Britomar, 5 mg 30 pcs.

Pharmgroup:

Diuretic agent.

Pharmic action:

Britomar is a “loop” diuretic. The main mechanism of action of the drug is due to the reversible binding of torasemide to the sodium/chlorine/potassium transporter located in the apical membrane of the thick segment of the ascending loop of Genle, resulting in a reduction or complete inhibition of sodium ion reabsorption and reduction of the osmotic pressure of intracellular fluid and water reabsorption.

Thorasemide causes hypokalemia to a lesser extent than furosemide, but it is more active and its effect is prolonged.

The diuretic effect develops within about an hour after oral administration of the drug, reaching a maximum after 3 to 6 hours, and lasts for 8 to 10 hours.

Limits systolic and diastolic BP in lying and standing position.

Pharmacokinetics:

The drug Britomar prolonged-acting tablets provide gradual release of torasemide, reducing fluctuations in its blood concentrations, compared to torasemide preparations in the dosage form of a normally-released tablet.

Intake

After multiple doses of the drug, the relative bioavailability of the prolonged form, compared to the conventional dosage form, is about 102%. The active substance is absorbed from the gastrointestinal tract with limited “first pass” effect through the liver. Cmax in plasma is reached within 1.5 h after oral administration. Food intake has no significant effect on absorption of the drug. Impaired renal and/or hepatic function has no effect on absorption of the drug.

Distribution

More than 99% of torasemide is bound to plasma proteins.

The Vd in healthy volunteers and in patients with mild to moderate renal impairment or chronic heart failure is 12 to 15 L. In patients with cirrhosis, Vd is doubled.

Metabolism

Metabolized in the liver with the participation of CYP2C9 isoenzyme to form three metabolites.

The main metabolite is a carboxylic acid derivative and is pharmacologically inactive. The other two metabolites, which are formed in small amounts in the body, have some diuretic activity, but their concentrations are too low to have any significant clinical effect.

The T1/2 of thoracemide in healthy volunteers is 4 h. About 80% of the oral dose is excreted by the kidneys as metabolites and about 20% unchanged (in patients with normal renal function). Total clearance of torasemide is 41 ml/min and renal clearance is about 10 ml/min, which corresponds to about 25% of the total.

Pharmacokinetics in special clinical cases

In patients with decompensated chronic heart failure, hepatic and renal clearance of the drug is reduced. In these patients, the total clearance of thoracemide is 50% lower than in healthy volunteers, and the T1/2 and total bioavailability are correspondingly higher.

In patients with renal insufficiency, the renal clearance of thorasemide is markedly reduced, but this is not reflected in the total clearance of the drug. Diuretic effect in renal insufficiency can be achieved by using the drug in high doses. Total clearance of Torasemide and T1/2 remain at the same level in case of reduced renal function, due to metabolism in the liver.

In patients with cirrhosis, Vd, T1/2 and renal clearance of the drug are increased, but total clearance remains unchanged.

The pharmacokinetic profile of thoracemide in elderly patients is similar to that in younger patients, with the exception that there is a decrease of renal clearance due to the characteristic age-related impairment of renal function in elderly patients. Total clearance and T1/2 are unchanged.

Indications

Edema syndrome of different genesis, including chronic heart failure, liver and kidney disease; arterial hypertension.

Active ingredient

Composition

1 tablet contains:

Active ingredient:

torasemide 5 mg;

Associates:

Guar gum, 3.4 mg;

Corn starch, 30.77 mg;

Colloidal silicon dioxide – 0.42 mg;

Magnesium stearate – 0.25 mg;

Lactose monohydrate – up to 85 mg.

How to take, the dosage

Ingestion.

The tablets are swallowed whole, without chewing, with liquids. The pills can be taken at any convenient fixed time, regardless of meals.

Oedema syndrome in chronic heart failure. The usual initial dose is 10-20 mg orally once a day. If necessary, the dose can be doubled until the desired effect is achieved.

Oedema syndrome in kidney disease. The usual starting dose is 20 mg orally once a day. If necessary, the dose can be doubled until the desired effect is achieved.

Oedema syndrome in liver disease. The usual starting dose is 5-10 mg orally once daily along with aldosterone antagonists or potassium-saving diuretics. If necessary, the dose of Britomar can be doubled until the desired effect is achieved. A single dose of more than 40 mg is not recommended, since its effect has not been studied. The drug is prescribed for a long period or until edema disappears.

Hypertension. The usual starting dose is 5 mg once a day.

If there is no adequate BP reduction within 4-6 weeks, the dose is increased to 10 mg once daily. If this dose does not give the desired effect, a hypotensive drug of another group should be added to the treatment regimen.

There is no need for dose adjustment in elderly patients.

Dose skipping: If the next dose is missed, do not take a double dose of the drug. The forgotten dose should be taken immediately. The next dose is taken at the usual time the next day.

Interaction

Torasemide increases toxicity of cardiac glycosides.

In concomitant use with mineral and glucocorticoids, laxatives may increase potassium excretion.

Torasemide increases the effect of hypotensive drugs.

Thorasemide, especially in high doses, may increase the nephrotoxic and ototoxic effects of aminoglycosides, antibiotics, platinum (Pt) drugs, cephalosporins. Torasemide may increase the effect of curare-like muscle relaxants and theophylline. When using salicylates in high doses their toxic effects may increase.

Torasemide weakens the effect of hypoglycemic drugs.

