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

Composition:1 tablet contains active substance digoxin 0.1 mg; Excipients: refined sugar (sucrose), potato starch, glucose (dextrose), vaseline oil, talc, calcium stearate.

Description:Tablets of white color of round form, with biconvex surface.

Pharmacotherapeutic group:Cardiotonic is a cardiac glycoside.

ATX: & nbsp

C.01.A.A.05 Digoxin

C.01.A.A Glycosides of Digitalis

Pharmacodynamics:

Cardiac glycoside blocks transport N⁺/TO⁺-ATP-ase, resulting in increased content Na⁺ in the cardiomyocyte, which leads to the discovery of Ca²⁺channels and occurrence of Ca²⁺ in cardiomyocytes. Excess Na⁺ also leads to an acceleration of the isolation of Ca²⁺from the sarcoplasmic reticulum.

Increase in Ca concentration²⁺ leads to inhibition of the troponin complex, which exerts a depressant effect on interaction of actin and myosin. The increase in the force and rate of myocardial contraction occurs according to 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 (IOC) increase.

Reduces the end systolic and terminal diastolic volumes of the heart, which, along with an increase in the tone of the myocardium, leads to a reduction in its size, and so on. to a decrease in myocardial oxygen demand. The negative dromotropic effect is manifested in the increased refractoriness of the atrioventricular (AV) node, which allows using for paroxysms of supraventricular tachycardias and tachyarrhythmias.

Atrial fibrillation helps slow heart rate (heart rate), prolongs diastole, improves intracardiac and systemic hemodynamics. Decrease in heart rate occurs as a result of direct and indirect effects on the regulation of the heart rhythm. Positive batmotropic effect is evident in the appointmenttoxic and toxic doses. The direct action is to reduce the automatism - the sinus node. The change in the reflex regulation of the heart rhythm has a greater significance in the formation of a negative chronotropic action: in patients with ciliary tachyarrhythmia, the blockade of the conducting of the weakest impulses occurs; toning n.vagus as a result of a reflex from the aortic arch and carotid sinus receptors as the IOC increases; decrease in pressure in the mouth of the hollow veins and right atrium (as a consequence of increased left ventricular myocardial contractility, more complete emptying, lower pulmonary artery pressure and hemodynamic discharge of the right heart), elimination of the Bainbridge reflex and reflex activation of the sympatoadrenal system (in response to an increase in the IOC ).

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 IOC and a decrease in excessive sympathetic stimulation vascular tone), as a rule, prevails over direct vasoconstrictive action, as a result of which the overall peripheral vascular resistance decreases.

Pharmacokinetics:

The absorption by oral administration is variable, depends on the motility of the gastrointestinal tract (GIT), on the dosage form, on the concomitant intake of food, on the interaction with other drugs (JIC). Bioavailability of various oral dosage forms of digoxin (bioavailability, onset, maximum action, respectively): tablets - 60-80%, 0.5-2 h, 2-6 h; Elixir - 70-85%, 0.5-2 hours, 2-6 hours; 5-30 minutes, 1-4 hours; capsules - 90-100%, 0.5-2 h, 2-6 h.

At a normal acidity of gastric juice, an insignificant 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 motility of the gastrointestinal tract, the bioavailability of the drug is maximal, with minimal peristalsis. The connection with plasma proteins is 20-25%. 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 plasma. Metabolised. in the liver. Excretion and Tg are determined by a function of the kidneys. T1 / 2 - 30-40 hours. The intensity of renal excretion is determined by the magnitude of glomerular filtration. With oral intake, the intensity of metabolism increases.

With minor chronic renal failure (CRF), 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. The optimal concentration of digoxin in the plasma 6 h after the administration is 1-2 ng / ml, higher concentrations are toxic.

Indications:

In the complex therapy of chronic heart failure of the II functional class (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, glycoside intoxication, Wolff-Parkinson-White syndrome (WPW syndrome), AV blockade II, v., intermittent complete blockade.

