Torasemide, tablets 5 mg 20 pcs

Pharmacotherapeutic group: Diuretic

ATC code: C03CA

Pharmacodynamics:

Torasemide is a “loop” diuretic.

The maximum diuretic effect develops 2-3 hours after oral administration.

The basic mechanism of action of the drug is due to the reversible binding of thorasemide to the sodium/chloride/potassium ion transporter situated in the apical membrane of the thick segment of the ascending loop of Genle. As a result, reabsorption of sodium ions is reduced or completely inhibited and osmotic pressure of intracellular fluid and reabsorption of water are decreased. It blocks myocardial aldosterone receptors; reduces fibrosis and improves diastolic function of the myocardium.

The diuretic effect is maintained for up to 18 hours which facilitates tolerance of therapy because there is no very frequent urination in the first hours after ingestion of the drug which limits patient activity.

Thorasemide causes hypokalemia to a lesser extent than furosemide but it is more active and its effect is longer lasting.

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

Pharmacokinetics:

After oral administration, torasemide is quickly and almost completely absorbed in the gastrointestinal tract. Food intake has no significant effect on absorption of the drug.

The maximum concentration of torasemide in blood plasma is noted 1-2 hours after oral administration. Bioavailability is 80 – 90% with slight individual variations.

The binding to plasma proteins is more than 99%. Visible volume of distribution is 16 liters.

It is metabolized in the liver by cytochrome P450 system isoenzymes. As a result of sequential oxidation hydroxylation or ring hydroxylation reactions three metabolites (M1 M3 and M5) are formed, which bind to plasma proteins by 86% 95% and 97% respectively.

The half-life (T1/2) of torasemide and its metabolites is 3-4 hours and does not change in chronic renal failure.

The total clearance of thoracemide is 40 ml/min renal clearance is 10 ml/min. On average, about 83% of the taken dose is excreted by the kidneys: unchanged (24%) and as mainly inactive metabolites (M1 – 12% M3 – 3% M5 – 41%).

In renal insufficiency, the T1/2 is unchanged T1/2 of M3 and M5 metabolites is increased. Torasemide and its metabolites are slightly excreted by hemodialysis and hemofiltration.

In case of hepatic insufficiency, plasma concentrations of thoracemide are increased due to decreased metabolism of the drug in the liver. In patients with cardiac or hepatic insufficiency the T1/2 of thorasemide and M5 metabolite is slightly increased cumulation of the drug is unlikely.

Elderly patients

The pharmacokinetic profile of thorasemide in elderly patients is similar to that in younger patients with the exception that there is a decrease in renal clearance of thorasemide due to the characteristic age-related impairment of renal function in elderly patients. Total clearance and elimination half-life are unchanged.

Indications

– Edema syndrome of various genesis including chronic heart failure liver and kidney diseases;

– arterial hypertension.

Active ingredient

Composition

For 1 tablet of 5.0 mg:

The active ingredient:

torasemide – 5.0 mg.

Excipients:

Lactose monohydrate (milk sugar) – 90.4 mg,

sodium carboxymethyl starch – 3.0 mg,

Magnesium stearate – 0.8 mg,

colloidal silicon dioxide – 0.8 mg.

How to take, the dosage

To be taken by mouth once a day without chewing and with plenty of water. The tablets can be taken at any convenient fixed time, regardless of meals.

Oedema syndrome in chronic heart failure

The usual starting dose is 10-20 mg once daily. If necessary, the dose may be doubled until the desired effect is achieved.

Oedema syndrome in renal disease

The usual starting dose is 20 mg once daily. If necessary, the dose may be doubled until the desired effect is achieved.

Oedema syndrome in liver disease

The usual starting dose is 5-10 mg once daily. If necessary, the dose may be doubled until the desired effect is achieved. The maximum single dose is 40 mg; it is not recommended to exceed this dose (no experience of use). The drug is used for a long period or until edema disappears.

Hypertension

The starting dose is 25 mg once daily. If there is no therapeutic effect within 4 weeks, the dose is increased to 5 mg once daily. If there is no adequate decrease in blood pressure when administered in a dose of 5 mg once a day for 4-6 weeks, the dose is increased to 10 mg once a day. If the use of the drug in a dose of 10 mg per day does not give the desired effect, a hypotensive drug of another group is added to the treatment regimen.

Patients of advanced age do not need dose adjustment.

Interaction

In concomitant use of thorasemide with amphotericin B mineral and glucocorticosteroids the risk of hypokalemia increases; with cardiac glycosides – the risk of glycoside intoxication due to hypokalemia (for high and low-polar cardiac glycosides) and lengthening of the elimination half-life (for low-polar cardiac glycosides) increases.

The administration of torasemide increases the concentration and risk of nephro- and ototoxic effects of cephalosporins aminoglycosides chloramphenicol etacrynic acid cisplatin amphotericin B (due to competitive renal excretion). Increases the effectiveness of diazoxide and theophylline reduces the effectiveness of hypoglycemic agents allopurinol.

