Britomar

General characteristics. Structure:

1 tablet of the prolonged action of 5 mg contains: active agent - торасемид 5 mg

excipients: gum of guar 3.40 mg, starch of corn 30.77 mg, silicon dioxide of colloid 0.42 mg, magnesium stearate of 0.25 mg, lactoses monohydrate to 85 mg; 1 tablet of the prolonged action of 10 mg contains: active agent - торасемид 10 mg

excipients: gum of guar 6.80 mg, starch of corn 61.54 mg, silicon dioxide of colloid 0.85 mg, magnesium stearate of 0.51 mg, lactoses monohydrate to 170 mg;

Description
 Round biconvex tablets of white or almost white color with an engraving of "SN" on one party.

Pharmacological properties:

Pharmacodynamics. Torasemid is "loopback" diuretic. The main mechanism of effect of drug is caused by reversible linkng of a torasemid with a kontransporter of sodium/chlorine/potassium,
located in an apical membrane of a thick segment of ascending Geshte's loop therefore decreases or the reabsorption of ions of sodium is completely inhibited and the osmotic pressure of intracellular liquid and a reabsorption of water decreases. Torasemid to a lesser extent, than furosemide, causes a hypopotassemia, at the same time he shows big activity and its action is more long. The diuretic effect develops about an hour after administration of drug inside, reaching a maximum in 3-6 h, and lasts from 8 to 10 h.

Reduces the systolic and diastolic arterial pressure (AP) in situation "lying" and "standing".

Pharmacokinetics. Drug Britomar of a tablet of the prolonged action provides gradual release of a torasemid, reducing fluctuations of its concentration in blood, in comparison with drugs of a torasemid in a dosage form of a tablet with usual release.

Absorption

After reception of several doses of drug, relative bioavailability of the prolonged form, in comparison with a usual dosage form, makes about 102%. Active agent is soaked up in the digestive tract (DT) with limited effect of "the first passing" through a liver and the maximum concentration (With max) in a blood plasma is reached during 1,5 h after intake. Meal does not exert considerable impact on drug absorption. A renal failure and/or a liver do not influence drug absorption. 

Distribution

More than 99% of a torasemid contact proteins of a blood plasma.

The volume of distribution (Vd) at healthy volunteers and at patients with a slight and moderate renal failure or chronic heart failure - from 12 to 15 l. At patients with cirrhosis pecheniv d increases twice.

Metabolism

It is metabolized under the influence of a P450 cytochrome CYP2C9 isoenzyme in a liver with formation of three metabolites.

The main metabolite is derivative carboxylic acid, is pharmacological inactive. Two other metabolites which in an organism are formed in insignificant quantity have some diuretic activity, but their concentration is not enough to have any significant clinical effect.

Removal

The elimination half-life (T1/2) of a torasemid at healthy volunteers makes 4 h.

About 80% from accepted in inside doses are removed by kidneys in the form of metabolites and near

20% in an invariable look (at patients with normal function of kidneys).

The general clearance of a torasemid makes 41 ml/min. and renal clearance - about 10 ml/min.,

what corresponds to about 25% of the general.

Pharmacokinetics in special clinical cases

At patients with chronic heart failure in a stage of a decompensation the hepatic and renal clearance of drug is reduced. At such patients, the general clearance of a torasemid is 50% less, than at healthy volunteers, аТ 1/2 and the general bioavailability, respectively, higher.

At patients with a renal failure, the renal clearance of a torasemid is considerably reduced, but it does not affect the general clearance of drug. The diuretic effect at a renal failure can be reached by use of high doses of drug. The general clearance of a torasemid and T1/2 remain at the same level in case of reduced function of kidneys, due to metabolism in a liver.

At patients with cirrhosis of Vd, T1/2 and renal clearance of drug are raised, but the general clearance remains invariable.