Carefully:

atrioventricular (AV) blockade of the I stage, sinus node weakness syndrome without rhythm driver, probability of unstable AV assembly, Morgagni-Adams-Stokes attacks in history, hypertrophic obstructive cardiomyopathy (GOKMP), isolated mitral stenosis with a rare heart rate ), cardiac asthma with mitral stenosis (in the absence of tachysystolic form of atrial fibrillation), acute myocardial infarction, unstable angina, arteriovenous shunt, hypoxia, heart failure with impaired diastolic function (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, renal and / or hepatic impairment, obesity.

Information for patients with diabetes: the tablet contains sucrose and glucose (dextrose) monohydrate; one tablet contains 0.003 bread units.

Dosing and Administration:

Inside. In the process of treatment, two periods are distinguished: the period of initial digitalization (saturation) and the period of maintenance therapy.

During the initial digitalization, the body becomes gradually saturated with cardiac glycoside until the optimal therapeutic effect is achieved: The individual saturating dose (ID) is the total dose (with allowance for bioavailability and daily elimination), which leads to adequate, digitalization of a particular patient. The appearance of signs of saturation with glycosides (primarily clinical) means that the patient received an IND.

The therapeutic effect of glycosides is preserved if there is at least 80% of the body in the body. Exceeding it by 50% usually causes the development of intoxication; The average value of IND in patients without concomitant pathology of the organs responsible for elimination and metabolism is the average saturating dose (SND). This is a dose of cardiac glycoside, at which a full therapeutic effect is observed in most patients without the appearance of toxic symptoms.

The maximum tolerated dose of cardiac glycoside (without intoxication) - the individual maximum tolerated dose may exceed the average saturating dose, coincide with it and be less than the SNR. IND ranges from 50 to 200% of the average full dose. Significant reduction in the individual maximum tolerated dose occurs in patients with severe myocardial damage and far-reaching decompensation, with myocardial infarction, "pulmonary" heart. In these patients, signs of intoxication develop earlier than clinical manifestations of positive inotropic action of cardiac glycosides. The digoxin elimination factor is 20%; SND - 3 mg; SPD (average maintenance dose) is 0.6 mg.

As with all cardiac glycosides, the dose should be selected with caution, individually for each patient. Patients with hypersensitivity to cardiac glycosides are given smaller doses and digitize at a slower rate.

When switching from one dosage form to another, the dosage regimen may need to be corrected (different dosage forms have differences in bioavailability).A dose of 100 μg in the form of a solution for injection is bioequivalent to a dose of 125 μg in the form of tablets or an elixir.

The saturation dose for children is 0.05-0.08 mg / kg; this dose is administered 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.

Children over 10 years of age: 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: a daily dose of 0.8-1.2 mg of digoxin 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 0.1-0.5 mg of digoxin 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 0.2 mg per day (for patients with a body weight of more than 85 kg to 0.3 mg per day).

Supportive therapy: The daily dose for maintenance therapy is set individually and amounts to 0.1-0.7 mg. Supportive therapy, as a rule, is carried out for a long time.

Children from 3 to 10 years: the saturating dose is approximately 0.05-0.08 mg / kg / day; this dose is prescribed within 1-2 days (rapid digitalization) or 3-5 days with moderately rapid digitalization or within 6-7 days with slow digitalization. The maintenance dose is 0.01-0.02 mg / kg per day, divided into 2 doses.

If the excretory function of the kidneys is impaired, the dose of digoxin should be reduced: at 50% decrease in creatinine clearance, SPD is 50% of SPD for patients with normal renal function; with a 75% reduction in CK - 25% of the usual dose.

Side effects:

Allergic reactions; Thrombocytopenia, thrombocytopenic purpura, nosebleeds, petechiae, gynecomastia; sleep disorders, headache, dizziness.

Overdose:

Symptoms - decreased appetite, nausea, vomiting, diarrhea, abdominal pain, intestinal necrosis; ventricular paroxysmal tachycardia, ventricular extrasystole (often polytopic or bigemia), nodular tachycardia, SA blockade, atrial fibrillation and flutter, AV blockade, drowsiness, confusion, delirious psychosis, decreased visual acuity, staining of visible objects in yellow-green color, flickering " flies "before the eyes, the perception of objects in a reduced or enlarged form; neuritis, radiculitis, manic-depressive syndrome, paresthesia.