The sequential or simultaneous use of thorasemide with angiotensin-converting enzyme inhibitors (ACE) may lead to a transient drop in blood pressure. This can be avoided by reducing the starting dose of the ACE inhibitor or by reducing the dose of thorasemide (or temporarily withdrawing it).

Non-steroidal anti-inflammatory drugs (NSAIDs) and probenecid may decrease the diuretic and hypotensive effects of thoracemide.

The bioavailability and, consequently, the effectiveness of thoracemide may be reduced when co-therapy with colestyramine.

The toxicity of lithium preparations (Li+) and the ototoxicity of etacrypic acid may be increased by torasemide.

Special Instructions

The drug should be used strictly on prescription.

Patients with hypersensitivity to sulfonamides and sulfonylurea derivatives may have cross-sensitivity to Britomar. In patients, especially at the beginning of treatment with Britomar and elderly individuals, monitoring of electrolyte balance, circulating blood volume and concentration is recommended.

In long-term treatment with Britomar, regular monitoring of electrolyte balance (especially potassium levels), glucose, uric acid, creatinine, lipids and cellular blood components is recommended.

Patients receiving Britomar at high doses should not limit their intake of table salt to avoid the development of hyponatremia and metabolic alkalosis.

The risk of hypokalemia is greatest in patients with cirrhosis, marked diuresis, inadequate dietary electrolyte intake, and concurrent treatment with corticosteroids or ACTH.

The increased risk of development of water-electrolyte balance disorders is noted in patients with renal insufficiency. During the course of treatment it is necessary to monitor periodically the concentration of plasma electrolytes (including sodium, calcium, potassium, magnesium), acid-base status, residual nitrogen, creatinine, uric acid and if necessary carry out the appropriate corrective therapy (with greater frequency in patients with frequent vomiting and with parenteral administration of fluids).

In patients with developed water-electrolyte disorders, hypovolemia or prerenal azotemia the laboratory data may include: hyper- or hyponatremia, hyper- or hypochloremia, hyper- or hypokalemia, acid-base balance disorders and increased blood urea level. If these disorders occur, discontinue Britomar until normal values are restored, and then resume treatment with Britomar at a lower dose. If azotemia and oliguria appear or worsen in patients with severe progressive renal disease, it is recommended that treatment be suspended.

The dosage regimen of patients with ascites against liver cirrhosis should be chosen under hospital conditions (disorders of water-electrolyte balance may lead to hepatic coma). Regular monitoring of plasma electrolytes is indicated for this category of patients.

In order to prevent hypokalemia the use of potassium preparations and potassium-saving diuretics (especially spironolactone) is recommended, as well as the observance of a diet rich in potassium.

The use of the drug Britomar may cause an aggravation of gout.

In patients with diabetes mellitus or with reduced glucose tolerance, periodic monitoring of blood and urine glucose concentrations is required.

In patients with prostatic hyperplasia, ureteral narrowing, diuresis control is necessary due to the possibility of acute urinary retention.

In patients with cardiovascular disease, especially those taking cardiac glycosides, diuretic-induced hypokalemia may cause arrhythmias.

Contraindications

Side effects

Metabolic disorders: infrequent – hypercholesterolemia (increase in blood cholesterol levels), hypertriglyceridemia (increase in blood TG levels), polydipsia (increased thirst).

Nervous system disorders: frequently – dizziness, headache, somnolence; infrequently – cramps of the lower extremities; frequency is unknown – mental confusion, fainting, paresthesia in extremities (feeling of numbness, “creeping shivers” and tingling).

Cardiovascular system disorders: infrequent – extrasystole (heart rhythm disorders), tachycardia (increased heart rate), palpitations, red face; frequency is not known – excessive arterial hypotension, deep vein thrombosis (blood clots formation), thromboembolism, hypovolemia (decrease of the blood circulation).

Respiratory system disorders: infrequent – nasal bleeding.

The digestive system: frequent – diarrhea; infrequent – abdominal pain, flatulence; frequency unknown – nausea, vomiting, loss of appetite, pancreatitis, dyspeptic phenomena.

Renal and urinary tract disorders: often – increased frequency of urination, polyuria (increased urine production), nycturia (increased frequency of urination at night); infrequent – frequent urge to urinate; frequency unknown – urinary retention (in patients with urinary obstruction), increased concentration of urea and creatinine in blood.

Laboratory measures: infrequent – increased platelet count; frequency unknown – hyperglycemia, hyperuricemia, hypokalemia, decreased number of erythrocytes, leukocytes and platelets, slightly increased ALP activity in blood, increased activity of some liver enzymes (e.g., GGT), hyponatremia, hypochloremia, metabolic alkalosis.

Senses: frequency is unknown – visual disturbances, tinnitus and hearing loss (usually reversible).

Skin disorders: frequency unknown – skin itching, rash, photosensitization.

Others: infrequent – asthenia (exhaustion), weakness, thirst, hyperactivity, nervousness, increased fatigue.

Overdose

Symptoms: excessively increased diuresis accompanied by decreased CBC and disturbed electrolyte balance of the blood, followed by a pronounced decrease in BP, drowsiness and confusion, collapse. Gastrointestinal disorders may be observed.

Treatment: there is no specific antidote. Provocation of vomiting, gastric lavage, activated charcoal. Treatment is symptomatic, dose reduction or discontinuation of the drug and simultaneous refilling of the blood circulation and correction of the parameters of water-electrolyte balance and acid-base state under control of serum concentrations of electrolytes, hematocrit.

Hemodialysis is ineffective because excretion of torasemide and its metabolites is not accelerated.

Similarities