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

Excipients: lactose monohydrate - 75.00 mg; corn starch - 17.50 mg; carboxymethyl starch sodium (sodium starch glycolate, type A) - 1.00 mg; silicon dioxide colloidal - 0.75 mg; magnesium stearate - 0.75 mg.

Dosage of 10 mg

active substance: torasemide - 10.00 mg;

Excipients: lactose monohydrate - 150.00 mg: corn starch - 35.00 mg; carboxymethyl starch sodium (sodium starch glycolate, type A) - 2.00 mg; silicon dioxide colloidal - 1.50 mg; magnesium stearate - 1.50 mg.

Description:Round flat-cylindrical tablets of white or almost white color with a facet and a risk.

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 the torassmide to the sodium / chlorine / potassium ion transportator located in the apical membrane of the thick segment of the ascending loop of Henle, as a result of which the sodium ions are reabsorbed or decreased and the osmotic pressure of the intracellular fluid decreases and the water is reabsorbed. Thorassmide blocks aldosterone receptors of the myocardium, reduces fibrosis and improves diastolic function of the myocardium.

Thanks to the anti-aldosteron 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 about an hour after ingestion, reaching a maximum in 2-3 hours, and lasts up to 18 hours, which facilitates the tolerability of therapy due to the lack of very frequent urination during the first hours after ingestion, limiting the activity of patients.

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

The use of torassmide 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 of torasemide in the blood plasma is noted 1-2 hours after ingestion. Bioavailability is 80-90% with minor individual variations.

Distribution

Communication with plasma proteins is more than 99%. The volume of distribution in healthy volunteers and in patients with mild or moderate renal failure or chronic heart failure is from 12 to 16 liters. In patients with cirrhosis, the volume of distribution is doubled.

Metabolism

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

Excretion

The half-life (T₁_/2) Thorassmide and its metabolites in healthy volunteers is 3-4 hours. The total clearance of thorassmide 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 (Ml - 12%, M3 - 3%, M5 - 41%).

Pharmacokinetics in specific patient groups

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

With liver failure, the concentration of torassmide in the blood plasma is increased due to a decrease in the metabolic rate of the drug in the liver.

In patients with cardiac or hepatic insufficiency T_1/2 thorassmide and metabolite M5 are slightly increased, cumulation of the drug is unlikely.

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 renal impairment in elderly patients. Total ground clearance and T_1/2 they do not change.

Indications:

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

- arterial hypertension.

Contraindications:

- Pincreased sensitivity to torasemide or to any of the components of the drug;

- allergy to sulfonamides (sulfanilamide antimicrobial agents or sulfonylureas);

- renal failure with anuria;

- hepatic coma and precoma;

- refractory hypocalcism;

- refractory hyponatremia;

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

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

- glycosidia intoxication:

- acute glomerulonephritis;

- sinoatrial and atrioventricular 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;

- hyperuricemia;

- age under 18 years (safety and efficacy not established);

- 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;

- giioproteinemia;

- 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;

- ginonatremia;

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

- diabetes mellitus (decreased glucose tolerance);

- gout, predisposition to hyperuricemia;

- anemia;

- simultaneous use of cardiac glycosides, corticosteroids and adrenocorticotropic hormone (AKTG).

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.

Controlled studies on the use of torasemide in pregnant women have not been conducted, the drug is not recommended for use during pregnancy.

There is no data on the release of thorasemide into breast milk, so if thorasemide is needed during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, once a day, without chewing, squeezed with enough 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 syndrome with 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.

The maximum single dose is 40 mg, it is not recommended to exceed it (no experience is available).

The drug is used for a long period or until the edema disappears.

Arterial hypertension

The initial dose is 2.5 mg (1/2 tablet of 5 mg) once a day. In the absence of a therapeutic effect for 4 weeks, the dose is increased to 5 mg once a day. In the absence of an adequate reduction in blood pressure with 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 effect, 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.

Side effects:

The incidence of adverse events is classified according to the recommendations World Health Organization:

Often: ≥1/10 (> 10%);

often: from ≥1 / 100 to <1/10 (> 1% and <10%);

infrequently: from ≥1 / 1000 to <1/100 (> 0.1% and <1%);

rarely: from ≥1 / 10000 to <1/1000 (> 0.01% and <0.1%);

very rarely: <1/10000 (<0.01%);

frequency is unknown: the frequency can not be estimated from the available data.

From the nervous system:

often - headache, dizziness, snotty;

infrequently - cramps of the muscles of the lower limbs;

frequency unknown - confusion, fainting, paresthesia in the extremities (numbness, "crawling" and tingling).

From the sense organs:

frequency is unknown - visual impairment, hearing loss, tinnitus and hearing loss (usually reversible), usually in patients with renal failure or hypoproteinemia (nephrotic syndrome).

From the cardiovascular system:

infrequently - extrasystole, arrhythmia, tachycardia;

frequency unknown - excessive decrease in blood pressure, orthostatichypotension, collapse, deep vein thrombosis, thromboembolism, decreased volume circulating blood.

From the respiratory system.

infrequently - epistaxis.

From the digestive system:

often - diarrhea;

infrequently - abdominal pain, flatulence, polydipsia;

frequency unknown - dry mouth, nausea, vomiting, loss of appetite, pancreatitis, dyspeptic disorders, intrahepatic cholestasis.

