Talipres Asino tablets 25 mg blister No. 30

Instructions for use Talipres Asino tablets 25 mg blister No. 30

Composition

active ingredient: chlortalidone;

1 tablet contains 25 mg or 50 mg of chlorthalidone (calculated as 100% dry substance chlorthalidone);

Excipients: lactose monohydrate; microcrystalline cellulose; colloidal anhydrous silica; magnesium stearate; hypromellose; sodium starch glycolate.

Dosage form

Pills.

Main physicochemical properties:

Talipres® Asino, tablets, 25 mg: white or almost white, round tablets with a biconvex surface;

Talipres® Asino, tablets, 50 mg: white or almost white, flat-cylindrical tablets, with a bevel and a score on one side.

Pharmacotherapeutic group

Diuretics. Non-thiazide diuretics with moderate activity. Sulfonamides, simple. ATX code C03B A04.

Pharmacological properties

Pharmacodynamics.

Chlorthalidone is a diuretic that belongs to the long-acting benzothiosides (thiazides).

Chlorthalidone primarily increases electrolyte excretion, followed by increased urinary water excretion through osmotic mechanisms.

Chlorthalidone slows down the reabsorption of sodium, mainly in the distal tubules, so that about 15% of the sodium filtered by the glomeruli can be excreted. The rate of chloride excretion is similar to that of sodium excretion. Chlorthalidone also increases the excretion of potassium, which is mainly determined by the secretion of potassium in the distal tubules and collecting ducts (increased exchange between sodium and potassium ions).

High doses of chlorthalidone may cause increased bicarbonate excretion through inhibition of carbonic anhydrase, which alkalizes the urine.

Acidosis or alkalosis have no significant effect on the saluretic or diuretic effects of chlorthalidone. With prolonged therapy with chlorthalidone, renal calcium excretion is reduced, which may lead to hypercalcemia.

The diuretic effect occurs 2–3 hours after administration, reaches a maximum after 4–24 hours, and can persist for 2–3 days.

Chlorthalidone-induced diuresis leads to a decrease in plasma volume, cardiac output, and systemic blood pressure. In patients with hypertension, chlorthalidone reduces blood pressure. The antihypertensive effect of chlorthalidone occurs at the beginning of therapy due to a decrease in extracellular fluid volume and, as a result, a decrease in peripheral resistance. With prolonged treatment, the extracellular volume normalizes and the antihypertensive efficacy is maintained, which may be due to a later decrease in the concentration of sodium in the vascular walls and, thus, a decrease in sensitivity to norepinephrine.

Chlorthalidone has an antidiuretic effect in patients with nephrogenic diabetes insipidus. The mechanism of action is not yet clear.

Chlorthalidone is ineffective in patients with severe renal impairment (creatinine clearance below 30 ml/min and/or serum creatinine above 1.8 mg/100 ml).

Pharmacokinetics.

Absorption

Chlorthalidone is absorbed from the gastrointestinal tract relatively slowly (t50 of absorption is approximately 2.6 hours). The bioavailability of an oral dose of 50 mg of chlorthalidone is approximately 64%, with peak blood concentrations occurring 8–12 hours after administration.

Distribution

The binding of chlorthalidone to plasma proteins is approximately 75%, the volume of distribution is 4 l/kg. Only a small part of free chlorthalidone is found in the blood due to the high accumulation in erythrocytes and binding to plasma proteins.

Metabolism and excretion

Within 120 hours after administration, approximately 70% of the dose is excreted in the urine and feces, mainly unchanged. Hepatic metabolism and biliary excretion constitute a minor part of the elimination pathway. The half-life is on average 50 hours.

Special patient groups

The elimination of chlorthalidone is slowed in elderly patients compared to healthy young volunteers, although absorption is similar.

Chlorthalidone crosses the placental barrier and enters breast milk.

Indication

Treatment:

• arterial hypertension;
• cardiac, hepatic and nephrogenic edema;
• chronic heart failure;
• nephrogenic diabetes insipidus when other pharmacotherapy is not suitable.

Contraindication

• Hypersensitivity to chlorthalidone, other thiazides and sulfonamide derivatives (possibility of cross-reactions, use with caution in patients with bronchial asthma) or to any of the components of the drug;
• anuria (diuresis less than 100 ml/day);
• severe renal failure (significantly reduced diuresis, creatinine clearance <30 ml/min and/or serum creatinine more than 1.8 mg/100 ml);
• glomerulonephritis;
• severe liver failure (hepatic precoma and coma);
• hypercalcemia;
• therapy-resistant hypokalemia or conditions with increased potassium loss;
• severe hyponatremia;
• symptomatic hyperuricemia.

