of action of the troponinovy complex exerting the oppressing impact on interaction of actin and a myosin.

As a result of increase in contractility of a myocardium the stroke output of blood increases. Decreases final systolic and final diastolic heart volumes that, along with increase in a tone of a myocardium, leads to reduction of its sizes and thus to decrease in need of a myocardium for oxygen. Has negative chronotropic effect, reduces excessive sympathetic activity by increase in sensitivity of cardiopulmonary baroreceptors.

The negative dromotropic effect is shown in increase in a refrakternost of an atrioventricular (AV) node that allows to use at paroxysms of supraventricular tachycardias and tachyarrhythmias.

At a ciliary tachyarrhythmia promotes delay of frequency of ventricular reductions, extends a diastole, improves an endocardiac and system hemodynamics. The positive bathmotropic effect is shown at purpose of subtoxic and toxic doses.

Has direct vasopressor effect which is most accurately shown in the absence of congestive peripheral hypostases.

At the same time the indirect vazodilatiruyushchy effect (in response to increase in minute volume of blood and decrease in excessive sympathetic stimulation of a vascular tone), as a rule, prevails over direct vasopressor action therefore the general peripheric vascular resistance (GPVR) decreases.

Pharmacokinetics. Absorption from the digestive tract (DT) - is variable, makes 70-80% of a dose and depends on motility of a GIT, a dosage form, the accompanying meal, on interaction with other medicines. Bioavailability of 60-80%. At normal acidity of a gastric juice the insignificant amount of digoxin collapses, at hyperacid states its bigger quantity can collapse. Full absorption requires sufficient exposure in intestines: at decrease in motility of a GIT bioavailability maximum, at a hyperperistalsis - minimum. Ability to collect in fabrics (to kumulirovat) explains lack of correlation in an initiation of treatment between expressiveness of pharmakodinamichesky effect and its concentration in a blood plasma. The maximum concentration of digoxin in a blood plasma is reached in 1-2 h. Communication with proteins of a blood plasma makes 25%. The seeming distribution volume - 5 l/kg.

It is metabolized in a liver. Digoxin is removed preferential by kidneys (60-80% in not changed look). The elimination half-life makes about 40 h. Removal and an elimination half-life is defined by function of kidneys. Intensity of renal removal is defined by the size of glomerular filtering. At an insignificant chronic renal failure decrease in renal removal of digoxin is compensated for the account of hepatic metabolism of digoxin to inactive metabolites. At a liver failure compensation happens due to strengthening of renal removal of digoxin.

Indications to use:

As a part of complex therapy of chronic heart failure of II (in the presence of clinical manifestations) and the III-IV functional class on NYHA classification; a takhisistolichesky form of blinking and trembling, auricles of a paroxysmal and chronic current (especially in combination with chronic heart failure).

Route of administration and doses:

Route of administration - inside. As well as for all cardiac glycosides, the dose should be selected with care, indiviyodualno for each patient. If the patient before purpose of digoxin accepted cardiac glycosides, in this sluyocha the dose of drug needs to be reduced. Adults and children are more senior than 10 years. The dose of the drug Digoxin depends on need of bystry achievement of terapevticheyosky effect.

Moderately bystry digitalization (24-36 h) is applied in case of emergency
The daily dose makes 0,75-1,25 mg, divided into 2 receptions, under control of an ECG пе­ред each subsequent dose. After achievement of saturation pass to the supporting treatment.

Slow digitalization (5-7 days). The daily dose of 0,125-0,5 mg is appointed 1 time a day within 5-7 days (before achievement of saturation) then pass to the supporting treatment.

Chronic Heart Failure (CHF). At patients with HSN the drug Digoxin has to be used in small doses: to 0,25 mg a day (for patients with body weight more than 85 kg to 0,375 mg a day). At elderly patsiyenyot the daily dose of digoxin has to be lowered to 0,0625-0,0125 mg (1/4; 1/2 tablets).

Maintenance therapy. The daily dose for a maintenance therapy is established individually and sostavlyayot 0,125-0,75 mg. The maintenance therapy is carried out, as a rule, it is long.