The pharmacokinetic profile of a torasemid at elderly patients is similar to that at young patients, behind that exception that decrease in renal clearance of drug because of characteristic age disturbance of depression of function of kidneys at elderly patients takes place. The general clearance иТ 1/2 at the same time do not change.

Indications to use:

• An edematous syndrome of various genesis, including at chronic heart failure, liver diseases, and kidneys;
• arterial hypertension.

Route of administration and doses:

To accept inside. Tablets are swallowed entirely, without chewing, washing down with liquid. A pill can be taken in any convenient constant time, irrespective of meal.

Edematous syndrome at chronic heart failure

The usual initial dose makes 10-20 mg inside once a day. If necessary the dose can be doubled before obtaining required effect.

Edematous syndrome at a disease of kidneys

The usual initial dose makes 20 mg inside once a day. If necessary the dose can be doubled before obtaining required effect.

Edematous syndrome at a liver disease

The usual initial dose makes 5-10 mg inside once a day together with drugs antagonists of Aldosteronum or kaliysberegayushchy diuretics. If necessary the drug dose Britomar can be doubled before obtaining required effect.

The single dose more than 40 mg since its action is not studied is not recommended. Drug is appointed to the long period or until disappearance of hypostases.

Arterial hypertension

The usual initial dose makes 5 mg once a day.

In the absence of an adequate lowering of arterial pressure within 4-6 weeks the dose is increased to 10 mg once a day. If this dose does not give required effect, it is necessary to add hypotensive drug of other group to the medical scheme.

Psshchiyentam of advanced age of dose adjustment is not required,

Admission of a dose: In case of the admission of the next dose it is impossible to accept a double dose of drug. It is necessary to accept the forgotten dose at once. The following dose is accepted in usual time next day.

Features of use:

To apply strictly on doctor's orders.

Patients with hypersensitivity to streptocides and derivatives of sulphonylurea can have cross sensitivity to drug Britomar. At patients, especially in an initiation of treatment drug Britomar and elderly people, is recommended to carry out control of electrolytic balance, volume and concentration of the circulating blood.

At prolonged treatment by drug Britomar is recommended to carry out regular control of electrolytic balance (especially potassium level), glucose, uric acid, creatinine, lipids and cellular components of blood.

To the patients receiving high doses of drug Britomar in order to avoid development of a hyponatremia and a metabolic alkalosis it is inexpedient to limit consumption of table salt.

Risk of a hypopotassemia the greatest at patients with the cirrhosis expressed by a diuresis at insufficient consumption of electrolytes with food, and also at simultaneous treatment by corticosteroids or AKTG.

The increased risk of development of disturbances of water and electrolytic balance is noted at patients with a renal failure. During course treatment it is necessary to control periodically concentration of electrolytes of a blood plasma (including sodium, calcium, potassium, magnesium), an acid-base state, residual nitrogen, creatinine, uric acid and to carry out if necessary the corresponding correctional therapy (with bigger frequency rate at patients with frequent vomiting and against the background of parenterally entered liquids).

At patients with the developed water and electrolytic frustration, a hypovolemia or prerenalny azotemia data of laboratory analyses can include: hyper - or a hyponatremia, hyper - or a hypochloraemia, hyper - or a hypopotassemia, disturbances of acid-base balance and increase in level of urea of blood. At emergence of these frustration, it is necessary to stop administration of drug Britomar before recovery of normal values, and then to resume treatment by drug Britomar in a smaller dose. At emergence or strengthening of an azotemia and oliguria in patients with the serious progressing illness of kidneys, it is recommended to suspend treatment. Selection of the mode of doses by the patient with ascites against the background of cirrhosis, it is necessary to carry out in stationary conditions (disturbances of water and electrolytic balance can entail development of a hepatic coma). Regular control of electrolytes of a blood plasma is shown to this category of patients.

For prevention of a hypopotassemia use of drugs of potassium and kaliysberegayushchy diuretics is recommended (first of all Spironolactonum), and also to keep to the diet rich with potassium.

