Active substanceDigoxinDigoxin
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  • Dosage form: & nbspSolution for intravenous administration.
    Composition:1 ml of the solution contains active substance digoxin 0.25 mg, excipients (glycerol, alcohol 96% (ethanol), disodium hydrophosphate anhydrous, citric acid, water for injection).
    Description:
    Colorless transparent liquid;

    Pharmacotherapeutic group:Cardiotonic is a cardiac glycoside.
    ATX: & nbsp

    C.01.A.A.05   Digoxin

    C.01.A.A   Glycosides of Digitalis

    Pharmacodynamics:
    The cardiac glycoside blocks the transport Na + / K + -ATPase, which increases the Na + content in the cardiomyocyte, which leads to the discovery of Ca2 + channels and the entry of Ca2 + into the cardiomyocytes. Excess Na + also leads to an acceleration of the release of Ca2 + from the sarcoplasmic reticulum.

    An increase in the concentration of Ca2 + leads to inhibition of the troponin complex, which has a depressing effect on the interaction of actin and myosin. Increased strength and rate of contraction, the myocardium occurs by a mechanism different from the Frank-Starling mechanism (does not depend on the degree of pre-stretching of the myocardium). The systole becomes shorter and energy-efficient .. As a result of the increase. myocardial contractility is increasing in the UCC and in the IOC.

    Reduces CSR and BDW of the heart, which, along with an increase in myocardial tone leads to a reduction in its size and thus. to a decrease in myocardial oxygen demand. The negative dromotropic effect is manifested in the increased refractoriness of the AV node, which allows the use of supraventricular tachycardias and tachyarrhythmias in paroxysms.

    Atrial fibrillation contributes to heart rate slowing, 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. 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.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; increase in n.vagus tone as a result of .reflex from the aortic arch and carotid sinus receptors with an increase in IOC; decrease in pressure in the mouth of the hollow veins and right atrium (as a result of increased LV myocardial contractility, more complete emptying of it, decrease of pulmonary artery pressure 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 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 effects of the response to increased IOC and reduction of excessive sympathetic stimulation of vascular tone) tend to predominate over direct vasoconstrictor action, resulting in a decreased OPSS.
    Pharmacokinetics:

    - suction: the bioavailability of the drug is 100%.The initial effect is observed after 5-30 minutes with a maximum reaching 1-4 hours. The connection with plasma proteins is 20-25%.

    - distribution: 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 plasma. Metabolised in the liver. Elimination and T1/2 are determined by the kidney function. T1/2 - 30-40 hours. With IV administration 50-70% of digoxin is excreted by the kidneys unchanged. The intensity of renal excretion is determined by the magnitude of glomerular filtration. With oral intake, the intensity of metabolism increases.

    - excretion: with insignificant CKD, the decrease 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 CHF II f.k. (in the presence of clinical manifestations), III-IV f. tahisystolic form of flicker and atrial flutter of paroxysmal and chronic course (especially in combination with CHF).
    Contraindications:hypersensitivity, glycoside intoxication, WPW syndrome, AV blockade II stage, intermittent complete blockade.
    Carefully:AV blockade of I st, SSS without pacemaker, probability of unstable AV assembly, Morganyi-Adams-Stokes attacks in history, GOKMP, isolated mitral stenosis with rare heart rate, cardiac asthma 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 I, marked dilatation of the cavities of the heart, "pulmonary" heart, electrolyte disorders (hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia), hypothyroidism, alkalosis, myocarditis, advanced age, renal / hepatic insufficiency, obesity.

    Pregnancy and lactation:
    during pregnancy and during breastfeeding, the drug can be used only on strict indications, assessing the relationship between benefit and risk. Digoxin penetrates through the placenta, in very small quantities excreted in breast milk. There is no evidence of a teratogenic effect of the drug. When prescribing a drug, it is necessary to consider that the clearance of digoxin in pregnant women is prolonged.
    Dosing and Administration:
    intravenously (drip, jet). In the process of treatment, two periods are distinguished: the period of initial digitalization (saturation) and the period of maintenance therapy.

    During the period of initial digitalization, the body becomes gradually saturated with cardiac glycoside until the optimal therapeutic effect is achieved. The individual saturating dose (IDA) is the total dose (taking into account bioavailability and daily elimination), leading to adequate digitalization of the individual 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 the body is not less. 80% of the? IND. 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 the dose of cardiac glycoside, at which it is noted, the full therapeutic effect 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 SND. IND ranges from 50 to 200% of the average full dose. A significant reduction in the individual maximum tolerated dose occurs in patients with severe myocardial damage and far-reaching decompensation, with myocardial infarction, a "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. With moderately fast digitalization digoxin is administered intravenously. in a daily dose of 0.75 mg in 3 injections. Digitalization is achieved on average 2-3 days.

