Torasemid Darnitsa of the tab. of 10 mg No. 30

Pharmacological properties

Pharmacodynamics. torasemid works as saluretic, its influence is connected with oppression of renal absorption of ions of sodium and chlorine in the ascending part of a Henle's loop. at the person the diuretic effect quickly reaches a maximum during the first 2–3 h after parenteral and oral administration respectively and remains to constants on continuation of nearly 12 h at healthy probands in the range of doses of 5-100 mg the increase in a diuresis proportional to a dose logarithm (loopback activity of diuretic) was observed. increase in a diuresis was noted even when other diuretics, also as distally the operating effective diuretics of a tiazidovy row, did not render the required effect, for example in a renal failure any more. thanks to such mechanism of action torasemid leads to reduction of hypostases. in case of heart failure torasemid reduces manifestations of a disease and improves functioning of a myocardium due to reduction pre- and afterloads.

Pharmacokinetics. Linking of a torasemid with proteins of blood plasma makes more than 99%, metabolites of M ₁ , M ₃ , and M ₅ — 86; 95 and 97% respectively. The visible volume of distribution (Vz) is 16 l.

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In a human body torasemid it is metabolized with formation of three metabolites: M ₁ , M ₃ and M ₅ . Proofs of existence of other metabolites are absent. Metabolites of M ₁ , and M ₅ are formed by M ₃ as a result of step oxidation of the methyl group of carboxylic acid attached to a phenolic ring, the metabolite of M ₃ is formed as a result of hydroxylation of a ring.

At the person did not manage to reveal metabolites of M ₂ and M ₄ which were found in experiments on animals.

Pharmacokinetics of a torasemid and its metabolites is characterized by linear dependence. It means that its C _max in blood serum and the area under a curve of content in blood serum increases in proportion to a dosage. Final time of semi-removal (T _½ ) a torasemid and its metabolites at healthy people is 3–4 h. The general clearance of a torasemid is 40 ml/min., renal clearance — about 10 ml/min. At healthy people about 80% of the entered dose it is removed in the form of a torasemid and its metabolites with urine with such average percentage: torasemid — about 24%, a metabolite of M ₁ — about 12%, a metabolite of M ₃ — about 3%, a metabolite of M ₅ — about 41%. The main metabolite of M ₅ has no diuretic effect, and on a share of metabolites of M ₁ and M ₃ , combined, about 10% of all pharmakodinamichesky action are necessary. In a renal failure the general clearance and T _½ a torasemida do not change, and T _½ and M ₅ is extended with M ₃ . However pharmakodinamichesky characteristics remain invariable, and the severity of a renal failure does not influence duration of action.

At patients with an abnormal liver function or heart failure of T _½ a torasemid and a metabolite of M ₅ slightly increases, and the amount of the substance removed with urine is almost completely equal to amount of the substance removed at healthy people therefore accumulation of a torasemid and its metabolites does not happen. Torasemid and his metabolites are practically not removed at a hemodialysis and haemo filtration.

Indication

Treatment in the hypostases and/or exudates caused by heart failure if it is necessary in/in medicine use, for example in case of a fluid lungs owing to an acute heart failure.

Use

Adult. treatment it is necessary to begin 2 ml of medicine of torasemid-darniyets with reception of a single dose that is equivalent to 10 mg of a torasemid a day. if the effect is insufficient, then the single dose can be raised to 4 ml of medicine that is equivalent to 20 mg of a torasemid. if the effect also in this case is insufficient, it is possible to perform short-term (during no more than 3 days) therapy with introduction of a daily dose of 8 ml of medicine of torasemid-darniyets that is equivalent to 40 mg of a torasemid.

Acute fluid lungs. Treatment needs to be begun with in/in introductions of a single dose of 4 ml of Torasemid-Darnitsa medicine that is equivalent to 20 mg of a torasemid.

Depending on the gained clinical effect introduction of this dose can be repeated at an interval of 30 min.

Is forbidden to exceed the maximum daily dose of 20 ml of medicine that is equivalent to 100 mg of a torasemid.

Solution for injections to enter

in/in slowly. It is forbidden to enter solution in / and! To enter only pure solution. At prolonged use in/in introduction it is necessary to replace with oral administration as torasemid it is not recommended to carry out in to medicine use for more than 7 days

Patients with a liver failure as soon as possible. Treatment of these patients should be carried out with care as increase in concentration of a torasemid in blood plasma is possible.

Patients of advanced age. Treatment of this category of patients does not demand special selection of a dose. However the corresponding researches concerning people of advanced age in comparison with younger patients were not conducted.

Contraindication

Hypersensitivity to active ingredient, medicaments of sulphonylurea and to medicine excipients. a renal failure with an anury. hepatic coma or prekoma. arterial hypotension. hypovolemia. hyponatremia. hypopotassemia. an acute disorder of urination, for example as a result of a prostatauxe. feeding period breast.

