Veroshpiron capsules 50mg №10×3

Name Veroshpiron tabl 25mg in bl. in pack. No. 20×1 The main active ingredient Spironolactone Release formCapsule CompositionVeroshpiron capsules 50 mg Each capsule contains: Active ingredient: spironolactone 50 mg Excipients: sodium lauryl sulfate, magnesium stearate, corn starch, lactose monohydrate Capsule shell Upper part of the capsule: quinoline yellow (E 104), titanium dioxide (E 171), gelatin The lower part of the capsule: titanium dioxide (E 171), gelatin Veroshpiron capsules 100 mg Each capsule contains: Active ingredient: spironolactone 100 mg Excipients: sodium lauryl sulfate, magnesium stearate, corn starch, lactose monohydrate Capsule shell Upper part capsules: sunset yellow (E 110), titanium dioxide (E 171), gelatin Lower part of the capsule: sunset yellow (E 110), titanium dioxide (E 171), quinoline yellow (E 104), gelatin : hard gelatin, size #3 Top: opaque, yellow Bottom: opaque, white Veroshpiron capsules 100 mg Capsule: hard gelatin, size No. 0 Upper part: opaque, orange Lower part: opaque, yellow Dosage 50 mg and 100 mg Pharmacological properties Pharmacodynamics Pharmacodynamics Spironolactone is a competitive aldosterone antagonist. In the distal nephron, spironolactone prevents aldosterone from retaining sodium and water and inhibits potassium excretion under the action of aldosterone. The drug not only enhances the excretion of Na + ions, Cl – and weakens the excretion of K + ions, it also inhibits the excretion of H + ions in the urine. Due to the diuretic effect, spironolactone lowers blood pressure. The RALES Study The Aldactone Randomized Trial (RALES) was a double-blind, multicentre study conducted in 1663 patients with an ejection fraction of less than 35% who had been diagnosed with NYHA class IV heart failure within 6 months prior to enrollment and had at the time of randomization heart failure III-IV class. All patients were taking loop diuretics, 97% of patients were taking an ACE inhibitor, and 78% were taking digoxin (beta-blockers were not widely available at the time of the study, with only 15% of patients receiving beta-blockers). Patients with a baseline increase in serum creatinine greater than 2.5 mg/dL or an increase in baseline serum potassium greater than 5.0 mEq/L were excluded from the study. Patients who had an increase in serum potassium by 25% compared with baseline were also excluded from the study. Patients were randomized in a 1:1 ratio to either spironolactone 25 mg once daily or to a matching placebo group. For patients who tolerated the drug at a dose of 25 mg/day, according to clinical indications, the dose of the drug was increased to 50 mg/day. For patients who did not tolerate the drug at a dose of 25 mg / day, the dose of spironolactone was reduced to 25 mg 1 time in 2 days. The primary endpoint in the RALES study was all-cause mortality. After a median of 24 months of follow-up, the RALES trial was terminated early because a routine interim analysis found a significant reduction in mortality in the spironolactone group. Spironolactone reduced the risk of death by 30% compared with placebo (p < 0.001; 95% CI, 18% to 40%). In addition, spironolactone significantly reduced the risk of cardiac death, primarily sudden cardiac death and death from progressive heart failure, as well as the risk of hospitalization for heart disease. NYHA stage changes were more favorable in the spironolactone group. Gynecomastia and chest pain were observed in 10% of men treated with spironolactone compared with 1% of men in the placebo group (p<0.001). The incidence of severe hyperkalemia was equally low in both groups of patients. Pharmacokinetics Spironolactone is rapidly and completely absorbed from the gastrointestinal tract. Actively binds to plasma proteins (approximately 90%). Spironolactone is rapidly metabolized in the human body. The pharmacologically active metabolites of spironolactone are 7-alpha-thiomethylspironolactone and canrenone. Despite the fact that the half-life of unchanged spironolactone from the blood is short (1.3 hours), the half-life of active metabolites is longer (in the range from 2.8 to 11.2 hours). Metabolites are excreted mainly by the kidneys, small amounts are excreted through the intestines. Spironolactone and its metabolites cross the placenta and into breast milk. After fasting 100 mg of spironolactone per day for 15 days in healthy volunteers, the time to reach the maximum plasma concentration (tmax), the maximum plasma concentration (Cmax), and the half-life (t1 / 2) of spironolactone was 2.6 hours, 80 ng/ml and about 1.4 hours, respectively. For 7-alpha-thiomethylspironolactone and canrenone metabolites, tmax was 3.2 hours and 4.3 hours, Cmax was 391 ng/ml and 181 ng/ml, and t1/2 was 13.8 hours and 16.5 hours, respectively. Renal activity after a single dose of spironolactone peaks after 7 hours and persists for at least 24 hours. Indications for use Congestive heart failure in patients who do not respond to or tolerate other therapy, as well as to enhance the action of other diuretics Essential hypertension, mainly in case of hypokalemia, usually in combination with other antihypertensive drugs Cirrhosis of the liver, accompanied by ascites and / or edema Treatment of primary hyperaldosteronism Edema in nephrotic syndrome Treatment of hypokalemia in case the patient cannot