    With slow digitalization, adults are usually administered in a dose of 0.25-0.5 mg (1-2 ml of 0.025% solution) per day. Enter slowly into 10 ml of 5%, 20% or 40% glucose solution or isotonic sodium chloride solution. In the first days of treatment, inject 1-2 times a day, the next - once a day.Digitalization in this case occurs in a week in most patients. Then the patient is transferred to a maintenance dose, which, with IV administration, is usually 0.125-0.25 mg.

    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. .

    In paroxysmal supraventricular arrhythmias, iv injection, 1-4 ml, 0.025% solution (0.25-1 mg) in 10-20 ml of 20% dextrose solution is administered. For IV injection, the same dose is diluted in 100-200 ml of a 5% solution of dextrose or 0.9%. solution of NaCl. 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.

    If the excretory function of the kidneys is impaired, it is necessary to reduce the dose of digoxin: with KK 50-80 ml / min, SPD is 50% of SPD for persons with normal renal function; with SC less than 10 ml / min - 25% of the usual dose.

    CHF: small doses are used up to 0.25 mg / day, for patients with a body weight of more than 85 kg, up to 0.375 mg / day. In elderly ptsints, the daily dose is reduced to 0.0625-0.125 mg.

    Side effects:

    Side effects of digoxin are mainly related to its overdose or increased individual sensitivity of the patient to cardiac glycosides. When using the drug, side effects are possible:,

    Allergic reactions: skin rash and skin hyperemia.

    From the cardiovascular system: sinus bradycardia, extrasystole, AV-blockade, paroxysmal atrial tachycardia, ventricular fibrillation.

    From the digestive system: nausea, vomiting, diarrhea.

    From the hematopoiesis: violation of visceral circulation, thrombocytopenia, thrombocytopenic purpura, eosinophilia.

    From the nervous system: headache, dizziness, neuralgia, drowsiness, confusion, depression, sleep disturbances.

    From the sense organs: violation of color vision (coloring of surrounding objects in green, yellow or white color).

    Other: nosebleeds, petechiae, gynecomastia.

    If any of the side effects listed in the manual are aggravated / or you notice any other side effects not listed in the instructions, inform your doctor.

    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 medicines use drugs I class (lidocaine, phenytoin). With hypokalemia - iv administration of KC1 (6-8 g / day at the rate of 1-1.5 g per 0.5 L of a 5% solution of dextrose and 6-8 units of insulin, injected drip, 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 methylsulfate (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 intensify the severity of the 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.

    BCS (development of hypokalemia) and thiazide diuretics (development of hypokalemia and hypercalcemia), salts of Ca2 + (especially, with iv introduction) reduce the tolerance 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:
    When GOKMP (obstruction of the output tract of the left ventricle 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 accession of right ventricular failure orin the presence of ciliary 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 LC, 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:
    Solution for intravenous administration 0.25 mg / ml.
    Packaging:
    In the production of OOO "Experimental Plant" GNTSLS ", Ukraine.
    1 ml in ampoules.
    For 10 ampoules together with instructions for use and scarifier ampoule or disk cutting ceramic
    in a pack of cardboard.
    If there are fracture rings or break points on the ampoule, the ampoule scarifier or ceramic cutting disc is not put into the pack.

    In the production of LLC "Pharmaceutical company" Health ", Ukraine.
    1 ml in ampoules.
    For 10 ampoules together with the instruction for use and scarifier ampoule or disk cutting ceramic in a pack of cardboard.
    For 5 ampoules in a planar cell packaging of a polyvinylchloride film or a polyvinylchloride film and aluminum foil, 1 or 2 contourcell packs together with an instruction for use and a scarifier with an ampoule or a cutting ceramic disc in a pack of cardboard. For 10 ampoules in a contoured cell pack of a polyvinylchloride film or a polyvinylchloride film and aluminum foil, 1 contour pack together with an instruction for use and a scarifier or ampoule cutter disk in a pack of cardboard.
    If there are fractures on the ampoule, or dots and incisions, the ampoule scarifier or the ceramic cutting disc are not inserted into the pack.
    Storage conditions:Store in a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.
    Shelf life:3 years. Do not use after expiration date, indicated on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:П N016105 / 01
    Date of registration:30.11.2009
    The owner of the registration certificate:EXPERIMENTAL FACTORY ГНЦЛС, ООО EXPERIMENTAL FACTORY ГНЦЛС, ООО Ukraine
    Manufacturer: & nbsp
    Information update date: & nbsp22.01.2016
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