Drug use Britomar can cause an exacerbation of gout.

Periodic control of concentration of glucose in blood and urine is required from patients with a diabetes mellitus or with reduced tolerance to glucose.

At patients with a prostate hyperplasia, narrowing of ureters control of a diuresis in connection with a possibility of an acute ischuria is necessary.

At patients with diseases of cardiovascular system, especially, accepting cardiac glycosides, the hypopotassemia caused by diuretics can become the reason of development of arrhythmias.

Influence on ability to manage vehicles and mechanisms

During treatment it is necessary to avoid occupations potentially dangerous types of activity requiring special attention and speed of psychomotor reactions.

Side effects:

Classification of the undesirable side reactions (USR) by development frequency:
very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); seldom (> 1/10 Ltd companies, <1/1 Ltd companies); very seldom (1/10 Ltd companies, including separate messages); frequency is unknown (it is impossible to estimate on the basis of the available data).

Disturbances from a metabolism and food:

Infrequently: a hypercholesterolemia (increase of level of cholesterol in blood), a gipertriglitseridemiya (increase of level of triglycerides in blood), a polydipsia (the increased thirst).

Disturbances from a nervous system:

Often: dizziness, headache, drowsiness.

Infrequently: myotonia of the lower extremities.

Frequency is not known: confusion of consciousness, a syncope, paresthesias in extremities (feeling of numbness, "crawlings of goosebumps" and a pricking),

Disturbances from cardiovascular system:

Infrequently: premature ventricular contraction (disturbance of a heart rhythm), tachycardia (increase in heart rate), the strengthened heartbeat, face reddening. Frequency is not known: excessive arterial hypotension, a deep vein thrombosis (formation of clots), a thromboembolism, a hypovolemia (reduction of volume of the circulating blood).

Disturbances from respiratory system, bodies of a thorax and a mediastinum:

Infrequently: nasal bleedings.

Disturbances from the alimentary system:

Often: diarrhea.

Infrequently: abdominal pain, meteorism.

Frequency is not known: nausea, vomiting, appetite loss, pancreatitis, dispepsichesky frustration.

Disturbances from kidneys and urinary tract:

Often: increase in frequency of an urination, a polyuria (the increased formation of urine), a nocturia (increase of an urination at night). Infrequently: the speeded-up desires to an urination.

Frequency is not known: an ischuria (at patients with obstruction of urinary tract), increase in concentration of urea and creatinine in blood, the General frustration and disturbances in an injection site:

Infrequently: adynamy (exhaustion), thirst, weakness, increased fatigue, hyperactivity, nervousness. Laboratory and tool data:

Infrequently: increase in number of thrombocytes.

Frequency is not known: a hyperglycemia (increase in concentration of glucose in blood), hyperuricemias (increase in concentration of uric acid in blood serum), a hypopotassemia (decrease in content of potassium in blood), decrease in concentration of cellular components of blood (erythrocytes, leukocytes and thrombocytes), small increase in concentration of an alkaline phosphatase in blood, increase in activity of some "hepatic" enzymes (for example, gamma GT), a hyponatremia, a hypochloraemia, a metabolic alkalosis.

Disturbances from an organ of sight Frequency is not known: vision disorders,

Disturbances from an acoustic organ and labyrinth disturbances

Frequency is not known: a ring in ears and a hearing loss (has, as a rule, reversible character),

Disturbances from skin and hypodermic fabrics

Frequency is not known: skin reactions (skin itch, rash, photosensitization).

If any of the side effects specified in the instruction are aggravated or any other side effects which are not specified in the instruction were noticed it is necessary to report about it to the doctor.

Interaction with other medicines:

Torasemid increases toxicity of cardiac glycosides.

At a concomitant use with mineralo-and glucocorticoids, purgatives increase in removal of potassium is possible.

