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

Lactose monohydrate 79.0 mg / 158.0; cellulose microcrystalline 10.0 mg / 20.0 mg, crospovidone 3.0 mg / 6.0 mg; Povidone K30 2.0 mg / 4.0 mg; magnesium stearate 1.0 mg / 2.0 mg.

Description:

Dosage of 5 mg:

Oval biconvex tablets white or almost white with a risk. On the side with the risk of engraving "56", on the opposite side of the engraving "H".

Dosage of 10 mg:

Oval biconvex tablets white or almost white with a risk. On the side with the risk of engraving "57", on the opposite side of the engraving "H".

Pharmacotherapeutic group:Diuretics

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 ion transportator located in the apical membrane of the thick segment of the ascending portion of the Henle loop, resulting in decreased or completely inhibited reabsorption of sodium ions and decreases the osmotic pressure of the intracellular fluid and reabsorption of water. It blocks aldosterone receptors of the myocardium, reduces fibrosis and improves diastolic function of the myocardium.

Torasemide is less than furosemide, causes hypokalemia, while it shows great activity, and its effect is more prolonged.

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 into the digestive tract. The maximum concentration of torasemide in the blood plasma is noted 1-2 hours after ingestion after eating. Bioavailability is 80-90% with minor individual variations.

Diuretic effect persists up to 18 hours, which facilitates the tolerability of therapy because of the lack of very frequent urination in the first hours after taking the drug inside, limiting the activity of patients.

Distribution

Communication with plasma proteins is more than 99%. Visible volume of distribution is 16 liters.

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 (M1, M3 and M5), which bind to plasma proteins at 86, 95 and 97%, respectively.

Excretion

The half-life (T1 / 2) of torasemide and its metabolites is 3-4 hours and does not change with chronic renal failure. The total clearance of torasemide is 40 ml / min, 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 (M1 - 12%, M3 - 3%, M5 - 41%).

Pharmacokinetics in specific patient groups

With renal insufficiency, T1 / 2 does not change, T1 / 2 metabolites M3 and M5 increases. Torasemide and its metabolites are slightly excreted by hemodialysis and haemofiltration.

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, T1 / 2 torasemide and metabolite M5 is slightly increased, cumulation of the drug is unlikely.

Indications:

* Ocular syndrome of various genesis, incl. with chronic heart failure, liver, lung and kidney diseases;

* arterial hypertension.

Contraindications:

- Hypersensitivity to torasemide or any of the components of the drug; - allergy to sulfonamides (sulfanilamide antimicrobial agents or sulfonylureas);

- Renal failure with anuria;

- hepatic coma and precoma;

- refractory hypokalemia;

- refractory hyponatremia;

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

- pronounced violations of the outflow of urine of any etiology (including unilateral urinary tract damage);

- glycosidic intoxication;

- acute glomerulonephritis;

- sinoatrial and atrioventricular block II-III degree;

- Decompensated aortic and mitral stenosis;

- hypertrophic obstructive cardiomyopathy;

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

- Arrhythmia;

- chronic renal failure with increasing azotemia;

- Hyperuricemia;

- age up to 18 years;

- Pregnancy;

- the period of breastfeeding;

- simultaneous use of aminoglycosides and cephalosporins;

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

- Arterial hypotension;

- stenosing arteriosclerosis of cerebral arteries;

- hypoproteinemia;

- predisposition to hyperuricemia, disturbances of urinary outflow (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis);

- a ventricular arrhythmia in the anamnesis;

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

- diarrhea;

- pancreatitis;

- hypokalemia;

- hyponatremia;

- diabetes mellitus (decreased tolerance to glucose);

- a violation of the liver, cirrhosis, hepatorenal syndrome;

- kidney failure, gout;

- Anemia;

- simultaneous use of cardiac glycosides, corticosteroids and adrenocorticosteroid hormone (ACTH).

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.

It is not known whether the torasemide in breast milk. If it is necessary to use the drug Torasemide During lactation it is necessary to stop breastfeeding.

Dosing and Administration:

Inside, once a day, after breakfast, without chewing, squeezed a small amount water.

Edema Syndrome in Chronic Heart Failure

The usual therapeutic dose is 10-20 mg orally once a day. If necessary, the dose should be gradually increased to 20-40 mg once a day, until the desired effect is obtained.

Edema syndrome with kidney disease

The usual therapeutic dose is 20 mg orally once a day. If necessary, the dose should be gradually increased by half, until the desired effect is obtained.