receive any other drugs Prevention of hypokalemia in patients taking cardiac glycosides when other methods of treatment are not applicable Contraindications Hypersensitivity to the active substance of the drug or to any of the excipients listed in the Composition section Anuria Acute renal failure Severe renal impairment (glomerular filtration rate less than 10 ml/min) Heart failure (glomerular filtration rate less than 30 ml/min or serum creatinine concentration greater than 220 µmol/l) Hyperkalemia Hyponatremia Addison's disease Concomitant use of eplerenone or other potassium-sparing diuretics Pregnancy and lactation. Application during pregnancy and lactation Pregnancy Spironolactone has an antiandrogenic effect in humans, so it should not be used during pregnancy (see section "Contraindications"). Spironolactone or its metabolites pass through the hematoplacental barrier. During the use of spironolactone in pregnant rats, feminization of male fetuses was observed, and after birth, endocrine disorders were observed in female and male offspring. The use of spironolactone in pregnant women is possible only if the intended benefit outweighs the possible risks to the mother and fetus. Breastfeeding Spironolactone metabolites have been found in breast milk. If it is necessary to use spironolactone, breastfeeding should be interrupted and a different method of feeding the child should be used. Route of administration and doses Dosing regimens Adults If a dose of 25 mg is required, Veroshpiron tablets 25 mg should be used. Primary hyperaldosteronism For diagnostic purposes Long-term test: Spironolactone is taken at 400 mg/day for 3–4 weeks. When correction of hypokalemia and arterial hypertension is achieved, the presence of primary hyperaldosteronism can be assumed. Short-term test: spironolactone is taken at 400 mg/day for 4 days. With an increase in the content of potassium in the blood while taking the drug Veroshpiron and a decrease after its withdrawal, one can assume the presence of primary hyperaldosteronism. Treatment In preparation for surgical treatment, spironolactone is used at doses of 100 to 400 mg/day. If surgery is not indicated, spironolactone may be used for long-term maintenance therapy at the lowest effective dose. In this case, the initial dose of the drug may be reduced every 14 days until the lowest effective dose is reached. To reduce the severity of side effects with prolonged use of the drug, Veroshpiron is recommended to be used in combination with other diuretics. Edema due to congestive heart failure or nephrotic syndrome The initial dose is 100 mg and can vary from 25 to 200 mg / day, the drug can be taken in 1-2 doses. When taking higher doses of the drug, Veroshpiron can be used in conjunction with a diuretic acting in the more proximal renal tubule. In this case, the dose of Veroshpiron should be adjusted. Adjunctive therapy in the treatment of severe heart failure (New York Heart Association (NYHA) class III-IV and with an ejection fraction of ≥ 35%) that if the serum potassium content does not exceed 5.0 mEq / l, and the serum creatinine concentration does not exceed 2.5 mg / dl, at the beginning of use against the background of basic standard therapy, the dose of spironolactone should be 25 mg / day. Patients with good tolerability of the drug at a dose of 25 mg / day, according to clinical indications, the dose can be increased to 50 mg / day. In patients who cannot tolerate the drug at a dose of 25 mg / day, the dose of the drug can be reduced to 25 mg once every 2 days. (See Precautions section). Additional therapy in the treatment of arterial hypertension in case of insufficient effectiveness of previously used antihypertensive drugs The initial dose of spironolactone when used simultaneously with other antihypertensive drugs is 25 mg / day. If after 4 weeks blood pressure does not reach the target values, the dose of the drug can be doubled. In patients with arterial hypertension receiving drugs that can cause the development of hyperkalemia (for example, ACE inhibitors or angiotensin receptor blockers), serum potassium and creatinine levels should be assessed before starting the use of spironolactone. Veroshpiron should not be used in patients whose serum potassium exceeds 5.0 mmol/l and the serum creatinine concentration exceeds 2.5 mg/dl. Within 3 months after the start of taking spironolactone, the content of potassium and creatinine in the blood should be carefully monitored. Ascites and edema due to cirrhosis of the liver If the ratio of Na / K ions in the urine exceeds 1.0, the daily dose of the drug should be 100 mg. If the specified ratio is less than 1.0, the dose of the drug should be in the range from 200 to 400 mg / day. The maintenance dose should be determined individually for each patient. Hypokalemia The drug is prescribed at a dose of 25-100 mg / day, if the use of potassium supplements or other potassium-sparing methods is insufficient. Children and adolescents under 18 years of age The initial dose of the drug is 1-3 mg / kg of body weight per day in 1-4 doses. When conducting maintenance therapy or when used simultaneously with other diuretics, the dose of spironolactone should be reduced to 1-2 mg / kg of body weight. If necessary, a suspension can be prepared from crushed 25 mg tablets. Elderly patients Treatment with the drug