Interaction with other medicinal products and other types of interactions

Not recommended combinations

Concomitant use of chlorthalidone and lithium leads to increased cardio- and neurotoxic effects of lithium due to reduced lithium excretion. If diuretic therapy is essential, careful monitoring of lithium blood levels and dose adjustment are required.

Combinations requiring special precautions

Drugs that can cause torsade de pointes:

• Class Ia antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide);
• class III antiarrhythmics (e.g. amiodarone, sotalol);
• certain antipsychotics: phenothiazines (e.g. chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (e.g. amisulpiride, sulpiride, sultopride, tiapride), butyrophenones (e.g. droperidol, haloperidol);
• others: bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine IV.

Concomitant administration of these drugs with chlorthalidone, especially in the presence of hypokalemia, increases the risk of ventricular arrhythmias, especially torsade de pointes. Before using the above drugs simultaneously with chlorthalidone, it is necessary to determine and correct the serum potassium level. Regular ECG monitoring and determination of plasma electrolyte levels are necessary. In the presence of hypokalemia, it is recommended to use drugs that do not cause torsade de pointes.

ACE inhibitors (e.g., captopril, enalapril)

Concomitant use of chlorthalidone and ACE inhibitors (e.g. captopril, enalapril), especially at the beginning of treatment, may result in a significant decrease in blood pressure and deterioration of renal function. Therefore, diuretic therapy should be discontinued 2-3 days before starting treatment with an ACE inhibitor to reduce the likelihood of hypotension at the beginning of therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g. indomethacin, acetylsalicylic acid), including COX-2 inhibitors, salicylates

NSAIDs (e.g. indomethacin, acetylsalicylic acid), including COX-2 inhibitors and salicylates, may reduce the antihypertensive and diuretic effects of chlorthalidone. When using high doses of salicylates, the toxic effects of salicylates on the central nervous system may be enhanced. If patients develop hypovolemia during chlorthalidone therapy, concomitant use of NSAIDs may provoke acute renal failure.

Kaliuretic diuretics (e.g., furosemide), glucocorticoids, adrenocorticotropic hormone (ACTH), carbenoxolone, penicillin G, salicylates, stimulant laxatives, amphotericin B (parenteral)

Concomitant use of chlorthalidone and these medicinal products may lead to electrolyte imbalance, in particular increased potassium loss. This is particularly important during concomitant treatment with cardiac glycosides. Plasma potassium levels should be monitored regularly and, if necessary, corrected.

Other diuretics, other antihypertensive agents (e.g. beta-blockers, calcium channel blockers, ACE inhibitors, vasodilators, methyldopa, guanethidine), nitrates, barbiturates, phenothiazines, tricyclic antidepressants, alcohol

The hypotensive effects of chlorthalidone may be enhanced by the use of these drugs or by the consumption of alcohol.

Cardiac glycosides

If hypokalemia and/or hypomagnesemia develop during the simultaneous use of chlorthalidone with cardiac glycosides, the sensitivity of the myocardium to cardiac glycosides increases, and the effects and side effects of cardiac glycosides are accordingly enhanced.

Interactions with the following medications are also possible:

Insulin, oral antidiabetic agents, uric acid lowering agents, sympathomimetics (noradrenaline [norepinephrine], adrenaline [epinephrine])

The effects of these drugs may be reduced when used concomitantly with chlorthalidone. Dosage adjustments of insulin and oral antidiabetic drugs may be required.

Non-depolarizing (curare-like) muscle relaxants (e.g., tubocurarine)

The effect of curare-like muscle relaxants may be enhanced or prolonged by chlorthalidone. If chlorthalidone cannot be discontinued prior to the use of curare-like muscle relaxants, the anaesthetist should be informed of the chlorthalidone treatment.

Cytostatics (e.g. cyclophosphamide, fluorouracil, methotrexate)

Chlorthalidone may reduce the renal excretion of cytostatics (e.g. cyclophosphamide, fluorouracil, methotrexate). With simultaneous use of cytostatics, increased bone marrow toxicity (especially the development of granulocytopenia) can be expected.

Cholestyramine, colestipol

Concomitant use of cholestyramine or colestipol reduces the absorption of chlorthalidone.

Therefore, chlorthalidone should be taken at least one hour before or 4-6 hours after taking these medications.

Calcium salts, vitamin D

Concomitant use of chlorthalidone and calcium or vitamin D may increase serum calcium levels due to decreased excretion.

Allopurinol

Chlorthalidone may enhance hypersensitivity reactions to allopurinol.

Amantadine

Chlorthalidone may increase the risk of side effects of amantadine.

