Torikard

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TORICARD (TORICARD)

Composition:

Active substance: torasemide;

1 tablet contains 5 mg or 10 mg of torasemide;

Excipients: lactose monohydrate; microcrystalline cellulose; crospovidone; povidone; magnesium stearate; purified water.

Pharmaceutical form. Tablets.

Main physicochemical properties:

Toricard 5 mg tablets: white to almost white, oval-shaped tablets with a score line and embossing "5" and "6" on one side, embossing "H" on the other side.

Toricard 10 mg tablets: white to almost white, oval-shaped tablets with a score line and embossing "5" and "7" on one side, embossing "H" on the other side.

Pharmacotherapeutic group. Diuretics. High-ceiling diuretics. Sulfonamide-type agents. ATC code C03CA04.

Pharmacological Properties

Pharmacodynamics

Torasemide is a loop diuretic; at low doses used for antihypertensive treatment, it exerts mild diuretic and saluretic effects. At higher doses, torasemide induces a pronounced diuresis, which is dose-dependent. The maximum diuretic activity of torasemide occurs 2–3 hours after oral administration and remains consistent for approximately 12 hours.

Pharmacokinetics

After oral administration, torasemide is rapidly and almost completely absorbed, with peak plasma concentrations reached within 1–2 hours after intake. Systemic bioavailability is 80–90% and is unaffected by food intake. Plasma protein binding of torasemide exceeds 99%, while for metabolites M1, M3, and M5 it is 86%, 95%, and 97%, respectively. The volume of distribution is 16 L. Torasemide is metabolized via oxidation and hydroxylation, forming three metabolites: M1, M3, and M5.

Metabolite M5 is pharmacologically inactive, while metabolites M1 and M3 account for approximately 10% of the drug's pharmacological activity. The terminal half-life (t1/2) of torasemide and its metabolites is 3–4 hours in healthy volunteers. Total clearance of torasemide is 40 mL/min, with renal clearance being approximately 10 mL/min. Approximately 80% of the dose is excreted as unchanged torasemide (24%) and its metabolites: M1 (12%), M3 (3%), and M5 (41%). In renal insufficiency, the t1/2 of torasemide remains unchanged, while the t1/2 of metabolites M3 and M5 is prolonged. Torasemide and its metabolites are poorly removed by hemodialysis or hemofiltration. In patients with impaired liver function or heart failure, the t1/2 of torasemide and metabolite M5 is slightly prolonged, but accumulation of torasemide and its metabolites does not occur.

Clinical characteristics.

Indications.

Treatment of essential hypertension (as monotherapy or in combination therapy with other antihypertensive agents).

Treatment of edema associated with congestive heart failure, kidney or liver diseases.

Contraindications.

• Hypersensitivity to the active substance, other sulfonamide drugs, or excipients of the drug.
• Renal failure with anuria.
• Hepatic coma or precoma.
• Arterial hypotension.
• Hypovolemia. Hyponatremia. Hypokalemia.
• Significant impairment of urination, for example due to prostatic hypertrophy.
• Pregnancy, breastfeeding.
• Pediatric age (under 18 years).
• Concomitant use of aminoglycoside antibiotics or cephalosporins, or renal failure following administration of other nephrotoxic drugs.
• Arrhythmia.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of torasemide with cardiac glycosides may increase myocardial sensitivity to these drugs due to potassium or magnesium deficiency. Concomitant use with mineralocorticoids, glucocorticoids, or laxatives increases the risk of potassium deficiency.

Torasemide enhances the effect of other antihypertensive drugs, particularly angiotensin-converting enzyme (ACE) inhibitors. Concurrent use with ACE inhibitors may lead to severe hypotension. This can be prevented by reducing the initial dose of the ACE inhibitor or by reducing the dose of torasemide 2–3 days prior to starting ACE inhibitor therapy.

Torasemide may reduce the vasoconstrictive effects of adrenaline and noradrenaline.

The drug reduces the effectiveness of antidiabetic agents.

Torasemide, especially in high doses, may potentiate the nephrotoxic and ototoxic effects of aminoglycoside antibiotics (e.g., kanamycin, gentamicin, tobramycin), the toxic effects of platinum-containing drugs, and the nephrotoxic effects of cephalosporins.

Torasemide enhances the effects of theophylline and curare-like muscle relaxants.

Probenecid and nonsteroidal anti-inflammatory drugs (e.g., indomethacin, propionic acid derivatives) reduce the diuretic and antihypertensive effects of torasemide.