Children aged from the 3rd up to 10 years. The sating dose for children makes 0,05-0,08 mg/kg/days; this dose is appointed in teyocheny 3-5 days at moderately bystry digitalization or within 6-7 days at a medlenyony digitalization. The maintenance dose for children makes 0,01-0,025 mg/kg/days.

Renal failure. At disturbance of secretory function of kidneys it is necessary to reduce a digoxin dose: at value of the clearance of creatinine (CC) of 50-80 ml/min. the average maintenance dose (AMD) makes 50% of SPD for persons with normal function of kidneys; at KK less than 10 ml/min. - 25% of a usual dose.

Features of use:

Pregnancy and lactation. Drugs of a foxglove get through a placenta. At the time of delivery concentration of digoxin in blood serum of the newborn and mother is identical. Digoxin on safety of its use at pregnancy on classification of administration of foodstuff and medicines of the USA belongs to the category "C" (the risk at use is not excluded). Researches of use of digoxin for pregnant women are not enough, however the advantage for mother can justify risk of its use.

Lactation period. Digoxin gets into mother's milk. As there are no data on the impact on the newborn caused by drug when feeding by a breast, in need of therapy during this period feeding by a breast is recommended to be stopped.

All the time of treatment by the drug Digoxin the patient has to be under observation of the doctor to avoid development of side effects. The patients receiving foxglove drugs cannot appoint calcium drugs for parenteral administration.

It is necessary to lower a drug Digoxin dose to patients with chronic "pulmonary" heart, coronary insufficiency, disturbances of water and electrolytic balance, a renal or liver failure. Careful selection of a dose is also required from patients of advanced age, especially in the presence at them is one or several above-named states. At the same time it is necessary to consider that at these patients even at a renal failure of value of the clearance of creatinine (CC) can be within norm that is connected with decrease in muscle bulk and reduction of synthesis of creatinine. As at a renal failure pharmacokinetic processes are broken, selection of a dose should be carried out under control of concentration of digoxin in blood serum. If it is impracticable, then it is possible to use the following recommendations: generally, the dose should be reduced approximately on as much percent on how many the clearance of creatinine is reduced. If KK was not defined, then it can be calculated approximately, proceeding from an indicator of concentration of creatinine in blood serum (KKS). For men on a formula (140 - age) / KKS. For women the received result should be increased on 0,85. At a heavy renal failure (KK less than 15 ml/min.) concentration of digoxin in blood serum should be defined every 2 week, at least, during the nachalyyony period of treatment.

At an idiopathic subaortal stenosis (obstruction of an output path of the left zheluyodochk asymmetric a hypertrophied interventricular partition) purpose of Digoxin leads to increase of expressiveness of obstruction.

At the expressed mitral stenosis and normo-or bradycardia the cordial nedostatochyonost develops owing to decrease in diastolic filling of a left ventricle. Digoxin, increasing contractility of a myocardium of a right ventricle, causes further increase in pressure in system of a pulmonary artery that can provoke a fluid lungs or aggravate a left ventricular failure. The patient with a mitral stenosis seryodechny glycosides are appointed at accession of right ventricular insufficiency, or in the presence of a ciliary tachyarrhythmia.

At patients with AV with blockade of the II degree purpose of cardiac glycosides can usuguyobit and lead it to development of an attack of Morganyi-Adams-Stokes. Purpose of cardiac glycosides at HEY blockade of 1 degree demands care, frequent control of an ECG, and in some cases - pharmacological prevention by the means improving AV a provoyodimost.

Digoxin at a WPW-syndrome, slowing down AV conductivity, sposobyostvut to carrying out impulses in additional ways of carrying out bypassing an AV node and, thereby, provokes development of a Bouveret's disease.

The probability of developing of glikozidny intoxication increases at a hypopotassemia; a hypomagnesiemia, a hypercalcemia, the hypernatremia, a hypothyroidism expressed to dilatation of cardial cavities, "pulmonary" heart, myocarditis and at elderly people. As one of digitalization control methods at appointment of warm-hearted glycoyazidi use monitoring of their plasma concentration.

