Torasemide Canon - instructions for use, dose, side effects, contraindications

Excipients: corn pregelatinized corn starch 37 mg, colloidal silicon dioxide 0.7 mg, croscarmellose sodium 7 mg, mannitol 52 mg, magnesium stearate 0.7 mg, microcrystalline cellulose 37.6 mg.

Dosage of 10 mg

1 tablet contains:

active substance: Torasemide 10 mg;

Excipients: starch corn pregelatinized 53.5 mg, silicon dioxide colloid 1 mg, croscarmellose sodium 10.5 mg, mannitol 78 mg, magnesium stearate 1 mg, cellulose microcrystalline 56 mg.

Description:Tablets are round, biconcave with a risk, white or almost white. Allowed a slight marbling.

Pharmacotherapeutic group:Diuretic agent.

ATX: & nbsp

C.03.C.A Sulfonamide diuretics

C.03.C.A.04 Torasemide

Pharmacodynamics:

Torasemide is a "loop" diuretic. The main mechanism of action of the drug is due to the reversible binding of torasemide to the sodium / chlorine / potassium transporter located in the apical membrane of the thick segment of the ascending loop of Henle, as a result of which the reabsorption of sodium ions decreases and completely inhibits and the osmotic pressure of the intracellular fluid decreases and water reabsorption. Torasemide blocks aldosterone receptors of the myocardium, reduces fibrosis and improves diastolic function of the myocardium.

Due to anti-aldosterone action torasemide to a lesser extent than furosemide, causes hypokalemia, while it shows great activity and its effect is more prolonged. The diuretic effect develops approximately an hour after ingestion, reaching a maximum after 2-3 hours and remaining up to 18 hours, which facilitates the tolerability of the therapy due to the lack of very frequent urination during the first hours after taking the drug inside, limiting the activity of patients.

Torasemide reduces systolic and diastolic arterial pressure in the "lying" and "standing" positions.

The use of torasemide is the most reasonable choice for long-term therapy.

Pharmacokinetics:

Suction

After oral administration torasemide quickly and almost completely absorbed in the gastrointestinal tract. Eating does not have a significant effect on the absorption of the drug. The maximum concentration (C_m_Oh) torasemide in plasma is noted 1 to 2 hours after ingestion. Bioavailability is 80-90% with minor individual variations.

Impaired renal and / or liver function does not affect the absorption of the drug. Distribution

Communication with plasma proteins is more than 99%.

Volume of distribution (V_d) in healthy volunteers and in patients with mild and moderate renal failure or chronic heart failure is from 12 to 16 liters. In patients with cirrhosis of the liver Vd doubled.

Metabolism

Metabolised in the liver with the help of cytochrome P450 isoenzymes. As a result of successive oxidation, hydroxylation or ring hydroxylation reactions, three metabolites (Ml, M3 and M5), which bind to plasma proteins by 86%, 95% and 97%, respectively.

Excretion

The half-life (T_1/2) torasemide and its metabolites in healthy volunteers is 3-4 hours and does not change with chronic renal failure. The total clearance of torasemide is 40 ml / min and the renal clearance is 10 ml / min. On the average, about 83% of the accepted dose is excreted by the kidneys: in unchanged form (24%) and in the form of predominantly inactive metabolites (Ml - 12%, M3 - 3%, M5 - 41%).

Pharmacokinetics in special clinical cases

Renal insufficiency: With renal insufficiency T_1/2 does not change, T_1/2 metabolites M3 and M5 increases. Torasemide and its metabolites are slightly excreted by hemodialysis and haemofiltration.

Liver failure: In liver failure, the concentration of torasemide in the blood plasma increases due to a decrease in the metabolism of the drug in the liver. In patients with cardiac or hepatic insufficiency T_1/2 torasemide and metabolite M5 is slightly increased, cumulation of the drug is unlikely.

Age: The pharmacokinetic profile of torasemide in elderly patients is similar to that in young patients, except that there is a decrease in renal clearance of the drug due to a characteristic age-related impairment of decreased renal function in elderly patients. Total ground clearance and T_1/2 they do not change.

