Torasemid Reneval (Tablets) Instructions for Use

Marketing Authorization Holder

Obnovlenie Pfc, JSC (Russia)

ATC Code

C03CA04 (Torasemide)

Active Substance

Torasemide (Rec.INN registered by WHO)

Dosage Forms

	Torasemide Reneval	Tablets 5 mg
		Tablets 10 mg

Dosage Form, Packaging, and Composition

Tablets

10 pcs. – blister packs (2) – cartons (20 pcs.) – By prescription
10 pcs. – blister packs (3) – cartons (30 pcs.) – By prescription
10 pcs. – blister packs (6) – cartons (60 pcs.) – By prescription
14 pcs. – blister packs – cartons (14 pcs.) – By prescription
14 pcs. – blister packs (2) – cartons (28 pcs.) – By prescription
14 pcs. – blister packs (4) – cartons (56 pcs.) – By prescription
15 pcs. – blister packs (2) – cartons (30 pcs.) – By prescription
15 pcs. – blister packs (4) – cartons (60 pcs.) – By prescription

Tablets

10 pcs. – blister packs (2) – cartons (20 pcs.) – By prescription
10 pcs. – blister packs (3) – cartons (30 pcs.) – By prescription
10 pcs. – blister packs (6) – cartons (60 pcs.) – By prescription
14 pcs. – blister packs – cartons (14 pcs.) – By prescription
14 pcs. – blister packs (2) – cartons (28 pcs.) – By prescription
14 pcs. – blister packs (4) – cartons (56 pcs.) – By prescription
15 pcs. – blister packs (2) – cartons (30 pcs.) – By prescription
15 pcs. – blister packs (4) – cartons (60 pcs.) – By prescription

Clinical-Pharmacological Group

Diuretic

Pharmacotherapeutic Group

Diuretics; “loop” diuretics; sulfonamides

Pharmacological Action

“Loop” diuretic. The main mechanism of action is due to the reversible binding of torasemide to the sodium/chloride/potassium cotransporter located in the apical membrane of the thick ascending limb of the loop of Henle, as a result of which the reabsorption of sodium ions is reduced or completely inhibited and the osmotic pressure of the intracellular fluid and the reabsorption of water are reduced.

Torasemide causes hypokalemia to a lesser extent than furosemide, while it exhibits greater activity and its action is more prolonged.

The diuretic effect develops within about an hour after oral administration, reaching a maximum after 3-6 hours, and lasts from 8 to 10 hours.

It reduces systolic and diastolic blood pressure in the supine and standing positions.

Pharmacokinetics

After oral administration, Torasemide is absorbed from the gastrointestinal tract with a limited first-pass effect through the liver. C_max in blood plasma is reached within 1.5 hours after oral administration. Food intake does not have a significant effect on absorption. Impaired renal and/or liver function does not affect absorption.

More than 99% of torasemide is bound to blood plasma proteins.

V_d in healthy volunteers and in patients with mild to moderate renal failure or chronic heart failure is from 12 to 15 L. In patients with liver cirrhosis, V_d doubles.

It is metabolized in the liver with the participation of the isoenzyme CYP2C9 to form three metabolites.

The main metabolite is a carboxylic acid derivative and is pharmacologically inactive. The other two metabolites, which are formed in the body in insignificant amounts, have some diuretic activity, but their concentration is too low to have any significant clinical effect.

T_1/2 of torasemide in healthy volunteers is 4 hours. About 80% of the orally administered dose is excreted by the kidneys as metabolites and about 20% unchanged (in patients with normal renal function). The total clearance of torasemide is 41 ml/min and renal clearance is about 10 ml/min, which corresponds to approximately 25% of the total.

In patients with decompensated chronic heart failure, the hepatic and renal clearance of the drug is reduced. In such patients, the total clearance of torasemide is 50% less than in healthy volunteers, and T_1/2 and total bioavailability are correspondingly higher.

In patients with renal failure, the renal clearance of torasemide is noticeably reduced, but this does not affect the total clearance. The diuretic effect in renal failure can be achieved by using high doses. The total clearance of torasemide and T_1/2 remain at the same level in case of reduced renal function, due to metabolism in the liver.

In patients with liver cirrhosis, V_d, T_1/2 and renal clearance are increased, but the total clearance remains unchanged.

The pharmacokinetic profile of torasemide in elderly patients is similar to that in young patients, with the exception that there is a decrease in the renal clearance of the drug due to the characteristic age-related impairment of renal function in elderly patients. The total clearance and T_1/2 do not change.

Indications

Edematous syndrome of various origins, including in chronic heart failure, liver and kidney diseases. Arterial hypertension.

ICD codes

Dosage Regimen

Take tablets orally, with or without food.

For edematous syndrome in chronic heart failure, renal or hepatic disease, initiate therapy with 5 mg or 10 mg once daily.

For arterial hypertension, the usual initial dose is 5 mg once daily.

Adjust the dose based on individual patient response and clinical need. The typical therapeutic range is 5 mg to 20 mg once daily.

Administer a single dose in the morning to avoid nocturia.

For severe edematous conditions, the dose may be increased until the desired diuretic response is achieved. The maximum recommended single dose is 40 mg; higher doses have not been studied.

In patients with liver cirrhosis and ascites, initiate therapy in a hospital setting to monitor electrolyte balance and renal function.

Use for long-term control of chronic conditions or until the resolution of acute edema.

Monitor serum electrolytes (particularly potassium), renal function, and blood pressure regularly, especially at the start of therapy and in elderly patients.

Adverse Reactions

Metabolism disorders: infrequently – hypercholesterolemia, hypertriglyceridemia, polydipsia.

Nervous system disorders: frequently – dizziness, headache, drowsiness; infrequently – muscle cramps of the lower extremities; frequency unknown – confusion, fainting, paresthesia in the extremities.