is recommended to start with the lowest dose with a gradual increase until the maximum desired effect is achieved. Caution should be exercised in patients with severe renal and hepatic impairment, which may affect the metabolism and excretion of spironolactone. In addition, when using the drug in elderly patients, the risk of developing hyperkalemia should be taken into account (see section "Precautions"). How to use As a rule, the daily dose of spironolactone is taken after meals 1 or 2 times a day. Taking the daily dose or the first part of the daily dose of the drug is recommended in the morning. Side effects Undesirable reactions are due to the competitive antagonism of spironolactone against aldosterone (which leads to increased potassium excretion), as well as the antiandrogenic effect of spironolactone. Adverse reactions are presented as a distribution by system organ class according to MedDRA and with an indication of the frequency of occurrence according to MedDRA: very often (? 1/10); often (from? 1/100 to <1/10); infrequently (from? 1/1000 to <1/100); rarely (from? 1/10,000 to <1/1000); very rare (< 1/10,000), frequency not established (cannot be estimated from the available data). Blood and lymphatic system disorders Very rare: thrombocytopenia, agranulocytosis, eosinophilia Immune system disorders Rare: hypersensitivity Endocrine system disorders Very rare: hirsutism Metabolic and nutritional disorders Very common: hyperkalemia1 Common: hyperkalemia2 Rare: hyponatremia, dehydration, porphyria Not known: hyperchloraemic acidosis Psychiatric disorders Uncommon: confusion Nervous system disorders Uncommon: drowsiness3, headache Very rare: paralysis, paraplegia Cardiac disorders Very common: arrhythmias4 Vascular disorders Very rare: vasculitis Frequency not established : unwanted arterial hypotension Respiratory, thoracic and mediastinal disorders Very rare: voice change Gastrointestinal tract disorders Common: nausea, vomiting Rare: gastritis, ulcer, gastric bleeding, stomach pain, diarrhea on the side of the liver and biliary tract Very rare: hepatitis Skin and subcutaneous tissue disorders Rare: rash, urticaria Very rare: alopecia, eczema, erythema annulare, lupus-like skin changes Frequency not established: bullous pemphigoid6 Musculoskeletal and connective tissue disorders Very rare: osteomalacia Renal and urinary tract disorders Very rare: acute renal failure Genital and breast disorders Very common: decreased libido, erectile dysfunction, gynecomastia (in men), breast tenderness, chest pain (in men) ), breast enlargement, menstrual disorders (in women) Common: infertility5 General disorders and disorders at the injection site Uncommon: asthenia, fatigue Laboratory and instrumental findings Very rare: increased blood urea, increased blood creatinine Frequency not established: increased levels of glycosylated hemoglobin lobina (HbA1c) 1 In patients with renal insufficiency and in patients simultaneously receiving potassium preparations. 2 In elderly patients, with diabetes mellitus and in patients concomitantly taking ACE inhibitors. 3 In patients with cirrhosis of the liver. 4 In patients with renal insufficiency and in patients receiving potassium preparations simultaneously with spironolactone. 5 When using the drug in high doses (450 mg / day). 6 As a rule, with prolonged use. Usually, after discontinuation of spironolactone, unwanted effects disappear. OverdoseSymptoms An overdose of spironolactone can cause conditions and symptoms that are related to adverse reactions observed during its use (eg, drowsiness, confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, diarrhea). In rare cases, hyponatremia or hyperkalemia may occur, especially in patients with impaired renal function; in patients with severe liver disease, overdose can lead to hepatic coma. Treatment Symptomatic, there is no specific antidote. Water-electrolyte and acid-base balance should be maintained with potassium-releasing diuretics, parenteral administration of glucose and insulin. In severe cases, hemodialysis is performed. Interaction with other drugs Simultaneous administration of the drug Veroshpiron: with other potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, aldosterone blockers, potassium preparations, as well as a diet rich in potassium, or the use of potassium-containing salt substitutes, can lead to the development of severe hyperkalemia; in addition to drugs known to cause hyperkalemia, co-administration of trimethoprim/sulfamethoxazole (an antibiotic called co-trimoxazole) with spironolactone may result in clinically significant hyperkalemia; taking other diuretics - increases diuresis; immunosuppressants, cyclosporine and tacrolimus may increase the risk of spironolactone-induced hyperkalemia; cholestyramine, ammonium chloride may also increase the risk of hyperkalemia and hyperchloremic metabolic acidosis; tricyclic antidepressants and antipsychotics may enhance the antihypertensive effect of spironolactone; antihypertensive drugs - spironolactone potentiates the action of antihypertensive drugs, the dose of which, when taken simultaneously with spironolactone, may need to be reduced and adjusted in the future if necessary. Since ACE inhibitors reduce the production of aldosterone, drugs of this group should not be used in conjunction with spironolactone on an ongoing