Indications:

- edematous syndrome of various genesis, including chronic heart failure, liver, lung and kidney diseases;

- arterial hypertension.

Contraindications:

- hypersensitivity to torasemide or to any of the components of the drug;

in patients with an allergy to sulfonamides (sulfonamide antimicrobial agents or sulfonylureas), there may be a cross-allergy to torasemide;

- renal failure with anuria;

- hepatic coma and precoma;

- pronounced hypokalemia;

- severe hyponatremia;

- hypovolemia (with or without arterial hypotension) or dehydration;

- marked abnormalities of urine outflow from any etiology (including unilateral urinary tract damage);

- glycoside intoxication;

- acute glomerulonephritis;

- sinoatrial and atrioventricular (AV) blockade of II-III degree;

- decompensated aortic and mitral stenosis;

- hypertrophic obstructive cardiomyopathy;

- increased central venous pressure (more than 10 mm Hg);

- arrhythmia;

- chronic renal failure with increasing azotemia;

- age under 18 years (safety and efficacy in children not studied);

- lactation period.

Carefully:

- arterial hypotension;

- stenosing arteriosclerosis of cerebral arteries;

- hypoproteinemia;

- disorders of urinary outflow (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis);

- ventricular arrhythmia in the anamnesis;

- acute myocardial infarction (increased risk of developing cardiogenic shock);

- diarrhea;

- pancreatitis;

- hypokalemia;

- hyponatremia;

- impaired liver function, cirrhosis, renal failure, hepatorenal syndrome;

- diabetes mellitus (decreased glucose tolerance);

- gout, hyperuricemia;

- anemia;

- simultaneous reception of cardiac glycosides, aminoglycosides or cephalosporins, corticosteroids or adrenocorticotropic hormone (ACTH);

- pregnancy.

Pregnancy and lactation:

Torasemide does not have a teratogenic effect and fetotoxicity, it penetrates the placental barrier, causing disturbances in water-electrolyte metabolism and thrombocytopenia in the fetus.

The preparation Torasemide Canon can be used during pregnancy only in the event that,when the possible benefit for the mother exceeds the potential risk to the fetus, under the close supervision of the doctor and only in minimal doses.

There is no data on the release of thorasemide into breast milk, so if Torasemide Canon is needed, breastfeeding should be discontinued.

Dosing and Administration:

Inside, not liquid, squeezed water. Tablets can be taken at any convenient constant time, regardless of food intake.

Edema Syndrome in Chronic Heart Failure: the usual initial dose is 10-20 mg once a day. If necessary, the dose can be doubled until the desired effect is achieved.

Edema in kidney disease: the usual initial dose is 20 mg once a day. If necessary, the dose can be doubled until the desired effect is achieved.

Edema syndrome with liver disease: the usual initial dose is 5-10 mg once a day. If necessary, the dose can be doubled until the desired effect is achieved.

A single dose of more than 40 mg is not recommended, since its effect has not been studied. The drug Torasemide Canon is prescribed for a long period or until the disappearance of edema.

Arterial hypertension: The usual initial dose is 5 mg once a day.

In the absence of an adequate reduction in blood pressure for 4-6 weeks, the dose is increased to 10 mg once a day. If this dose does not give the desired effect, a hypotensive drug of another group should be added to the treatment regimen.

Older patients do not need a dose adjustment.

Side effects:

Classification of WHO frequency of development of side effects:

Often - >1/10 appointments (> 10%)

often from >1/100 to <1/10 of appointments (> 1% and <10%)

infrequently - from >1/1000 to <1/100 of prescriptions (> 0.1% and <1%)

rarely from >1/10000 to <1/1000 appointments (> 0.01% and <0.1%)

very rarely - <1/10000 prescriptions (<0.01%)

frequency is not known - can not be estimated based on available data

Violations of the blood and lymphatic system

Frequency not known: Thrombocytopenia, leukopenia, agranulocytosis, aplastic or hemolytic anemia.

Disorders from the metabolism and nutrition

Infrequently: polydipsia, hypercholesterolemia, hypertriglyceridemia.

