APPROVED BY

Order of the Ministry of Health

of Ukraine

___24.02.2016__№_130__

Registration certificate

№ _UA/14844/01/01___

 

 

INSTRUCTION

for medical use of the preparation

TORICARD

 

Composition:

Active substance: torasemide;

1 tablet contains: torasemide 5 mg or 10 mg;

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

Pharmaceutical form. Tablets.

Basic physical and chemical properties:

Toricard, 5 mg tablets: White to off-white, oval tablet with a scoreline and mark "5" and "6" on one side and mark Н on another.

Toricard, 10 mg tablets: White to off-white, oval tablet with a scoreline and mark "5" and "7" on one side and mark Н on another.

Pharmaceutical group. Diuretic drugs. Highly diuretics.

ATC Code: C03C A04.

Pharmacological properties.

Pharmacodynamics.

Torasemide is a loop diuretic; at low doses, used to antihypertensive treatment, it induces a mild diuretic and saluretic action.  At higher doses, torasemide induces a brisk diuresis in a dose dependant manner. Torasemide shows the maximum diuretic activity in 2-3 hours after intake and it remains constant for about 12 hours.

Pharmacokinetics.

Torasemide is absorbed rapidly and almost completely after oral administration, and peak serum levels are reached after one to two hours after intake. Systemic bioavailability makes 80-90% and does not depend on food intake. Torasemide binding to plasma proteins is more than 99%, metabolites M₁, M₃ and M₅ – 86%, 95% and 97% respectively. The distribution volume is 16 litres. Torasemide is metabolised to three metabolites, M₁, M₃ and M₅ by stepwise oxidation and hydroxylation. M₅ is pharmacologically inactive, and M₁ and M₃ metabolites account for about 10% of the pharmacological action of the drug. The terminal half-life of torasemide (t_1/2) and its metabolites is three to four hours in healthy subjects. Total clearance of torasemide is 40ml/min and renal clearance about 10ml/min. About 80% of the dose is excreted as unchanged torasemide (24 %) and its metabolites: М₁ (12 %), М₃ (3 %) and М₅ (41 %). In the presence of renal failure, elimination half-life of torasemide is unchanged, and elimination half-life of M₃ and M₅ metabolites is continued. Torasemide and its metabolites are not excreted by hemodialysis or hemofiltration, completely. In patients with impaired liver function or heart failure the half-life period of torasemide and M₅ metabolite is slightly extended, however accumulation of torasemide and its metabolites are not observed.

Clinical particulars.

Indications.

Essential hypertension as monotherapy or combined therapy with other antihypertensive agents.

Treatment of oedema due to congestive heart failure; hepatic, pulmonary or renal oedema.

Contraindications.

• Hypersensitivity to torasemide, sulphonylureas and other excipients of the drug.
• Renal failure with anuria.
• Hepatic coma and pre-coma.
• Hypotension.
• Hypovolemia. Hyponatremia. Hypokalemia.
• Severe urination disorder, e.g., due to prostate hypertrophy.
• Lactation.
• Children (under 18 years).

Interaction with other medicinal products and other forms of interaction.

When torasemide is used simultaneously with cardiac glycosides, a potassium and/or magnesium deficiency may increase sensitivity of the cardiac muscle to such drugs. Concomitant administration of mineralo- and glucocorticoids and laxatives increased risk of potassium deficiency.

Torasemide enhances the action of other antihypertensive agents, including inhibitors of angiotensin-converting enzyme (ACE). Concomitant use with ACE inhibitors may result in transient hypotension. This may be minimized by lowering the starting dose of the ACE inhibitor or reducing the dose of torasemide. 2-3 days before the use of ACE inhibitors.

Torasemide may decrease arterial responsiveness to presser agents e.g. adrenaline, noradrenaline.

Torasemide reduces the effect of antidiabetic agents.

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

Torasemide increases the effects of theophylline and curare-containing muscle relaxants.

Probenecid and NSAIDs (e.g. indomethacin, propionic acid derivatives) inhibit the diuretic and hypotensive effect of torasemide.

Concomitant use of torasemide and lithium drugs may increase the lithium concentration in blood plasma and enhance cardio and neurotoxicity of the last one.