Side effects

estimated the Frequency of side reactions as follows: very often ≥1/10, it is frequent ≥1/100–1/10, infrequently ≥1/1000–1/100, is rare ≥10 000–1/1000, is very rare 10,000, frequency is unknown — it is impossible to define from the available data.

from digestive system. Often — multiple disturbances of digestive system (especially in an initiation of treatment), including lack of appetite, a meteorism, a stomach ache, nausea, vomiting, a diarrhea, a constipation. Very seldom — pancreatitis.

from a liver and biliary tract. Often — increase in concentration of some liver enzymes (gamma glutamiltranspeptidazy) in blood.

from kidneys and an urinary system. Seldom — increase in concentration of creatinine and urea in blood, desires to urination. When there is a considerable loss of water and electrolytes caused by excess formation of urine especially in an initiation of treatment and at elderly people the decrease in the ABP, a headache, an asthenia and drowsiness is possible.

increased formation of urine can lead

At patients with urination disorders (for example with a prostate hypertrophy) to its delay and hyperdystension of a bladder.

from a metabolism, metabolism. Often — strengthening of a metabolic alkalosis. Spasms of muscles (especially in an initiation of treatment). Increase in concentration of uric acid and glucose in blood and also XC and TG. A hypopotassemia at accompanying bezkaliyeviya to a diet, in vomiting, a diarrhea, after excessive use of depletive and also at patients with chronic dysfunction of a liver. Depending on dosing and duration of treatment disturbances of water and electrolytic balance, for example a hypovolemia, a hypopotassemia and/or a hyponatremia are possible.

from a cardiovascular system. Very seldom — tromboembolic episodes, confusion of consciousness, arterial hypotension and also circulatory disturbances and warm activity, including ischemia of heart and brain which can lead to arrhythmia, stenocardia, an acute myocardial infarction, a syncope because of possible haemo concentration.

from blood and lymphatic system. Very seldom — reduction of quantity of thrombocytes, erythrocytes and/or leukocytes, anemia.

from the immune system. Very seldom — allergic reactions, including an itching, a dieback, a photosensitization, skin reactions. Later in/in uses intense, potentially life-threatening reactions of hypersensitivity are possible (acute anaphylaxis).

General disturbances and reactions in the injection site. Often — a headache, dizziness, increased fatigue, the general weakness (especially in an initiation of treatment). Seldom — dryness in a mouth, unpleasant feelings in extremities (paresthesia). Very seldom — disorders of vision, a ring in ears, a hearing loss. Frequency is unknown — local reactions after injections.

Special instructions

needs to eliminate with

before use of medicine a hypopotassemia, a hyponatremia or a hypovolemia.

regular control of electrolytic balance, in particular potassium in blood serum, especially at the patients who are at the same time accepting glycosides of a foxglove, GKS, a mineralokortikosteroida or depletive is necessary for

At prolonged use of a torasemid. Besides, it is regularly necessary to control the content of glucose, uric acid, creatinine and lipids in blood. Torasemid patients should apply with extra care with the liver diseases which are followed by cirrhosis and ascites as sudden changes of water and electrolytic balance can lead to a hepatic coma. These patients need to carry out therapy using a torasemid (as well as other diuretics) in the conditions of a hospital. For prevention of a hypopotassemia and a metabolic acidosis it is necessary to appoint medicine with medicaments — antagonists of Aldosteronum or the means promoting a potassium delay in an organism. After use of a torasemid noted ototoxicity cases (sonitus and a hearing loss) which had reversible character, however direct link with use of medicine is not established. When prescribing diuretics it is necessary to control carefully clinical symptoms of disturbance of electrolytic balance, a hypovolemia, an extrarenal azotemia and other disturbances which can be shown in the form of dryness in a mouth, thirst, weakness, slackness, drowsiness, excitement, muscular pain or spasms, a myasthenia, hypotonia, an oliguria, tachycardia, nausea, vomiting. The excessive diuresis can become the cause of dehydration of an organism, lead to reduction to OCK, a thrombogenesis and an embolism, especially at elderly people.

to Patients with disturbances of water and electrolytic balance needs to stop medicine use, and after elimination of undesirable effects to restore therapy, since lower doses.

As at treatment torasemidy increase in content of glucose in blood is possible

, at patients with latent and obvious diabetes it is necessary to carry out a continuous careful inspection of metabolism of carbohydrates. Also regular control of a picture of blood (erythrocytes, leukocytes, thrombocytes) is required. During treatment of patients of advanced age it is necessary to pay attention to emergence of symptoms of loss of electrolytes and a pachemia, especially in an initiation of treatment.

should not appoint

in case of lack of sufficient clinical experience of use torasemid in the presence of the following diseases and states: gout; arrhythmia, for example at sinuatrial blockade, AV blockade of II and III degree; pathological changes of acid-base metabolism; the accompanying therapy using medicaments of lithium, aminoglycosides or cephalosporins; pathological changes of a picture of blood, for example thrombocytopenia or anemia at patients without renal failure; the renal failures caused by nefrotoksichny substances.