Simultaneous or concomitant use of thorasemide with angiotensin-converting enzyme inhibitors (ACE) or angiotensin II receptor antagonists may lead to a sharp decrease in blood pressure. This can be avoided by reducing the dose of thoracemide or temporarily cancelling it.

The nonsteroidal anti-inflammatory drugs sucralfate decrease the diuretic effect of thorasemide due to inhibition of prostaglandin synthesis, disruption of plasma renin activity and excretion of aldosterone.

Torasemide increases the antihypertensive effect of hypotensive agents neuromuscular blockade of depolarizing myorelaxants (suxamethonium) and reduces the effect of nondepolarizing myorelaxants (tubocurarin).

Thorasemide decreases renal clearance of lithium preparations and increases the likelihood of intoxication.

Thorasemide increases the effectiveness of diazoxide and theophylline decreases the effectiveness of hypoglycemic agents allopurinol.

Presor amines and thorasemide mutually reduce the efficacy of each other.

Drugs that block tubal secretion increase plasma concentrations of thorasemide.

The simultaneous use of high doses of salicylates with torasemide therapy increases the risk of their toxicity (due to competitive renal excretion).

Concomitant use of cyclosporine and thorasemide increases the risk of gouty arthritis because cyclosporine may cause renal impairment of urate excretion and thorasemide may cause hyperuricemia.

The concomitant use of probenecid or methotrexate may decrease the effectiveness of thoracemide (same secretion pathway). On the other hand, thorasemide may lead to decreased renal elimination of these drugs.

It has been reported that in patients at high risk of nephropathy, oral thorasemide administered with contrast agents showed more renal dysfunction than did patients at high risk of nephropathy who received intravenous hydration prior to contrast agent administration.

The bioavailability and consequent efficacy of thoracemide may be reduced by co-therapy with colestyramine.

Special Instructions

Use strictly as directed by the physician.

Patients with hypersensitivity to sulfonamides and sulfonylurea derivatives may have cross-sensitivity to Torasemide.

In patients, especially at the beginning of treatment with Torasemide and in elderly patients, monitoring of electrolyte balance of blood volume and circulating blood concentration is recommended.

In long-term treatment with Toracemide, regular monitoring of electrolyte balance (especially potassium levels) of glucose, uric acid, creatinine lipids and cellular blood components is recommended.

Patients who have been treated with high doses of Torasemide for a prolonged period to avoid the development of hyponatremia. Metabolic alkalosis and hypokalemia should have a diet with sufficient table salt (it is not reasonable to restrict table salt intake) and use potassium preparations.

The risk of hypokalemia is greatest in patients with cirrhosis with significant diuresis if there is insufficient intake of electrolytes with food and also with concurrent treatment with corticosteroids or ACTH.

A higher risk of electrolyte-water balance disorders is noted in patients with renal insufficiency. During the course of treatment it is necessary to monitor periodically the concentration of plasma electrolytes (including sodium calcium potassium magnesium) acid-base status residual nitrogen creatinine uric acid and if necessary carry out an appropriate corrective therapy (with greater frequency in patients with frequent vomiting and against parenteral administration of fluids).

In patients with developed water-electrolyte disorders or prerenal azotemia, laboratory findings may include hyper- or hyponatremia hyper- or hypochloremia hyper- or hypokalemia acid-base balance disorders and increased blood urea levels. If these disorders occur, discontinue Torasemide until normal values are restored and then resume treatment with Torasemide at a lower dose.

If azotemia and oliguria appear or worsen in patients with severe progressive renal disease, it is recommended that treatment be stopped.

The dosage regimen of patients with ascites with liver cirrhosis should be chosen under hospital conditions (disruptions of water-electrolyte balance can lead to hepatic coma). Regular monitoring of plasma electrolytes is indicated for this category of patients.

In order to prevent hypokalemia it is recommended to use potassium preparations and potassium-saving diuretics (especially spironolactone), as well as to follow a diet rich in potassium.

The use of Torasemide may cause an aggravation of gout.

In patients with diabetes mellitus or impaired glucose tolerance, periodic monitoring of blood and urine glucose concentrations is required.

In unconscious patients with prostatic hyperplasia with ureteric narrowing, diuresis control is necessary due to the possibility of acute urinary retention.

In patients with cardiovascular disease, especially those taking cardiac glycosides, hypokalemia caused by diuretics may cause arrhythmias.

Patients should refrain from driving and engaging in other potentially dangerous activities that require increased concentration and quick psychomotor reactions during treatment because of the risk of dizziness and somnolence.

