Pharmacological properties

Pharmacodynamics. the main mechanism of diuretic action is caused by reversible linking with a kotransporter of na+/2cl —/k + in an apical part of a Henle's loop owing to what decreases or the renal reabsorption of ions of sodium and chlorine in the ascending part of a Henle's loop is completely oppressed, the osmotic pressure of intracellular liquid and a reabsorption of water decrease. in the range of doses of 5-100 mg the increase in a diuresis is proportional to a dose. increase in a diuresis arises and when other diuretic medicaments (for example tiazida) do not render sufficient effect, for example, at bounded function of kidneys any more. eliminates hypostases, has antihypertensive effect which is caused by reduction opss due to decrease in content of free calcium in cells of a muscular layer of arteries and normalization of the broken electrolytic balance. thereof the contractilnost and reaction of vessels to own pressor substances of an organism, in particular catecholamines decrease. improves operating conditions of heart due to reduction before - and afterloads. after oral administration the maximum diuretic action continues 1–3 h, and the diuretic effect remains for nearly 12 h the hypotensive action of a torasemid develops gradually within 1 week and the Pharmacokinetics reaches a maximum no later than 12 weeks

. After oral administration it is quickly and almost completely soaked up in a GIT. The C _max in blood plasma is reached in 1–2 h. 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 bioavailability is about 80% with insignificant individual variations and does not depend on meal. The M _{3 is metabolized in a liver by the system of P450 cytochrome with formation of metabolites (M 1 ,} and M ₅ ). The main metabolite of M ₅ does not show diuretic effect, the operating metabolites of M ₁ and M ₃ in common cause about 10% of pharmakodinamichesky action. T _½ a torasemid and its metabolites at healthy volunteers makes 3–4 h. About 83% of the accepted dose are removed through renal tubules: in not changed look (24%) and in the form of metabolites (M ₁ — 12%, M ₃ — 3%, M ₅ — 41%). The general clearance is 40 ml/min., renal clearance — about 10 ml/min. 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, the severity of a renal failure does not influence action duration. At patients with abnormal liver functions or heart failure of T _½ a torasemid and a metabolite of M ₅ are slightly extended, cumulation of a torasemid and its metabolites is not observed.

Indication

Essentsialnaya ag. treatment and prevention of a recurrence of the hypostases and/or an exudate caused by heart failure.

Use

Adult: to accept in 1 times a day in the morning after a meal, not to chew, wash down with a small amount of liquid. the dose and duration of a course of treatment are established individually taking into account indications, efficiency and shipping of therapy.

At essential AG. Usually the dose makes 2.5 mg of Torsid. If after 12 weeks therapy by medicament in a dose of 2.5 mg/days the normalization of the ABP is not reached, the dose can be raised to 5 mg. Further increase in a dose is inexpedient as it will not lead to further decrease in the ABP.

In hypostases or an exudate: the initial dose makes 5 mg of Torsid a day. Usually this dose is considered supporting. If the daily dose of 5 mg is insufficient, then apply 10 mg of a torasemid a day. The dose can be raised depending on disease severity to 20 mg of medicament a day.

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

Patients of advanced age. Special selection of a dose is not required. Adequate researches concerning comparison of treatment of patients of advanced age and young patients are absent.

Contraindication

Hypersensitivity to active ingredient, other medicaments of sulphonylurea and excipients. a renal failure with an anury. hepatic coma or prekoma. arterial hypotension. hypovolemia. hyponatremia. hypopotassemia. the significant disturbances of urination, for example, as a result of a prostatauxe.

Side effects

from a cardiovascular system: disturbances of water and electrolytic balance (hypovolemia, hypopotassemia, hyponatremia); strengthening of a metabolic alkalosis. at considerable loss of liquid and electrolytes owing to strong urination the arterial hypotension, confusion of consciousness, fibrinferment, cardial and cerebral ischemia with possible development of disturbances of a warm rhythm, stenocardia, acute myocardial infarction, a syncope can be observed.

from central nervous system: headache, dizziness, increased fatigue, myotonia.

from a digestive tract: constipation, anorexia, nausea, vomiting, stomach ache, diarrhea, increase in level of some enzymes of a liver (in particular gamma glutamiltranspeptidazy), pancreatitis.

from an urinary system: at patients with urination disorders (for example in a prostatauxe) intensive urination can lead to an ischuria and hyperdystension of a bladder; increase in creatinine and urea in blood.

from a metabolism: increase in level in blood of uric acid, glucose, lipids (TG, XC).

from the system of blood: reduction of quantity of thrombocytes, erythrocytes and/or leukocytes.

from the immune system: allergic reactions, including rashes, itching, dieback, photosensitivity, heavy skin reactions.