Cross sensitivity. Allergic reactions to digoxin and other drugs of a foxglove develop seldom. If there is a hypersensitivity concerning some one preyoparat of a foxglove, other representatives of this group it is possible to apply as peyorekrestny sensitivity is not inherent to drugs of a foxglove.

The patient is obliged to follow the following instructions precisely:
1. To use drug just as it is appointed, not to change a dose independently;

2. Every day to use drug only in due time;

3. If heart rate less than 60 beats per minute, it is neyomedlenno necessary to consult with the doctor;

4. If reception of the next dose of drug is missed, it needs to be accepted at once as soon as an opportunity appeared;

5. It is impossible to increase or double a dose;

6. If the patient did not accept drug more than 2 days, it is necessary to report about it to the doctor.

Before phase-out of drug it is necessary to inform on it the doctor. At emergence of vomiting, nausea, a diarrhea, the speeded-up pulse it is necessary to obyoratitsya immediately to the doctor.

Before surgical intervention or when rendering acute management it is necessary to warn the doctor about Digoxin use.

Without the permission of the doctor use of other medicines is undesirable. Drug contains sucrose, lactose, potato starch, glucose in quantity, to soyootvetstvuyushchy 0,006 grain units.

Influence on ability to manage vehicles and mechanisms. Researches on Digoxin impact assessment on ability to manage vehicles and to service the mechanisms demanding the increased concentration of attention and speed of psychomotor reactions are not enough, however it is necessary to be careful.

Side effects:

Noted side effects often are initial signs of overdose. Digitalis intoxication:

- from cardiovascular system: ventricular Bouveret's disease, ventricular premature ventricular contraction (often bigeminal pulse, polytopic ventricular premature ventricular contraction), nodal tachycardia, sinus bradycardia, sinoaurikulyarny (SA) blockade, meryotsaniye and atrial flutter, AV blockade; on an ECG - decrease in a segment of ST with образова­ niy a two-phase tooth of T;

- from a digestive tract: anorexia, nausea, vomiting, diarrhea, abdominalyyony pains, intestines necrosis;

- from the central nervous system: sleep disorders, a headache, golovokruzheyony, neuritis, radiculitis, a maniac-depressive syndrome, paresthesias and a faint, in rare instances (it is preferential at patients of advanced age with atherosclerosis) - a disorientation, confusion of consciousness, one-color visual hallucinations;

- from sense bodys: coloring of visible objects in flavovirent color, flashing of "front sights" before eyes, decrease in visual acuity, macro - and a micropsia; allergic reactions are possible: skin rash, it is rare - a small tortoiseshell;

- from bodies of a hemopoiesis and system of a hemostasis: thrombocytopenic purpuyora, nasal bleedings, petechias;

- others: hypopotassemia, gynecomastia.

Interaction with other medicines:

At co-administration of digoxin with the drugs causing disturbances of electrolytic balance, in particular a hypopotassemia (for example, diuretics, glucocorticosteroids, insulin, beta-adrenergic agonists, Amphotericinum In), the risk of developing of arrhythmias and development of other toxic effects of digoxin increases. The hypercalcemia can also lead to development of toxic effects of digoxin therefore it is necessary to avoid intravenous administration of salts of calcium by the patient accepting дигок­син. In these cases the dose of digoxin needs to be reduced. Some drugs can increase concentration of digoxin in blood serum, for example, quinidine, blockers of "slow" calcium channels (especially verapamil), Amiodaronum, Spironolactonum and Triamterenum.

Absorption of digoxin in intestines can be reduced under the influence of Colestyraminum, a kolestipol, aluminum-bearing antacids, Neomycinum, tetracyclines. There are data that simultaneous use of Spironolactonum not only changes a digoxin kontsentrayotion in blood serum, but also can influence results of a method of an opredeyoleniye of concentration of digoxin therefore the special attention at assessment of poluchenyony results is required.