Contraindications

– Hypersensitivity to thorasemide or to any of the drug components; patients with an allergy to sulfonamides (sulfonamide antimicrobials or sulfonylurea preparations) may have cross-allergy to thorasemide;

– renal failure with anuria;

– hepatic coma and precoma;

– refractory hypokalemia/refractory hyponatremia;

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

– acute urinary outflow disorders of any etiology (including unilateral urinary tract involvement);

– glycoside intoxication;

– acute glomerulonephritis;

– decompensated aortic and mitral stenosis hypertrophic obstructive cardiomyopathy;

– sinoatrial and atrioventricular block of II-III degree arrhythmia;

– increase in central venous pressure (>10 mmHgsyst.

– hyperuricemia;

– age less than 18 years;

– pregnancy – breastfeeding period;

– concomitant use of aminoglycosides and cephalosporins;

– lactose intolerance lactase deficiency or glucose-galactose malabsorption.

– Arterial hypotension;

– stenotic atherosclerosis of cerebral arteries;

– hypoproteinemia;

– urine outflow disorders (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis); – diabetes mellitus (impaired glucose tolerance);

– hepatorenal syndrome;

– impaired liver function cirrhosis;

– renal insufficiency;

– gout;

– predisposition to hyperuricemia;

– anemia;

– concomitant use of cardiac glucocorticosteroid glycosides and adrenocorticotropic hormone (ACTH);

– hypokalemia;

– hyponatremia.

Side effects

The incidence of side effects is classified according to World Health Organization recommendations: very frequently: ≥ 1/10 (> 10%); frequently: ≥ 1/100 to < 1/10 (> 1% < 10%); infrequently: ≥ 1/1000 to < 1/100 (> 01% and < 1%); infrequent: ≥ 1/10000 to < 1/1000 (> 001% and < 01%); very rare: < 1/10000 (< 001%); frequency unknown: frequency cannot be estimated from available data.

Nervous system disorders:

often – headache dizziness drowsiness;

infrequent – muscle cramps of the lower extremities hyperactivity nervousness;

frequency unknown – confusion fainting paresthesia in the extremities (feeling of numbness “creeping goosebumps” and tingling).

Visual disturbances:

frequency unknown – visual disturbances

Hearing and labyrinth disturbances:

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

Disorders of the cardiovascular system:

infrequent – extrasystole arrhythmia tachycardia;

frequency unknown – excessive reduction of blood pressure orthostatic hypotension collapse deep vein thrombosis thromboembolism hypovolemia (reduced circulating blood volume).

Respiratory system disorders:

infrequent – nasal bleeding.

Disorders of the digestive system:

often – diarrhea;

infrequent – abdominal pain flatulence polydipsia;

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

Skin and subcutaneous tissue disorders:

incidence unknown – skin itching skin rash urticaria erythema polymorphic exfoliative dermatitis purpura vasculitis photosensitization.

Musculoskeletal disorders:

frequency unknown – muscle weakness.

Disorders of the urinary system:

often – increased frequency of urination polyuria nycturia;

infrequent – frequent urge to urinate;

frequency unknown – polyuria urinary retention (in patients with urinary tract obstruction) interstitial nephritis hematuria.

Reproductive system disorders:

frequency unknown – decreased potency.

Metabolic disorders:

infrequent – polydipsia

Hypokalemia hypomagnesemia hypomagnesemia hypocalcemia hypochloremia metabolic alkalosis hypovolemia dehydration (more frequent in elderly patients) impaired glucose tolerance (possible manifestation of latent diabetes mellitus)

(frequency unknown)/p>

Disorders of laboratory parameters:

infrequent – hypercholesterolemia hypertriglyceridemia thrombocytosis;

frequency unknown – hyperglycemia hyperuricemia slight increase in plasma alkaline phosphatase activity increased plasma creatinine and urea concentrations increased plasma activity of some “hepatic” enzymes (e.g. gamma-glutamyltransferase) thrombocytopenia leukopenia agranulocytosis.

Disorders of the blood and lymphatic system:

frequency unknown – aplastic or hemolytic anemia.

General disorders and disorders at the site of administration

frequent – asthenia thirst weakness increased fatigue

Overdose

Symptoms: increased diuresis accompanied by decreased circulating blood volume and disturbed water-electrolyte balance of the blood, followed by a marked decrease in blood pressure, drowsiness and confusion and collapse. Gastrointestinal disorders may be observed.

Treatment: there is no specific antidote. Provocation of vomiting gastric lavage activated charcoal. Treatment: Symptomatic dose reduction or drug withdrawal and concomitant replenishment of the blood circulation and parameters of water-electrolyte balance and acid-base status under control of serum concentrations of electrolytes hematocrit symptomatic treatment. Hemodialysis is ineffective.

Pregnancy use

Pregnancy

Torasemide has no teratogenic effect and fetotoxicity penetrates the placental barrier causing disorders of water-electrolyte exchange and thrombocytopenia in the fetus. No controlled studies on the use of thoracemide in pregnant women have been conducted; therefore, the drug is not recommended for use during pregnancy.

Breast-feeding period

It is unknown whether thoracemide penetrates into the breast milk. If it is necessary to use the drug Torasemide during lactation, breastfeeding should be stopped.

Similarities