Frequency not known: decrease in glucose tolerance (manifestation of latent diabetes mellitus is possible).

Disturbances from the nervous system

Often: dizziness, headache, drowsiness.

Infrequently: cramps of the muscles of the lower extremities.

Frequency not known: confusion, fainting, paresthesia in the extremities (sensation of numbness, "crawling crawling" and tingling).

Disturbances on the part of the organ of sight

Frequency not known: impaired vision.

Hearing disorders and labyrinthine disorders

Frequency not known: hearing impairment, tinnitus and hearing loss (usually,

reversible character) usually in patients with renal insufficiency or hypoproteinemia (nephrotic syndrome).

Heart Disease

Infrequently: extrasystole, arrhythmia, tachycardia.

Vascular disorders

Frequency not known: excessive reduction in blood pressure, orthostatic hypotension, collapse, deep vein thrombosis, thromboembolism.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequently: nasal bleeding.

Disorders from the gastrointestinal tract

Often: diarrhea.

Infrequently: abdominal pain, flatulence.

Frequency not known: dry mouth, nausea, vomiting, loss of appetite, pancreatitis, dyspeptic disorders.

Disturbances from the liver and bile ducts

Frequency not known: intrahepatic cholestasis.

Disturbances from the skin and subcutaneous tissues

Frequency not known: skin itching, rash, hives, polymorphic erythema, exfoliative dermatitis, purpura, vasculitis, photosensitivity.

Disturbances from musculoskeletal and connective tissue

Frequency not known: muscle weakness.

Disorders from the kidneys and urinary tract

Often: increased frequency of urination, polyuria, nocturia.

Infrequently: frequent urge to urinate.

Frequency not known: oliguria, urinary retention (in patients with obstruction of the urinary tract), interstitial nephritis, hematuria.

Violations of the genitals and mammary gland

Frequency not known: decreased potency.

General disorders and disorders at the site of administration

Infrequently: fever, asthenia, weakness, increased fatigue, hyperactivity, nervousness. Severe anaphylactic reactions up to shock, which until now have been described only after intravenous administration.

Laboratory and instrumental data

Frequency not known: hypercholesterolemia, hypertriglyceridemia, hyperuricemia,a slight increase in the concentration of alkaline phosphatase in the blood, a transient increase in the concentration of creatinine and urea in the blood, an increase in the activity of certain "hepatic" enzymes (for example, gamma-glutamyltransferase).

Violations from the water-electrolyte and acid-base balance

Frequency not known: hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, hypochloraemia, metabolic alkalosis, hypovolemia, dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop blood clots.

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

Overdose:

Symptoms: excessively increased diuresis, accompanied by a decrease in the volume of circulating blood (BCC) and a violation of the electrolyte balance of blood, followed by a marked decrease in blood pressure, drowsiness and confusion, collapse. Gastrointestinal disorders may occur.

Treatment: there is no specific antidote. Provocation of vomiting, gastric lavage, Activated carbon. Treatment is symptomatic, dose reduction or drug withdrawal and at the same time replenishment of bcc and indicators of water-electrolyte balance and acid-base state under the control of serum concentrations of electrolytes, hematocrit. Hemodialysis is not effective, since the excretion of torasemide and its metabolites is not accelerated.

Interaction:

With the simultaneous use of mineral and glucocorticosteroids, amphotericin B increases the risk of hypokalemia, with cardiac glycosides - the risk of developing glycosidic intoxication due to hypokalemia (for high and low-polar) and an increase in T_1/2 (for low-polarity).

The preparation Torasemide Canon raises the concentration and risk of developing nephrotoxic and ototoxic effects of chloramphenicol, ethacrynic acid, antibiotics, salicylates, platinum preparations (Pt), amphotericin B (due to competitive renal excretion).

Sequential or simultaneous administration of the Torasemide Canon preparation with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists can lead to a sharp drop in blood pressure.This can be avoided by decreasing the initial dose of an ACE inhibitor, or by lowering the dose of Torasemide Canon (or temporarily abolishing it).