Decrease in bioavailability: absorbent carbon, the knitting medicines, a kaolin, Sulfasalazinum, (binding in a GIT gleam); Metoclopramidum, neostigmin methyl sulfate (прозерин) (strengthening of motility of a GIT).

Increase in bioavailability: the antibiotics of a broad spectrum of activity suppressing kiyoshechny microflora (reduction of destruction in a GIT).

Beta adrenoblockers and verapamil increase expressiveness of negative chronotropic effect, reduce force of an inotropic effect.

Inductors of a microsomal oxidation (barbiturates, phenylbutazone, Phenytoinum, rifampicin, antiepileptic means oral contraceptives) can stimuliroyovat digoxin metabolism (at their cancellation digitalis intoxication is possible).

At simultaneous use with digoxin below the specified medicines their interaction owing to which decreases therapeutic deystyovy is possible or side or toxic effect of digoxin is shown: mineralo-, glyuko-corticosteroids; Amphotericinum In for injections; karboangidraza inhibitors; adreno-corticotropic hormone (AKTG); diuretic drugs, sposobstvuyushchiye.vydeleniya of water and potassium ions (буметанид, Acidum etacrynicum, furosemide, индапамид, Mannitolum and derivatives of a tiazid); sodium phosphate.

The hypopotassemia caused by the mentioned medicines increases risk of tokyosichesky effect of digoxin therefore, at their simultaneous use with digoxin constant observation of potassium concentration in blood is required.

- Drugs of the St. John's Wort which is made a hole: combined use reduces a digoxin biodostupyonost, increasing the speed of hepatic metabolism and significantly umenshayot concentration of digoxin in a blood plasma.

- Amiodaronum: increases concentration of digoxin in a blood plasma to a toxic urovyonya. Interaction of Amiodaronum and digoxin oppresses activity of sinus and atrioventricular nodes of heart and conductivity of nervous impulse on the carrying-out system of heart. Therefore, having appointed Amiodaronum, digoxin is cancelled or its dose reduce a napoyolovina;

- Drugs of salts of aluminum, magnesium and other means applied as antiacid can reduce absorption of digoxin and reduce its concentration in blood;

- Simultaneous use with digoxin: antiarrhytmic means, calcium salts, the pankuroniya of bromide, alkaloids of Rauwolfia, succinylcholine of iodide and sympathomimetics can provoke development of disturbances of a cordial rhythm therefore in these cases не­обходимо to control cordial activity and an ECG of the patient;

- The kaolin, pectin and other adsorbents, Colestyraminum, колестипол, laxative sredyostvo, Neomycinum and Sulfasalazinum reduce digoxin absorption and by that reduce its medical action;

- Blockers of "slow" calcium channels, captopril - increase concentration of digoxin in a blood plasma therefore, applying them together, it is necessary to reduce a dose of a digokyosin that toxic influence of drug was not shown;

- Edrofoniya chloride (antikholinesterazny means) raises a tone of a parasympathetic nervous system therefore interaction it with digoxin can cause the expressed bradycardia;

- Erythromycin - improves absorption of digoxin in intestines;

- Heparin - digoxin reduces anticoagulating effect of heparin, - therefore the dose it should be increased;

- Indometacin reduces digoxin removal; therefore increases, danger токсическо­го drug influences;

- Sulfate magnesium solution for injections is applied to decrease in a toxic vozdeyyostviye of cardiac glycosides;

- Phenylbutazone - reduces concentration of digoxin in blood serum;

- Drugs of salts of potassium: they cannot be accepted if under the influence of digoxin появи­лись disturbances of conductivity on an ECG. However potassium salts are often appointed together with foxglove preyoparata for the prevention of disturbances of a heart rhythm;

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

- Spironolactonum - reduces the speed of release of digoxin therefore it is necessary to korrigirovat a drug dose at soyovmestny use;

- Thallium [201T1] chloride - at a research of perfusion of a myocardium drugs the waist, ди­гоксин reduces extent of accumulation of thallium [201T1] in places of defeat of a cordial myshyotsa and distorts these researches;

- Hormones of a thyroid gland - at their appointment the metabolism therefore the digoxin dose surely should be increased amplifies.