Cardiovascular system disorders: infrequently – extrasystole, tachycardia, palpitations, facial flushing; frequency unknown – excessive arterial hypotension, deep vein thrombosis, thromboembolism, hypovolemia.

Respiratory system disorders: infrequently – nosebleeds.

Digestive system disorders: frequently – diarrhea; infrequently – abdominal pain, flatulence; frequency unknown – nausea, vomiting, loss of appetite, pancreatitis, dyspeptic symptoms.

Kidney and urinary tract disorders: frequently – increased frequency of urination, polyuria, nocturia; infrequently – frequent urge to urinate; frequency unknown – urinary retention (in patients with urinary tract obstruction), increased concentration of urea and creatinine in the blood.

Laboratory parameters: infrequently – increased platelet count; frequency unknown – hyperglycemia, hyperuricemia, hypokalemia, decreased red blood cell, white blood cell and platelet counts, slight increase in blood alkaline phosphatase activity, increased activity of some liver enzymes (e.g., GGT), hyponatremia, hypochloremia, metabolic alkalosis.

Sensory organ disorders: frequency unknown – visual disturbances, ringing in the ears and hearing loss (usually reversible).

Skin disorders: frequency unknown – skin itching, rash, photosensitivity.

Other: infrequently – asthenia, weakness, thirst, hyperactivity, nervousness, increased fatigue.

Contraindications

Anuria; hepatic coma and precoma; refractory hypokalemia; refractory hyponatremia; dehydration; severe urinary outflow disorders of any etiology (including unilateral urinary tract damage); glycoside intoxication; acute glomerulonephritis; sinoatrial and AV block of II and III degree; children and adolescents under 18 years of age; pregnancy; hypersensitivity to torasemide; allergy to sulfonamides (sulfonamide antimicrobial agents or sulfonylurea drugs).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy. Use with caution during lactation (breastfeeding).

Special Precautions

With caution: arterial hypotension; hypovolemia (with or without arterial hypotension); urinary outflow disorders (benign prostatic hyperplasia, urethral stricture or hydronephrosis); history of ventricular arrhythmia; acute myocardial infarction (increased risk of cardiogenic shock); diarrhea; pancreatitis; diabetes mellitus (reduced glucose tolerance); liver diseases complicated by cirrhosis and ascites, renal failure, hepatorenal syndrome; gout, hyperuricemia; anemia; simultaneous use of cardiac glycosides, aminoglycosides or cephalosporins, corticosteroids or ACTH; hypokalemia; hyponatremia; lactation period.

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 persons, it is recommended to monitor the electrolyte balance, volume and concentration of circulating blood.

During long-term treatment with torasemide, it is recommended to regularly monitor electrolyte balance (especially potassium levels), glucose, uric acid, creatinine, lipids and blood cellular components.

For patients receiving Torasemide in high doses, it is not advisable to limit salt intake in order to avoid the development of hyponatremia and metabolic alkalosis.

The risk of hypokalemia is greatest in patients with liver cirrhosis, severe diuresis, insufficient intake of electrolytes with food, as well as during simultaneous treatment with corticosteroids or ACTH.

An increased risk of developing water-electrolyte balance disorders is noted in patients with renal failure. During course treatment, it is necessary to periodically monitor the concentration of plasma electrolytes (including sodium, calcium, potassium, magnesium), acid-base status, residual nitrogen, creatinine, uric acid and, if necessary, carry out appropriate corrective therapy (more frequently in patients with frequent vomiting and against the background of parenterally administered fluids).

In patients with developed water-electrolyte disorders, hypovolemia or prerenal azotemia, laboratory data may include: hyper- or hyponatremia, hyper- or hypochloremia, hyper- or hypokalemia, acid-base balance disorders and increased blood urea levels. If these disorders occur, it is necessary to stop taking torasemide until normal values are restored, and then resume treatment with torasemide at a lower dose. If azotemia and oliguria appear or intensify in patients with severe progressive kidney diseases, it is recommended to suspend treatment.

Selection of the dosage regimen in patients with ascites due to liver cirrhosis should be carried out in a hospital setting (water-electrolyte balance disorders can lead to the development of hepatic coma). This category of patients is indicated for regular monitoring of plasma electrolytes.

To prevent hypokalemia, it is recommended to use potassium preparations and potassium-sparing diuretics (primarily spironolactone), as well as to follow a diet rich in potassium.

The use of torasemide can cause an exacerbation of gout.

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

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

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

Effect on the ability to drive vehicles and mechanisms

During the treatment period, patients should avoid engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Drug Interactions

Torasemide increases the toxicity of cardiac glycosides.

When taken simultaneously with mineralo- and glucocorticoids, laxatives, an increase in potassium excretion is possible.

Torasemide enhances the effect of antihypertensive drugs.

Torasemide, especially in high doses, can enhance the nephrotoxic and ototoxic effects of aminoglycosides, antibiotics, platinum drugs, cephalosporins.

Torasemide can enhance the effect of curare-like muscle relaxants and theophylline.

With simultaneous use of salicylates in high doses, their toxic effect may be enhanced.

Torasemide weakens the effect of hypoglycemic drugs.

Sequential or simultaneous administration of torasemide with ACE inhibitors can lead to a short-term drop in blood pressure. This can be avoided by reducing the initial dose of the ACE inhibitor or reducing the dose of torasemide (or temporarily discontinuing it).

NSAIDs and probenecid may reduce the diuretic and hypotensive effect of torasemide.

The bioavailability and, as a result, the effectiveness of torasemide may be reduced during combination therapy with cholestyramine.

Torasemide may increase the toxicity of lithium drugs and the ototoxicity of ethacrynic acid.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.