Torasemid strengthens effect of hypotensive drugs.

Torasemid, especially in high doses, can strengthen nephrotoxic and ototoksichesky effect of aminoglycosides, antibiotics, drugs of platinum (Pt), cephalosporins. Torasemid can strengthen action of kurarepodobny muscle relaxants and theophylline. At use of salicylates in high doses their toxic action can amplify.

Torasemid weakens effect of hypoglycemic drugs.

The consecutive or concomitant use of a torasemid with inhibitors of the angiotensin-converting enzyme (ACE) can lead to short-term falling of arterial pressure. It can be avoided, having reduced an initial dose of APF inhibitor or having lowered a dose of a torasemid (or having temporarily cancelled it).

Non-steroidal anti-inflammatory drugs (NPVS) and пробенецид can reduce diuretic and hypotensive action of a torasemid.

Bioavailability and as a result, efficiency of a torasemid can be reduced at joint therapy with Colestyraminum.

Torasemid can increase toxicity of drugs of lithium (Li+) and ototoxicity of etakripovy acid.

Contraindications:

• hypersensitivity to a torasemid or to any of drug components; at patients with an allergy to sulfonamides (sulfanamide antimicrobic means or drugs of sulphonylurea) the cross allergy on торасемид can be noted;
• anury;
• hepatic coma and prekoma;
• refractory hypopotassemia; refractory hyponatremia;
• dehydration;
• sharply expressed disturbances of outflow of urine of any etiology (including hemilesion of urinary tract);
• digitalis intoxication;
• acute glomerulonephritis;
• sinuatrial and AV blockade of P-Sh of degree;
• age up to 18 years (safety and efficiency at children are not studied);
• pregnancy;
• intolerance of a galactose, deficit of lactase or glyukozo-galaktozny malyabsobtion.

With care
• arterial hypotension;
• a hypovolemia (with arterial hypotension or without it)
• urine outflow disturbances (benign hyperplasia of a prostate, urethrostenosis or hydronephrosis);
• ventricular arrhythmia in the anamnesis;
• acute myocardial infarction (increase in risk of development of cardiogenic shock);
• diarrhea;
• pancreatitis;
• a diabetes mellitus (decrease in tolerance to glucose);
• the liver diseases which were complicated by cirrhosis and ascites, a renal failure, a gepatorenalny syndrome;
• gout, hyperuricemia;
• anemia,
• simultaneous use of cardiac glycosides, amnoglikozid or cephalosporins, corticosteroids or adrenocorticotropic hormone (AYuT);
• gipokalemiya;
• hyponatremia,
• lactation period.

Use during pregnancy and breastfeeding

Torasemid has no teratogenic effect and a fetotoksichnost, gets through a placental barrier, causing disturbances of water and electrolytic exchange and thrombocytopenia in a fruit.

Britomar is not recommended to use drug during pregnancy.

It is unknown whether gets торасемид into breast milk. Drug Britomar in the period of a lactation (breastfeeding) has to be appointed with care.

Overdose:

Symptoms: excessively raised diuresis which is followed by decrease in OTsK and disturbance of electrolytic balance of blood with the subsequent expressed lowering of arterial pressure, drowsiness and confusion of consciousness, a collapse. Gastrointestinal frustration can be observed.

Treatment: there is no specific antidote. Provocation of vomiting, gastric lavage, absorbent carbon. A symptomatic treatment, a dose decline or drug withdrawal and at the same time completion of OTsK and indicators of water and electrolytic balance and an acid-base state under control of serumal concentration of electrolytes, a hematocrit, a symptomatic treatment.

The hemodialysis is not effective since removal of a torasemid and its metabolites does not accelerate.

Storage conditions:

In the place protected from light, at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity 3 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action of 5 mg and 10 mg.
On 15 tablets in PVC/PVDH / the blister Is scarlet; 1 and 2 blisters with the application instruction place in a cardboard pack.