Instructions for use Torasemide-Teva tablets 5 mg blister No. 30
Composition
active ingredient: torasemide;
1 tablet contains torasemide 5 mg;
Excipients: lactose monohydrate, corn starch, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white or almost white, round, biconvex tablets with a break line on one side and embossed 915 (for 5 mg tablets) on the other side.
Pharmacotherapeutic group
Diuretics. Highly active diuretics. Simple sulfonamide preparations. ATX code C03C A04.
Pharmacological properties
Pharmacodynamics
Torsemide is a loop diuretic that inhibits the reverse renal reabsorption of sodium and chlorine ions in the ascending limb of the loop of Henle. However, in small doses, the pharmacodynamic profile of torasemide in terms of the degree and duration of diuresis brings it closer to the thiazide class. In large doses, torasemide provides diuresis with a dose-dependent intensity and a high threshold of effect. The maximum diuretic activity of torasemide is achieved 2-3 hours after oral administration. In healthy volunteers, doses from 5 to 100 mg caused a logarithmic increase in diuretic activity. The antihypertensive effect of torasemide is associated with a decrease in peripheral vascular resistance by reducing the increased activity of free Ca2+ in the cells of the muscle layer of arteries in patients with arterial hypertension. As a result, contractility and the response of vessels to the body's own pressor substances, for example, catecholamines, are probably reduced.
Pharmacokinetics
After oral administration, torasemide is rapidly and almost completely absorbed from the gastrointestinal tract. Peak serum levels are reached within 1-2 hours. Systemic bioavailability after oral administration is 80-90%. More than 99% of torasemide is bound to plasma proteins, and the protein binding of metabolites M1, M3 and M5 is 86%, 95% and 97%, respectively. The volume of distribution is 16 liters. During metabolism of torasemide, three metabolites are formed by stepwise oxidation, hydroxylation or ring hydroxylation - M1, M3 and M5. Hydroxyl metabolites have diuretic activity. The active metabolites M1 and M3 account for approximately 10% of the pharmacodynamic effect, and metabolite M5 is inactive.
In healthy volunteers, the terminal half-life of torasemide and its metabolites is 3 to 4 hours. The total clearance of torasemide is 40 ml/min, and the renal clearance is about 10 ml/min. Approximately 80% of the administered dose is excreted by the renal tubules in the form of torasemide and its metabolites - torasemide - 24%, M1 - 12%, M3 - 3%, M5 - 41%. In case of impaired renal function, the half-life of torasemide does not change, but the half-life of metabolites M3 and M5 increases. Hemodialysis and hemofiltration do not provide appreciable removal of torasemide and its metabolites. If an increase in plasma concentrations of torasemide is observed in patients with impaired renal function, this is most likely a consequence of impaired hepatic metabolism. In patients with heart failure or impaired liver function, the half-life of torasemide and the metabolite M5 is slightly increased, but accumulation is unlikely.
Indication
Essential hypertension.
Edema and/or effusions caused by congestive heart failure.
Contraindication
Hypersensitivity to torasemide, to sulfonylurea, to sulfonylurea derivatives or to any of the excipients of the medicinal product.
Renal failure with anuria.
Hepatic coma and precoma.
Arterial hypotension.
Hypovolemia, hypokalemia, hyponatremia.
Pregnancy, breastfeeding.
Arrhythmia (e.g. sinoatrial block, second- and third-degree atrioventricular block).
Concomitant therapy with aminoglycosides or cephalosporins.
Impaired kidney function caused by drugs that cause kidney damage.
Urinary disorders (e.g., benign prostatic hyperplasia).
Interaction with other medicinal products and other types of interactions
When used simultaneously with cardiac glycosides, potassium or magnesium deficiency may increase the sensitivity of the heart muscle to these medications. When used simultaneously with mineralocorticoids and glucocorticoids, laxatives, potassium excretion may increase.