Concomitant use of torasemide and lithium preparations may increase lithium blood concentration and enhance its cardiotoxic and neurotoxic effects.

When used with high-dose salicylates, torasemide may enhance their toxic effects on the central nervous system.

Concomitant use with cholestyramine may reduce absorption of torasemide, resulting in reduced efficacy.

Special precautions for use.

Before initiating treatment with the drug, existing hypokalemia, hyponatremia, hypovolemia, and disturbances in urine excretion should be corrected.

During prolonged treatment with torasemide, regular monitoring of electrolyte balance (especially in patients concurrently receiving cardiac glycosides, glucocorticoids, mineralocorticoids, or laxatives), blood glucose, uric acid, creatinine, and lipid levels, as well as blood cell counts (erythrocytes, leukocytes, and platelets) is recommended.

Patients predisposed to hyperuricemia and gout require special monitoring.

Patients with overt or latent diabetes mellitus should have carbohydrate metabolism carefully monitored.

Due to insufficient clinical experience, torasemide is not recommended in patients with pathological changes in acid-base balance; in patients with blood count abnormalities such as thrombocytopenia or anemia without renal insufficiency; when used concomitantly with lithium, aminoglycosides, or cephalosporins; in renal dysfunction caused by nephrotoxic agents; in children; and in elderly patients (dosing recommendations are lacking).

Torasemide should be used with particular caution in patients with liver diseases associated with liver cirrhosis and ascites, as sudden changes in water-electrolyte balance may precipitate hepatic coma. Therapy with torasemide (as with other diuretics) in these patients should be conducted under hospital conditions. To prevent hypokalemia and metabolic acidosis, the drug should be administered in combination with aldosterone antagonists or potassium-sparing agents.

Ototoxic effects (tinnitus and hearing loss) have been observed after torasemide administration. These effects were reversible, but a direct causal relationship with the drug has not been established.

When prescribing diuretics, clinical symptoms of electrolyte imbalance, hypovolemia, extrarenal azotemia, and other disturbances should be carefully monitored. These may manifest as dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, myasthenia, hypotension, oliguria, tachycardia, nausea, and vomiting. Excessive diuresis may lead to dehydration, reduced circulating blood volume, thrombosis, and vascular embolism, particularly in elderly patients.

Patients experiencing disturbances in water-electrolyte balance should discontinue the drug. After resolution of adverse effects, therapy may be resumed at lower doses.

Regular laboratory monitoring of serum potassium and other electrolytes is necessary during treatment.

Information on dosing in patients with renal or hepatic impairment is limited. Torasemide should be administered with caution in patients with hepatic insufficiency, as increased plasma concentrations of torasemide may occur.

The drug contains lactose and therefore should not be administered to patients with hereditary lactase deficiency, galactose intolerance, or glucose/galactose malabsorption. If intolerance to certain sugars is suspected, medical advice should be sought before taking this medication.

Use during pregnancy or breastfeeding.

There is insufficient clinical experience regarding the use of torasemide during pregnancy. Although animal studies in rats showed no teratogenic effects, fetal malformations were observed in rabbits after administration of high doses of torasemide. Torasemide crosses the placental barrier and may cause electrolyte disturbances in the fetus. There is also a risk of neonatal thrombocytopenia. Studies on the excretion of torasemide in human breast milk have not been conducted. Therefore, torasemide is contraindicated during pregnancy and breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

The drug may affect human reaction speed, potentially impairing the ability to drive vehicles or operate machinery. Therefore, caution should be exercised during treatment when driving or engaging in other potentially hazardous activities requiring heightened attention and rapid psychomotor responses.

Dosage and Administration.

Tablets should be taken in the morning, independently of food intake, without chewing, with a small amount of liquid.

The duration of treatment depends on the course of the disease.

Essential hypertension. The recommended dose for adults is 2.5 mg once daily. If blood pressure normalization is not achieved after two months of therapy with torasemide 2.5 mg daily, the dose may be increased to 5 mg (once daily). Maximum effect is usually observed within 3 months after initiation of treatment. Doses exceeding 5 mg do not result in enhanced antihypertensive effect.

Edema. Therapy should be initiated with a dose of 5 mg once daily. This dose is usually considered as maintenance. If the daily dose of 5 mg is insufficient, a daily dose of 10 mg should be prescribed and administered daily. Depending on the severity of the patient's condition, the daily dose may be gradually increased up to 20 mg of torasemide (once daily).

