Тригрим®

General characteristics. Structure:

Active ingredient: 2,5 mg, 5 mg or 10 mg of a torasemid.

Excipients: lactose, corn starch, silicon dioxide colloid, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. The main mechanism of effect of drug is caused by reversible linkng of a torasemid with the kontransporter ^{of Na+/2Cl-/K+} located in an apical membrane of a thick segment of the ascending Henle's loop therefore decreases or the reabsorption of ions of sodium is completely inhibited, reducing, thus, the osmotic pressure of intracellular liquid and a reabsorption of water.

At the same time thanks to an anti-aldosteronovomu to action торасемид to a lesser extent, than furosemide causes a hypopotassemia, at bigger activity and duration of action. 

Pharmacokinetics. After intake торасемид it is quickly and almost completely soaked up in digestive tract. The maximum concentration of a torasemid in plasma is noted in 1-2 hours after introduction. Bioavailability makes about 80-91% and more at hypostases. Communication with proteins of a blood plasma — 99%. The volume of distribution makes 16 liters.

It is metabolized in a liver in system of P450 cytochrome with formation of 3 metabolites of M1, M3 and M5.

The elimination half-life of a torasemid and its metabolites at healthy volunteers makes 3-4 hours. The general clearance of a torasemid makes 40 ml/min. and renal clearance — about 10 ml/min. On average 80-83% of the accepted dose are removed through renal tubules: in an invariable look (24-25%) and in the form of metabolites (M1 – 11-12%, M3 – 3%, M5 – 41-44%).

At a renal failure the elimination half-life of a torasemid does not change.

Indications to use:

• The hypostases caused by heart failure, diseases of a liver, kidneys and lungs.
• Primary hypertensia (it is applied in monotherapy or in combination with other hypotensive drugs).

Route of administration and doses:

Inside. Adults:

Hypostases. 5 mg of 1 times a day. If necessary it is possible to increase a dose gradually to 20 mg of 1 times a day. About 40 mg ^{of Trigrima®} a day are in some cases recommended.

Congestive heart failure. 5 – 20 mg of 1 times a day. If necessary it is possible to increase a daily dose gradually (doubling it), at most to 200 mg.

Chronic renal failure. The initial dose makes 20 mg a day. If necessary this dose can be increased gradually (doubling it), before achievement of the corresponding diuretic action. The maximum daily dose — 200 mg.

Cirrhosis. 5 – 10 mg of 1 times a day. If necessary this dose can be increased gradually (doubling it), before achievement of the corresponding diuretic action.

Appropriately controlled researches at patients with liver diseases using doses more than 40 mg a day were not conducted.

Primary arterial hypertension. 2,5 mg in 1 times a day. If necessary it is possible to increase a dose gradually to 5 mg a day. According to researches, the dose does not lead over 5 mg a day to a further lowering of arterial pressure. The maximum effect is reached approximately after twelve weeks of continuous treatment.

Patients of advanced age. Patients of advanced age do not demand special adaptation of a dose.

Children. There are no data on use ^{of Trigrima®} for children.

Food does not exert impact on absorbability ^{of Trigrima®} therefore medicine can be taken irrespective of meal.

Features of use:

• At prolonged treatment it is recommended to carry out monitoring of electrolytic balance, glucose, uric acid, creatinine and lipids to blood.
• At a hypopotassemia, a hyponatremia, a hypovolemia or frustration of an urination before purpose ^{of Trigrima®} carry out elimination of all listed states to purpose of this drug.
• With care to enter at gout or tendencies to increase in level of uric acid
• In the presence of a diabetes mellitus it is necessary to control carbohydrate metabolism.
• At thrombocytopenia or oppression of function of marrow, and also at skin rashes it is necessary to cancel drug.

Influence of drug on driving of motor transport and control of mechanisms. At the initial stage of reception it is not recommended to manage vehicles and to service mechanisms because of a possibility of emergence of dizziness.

Side effects:

From blood: in some cases changes in biochemical indicators of blood can be noted: decrease in number of erythrocytes and leukocytes, and also thrombocytes, a hypovolemia, disturbances of electrolytic balance, a hypopotassemia, increase in uric acid in blood serum, glucose and lipids. Increase in level of some enzymes of a liver, for example gamma-GT.

From cardiovascular system: in some cases, because of a pachemia, there are circulatory disturbances and thromboembolisms, a lowering of arterial pressure (ABP) of blood.

From a digestive tract: various dysfunctions of the digestive tract (DT), appetite loss, pancreatitis in some cases can develop.

From kidneys and urinary tract: an acute ischuria, increase in level of urea and creatinine in plasma.

From the central nervous system: headache, dizziness, weakness, drowsiness, confusion of consciousness, spasm, and also paresthesia of extremities.

Allergic reactions: skin itch, rashes and photosensitization.

From sense bodys: visual disturbances, sonitus, deafness.

Others: dryness in a mouth.

Interaction with other medicines:

Increases sensitivity of a myocardium to cardiac glycosides at insufficiency of potassium or magnesium.

At a concomitant use with mineralo-and glucocorticoids, purgatives potassium removal can increase.

• Strengthens effect of hypotensive drugs.
• In high doses can strengthen toxic effect of aminoglycosides, antibiotics, Cisplatinum; nephrotoxic effect of cephalosporins, and also kardio-and neurotoxic effect of lithium.
• Torasemid can strengthen action of kurarepodobny muscle relaxants and theophylline.
• At use of high doses of salicylates, their toxic action can amplify, and action of antidiabetic means, opposite to be weakened.
• The consecutive or concomitant use of a torasemid with inhibitors of the angiotensin-converting enzyme (ACE) can lead to passing falling of the ABP. It can be avoided, having reduced an initial dose of APF, or having lowered a dose of a torasemid (or having temporarily cancelled it).
• Torasemid reduces action of vasoconstrictors (Epinephrinum and Norepinephrinum)
• Non-steroidal anti-inflammatory drugs and пробеницид can reduce diuretic and hypotensive action of a torasemid.
• Colestyraminum can reduce absorption of a torasemid from a GIT (in animal experiments).

Contraindications:

• hypersensitivity to a torasemid and sulfonamides;

• anury;

• hepatic coma and prekomatozny state;

• chronic renal failure with the accruing azotemia;

• arrhythmia;

• arterial hypotension;

• pregnancy; the lactation period (there are no data on use in the period of a lactation);

• age up to 18 years (efficiency and safety are not established).

With care: diabetes mellitus, gout, disturbances of water and electrolytic balance, abnormal liver function, cirrhosis, predisposition to a hyperuricemia.

Overdose:

Symptoms: there is no typical picture of poisoning.

At overdose — the forced urination which is followed by a hypovolemia, disturbance of electrolytic balance with the subsequent falling of arterial pressure, drowsiness, confusion of consciousness, a collapse. Gastrointestinal frustration can be observed.

The specific antidote is unknown. The symptomatic treatment assumes a dose decline or drug withdrawal and at the same time completion of loss of liquid and electrolytes.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Not to use after the date specified on packaging. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

Tablets on 2,5 mg, 5 mg and 10 mg. On 10 tablets in the blister from a foil of Al/PVC. 3 blisters (30 tablets) with the application instruction in a cardboard pack.