Edema syndrome with liver disease

The usual therapeutic dose is 5-10 mg orally once a day. If necessary, the dose can be doubled, until the desired effect is obtained.The maximum single dose is 40 mg; it is not recommended to exceed it (there is no experience of application).

The drug is used for a long time, or until the desired effect is obtained.

Arterial hypertension

The initial dose is 2.5 mg (1/2 table, 5 mg each) once a day. If necessary, the dose may be increased to 5 mg once a day.

In the absence of an adequate reduction in blood pressure when taking the drug at a dose of 5 mg once a day for 4-6 weeks, the dose is increased to 10 mg once a day. If the dose of 10 mg does not give the desired result, a hypotensive drug of another group should be added to the treatment regimen.

To patients of advanced age correction of the dose is not required.

Dose Transmission: In case of missing the next dose, you can not take a double dose of the drug. Immediately take the forgotten dose. The next dose is taken at the usual time the next day.

Side effects:

Undesirable reactions are listed depending on the anatomical and physiological classification and occurrence. Frequency of occurrence is defined thus:

very often ≥1 / 10, often ≥1 / 100 and <1/10, infrequently ≥1 / 1000 and <1/100, rarely 1/10000 and <1/1000 and very rarely <1/10000.

Disorders from the metabolism and nutrition: frequency unknown - hyponatremia, hypochloraemia, hypokalemia, hypomagnesemia, hypocalcemia, metabolic alkalosis. Symptoms that indicate the development of violations of the water-electrolyte state and acid-base state can be: headache, confusion, convulsions, tetany, muscle weakness, heart rhythm disorders and dyspepsia; hypovolemia and dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop thrombosis.

Heart Disease: infrequently - extrasystole, tachycardia, arrhythmia.

Vascular disorders: frequency unknown - excessive decrease in blood pressure, orthostatic hypotension, collapse, decreased circulating blood volume, deep vein thrombosis, thromboembolism.

Violations from laboratory and instrumental data: infrequently - hypercholesterolemia, hypertriglyceridemia; transient increase in the concentration of creatinine and urea in the blood; increasing the concentration of uric acid in the blood, which can cause or intensify the manifestations of gout; a decrease in glucose tolerance (a manifestation of a latent sugardiabetes), increased activity of hepatic enzymes.

Disorders from the kidneys and urinary tract: often - increased frequency of urination, polyuria, nocturia; infrequent urge to urinate; frequency unknown - oliguria, acute urinary retention (eg, with prostatic hyperplasia, narrowing of the urethra, hydronephrosis); interstitial nephritis, hematuria, decreased potency.

Disorders from the gastrointestinal tract: often - diarrhea, infrequently - abdominal pain, flatulence, polydipsia; frequency unknown - dry mouth, nausea, vomiting, loss of appetite, acute pancreatitis.

Disorders from the liver and bile ducts: intrahepatic cholestasis.

Hearing disorders and labyrinthine disturbances: infrequently, hearing impairment, usually reversible, and / or tinnitus, especially in patients with renal insufficiency or hypoproteinemia (nephrotic syndrome),

Impaired nervous system: frequent headache, dizziness, drowsiness; infrequently paresthesia.

Disturbances from the skin and subcutaneous tissues: infrequent skin itching, hives,other types of skin rashes and whether bullous skin lesions, polymorphic erythema, exfoliative dermatitis, purpura, fever, vasculitis, eosinophilia, photosensitivity.

Disturbances from general disorders and at the place of administration: heavy anaphylactic or anaphylactoid reactions up to shock, which until now have been described only after intravenous administration.

Violations from the blood and lymphatic system: frequency unknown - thrombocytopenia; leukopenia; agranulocytosis, aplastic or hemolytic anemia.

Overdose:

Symptoms: excessively increased diuresis, accompanied by a decrease in the volume of circulating blood and a violation of the water-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 simultaneous replenishment of circulating blood volume and correction of water electrolyte balance and acid-base state under the control of serum concentrations of electrolytes, hematocrit.

Hemodialysis is ineffective, since the excretion of torasemide and its metabolism is not accelerated.

Interaction:

With the simultaneous use of torasemide with 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 cardiac glycosides) increases and the half-life is extended (for low-polar cardiac glycosides).

Reduces renal clearance of lithium preparations and increases the likelihood of development of intoxication.