When used simultaneously, torasemide enhances the effect of antihypertensive agents, in particular angiotensin-converting enzyme (ACE) inhibitors.
Sequential or combined therapy, as well as the initiation of a new concomitant therapy with an ACE inhibitor, may cause severe hypotension. This can be reduced by reducing the initial dose of the ACE inhibitor or by reducing the dose/temporarily discontinuing torasemide 2 or 3 days before starting the ACE inhibitor.
Torasemide may reduce the sensitivity of arteries to vasoconstrictors, for example, adrenaline, noradrenaline.
Torasemide, especially in high doses, may enhance the nephrotoxic and ototoxic effects of aminoglycoside antibiotics and ethacrynic acid, especially in patients with renal insufficiency; the toxicity of cisplatin drugs and the nephrotoxic effects of cephalosporins.
It is also possible to enhance the effects of theophylline and curare-based muscle relaxants.
Non-steroidal anti-inflammatory drugs (e.g. indomethacin) may reduce the hypotensive and diuretic effects of torasemide, probably by inhibiting prostaglandin synthesis.
Probenecid reduces the effectiveness of torasemide due to inhibition of tubular secretion.
Increased serum lithium concentrations and increased cardio- and neurotoxic effects are possible.
Torasemide inhibits the renal excretion of salicylates, which increases the risk of their toxicity in patients taking high doses of salicylates.
With simultaneous use of torasemide and cholestyramine, the absorption of torasemide may decrease, thereby weakening the effect of the latter.
Application features
Before starting the drug, it is necessary to correct hypokalemia, hyponatremia, hypovolemia, and urinary disorders.
Kidney and liver dysfunction
Limited information is available on dose adjustment in patients with renal and hepatic impairment. Patients with hepatic impairment should be treated with caution, as increased plasma concentrations of the drug may occur. Torsemide should be used with extreme caution in patients with liver disease accompanied by cirrhosis and ascites, as sudden changes in fluid and electrolyte balance may lead to hepatic coma. Torsemide (as with other diuretics) should be administered to patients in this group in a hospital setting. To prevent hypokalemia and metabolic alkalosis, the drug should be administered with aldosterone antagonists or potassium-sparing drugs.
During long-term treatment with torasemide, regular checks of electrolyte balance (especially in patients with concomitant therapy with digitalis glycosides, glucocorticoids, mineralocorticoids or laxatives), glucose, uric acid, creatinine and blood lipids, as well as blood cells (erythrocytes, leukocytes and platelets) are recommended.
Close monitoring is recommended in patients with a predisposition to hyperuricemia and gout. Blood sugar control is required in latent or overt diabetes mellitus.
Due to the lack of sufficient clinical experience, it is not recommended to prescribe torasemide for:
pathological changes in acid-base balance; concomitant use of lithium; pathological changes in the blood (for example, thrombocytopenia or anemia in patients without renal dysfunction).
Torasemide-Teva tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Ability to influence reaction speed when driving vehicles or other mechanisms
As with other drugs that affect blood pressure, patients taking torasemide should not drive or operate machinery that requires concentration of attention, as dizziness and other associated symptoms may occur. This is especially true during the initial period of treatment, dose increases, and when switching to other drugs.
Use during pregnancy or breastfeeding
There are no data on the effects of torasemide on the embryo and fetus in humans. Although studies in rats did not reveal a teratogenic effect, after administration of high doses of torasemide to female rabbits, malformations in fetuses were observed. Torasemide penetrates the fetal membrane and causes electrolyte disturbances. There is also a risk of neonatal thrombocytopenia.
No studies have been conducted on the penetration of torasemide into breast milk. Therefore, torasemide is contraindicated during pregnancy and breastfeeding.
Method of administration and doses
Essential hypertension: the recommended dose of torasemide is 2.5 mg (1/2 tablet of Torasemide-Teva 5 mg) once a day. If necessary, the dose can be increased to 5 mg per day. The use of doses above 5 mg/day does not cause an additional decrease in blood pressure. The maximum hypotensive effect is achieved after approximately 12 weeks of continuous treatment.