From the skin and subcutaneous tissues:

frequency unknown - skin itch, rash, urticaria, polymorphic erythema, exfoliative dermatitis, purpura, vasculitis, photosensitivity.

From the musculoskeletal system:

frequency unknown - muscle weakness.

From the urinary system:

often - increased frequency of urination, polyuria, nocturia; infrequent - frequent urge to urinate;

frequency unknown - oliguria, urinary retention (in patients with urinary tract obstruction), interstitial nephritis, hematuria.

On the part of the reproductive system:

frequency is unknown - decreased potency.

From the side of metabolism:

frequency unknown - hypocalEmission, ginonatremia, hypomagnesium, hypocalcemia, hypochloraemia, metabolic alkalosis, hypovolemia, dehydration (more often in elderly patients).

From the laboratory indicators:

infrequently - hypercholesterolemia, hypertriglyceridemia;

frequency is unknown - hyperuricemia, a slight increase in the activity of alkaline phosphatase in the blood plasma, an increase in the concentration of creatinine and urea in the blood plasma, an increase in the activity of certain "hepatic" enzymes in the blood plasma (eg, gamma-glutamyltransferase), thrombocytopenia, leukopenia, agranulocytosis, tolerance to glucose (possible manifestation of latent diabetes mellitus).

Other:

frequency unknown - aplastic or hemolytic anemia.

Overdose:

Symptoms

Reinforced diuresis, accompanied by a decrease in the volume of circulating blood and a violation of water-electrolytebalance 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 withdrawal of the drug and at the same time replenishment of the circulating blood volume and correction of indicators of water-electrolyte balance and acid-base state under the control of the content of electrolytes in blood plasma and the level of hematocrit. Hemodialysis is ineffective, since the excretion of torasemide and its metabolites is not accelerated.

Interaction:

With the simultaneous use of torasemide with mineral- and glucocorticosteroids, amphotericin B increases the risk of hypokalemia; with cardiac glycosides, there is an increased risk of developing glycosidic intoxication due to hypokalemia (for high and low-polar cardiac glycosides) and an elongation of the half-life (for low-polar cardiac glycosides).

The administration of torasemide increases the concentration and risk of developing nephro- and ototoxic effects of cephalosporins, aminoglycosides,chloramphenicol, ethacrynic acid, antibiotics, salicylates, cisplatin, platinum preparations, amphotricin 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 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 (or temporarily abolishing it).

Pest steroidal anti-inflammatory drugs, sucralfate reduce the diuretic effect of torasemide due to inhibition of prostaglandin synthesis, disturbance of renin activity in blood plasma and aldosterone withdrawal.

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

Torasemide reduces the renal clearance of lithium preparations and increases the likelihood of intoxication.

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

Pressor amines and torasemide mutually reduce the effectiveness of each other. Drugs that block tubular secretion, increase the concentration of torasemide in blood plasma.

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.

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. It was reported that in patients with a high risk of developing nephropathy, torasemide Inside, with the introduction of radiopaque means, disorders of the functions of the nights were observed more often than in patients with a high risk of developing nephropathy, who received intravenous hydration prior to the administration of X-ray contrast agents. Bioavailability and, as a consequence, the effectiveness of torasemide can be reduced by joint therapy with colestyramine.

Special instructions:

The drug LOTONEL® is used 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, hypokalemia and metabolic alkalosis, a diet with a sufficient content of common salt and the use of potassium preparations is recommended.

The risk of hypokalemia is greatest in patients with cirrhosis of the liver, with intensified diuresis, with insufficient intake of electrolytes with food, as well as with simultaneous use of corticosteroids or ACTH. An increased risk of developing water-electrolyte imbalance is noted in patients with renal insufficiency. During the course of treatment with LOTONEL®, it is necessary to periodically monitor the content of electrolytes in the blood plasma (including sodium, calcium, potassium, magnesium), acid-base state, concentration of residual nitrogen, creatinine, uric acid, and appropriate corrective therapy with a higher multiplicity in patients with frequent vomiting and against the background of parenteral administration of fluids).

In patients with developed water-electrolyte disorders, hypovolemia or prerenal azotemia, laboratory analysis data may include: hyper- or hyponatraemia, hyper- or hypochloraemia, hyper- or hypokalemia, acid-base balance disorders and an increase in urea concentration in the blood plasma. If these abnormalities occur, it is necessary to stop taking LOTONEL® before the normal values are restored, and then resume treatment with LOTONEL® in a smaller dose.

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

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 LOTONEL® 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 benign 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 the treatment period, patients should refrain from driving and other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions (risk of dizziness and drowsiness).

Form release / dosage:

Tablets 5 mg, 10 mg.

Packaging:

10, 15, 20 or 30 tablets in a planar cell packaging made of a polyvinylchloride film and aluminum foil.

20 or 60 tablets in a can of high-density polyethylene.

2, 3 or 6 contiguous cell packs of 10 tablets, 2 or 4 contour packs of 15 tablets, 1 or 3 contour packs of 20 tablets, 1 or 2 contourcell packs of 30 tablets or one bank together with instructions for medical use in the packfrom cardboard.

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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002907

Date of registration:13.03.2015 / 16.12.2015

Expiration Date:13.03.2020

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp20.03.2018

Illustrated instructions

Instructions

LOTONEL® (Lotonel)