In the therapy by salicylates in high doses, torasemide may enhance their toxic effect on the central nervous system.

Concomitant use of colestyramine may decrease absorption of torasemide as a result its action becomes low. 

Precautions of use.

Hypokalaemia, hyponatraemia, hypovolaemia and disorders of micturition must be corrected before treatment.

On long-term treatment with torasemide, regular monitoring of the electrolyte balance (especially in patients who are simultaneously used digitalis glycosides, glucocorticoidsteroids, mineralocorticoidsteroids or laxatives), glucose, uric acid, creatinine and lipids in the blood, is recommended.

Careful monitoring of patients with a tendency to hyperuricaemia and gout is recommended. Carbohydrate metabolism in latent or manifest diabetes mellitus should be monitored.

Because of the lack of experience of clinical use we do not recommend to prescribe torasemide in pathological changes of acid-base balance; pathological changes in the blood, such as thrombocytopenia or anemia in patients without renal failure; along with lithium, aminoglycosides, cephalosporins; with impaired renal function, caused by nephrotoxic agents; children; elderly patients (no recommendations for dosage).

Torasemide should be used with caution in patients with liver disease accompanied by cirrhosis and ascites, because sudden changes in water-electrolytic balance may lead to hepatic coma. For patients of this group, torasemide (and other diuretics) therapy should be carried out in a hospital. To prevent hypokalemia and metabolic acidosis, the drug should be prescribed along with aldosterone antagonist-agents or agents that promote the retention of potassium in the body.

After torasemide intake there were observed ototoxicity phenomena (tinnitus and hearing loss), which were reversible, but a direct connection with the use of the drug was not revealed.

When diuretics are prescribed, it is necessary to control clinical symptoms of electrolyte imbalance, hypovolemia, extrarenal azotemia and other disorders that can occur as dry mouth, thirst, weakness, drowsiness, agitation, muscle pain or seizures, myasthenia gravis, hypotension, oliguria, tachycardia, nausea and vomiting. Redundant diuresis may result in dehydration, reduced blood volume, blood clots and embolism blood vessels, especially in the elderly.

Patients with water-electrolytic imbalance should stop taking the drug. After elimination of adverse effects the therapy should be resumed, starting with lower doses.

When the drug is prescribed it is necessary to conduct regular laboratory monitoring of potassium indicators and other electrolytes in the blood serum.

Information about dosage for patients with renal or hepatic impairment is limited. For patients with hepatic insufficiency the drug should be used with caution, as it may increase plasma concentrations of torasemide.

The drug contains lactose; therefore it should not be administered to patients with hereditary deficiency of lactase, galactose intolerance or with impaired metabolism of glucose / galactose.

Pregnancy and lactation.

There is no sufficient experience of clinical use of torasemide during pregnancy, so the drug can be prescribed during pregnancy only if the expected benefit for the pregnant woman outweighs the potential risk for the foetus (according to vital rates and at the lowest possible effective dose). It is unknown whether torasemide gets into breast milk, so during the treatment breast-feeding should be discontinued.

Effects on ability to drive and use machines.

The drug can influence on human reaction rate. The drug reduces reaction rate when driving vehicle or operating machines. Therefore, during the treatment you must be careful when driving vehicle and doing other potentially hazardous activities that require high concentration and speed of psychomotor reactions.

Way of administration and dosage.

Tablets should be taken in the morning, regardless of the meal; not masticate; drink it with a small amount of liquid.

The duration of treatment depends on the disease.

Essential hypertension: For adults the dose of 2.5 mg of torasemide a day is recommended. If after two months of therapy with the dose of torasemide 2.5 mg the normalization of blood pressure is not reached, the dose can be increased up to 5 mg (once a day).The maximum effect is exhibited in 3 months after beginning the treatment. Doses greater than 5 mg do not contribute to the antihypertensive effect.

Oedema. Therapy should be started with a dose of 5 mg per day. Usually this dose is considered to be supportive. If the daily dose of 5 mg is insufficient, a daily dose of 10 mg should be prescribed. Depending on the severity of the patient's state the daily dose can be progressively increased up to 20 mg of torasemide (once a day).