Edema: The usual recommended dose is 5 mg once daily. This is usually a maintenance dose. If necessary, the dose may be gradually increased to 20 mg once daily.
Elderly patients
Use with caution, as there is insufficient information on the need for dose adjustment for elderly patients.
Patients with impaired liver and kidney function
Information on dose adjustment in patients with hepatic and renal impairment is limited. Patients with hepatic impairment should be used with caution as increased plasma concentrations of torasemide may occur.
Administer orally. Torasemid-Teva tablets should be taken in the morning, without chewing, with a small amount of liquid. The bioavailability of the drug Torasemid-Teva does not depend on food intake. The duration of treatment depends on the course of the disease.
Children
Safety and efficacy in children have not been established, therefore torasemide should not be prescribed to this age group of patients.
Overdose
Symptoms. Typical symptoms of intoxication are unknown. In case of overdose, adverse reactions may be exacerbated (strong diuresis, causing dehydration, hypovolemia, arterial hypotension, hyponatremia, hypochloremic alkalosis, hemoconcentration, drowsiness, confusion, cardiovascular failure, loss of consciousness). Gastrointestinal disorders are possible.
Treatment. Specific antidote is unknown. Symptoms and signs of overdose may necessitate dose reduction or discontinuation of Torasemide-Teva with parallel restoration of fluid and electrolyte balance and symptomatic treatment.
Adverse reactions
Metabolism: metabolic alkalosis, disturbance of water and electrolyte balance (especially with a significant restriction of salt in the diet), hypokalemia (especially in case of insufficient potassium in the diet, as well as with vomiting, diarrhea, frequent use of laxatives and impaired liver function); increased levels of uric acid, glucose and lipids in the blood serum; exacerbation of metabolic alkalosis, hyperuricemia, hypovolemia, hyponatremia.
With sufficiently strong diuresis, especially at the initial stage of treatment and in elderly patients, symptoms and signs of electrolyte and volume depletion may occur, such as headache, dizziness, hypotension, weakness, drowsiness, confusion, loss of appetite and convulsions. Dose adjustment is necessary.
Cardiovascular system: embolism, thromboembolic complications, cardiac ischemia, which may lead, in particular, to cardiac arrhythmia, angina pectoris, acute myocardial infarction or syncope, extrasystole, arterial hypotension, palpitations, tachycardia.
Gastrointestinal: gastrointestinal disorders (e.g. loss of appetite, upper abdominal pain, stomach pain, nausea, vomiting, diarrhea, constipation, flatulence); dry mouth, pancreatitis.
Renal and urinary disorders: urinary retention in patients with urinary tract obstruction, urinary urgency, bladder distension, increased serum creatinine and urea levels.
On the part of the hepatobiliary system: increased levels of certain liver enzymes, such as gamma-glutamyl transpeptidase (GGT).
From the blood and lymphatic system: decrease in the number of erythrocytes, leukocytes and platelets.
Immune system disorders: allergic skin reactions (e.g., itching, rash); severe skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).
Skin and subcutaneous tissue disorders: photosensitivity.
Musculoskeletal and connective tissue disorders: muscle spasms.
From the nervous system: headache, dizziness, weakness, cerebral ischemia, paresthesia, confusion, drowsiness, increased activity, nervousness.
Respiratory system: nosebleeds.
On the part of the organs of vision: visual disturbances.
From the auditory system: tinnitus, deafness.
General manifestations: increased fatigue, asthenia, thirst.
Laboratory tests: increased concentrations of uric acid, glucose, and lipids (e.g., triglycerides, cholesterol).
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 30 °C out of the reach of children.
Packaging
10 tablets in a blister, 3 blisters in a box.
Vacation category
According to the recipe.
Producer
PLIVA Hrvatska d.o.o.
Location of the manufacturer and its business address
Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.