Patients with hepatic and renal impairment. Information on dose adjustment in patients with hepatic or renal dysfunction is limited. Torasemide should be used with caution in patients with hepatic impairment due to the potential for increased plasma concentrations of torasemide. Torasemide is contraindicated in patients with hepatic coma or precoma (see section "Contraindications").

Elderly patients. No specific dose adjustment is required.

Children.

Clinical data on the efficacy and safety of the drug in pediatric patients are lacking; therefore, the drug is not recommended for use in this age group.

Overdose.

The typical symptomatology is unknown. Overdose may cause profound diuresis, including risk of excessive loss of water and electrolytes, somnolence, amnestic syndrome (a form of consciousness disturbance), symptomatic arterial hypotension, hypovolemia, hyponatremia, hypochloremic alkalosis, hemoconcentration, loss of consciousness, cardiovascular failure, and gastrointestinal disturbances.

Treatment. Specific antidote is unknown. Symptoms of intoxication usually resolve with dose reduction or discontinuation of the drug, along with appropriate fluid and electrolyte replacement (monitoring required). Torasemide is not removed from blood by hemodialysis. Treatment in case of hypovolemia: fluid volume replacement. Treatment in case of hypokalemia: administration of potassium supplements.

Anaphylactic shock (emergency measures). At the first signs of skin reactions (such as urticaria or skin redness), patient's agitation, headache, excessive sweating, nausea, cyanosis, perform venous catheterization; place the patient in a horizontal position, ensure free air access, administer oxygen. If necessary, administer epinephrine, volume-expanding solutions, and glucocorticoid hormones.

Side effects.

Metabolic disorders: worsening of metabolic alkalosis; increased plasma concentrations of uric acid, glucose, and lipids (cholesterol, triglycerides); hypokalemia in patients on a low-potassium diet, with vomiting, diarrhea, after excessive use of laxatives, or in patients with chronic liver dysfunction. Depending on dose and duration of treatment, disturbances in fluid and electrolyte balance may develop, such as hypovolemia, hypokalemia, and hyponatremia. Significant fluid and electrolyte losses due to enhanced diuresis may lead to arterial hypotension, headache, asthenia, drowsiness, particularly at the beginning of treatment and in elderly patients.

Cardiovascular system: embolism, thrombosis, arterial hypotension, cardiac and cerebral ischemia, possibly leading to cardiac arrhythmias, angina pectoris, acute myocardial infarction, syncope, extrasystoles, palpitations, tachycardia.

Gastrointestinal system: loss of appetite, nausea, vomiting, stomach pain, gastric discomfort, diarrhea, constipation, flatulence, pancreatitis, xerostomia (dry mouth).

Urinary system: possible increase in serum creatinine and urea levels; in patients with impaired micturition, e.g., due to prostatic hyperplasia, urinary retention and excessive bladder distension may occur; increased frequency of urination.

Hepatobiliary system: elevated levels of certain liver enzymes (γ-glutamyl transferase) in plasma.

Blood and lymphatic system: decreased platelet, erythrocyte, and/or leukocyte counts, blood thickening.

Skin and subcutaneous tissue: allergic reactions (e.g., pruritus, rash, exanthema, photosensitivity), severe skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Musculoskeletal and connective tissue disorders: muscle spasms.

Nervous system: headache, dizziness, weakness, paresthesia, confusion, drowsiness, increased activity, nervousness.

Respiratory system: epistaxis (nosebleeds).

Eye disorders: visual disturbances.

Ear disorders: tinnitus, deafness.

General disorders: increased fatigue, asthenia, thirst.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging. 10 tablets in a blister pack; 3 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Artura Pharmaceuticals Pvt. Ltd. – for Toricard tablets 5 mg or 10 mg.

or

Ananta Medicare Limited – for Toricard tablets 10 mg.

Manufacturer's name and address.

Artura Pharmaceuticals Pvt. Ltd.
1505 Portia Road, Sri City SEZ, Sedyavedu Mandal, Chittoor District – 517 588, Andhra Pradesh, India.

or

Ananta Medicare Limited
Chak 17 ML, Agro Food Park Road, RIICO Industrial Area, Udiog Vihar, Sri Ganganagar-335002 (Rajasthan), India.

Marketing Authorization Holder.

Ananta Medicare Limited

Address of the Marketing Authorization Holder. Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.