Receiving torasemide increases the concentration and risk of developing nephro- and ototoxic effects of cephalosporins, aminoglycosides, chloramphenicol, ethacrynic acid, antibiotics, salicylates, cisplatin, preparations of platinum, amphotericin B (due to competitive renal excretion).

Sequential or simultaneous use of torasemide with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists can lead to a marked decrease in blood pressure. This can be avoided by lowering the dose of torasemide or temporarily abolishing it.

Non-steroidal anti-inflammatory drugs, sucralfate reduce diuretic effect due to inhibition of prostaglandin synthesis, disturbance of renin activity in plasma and aldosterone removal.

Torasemide enhances the antihypertensive effect of antihypertensive drugs, neuromuscular blockade of depolarizing muscle relaxants (suxamethonium), and weakens the effect of nondepolarizing muscle relaxants (tubocurarine).

Simultaneous reception of large doses of salicylates on the background of torasemide therapy increases the risk of their toxicity (due to competitive renal excretion).

Increases the effectiveness of diazoxide and theophylline, reduces - hypoglycemic agents, allopurinol.

Pressor amines and torasemide mutually reduce efficiency.

Drugs that block the tubular secretion, increase the concentration of torasemide in serum.

The simultaneous use of probenecid or methotrexate may decrease the effectiveness of torasemide (the same pathway of secretion). On the other hand, torasemide can lead to a decrease in renal elimination of these drugs.

With the simultaneous use of cyclosporine and torasemide, the risk of gouty arthritis is increased due to the fact that ciclosporin may cause impairment of urate excretion by the kidneys, and torasemide hyperuricemia.

It was reported that in patients with a high risk of developing nephropathy, torasemide Inside, with the introduction of radiopaque agents, renal dysfunction was observed more often than in patients with a high risk of developing nephropathy, who received intravenous hydration prior to the administration of radiocontrast agents. Bioavailability and, as a consequence, the effectiveness of torasemide can be reduced by joint therapy with colestyramine.

Special instructions:

Apply the drug Torasemide strictly according to the doctor's prescription.

Patients with hypersensitivity to sulfonamides and sulfonylureas may have cross-sensitivity to torasemide. Patients receiving high doses of torasemide for a long period, in order to avoid the development of hyponatremia, metabolic alkalosis and hypokalemia, a diet with a sufficient content of table salt and the use of potassium preparations is recommended.

An increased risk of developing water-electrolyte imbalance is noted in patients with renal insufficiency. During the course of treatment is necessary to periodically monitor the concentration of electrolytes in blood plasma (including sodium, calcium, potassium, magnesium), acid-base status, residual nitrogen, creatinine, uric acid, and implement appropriate remedial treatment if necessary (with higher multiplicity y patients with frequent vomiting and amid parenterally administered fluids).

In patients with advanced water and electrolyte disorders, hypovolemia, or prerenal azotemia, laboratory data can include: hyper- or hyponatremia, hyper- or chloropenia, hyper- or hypokalemia, acid-base balance, and increasing concentrations of urea in blood plasma. If these disorders occur, you must stop taking the drug Torasemide before restoring normal values, and then resume treatment with the drug Torasemide in a smaller dose.

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

The choice of the 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.

Application of the drug Torasemide may 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 in the unconscious state, 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, diuretics-induced hypokyemia can cause arrhythmias.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, patients should refrain from driving vehicles and practicing other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, 5 mg, 10 mg.

Packaging:

When manufacturing at Hetero Labe Limited, India

100 tablets per bottle of high-density polyethylene.

The bottle together with instructions for use in a pack of cardboard.

When manufacturing and / or packaging and packaging at LLC "MAKIZ-PHARMA"

For 10 tablets in a planar cell pack of PVC / Al.

For 30, 60, 100 tablets in a bike made of high-density polyethylene (HDPE), ukuporennoy cover of low-density polyethylene (LDPE) with the control of the first autopsy. Free space, if necessary, is filled with cotton wool hygroscopic.

For 3 or 6 contour packs of 10 tablets or 1 can, together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004407

Date of registration:09.08.2017

Expiration Date:09.08.2022

The owner of the registration certificate:Heterose Labs LimitedHeterose Labs Limited India

Manufacturer: & nbsp

MAKIZ-PHARMA, LLC Russia

HETERO LABS, Limited India

Information update date: & nbsp31.08.2017

Illustrated instructions

Instructions

Torasemide (Torasemide)