There is an increased risk of hyperglycemia with the concomitant use of chlorthalidone and beta-blockers or diazoxide.

Cyclosporine

Concomitant use of cyclosporine may increase the risk of hyperuricemia and gouty complications.

Anticholinergics (e.g., atropine, biperidine)

Anticholinergic drugs (e.g. atropine, biperidine) may increase the bioavailability of thiazide diuretics, presumably by reducing gastrointestinal motility and slowing gastric emptying.

Application features

Kidney dysfunction

Chlorthalidone should be used with caution in patients with kidney disease.

In patients with mild to moderate renal impairment (creatinine clearance 30-60 ml/min and/or serum creatinine 1.1-1.8 mg/100 ml), the dosage should be adjusted according to therapeutic needs and tolerability (see section 4.2).

In patients with severe renal insufficiency (creatinine clearance below 30 ml/min and/or serum creatinine above 1.8 mg/100 ml), thiazide diuretics and thiazide analogues, including chlorthalidone, lose their diuretic effect (see section "Contraindications").

Thiazides may cause azotemia in patients with renal disease. Cumulative effects may occur in patients with impaired renal function. If renal failure progresses, as evidenced by an increase in total blood nitrogen without protein nitrogen, a decision should be made about the appropriateness of further treatment. Discontinuation of diuretic therapy should be considered.

Chronic diuretic abuse can lead to pseudo-Bartter syndrome, which is accompanied by the development of edema. Edema is a manifestation of increased renin levels, which leads to secondary hyperaldosteronism.

The hypotensive effect of ACE inhibitors is enhanced by drugs that increase plasma renin activity (diuretics). Therefore, diuretic therapy should be discontinued 2-3 days before treatment with an ACE inhibitor to reduce the risk of hypotension at the beginning of therapy.

Choroidal effusion, acute myopia, and secondary angle-closure glaucoma

Drugs containing sulfonamide or sulfonamide derivatives may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia, and acute angle-closure glaucoma. Symptoms include rapid onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug.

Untreated acute angle-closure glaucoma can lead to irreversible vision loss. The main treatment is to stop the medication as soon as possible. If the intraocular pressure remains uncontrolled, urgent medical or surgical treatment may be necessary. Risk factors for acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Liver dysfunction

Hortalidone should be used with caution in patients with impaired liver function or progressive liver disease, since even minor changes in water and electrolyte balance due to the effects of thiazide diuretics, especially in patients with cirrhosis, can lead to the development of hepatic coma (see section "Contraindications").

Metabolic and endocrine disorders

Patients with diabetes or gout need special attention.

Thiazide therapy may affect glucose tolerance. In patients with diabetes mellitus, metabolic disturbances may occur, which may require adjustment of the dose of insulin or oral hypoglycemic agents. Latent diabetes mellitus may become manifest during chlorthalidone therapy.

Blood uric acid levels may increase during treatment with chlorthalidone, but gout attacks rarely occur during long-term therapy.

In patients receiving long-term treatment with thiazide and thiazide-like diuretics, slight and partially reversible increases in plasma total cholesterol, low-density lipoprotein (LDL) or triglycerides have been observed.

Electrolyte disturbances

During treatment with diuretics, serum electrolytes (especially potassium, sodium, calcium) should be determined at appropriate intervals.

Continuous monitoring of serum electrolytes is particularly important in elderly patients, patients with ascites due to cirrhosis of the liver, and patients with nephrogenic edema. In such conditions, chlorthalidone should be used only under close supervision and only in patients whose serum potassium levels are within normal limits and who do not show signs of dehydration.

Thiazide diuretics, including chlorthalidone, may cause electrolyte disturbances (hypokalemia, hyponatremia, and hypochloraemic alkalosis). Signs of electrolyte disturbances include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular weakness, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

The risk of hypokalemia is greatest in patients with cirrhosis of the liver, in patients with increased diuresis, in patients without adequate electrolyte intake and in patients treated with corticosteroids, ACTH, cardiac glycosides or laxatives (see section "Interaction with other medicinal products and other types of interactions"). Such patients require careful monitoring.

As with all thiazide and thiazide-like diuretics, chlorthalidone-induced potassium loss is dose-dependent and varies in severity from person to person. At a dose of 25 mg/day, the average decrease in serum potassium is 0.5 mmol/l. During long-term treatment, serum potassium should be measured at the start of treatment and then every 3-4 weeks. Thereafter, in the absence of other factors affecting potassium levels (e.g. vomiting, diarrhoea, changes in renal function), serum potassium levels may be measured every 4-6 months.