Contraindications:

Hypersensitivity to drug, glikozidny intoxication, a WPW-syndrome, an atrioventricular block, the II degrees, the alternating total block, children's age up to 3 years, patients with rare hereditary diseases: intolerance of fructose and syndrome of disturbance of absorption of a glucose/galactose or insufficiency of invertase/isomaltase; deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption.

With care: AV blockade of the I degree, a sick sinus syndrome without pacemaker; probability of unstable carrying out on an AV node, instructions in the anamnesis on Morganyi-Adams-Stokes's attacks, a hypertrophic subaortic stenosis, the isolated mitral stenosis with the rare heart rate (HR), cardiac asthma at patients with a mitral stenosis (in the absence of a takhisistolichesky form of a ciliary arrhythmia), an acute myocardial infarction, unstable stenocardia, the arteriovenous shunt, a hypoxia, heart failure with disturbance of diastolic function (a restrictive cardiomyopathy, a heart amyloidosis, chronic cardial compression, a cardiac tamponade), premature ventricular contraction, the expressed dilatation of cardial cavities, "pulmonary" heart.

Electrolytic disturbances: hypopotassemia, hypomagnesiemia, hypercalcemia, hypernatremia. Hypothyroidism, alkalosis, myocarditis, advanced age, renal and/or liver failure, obesity.

Overdose:

Symptoms: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, intestines necrosis; a ventricular Bouveret's disease, ventricular premature ventricular contraction (often polytopic or a bigeminal pulse), nodal tachycardia, SA blockade, blinking and trembling of predyoserdiya, AV blockade, drowsiness, confusion сознания^ delirious psychosis, decrease in visual acuity, coloring of visible objects in flavovirent color, flashing of "muyoshka" before eyes, perception of objects in the reduced or increased look; does not trust, radiculitis, maniac-depressive psychosis, paresthesias.

Treatment: drug withdrawal Digoxin, purpose of absorbent carbon (for absorption reduction), introduction of antidotes (dimercaptopro-pan-sodium sulphonate, sodium of calcium of an edetat (EDTA), antibodies to digoxin), symptomatic therapy. To carry out continuous monitoring of an ECG.

In cases of a hypopotassemia potassium salts are widely applied: 0,5-1 g of potassium of chloride rastvoyoryat in water and accept several times a day to a total dose 3-6 g (40-80 мЭкв potassium ioyon) for adults on condition of adequate function of kidneys. Intravenous drop administration of 2% or 4% of solution of potassium of chloride is in case of emergency shown. The Sutochyony dose makes 40-80 мЭкв K+ (divorced to concentration 40 мЭкв K+ on 500 ml). The recommended rate of administering should not exceed 20 мЭкв / h (under a kontroyoly ECG).

At a hypomagnesiemia parenteral use of salts of magnesium is recommended. In cases of a ventricular tachyarrhythmia slow intravenous administration of lidocaine is shown. Patients to normal function of heart and kidneys usually have effectively slow intravenous administration (within 2-4 min.) lidocaine in an initial dose of 1-2 mg/kg of body weight, to the subsequent transition to drop introduction with a speed of 1-2 mg/min. At patients with a renal failure and/or hearts the dose needs to be reduced in a sootvetyostvuyushchy way.

In the presence And the V blockade of the II-III degree it is not necessary to appoint lidocaine and salts of potassium until the artificial pacemaker is established.

During treatment it is necessary to watch the content of calcium and phosphorus in blood and suyotochny urine. There is an experience of use of the following drugs with a possible positive effekyot: beta adrenoblockers, procaineamide, bretylium of tosylate and Phenytoinum. Cardioversion can provoke fibrillation of ventricles.

For treatment of bradyarrhythmias and AV of blockade atropine use is shown. At AV a bloyokada of the II-III degree, an asystolia and suppression of activity of a sinus node the ustayonovka of an artificial pacemaker is shown.

Storage conditions:

To store in the place protected from light at a temperature from 15 to 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. 1, 2 or 3 blister strip packagings together with the application instruction place in a pack from a cardboard.