Others: the general weakness, dryness in a mouth, paresthesia, disorders of vision, sonitus, decrease in hearing, a hearing loss.

At long therapy torsidy regular control of electrolytic balance (in particular potassium in blood plasma), the level of glucose, uric acid, creatinine and lipids in plasma of blood, a blood picture (erythrocytes, leukocytes, thrombocytes) is necessary for

.

needs to be considered that increase in level of glucose in blood of the patient can be connected with possible latent or manifest diabetes therefore such patients should carry out careful control of glucose to blood. Especially in an initiation of treatment of patients of advanced age it is necessary to pay special attention to emergence of symptoms of loss of electrolytes and a pachemia.

should not appoint

in the absence of sufficient clinical experience of use torasemid in following diseases and states: gout; arrhythmias, for example, at sinuatrial blockade, AV blockade of II and III degree; pathological changes of acid-base metabolism; the accompanying therapy with use of 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 nephrotoxic substances.

Drug contains lactose therefore it is not necessary to appoint him the patient with hereditary deficiency of lactase, intolerance of a galactose or disturbances of metabolism of a glucose/galactose.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Even at independent use torasemid can influence reaction of the patient to such an extent that it will cause considerable negative impact on ability to run vehicles or to perform work with other mechanisms, or to perform work without insurance. It substantially concerns such cases as an initiation of treatment, increase in a dose of drug, replacement of medicine or when assigning of the accompanying therapy and also the accompanying alcohol intake. Therefore during use of a torasemid it is necessary to be careful at control of vehicles or work with other mechanisms.

Use during pregnancy or feeding by a breast

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

feeding Period breast. Use is contraindicated. If it is necessary to apply torasemid, then feeding by a breast should be stopped.

Children. Not to use medicament at children due to the lack of data.

Interaction

Torsid strengthens effect of other medicinal antihypertensive drugs, in particular inhibitors apf therefore the corresponding combination therapy can lead hell to excessive decrease.

At simultaneous use with Torsid to expansion of range of side effect of both drugs.

Torsid weakens action of antidiabetic means. Probenetsid and NPVP reduce expressiveness of diuretic and hypotensive action of Torsid. At therapy by salicylates in high doses Torsid can strengthen their toxic action on central nervous system. Torsid, especially in high doses, can strengthen from - and nephrotoxic action of aminoglikozidny antibiotics and derivatives of platinum and also to increase expressiveness of nephrotoxic effect of cephalosporins. Torsid strengthens effect of theophylline and kurarepodobny muscle relaxants. Depletive and also mineralo- and glucocorticoids can strengthen the possible loss of potassium caused by Torsid. At simultaneous use of Torsid and medicaments of lithium the concentration of lithium in blood and by that to amplify effect of lithium and its side effects can increase. Torsid weakens vasoconstrictive action of catecholamines. At simultaneous use with holestiraminy the absorption of a torasemid can decrease and by that to weaken its action.

Overdose

At overdose strengthening of a diuresis with danger of loss of liquid and electrolytes, drowsiness, confusion of consciousness, arterial hypotension, cardiovascular insufficiency and disorders of a digestive tract.

Treatment. Specific antidote is unknown. Symptoms of intoxication disappear, as a rule, at a dose decline and 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: prescribing of medicaments of potassium. Treatment of cardiovascular insufficiency: sitting position of the patient and, if necessary, purpose of symptomatic therapy.

Acute anaphylaxis (urgent measures). At the first emergence of skin reactions (such as, for example, small tortoiseshell or erubescence), the excited condition of the patient, a headache, the increased sweating, nausea, cyanosis to carry out vein catheterization; to give to the patient horizontal position, to provide free access of air, to appoint oxygen. If necessary to apply administration of epinephrine, solutions to substitution of volume of liquid, GKS.

Storage conditions

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