If necessary, chlorthalidone can be combined with oral potassium-containing preparations or potassium-sparing diuretics (e.g. triamterene). In the case of combination therapy, serum potassium levels should be monitored. If hypokalemia is accompanied by clinical symptoms (e.g. muscle weakness, paresis and ECG changes), chlorthalidone should be discontinued.

The combination of chlorthalidone and potassium or potassium-sparing diuretics should not be used in patients receiving ACE inhibitors unless the combination is considered essential.

In hot weather, patients with edema may develop dilutional hyponatremia. Chloride deficiency is usually mild and does not require treatment.

Thiazide and thiazide-like diuretics, including chlorthalidone, may reduce urinary calcium excretion and cause a transient and minor increase in serum calcium without known disturbances of calcium metabolism. Significant hypercalcemia may be a sign of latent hyperparathyroidism. Chlorthalidone should be discontinued before testing parathyroid function.

Thiazide and thiazide-like diuretics have been shown to increase urinary magnesium excretion. This may lead to hypomagnesemia.

Heart failure

In patients with severe heart failure, the absorption of chlorthalidone may be reduced.

Others

Hypersensitivity reactions may occur in patients with a history of allergy or bronchial asthma or without a significant allergic history.

Special precautions

During chlorthalidone therapy, serum electrolytes (especially potassium, sodium, calcium ions), creatinine and urea, lipids (cholesterol and triglycerides), uric acid and blood glucose levels should be regularly checked.

Patients should be advised to drink plenty of fluids during treatment with chlorthalidone and to eat foods rich in potassium (bananas, vegetables, nuts) due to increased potassium loss.

Treatment of high blood pressure with chlorthalidone requires regular medical check-ups.

Chlorthalidone therapy should be discontinued if:

• therapy-resistant electrolyte imbalances;
• hypersensitivity reactions;
• pronounced complaints from the gastrointestinal tract;
• central nervous system disorders;
• pancreatitis;
• disorders of the blood system (anemia, leukopenia, thrombocytopenia);
• acute cholecystitis;
• the occurrence of vasculitis;
• exacerbation of existing myopia;
• serum creatinine levels above 1.8 mg/100 ml or creatinine clearance below 30 ml/min.

Doping use

The use of chlorthalidone may lead to positive doping control results. It is not possible to exclude negative consequences and serious health risks from the use of chlorthalidone as a doping agent.

Excipients

Talipres® Acin tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

Pregnancy

Chlorthalidone should not be used during pregnancy or breastfeeding.

Chlorthalidone, like other diuretics, may reduce placental blood flow. Thiazides and thiazide derivatives also penetrate the fetal circulation and may cause electrolyte disturbances. There are reports of neonatal thrombocytopenia associated with the use of thiazide diuretics.

Breastfeeding period

Chlorthalidone passes into breast milk. Breastfeeding women should not take chlorthalidone or should refrain from breastfeeding.

Ability to influence reaction speed when driving vehicles or other mechanisms

Due to the occurrence of various individually determined reactions, a violation of the reaction speed is possible, which may lead to the inability to actively participate in traffic, drive machinery or work without stable support. This is especially pronounced at the beginning of treatment, when increasing the dose, in combination with other antihypertensive agents, when changing drugs and when taken simultaneously with alcohol.

Method of administration and doses

Dosage depends on the clinical picture and the patient's response to therapy. It is recommended to use the lowest effective dose. In patients with ischemic disease or cerebral atherosclerosis, as well as after a heart attack or stroke, gradual dose adjustment is recommended.

Chlorthalidone should be taken orally with sufficient liquid (1 glass of water). If a single dose is prescribed by the doctor, take it in the morning with breakfast or in the morning and evening in the case of a double dose. If necessary, the dose should be increased no earlier than after 2-3 weeks.

The duration of use is determined by your doctor. After prolonged use, chlorthalidone should not be stopped suddenly, but the dose should be gradually reduced.

Edema of cardiac, hepatic or renal origin and heart failure

The recommended initial dose is 50-100 mg per day, the maximum daily dose is 200 mg (since higher doses do not enhance the effect), the maintenance dose is 25-50 mg of chlorthalidone per day.

Arterial hypertension

The initial dose is 12.5*-50 mg per day, the maintenance dose is 12.5*-25 mg of chlorthalidone per day.

The initial dose should be reduced individually in each case.

Nephrogenic diabetes insipidus

The initial dose is 100 mg 2 times a day, but with further therapy, the daily maintenance dose may be reduced to 50 mg per day.