Non-steroidal anti-inflammatory drugs (NSAIDs), sucralfate, methotrexate and probenecid reduce the diuretic effect due to inhibition of prostaglandin synthesis, disturbance of renin activity in plasma and aldosterone removal. Torasemide intensifies the hypotensive effect of antihypertensive drugs, neuromuscular blockade of depolarizing muscle relaxants (suxamethonium), and weakens the effect of nondepolarizing muscle relaxants (tubocurarine).

Torasemide may increase the toxicity of lithium preparations and the ethoxyrinic acid's ototoxicity.

Torasemide increases the effectiveness of diazoxide and theophylline, reduces the effectiveness of hypoglycemic agents, allopurinol.

Pressor amines and the preparation Torasemide Canon mutually reduce the effectiveness. Drugs that block tubular secretion, increase the concentration of the drug Torasemide Canon in the blood serum.

With the simultaneous use of cyclosporine and the preparation of Torasemide Canon, the risk of gouty arthritis is increased due to the fact that ciclosporin can cause a violation of urate extraction by the kidneys, and torasemide hyperuricemia. It has been reported that patients with a high risk of developing nephropathy who take torasemide inside, with the introduction of radiopaque agents, impaired renal function were observed more frequently than in patients at high risk of developing nephropathy who received intravenous hydration prior to administration of radiocontrast. Bioavailability and, as a consequence, the effectiveness of torasemide can be reduced by joint therapy with colestyramine.

Special instructions:

The drug Torasemide Canon should be used strictly according to the doctor's prescription. Patients with hypersensitivity to sulfonamides and sulfonylureas may have cross-sensitivity to the preparation Torasemide Canon. Patients receiving high doses of the preparation Torasemide Canon, in order to avoid the development of hyponatremia, hypokalemia and metabolic alkalosis, it is inappropriate to limit the intake of table salt and the use of potassium preparations. The risk of hypokalemia is greatest in patients with cirrhosis of the liver, expressed diuresis, inadequate intake of electrolytes with food, as well as with simultaneous treatment with corticosteroids or ACTH.

Increased risk of development of violations of water-electrolyte balance is observed in patients with renal insufficiency. During the course of treatment with Torasemide Canon, it is necessary to periodically monitor the concentration of plasma electrolytes (including sodium, calcium, potassium, magnesium), acid-base, residual nitrogen, creatinine, uric acid and, if necessary, appropriate corrective therapy in patients with frequent vomiting and against the background of parenterally injected fluids).

In patients with developed water-electrolyte disorders, hypovolemia or prerenal azotemia, laboratory analysis data may include: hyper- or hyponatremia, hyper- or hypochloraemia, hyper- or hypokalemia, acid-base balance disturbances, and increased urea levels. If these disorders occur, stop taking Torasemide Canon before restoring normal values, and then resume treatment at a lower dose.

When azotemia and oliguria appear or increase in patients with severe progressive kidney disease, it is recommended to suspend treatment with Torasemide Canon.

The choice of dosage regimen for patients with ascites on the background of cirrhosis of the liver should be carried out under stationary conditions (violations of the water-electrolyte balance may lead to the development of hepatic coma). This category of patients shows regular monitoring of plasma electrolytes.

The use of the drug Torasemide Canon can cause an exacerbation of gout. Patients with diabetes mellitus or with reduced glucose tolerance require periodic monitoring of glucose concentrations in the blood and urine.

In patients with prostatic hyperplasia, narrowing of the ureters, diuretic control is necessary in connection with the possibility of acute urinary retention.

In patients with diseases of the cardiovascular system, especially those taking cardiac glycosides, diuretic-induced hypokalemia can cause arrhythmias.

Effect on the ability to drive transp. cf. and fur:During treatment with the Torasemide Canon preparation, patients should refrain from driving vehicles and taking other potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:Tablets 5 mg, 10 mg.

Packaging:

For 10 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

According to 2, 6 contour cell packs of 10 tablets or 2 circuit packs of 30 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:Store in a dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002270

Date of registration:04.10.2013

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp11.09.2015

Illustrated instructions

Instructions

Torasemide Canon (Torasemide Canon)