Patients with hepatic insufficiency. Treatment of these patients should be performed with caution because of possible increased concentration of torasemide in blood plasma.

Patients with liver cirrhosis. The total initial dose is 5-10 mg once a day in combined use with aldosterone antagonist-agents or with diuretics that promote the retention of potassium in the body. In the absence of the necessary diuretic effect the dose should be doubled (10-20 mg daily) to achieve the desired effect.

Patients with renal insufficiency. The total starting dose is 20 mg once a day.

In the absence of the necessary diuretic effect the dose should be doubled (40 mg daily) to achieve the desired effect.

Elderly patients. Special adjust dose is not needed.

Children.

There are no clinical data on the efficacy and safety of the drug for treatment of children. It is not recommended to prescribe the drug for patients in this age category.

Overdose.

No typical picture of intoxication is known. Overdose may cause severe diuresis, including the risk of excessive loss of water and electrolytes, drowsiness, amentive syndrome (a form of impaired consciousness), symptomatic hypotension, cardiovascular insufficiency and digestive tract disorders.

Treatment. No specific antidote is known. Symptoms and signs of overdose require the reduction of the dose or withdrawal of torasemide, and simultaneous replacement of fluid and electrolytes (monitoring is required!). Torasemide is not excreted from blood by hemodialysis. Treatment in case of hypovolemia: replacement of fluid volume. Treatment in case of hypokalemia: prescribing potassium.

Anaphylactic shock (immediate action). At the first sings of skin reactions (such as, urticarial or redness of the skin), the excited state of patient, headache, sweating, nausea, cyanosis the vein catheterization is carried out; the patient is placed in a horizontal position, the free flow of air is ensured and oxygen is administered. If necessary, epinephrine, solutions that replace fluid volume and glucocorticoid hormones are administered.

Adverse reactions.

Metabolism disorders: increased metabolic alkalosis; muscle spasms (especially at the beginning of treatment); increased concentration of uric acid, glucose and lipids (cholesterol, triglycerides) in the blood plasma; hypokalaemia in concomitant diet with low potassium content, in vomiting, diarrhea, after redundant use of laxatives and in patients with chronic liver failure. Depending on the dosage and duration of therapy, the water-electrolytic imbalance, e.g. hypovolemia, hypokalemia, hyponatremia may be developed. The possible hypotension, headache, asthenia, somnolence, especially at the beginning of treatment and in elderly patients, may occur in significant loss of fluid and electrolytes due to enhanced urination.

Cardiovascular disorders: thrombosis, hypotension, cardiac and cerebral ischemia with possible development of cardiac arrhythmias, stenocardia, acute myocardial infarction and syncope.

Digestive tract disorders: loss of appetite, nausea, vomiting, stomach pain, indigestion and diarrhea, constipation, flatulence and pancreatitis.

Renal and Urinary system: increased serum creatinine and urea in serum; in patients with disorders of urination, such as prostatic hypertrophy, urinary retention and possible over-distention of the bladder; urination may occur.

Hepatobiliary system: increased level of some liver enzymes (γ-glutamyl) in blood plasma

Blood and lymphatic system: reduced amount of thrombocytes, red blood cells and/or leukocytes.

Skin and subcutaneous tissue: allergic reaction (e.g. itching, rash, exanthema, photosensitivity).

General disorders: headache, dizziness, confusion, increased fatigue, weakness (especially at the beginning of treatment), dry mouth, paresthesia of extremities, visual disturbances, tinnitus, hearing loss. 

Shelf life. 2 years.

Storage conditions.

Keep out of the reach of children.

Store in the original package at temperature not exceeding 30 °С.

Package. 10 tablets in a blister. 3 blisters in a carton box.

Terms of dispensing. On prescription.

Manufacturer.

Hetero Labs Limited.

Manufacturer’s registered address .

Unit-III, Formulations, Plot №. 22-110 IDA, Jeedimeetla, Hyderabad 500 055, (Andhra Pradesh), India

Applicant.

Ananta Medicare Ltd.

Applicant’s registered address.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, SW6 2PY, London, United Kingdom.

Date of last update.

24.02.2016