Elderly patients (65 years and older) and patients with renal impairment

In elderly patients and/or in patients with mild to moderate renal impairment (creatinine clearance 30-60 ml/min and/or serum creatinine 1.1-1.8 mg/dL), the dosage should be adjusted according to therapeutic requirements and tolerability. Thiazide and thiazide-like diuretics and thiazide analogues, including chlorthalidone, lose their diuretic effect at creatinine clearance <30 ml/min and/or serum creatinine above 1.8 mg/dL (see section 4.3).

Patients with liver dysfunction

The dose of chlorthalidone in patients with hepatic impairment should be titrated according to the condition. Chlorthalidone should not be used in severe hepatic impairment (see section 4.3).

Patients with heart failure

In patients with decompensated heart failure, chlorthalidone is practically not absorbed.

*use chlorthalidone preparations in the appropriate dosage.

Children.

Experience with the drug in the pediatric population is limited, therefore chlorthalidone should not be used in children.

Overdose

Symptoms of overdose

The clinical picture of acute or chronic overdose depends on the degree of fluid and electrolyte loss.

The following symptoms may occur:

dizziness and weakness, nausea, drowsiness, muscle pain and muscle spasms (e.g., calf muscle cramps), headache, tachycardia, hypotension, orthostatic and electrolyte disturbances (hypokalemia and/or hyponatremia).

Dehydration and hypovolemia can cause hemoconcentration, seizures, drowsiness, lethargy, confusion, collapse, and acute renal failure.

Hypokalemia can cause fatigue, muscle weakness, paresthesia, paresis, apathy, flatulence and constipation or cardiac arrhythmia. Significant loss of potassium can cause paralytic ileus or loss of consciousness up to hypokalemic coma.

Treatment. If there are signs of overdose, treatment should be stopped immediately. In addition to general measures, vital signs should be monitored and, if necessary, corrected in intensive care. There is no specific antidote for chlorthalidone. If the patient is conscious, gastric lavage should be performed, and sorbents should be administered to reduce absorption. According to clinical indications, intravenous administration of fluids and electrolytes, monitoring of blood pressure, water and electrolyte balance and metabolic functions may be required.

Side effects

Adverse reactions were classified by system organ class and frequency of occurrence.

The frequency of adverse reactions is defined as follows:

very common (≥1/10); common (≥1/100 - <1/10); uncommon (≥1/1000 - <1/100); rare (≥1/10000 - <1/1000); very rare (<1/10000); frequency unknown (frequency cannot be estimated from the available data).

From the blood and lymphatic system: rarely - thrombocytopenia, leukopenia, agranulocytosis and eosinophilia.

Metabolism and nutrition: very often - hypokalemia (mainly when using high doses), hyperuricemia (may lead to exacerbation of gout), increased cholesterol and triglyceride levels in the blood; often - hyponatremia, hypomagnesemia, hyperglycemia and glycosuria, worsening of the course of the disease in patients with diabetes mellitus, manifestation of latent diabetes mellitus, increased urea and creatinine levels (especially at the beginning of treatment); rarely - hypercalcemia; very rarely - hypochloremic alkalosis.

From the nervous system: often - headache, dizziness and weakness; rarely - paresthesia.

On the part of the organs of vision: rarely - visual impairment, decreased tear production; unknown - choroidal effusion.

From the respiratory system, thoracic and mediastinal organs: very rarely - idiosyncratic (allergic) pulmonary edema, difficulty breathing.

Gastrointestinal: often - loss of appetite, dry mouth, minor gastrointestinal disorders, nausea, vomiting, pain and cramps in the upper abdomen, constipation and diarrhea; very rarely - pancreatitis.

Hepatobiliary system: rarely - intrahepatic cholestasis or jaundice.

Skin and subcutaneous tissue disorders: often - urticaria and other forms of skin rashes, itching; rarely - photosensitivity, allergic vasculitis.

Musculoskeletal and connective tissue disorders: often – muscle hypotension, muscle cramps.

On the part of the kidneys and urinary system: very rarely - allergic interstitial nephritis.

From the reproductive system and mammary glands: often - impotence.

Reporting of adverse reactions

Reporting of suspected adverse reactions after the registration of a medicinal product is important. They allow for continuous safety monitoring, as well as an assessment of the benefit/risk balance of the medicinal product.

Expiration date

2 years.

Storage conditions

Store out of the reach of children, in the original packaging at a temperature not exceeding 25 ºС.

Packaging

10 tablets in a blister; 1 or 3 blisters in a cardboard pack.

Vacation category

According to the recipe.

Producer

"Pharma Start" LLC.

Location of the manufacturer and address of its place of business.

Ukraine, 03124, Kyiv, Vaclav Havel Boulevard, 8.