basis, especially in patients with established renal dysfunction; simultaneous administration with nitroglycerin, other nitrates or vasodilators may enhance the antihypertensive effect of spironolactone; alcohol, barbiturates or narcotic drugs - can potentiate orthostatic hypotension associated with spironolactone; pressor amines (norepinephrine) - spironolactone reduces vascular responses to norepinephrine. For this reason, caution should be exercised when administering local or general anesthesia in patients taking spironolactone; non-steroidal anti-inflammatory drugs (NSAIDs) - in some patients, NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Simultaneous use of NSAIDs (for example, acetylsalicylic acid, indomethacin and mefenamic acid) with potassium-sparing diuretics can lead to the development of severe hyperkalemia. Thus, while taking spironolactone with NSAIDs, the patient's condition should be carefully monitored to achieve the desired effect of the diuretic drug; glucocorticosteroids, ACTH - the rate of electrolyte excretion may increase, in particular, hypokalemia may occur; digoxin - spironolactone can increase the half-life of digoxin, which can lead to an increase in the concentration of digoxin in the blood serum and, as a result, an increase in its toxicity. When taking spironolactone, a dose reduction of digoxin may be required. The patient should be carefully monitored to prevent digoxin overdose or insufficient digitalisation; the influence of the drug on the results of laboratory studies - the literature describes several cases of the influence of spironolactone or its metabolites on the concentration of digoxin, determined by radioimmunoassay. The clinical significance of this interaction is not yet clear; in fluorometric analysis, spironolactone may interfere with the analysis of compounds with similar fluorescence parameters (eg cortisol, epinephrine); antipyrine - spironolactone accelerates the metabolism of antipyrine; lithium preparations - as a rule, lithium preparations should not be used in conjunction with diuretics. Diuretics reduce the renal clearance of lithium and increase the risk of developing toxic effects of lithium preparations; carbenoxolone - can cause sodium retention in the body and, as a result, reduce the effectiveness of spironolactone. The simultaneous use of carbenoxolone and spironolactone should be avoided; carbamazepine - when used simultaneously with diuretics, the drug can cause clinically significant hyponatremia; heparin, low molecular weight heparin - simultaneous use with spironolactone can lead to severe hyperkalemia; coumarin derivatives - the drug reduces the effectiveness of this group of drugs; Spironolactone can enhance the effect of GnRH analogs (gonadotropin-releasing hormone): triptorelin, buserelin, gonadorelin. Precautions With extreme caution, spironolactone should be used in patients whose underlying disease may provoke the development of acidosis and / or hyperkalemia. Patients with diabetic nephropathy have an increased risk of developing hyperkalemia. Taking spironolactone can cause a transient increase in blood urea nitrogen (BUN), especially against the background of existing renal dysfunction and hyperkalemia. Spironolactone can cause reversible hyperchloremic metabolic acidosis. Thus, when using the drug in patients with impaired renal and hepatic function, as well as in elderly patients, regular monitoring of blood serum electrolytes and kidney function is necessary. Concomitant use of spironolactone with drugs that cause hyperkalemia (eg, other potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, aldosterone blockers, heparin, low molecular weight heparin, potassium supplements, a potassium-rich diet, the use of potassium-containing salt substitutes) can lead to the development of severe hyperkalemia . Hyperkalemia can be fatal. It is critical to monitor and adjust potassium levels in patients with severe heart failure receiving spironolactone. Do not use the drug in conjunction with other potassium-sparing diuretics. In patients with a serum potassium content above 3.5 mEq / l, the use of potassium preparations is contraindicated. The recommended frequency of potassium and creatinine monitoring is one week after starting the drug or increasing the dose of spironolactone, monthly for the first 3 months, then quarterly for a year, and then every 6 months. If the content of potassium in the blood serum is more than 5 mEq / l or creatinine is more than 4 mg / dl, you should temporarily or completely stop taking spironolactone. (see section "Method of administration and doses. Additional therapy in the treatment of severe heart failure"). In patients with porphyria, Veroshpiron should be used with extreme caution, since many drugs provoke exacerbations of porphyria. When taking the drug, alcohol is prohibited. In case of lactose intolerance, it should be taken into account that each Verospiron tablet contains 146.0 mg of lactose monohydrate. This drug should not be taken by patients with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption syndrome. Capsules Veroshpiron 100 mg contain in their composition the dye "sunset" yellow (E 110), which can cause allergic reactions. Storage conditionsStore at a temperature not exceeding 30 °C. Keep out of the reach of children. Buy Veroshpiron capsules 50mg No. 10x3