Treatment: cancellation of cardiac glycosides, administration of antidotes (sodium dimercaptopropanesulfonate, calcium edetate sodium, antibodies to digoxin), symptomatic therapy. As antiarrhythmic drugs, I use class I drugs (lidocaine, phenytoin). With hypokalemia-iv injection of KC1 (6-8 g / day at a rate of 1-1.5 g per 0.5 L of a 5% solution of dextrose and 6-8 units of insulin, injected dropsy, for 3 hours). With severe bradycardia, AV blockade - m-holinoblokatory. Beta-adrenostimulyatorov enter dangerous because of the possible increase in the arrhythmogenic effect of cardiac glycosides. With a full transverse blockade with attacks of Morgagni-Adams-Stokes temporary pacing is shown.

Interaction:

Decreased bioavailability: Activated carbon, antacids, astringent LS, kaolin, sulfasalazine, colestramine (binding in the lumen of the gastrointestinal tract); metoclopramide, neostigmine methyl sulfate (increased motility of the gastrointestinal tract). Increased bioavailability: broad-spectrum antibiotics that suppress the intestinal microflora (reduction of destruction in the digestive tract).

Beta-adrenoblockers and verayamil increase the severity of negative chronotropic action, reduce the strength of the inotropic effect.

Quinidine, methyldopa, spironolactone, amiodarone, verapamil increase the concentration in the blood due to a competitive decrease in secretion of the proximal tubules of the kidneys.

GCS (development of hypokalemia), and thiazide diuretics (development of hypokalemia and hypercalcemia), salts of Ca2 + (especially with iv introduction) reduce the tolerability of cardiac glycosides.

Butadione, ibuprofen, reserpine, rifampicin, metoclopramide, potassium-sparing diuretics interfere with the development of hypokalemia and reduce the risk of a relative overdose.

Inducers of microsomal liver enzymes (barbiturates, phenylbutazone, phenytoin, rifampicin, antiepileptic, oral contraceptives) can stimulate digitoxin metabolism (when they are canceled, digitalis intoxication is possible).

Joint appointment with sympathomimetics increases the risk of arrhythmias.

Cholinesterase inhibitors increase the likelihood of bradycardia.

Special instructions:

With GOKMP (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, CHF develops as a result of a decrease in diastolic filling of the LV. Digoxin, increasing the contractility of the right ventricular myocardium, causes a further increase in pressure in the pulmonary artery system, which can provoke pulmonary edema or aggravate left ventricular failure. Patients with mitral stenosis are assigned cardiac glycosides upon adherence to right ventricular failure or in the presence of atrial tachyarrhythmia.

In patients with AV blockade II st. the appointment of cardiac glycosides can aggravate it and lead to the development of the attack of Morgagni-Adams-Stokes. Assignment of cardiac glycosides with AV blockade of I st. requires caution, frequent ECG monitoring, and in some cases - pharmacological prophylaxis of JIC, improving AV conduction.

Digoxin in WPW syndrome, reducing AV conduction, facilitates impulses through additional ways of bypassing the AV node and thereby provokes the development of paroxysmal tachycardia.

Do not wear contact lenses.

As one of the methods of digitalization control, monitoring of the plasma concentration of cardiac glycosides is used.

Form release / dosage:

tablets [for children] of 0.1 mg.

Packaging:For 50 tablets in polypropylene containers, enclosed with instructions for use in a pack of cardboard.

Storage conditions:

In dry, protected from light and out of reach of children, at a temperature not exceeding 25 ° C.

Shelf life:

4 years. Do not use the product after the expiration date printed on the package!

Terms of leave from pharmacies:On prescription

Registration number:П N015789 / 01

Date of registration:25.05.2009

The owner of the registration certificate:EXPERIMENTAL FACTORY ГНЦЛС, ООО EXPERIMENTAL FACTORY ГНЦЛС, ООО Ukraine

Manufacturer: & nbsp

EXPERIMENTAL FACTORY ГНЦЛС, ООО Ukraine

Information update date: & nbsp23.01.2016

Illustrated instructions

Instructions

Digoxin (Digoxin)