Use of a torasemid can be the cause of obtaining positive take of doping test. It is impossible to predict influence on the state of health if medicine is applied incorrectly, that is for the purpose of doping — in this case it is impossible to exclude harm for health.

Use during pregnancy and feeding by a breast

Pregnancy. Reliable data about influence of a torasemid on an embryo and a fruit at the person are absent. In experiments on animals the reproductive toxicity of a torasemid is shown. Torasemid gets through a placental barrier. Due to the above torasemid apply during pregnancy only according to vital indications and in minimum possible effective dose. Diuretics are unsuitable for the standard scheme of treatment at AG or hypostases at pregnant women as they are capable to reduce perfusion of a placental barrier and to make toxic impact on pre-natal fetation. If torasemid apply to treatment of pregnant women with heart failure or a renal failure, then it is necessary to make careful observation of the level of electrolytes and a hematocrit and also of fetation.

feeding Period breast. Now it is not established whether gets torasemid into breast milk at animals or the person. It is impossible to exclude harm from use of medicine for newborns/babies. Therefore use of a torasemid during feeding by a breast contraindicated. If it is necessary to apply torasemid during this period, then feeding by a breast it is necessary to stop.

Fertility. The research of influence of a torasemid on fertility at people was not conducted. In an experiment on animals such influence of a torasemid is not revealed.

Children. It is not necessary to apply Torasemid-Darnits at children and teenagers due to the lack of sufficient clinical experience.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Even at appropriate use torasemid can have negative effect on ability of the patient to run vehicles or to work with mechanisms, especially in an initiation of treatment, at increase in a medicament dose, replacement of medicament or when assigning of the accompanying therapy. Therefore during use of a torasemid it is necessary to be very careful at control of vehicles or work with other mechanisms.

Interaction

Torasemid strengthens effect of other antihypertensive drugs, in particular inhibitors apf that can lead to excessive decrease hell during their simultaneous use. at the combined use of a torasemid with foxglove medicines the deficiency of potassium caused by use of diuretics can lead to increase and strengthening of side effect of both medicines. torasemid can reduce efficiency of antidiabetic means. probenetsid and npvp (for example indometacin, acetylsalicylic acid) can slow down diuretic and hypotensive action of a torasemid. at treatment by salicylates in high doses torasemid can increase their toxic action on central nervous system. torasemid, especially in high doses, can strengthen from - and nephrotoxic action of aminoglikozidny antibiotics, for example Kanamycinum, gentamycin, Tobramycinum and tsitostatik — active derivatives of platinum and also nephrotoxic effect of cephalosporins. torasemid can strengthen theophylline influence and also kurarepodobny medicines on a relaxation of muscles. depletive and also mineralo- and glucocorticoids can strengthen the potassium loss caused torasemidy. at simultaneous use of a torasemid and medicaments of lithium the increase in concentration of lithium in blood plasma is possible that can lead to strengthening of side effects of lithium. torasemid can reduce vasoconstrictive action of catecholamines, for example epinephrine and Norepinephrinum.

Incompatibility. Torasemid-Darnitsa medicine cannot be mixed with other drugs.

Overdose to

Typical symptomatology is unknown to

. the overdose can cause a severe diuresis and as a result — excessive loss of water and electrolytes, drowsiness, an amental syndrome (one of consciousness disturbance forms), symptomatic arterial hypotension, cardiovascular insufficiency and disturbances from digestive system.

Treatment at overdose. Specific antidote is unknown. Symptoms of intoxication disappear, as a rule, at a dose decline or cancellation of medicine and at the corresponding substitution of liquid and electrolytes (it is necessary to carry out control!). Torasemid is not brought from blood by means of a hemodialysis. Treatment in case of a hypovolemia: substitution of volume of liquid. Treatment in case of a hypopotassemia: use of medicaments of potassium. Treatment at cardiovascular insufficiency: to turn the patient to a prone position and if necessary — to appoint symptomatic therapy.

Acute anaphylaxis (immediate measures). At emergence of skin reactions (such as small tortoiseshell or erubescence), excitement, a headache, the increased sweating, nausea, cyanosis it is necessary to carry out vein catheterization; the patient to put in horizontal position, to provide free intake of air, to appoint oxygen. In case of need to apply administration of epinephrine, the solutions substituting the volume of liquid, glucocorticoid hormones.

Storage conditions

In original packing at a temperature not above 25 °C. not to freeze.

to Use solution for injections right after the first opening.