Veroshpiron tablets p / o 25mg, No. 20

Veroshpiron tablets p / o 25mg, No. 20; 'essential hypertension (mainly with hypokalemia, as part of combination therapy); congestive heart failure (in patients who do not respond to another therapy or with its intolerance, as well as to enhance the effect other diuretics); cirrhosis of the liver, accompanied by ascites and / or edema, nephrotic syndrome; hypokalemia (for its prevention as an adjunct during treatment with digitalis drugs and for its treatment when it is impossible to use other methods of correcting potassium concentration); primary hyperaldosteronism (Conn's syndrome ); to establish the diagnosis of primary hyperaldosteronism.

The drug is taken orally, after meals, 1 or 2 times / day. Taking the daily dose or the first part of the daily dose of the drug is recommended in the morning.

Adults

Essential hypertension

Additional therapy in the treatment of 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 the blood pressure does not reach the target values, the dose of the drug can be doubled. In hypertensive patients receiving drugs that can cause hyperkalemia (for example, ACE inhibitors or angiotensin receptor blockers), serum potassium and creatinine should be assessed before spironolactone is used. Do not use Veroshpiron in patients whose serum potassium content exceeds 5.0 mmol / l, and the serum creatinine concentration exceeds 220 ?mol / l.Within 3 months after starting spironolactone, frequent monitoring of potassium and creatinine levels in the blood is required.

Congestive heart failure

Edema against the background of congestive heart failure or nephrotic syndrome The initial dose is 100 mg and can vary in the range from 25 * to 200 mg / day, the drug can be taken in 1-2 doses. When taking higher doses, Veroshpiron can be used in conjunction with a diuretic acting in the proximal renal tubule. In this case, the dose of spironolactone should be adjusted. Adjunctive therapy in the treatment of severe heart failure (NYHA class III-IV and ejection fraction ?35%) It has been established that if the serum potassium content does not exceed 5.0 mmol / L and the serum creatinine concentration does not exceed 220 ?mol / l, against the background of basic standard therapy, the dose of spironolactone at the beginning of use should be 25 mg / day *.For patients with good tolerance of the drug at a dose of 25 mg / day *, according to clinical indications, the dose can be increased to 50 mg / day. For patients with poor tolerance to therapy with Veroshpiron at a dose of 25 mg / day *, the dose of the drug can be reduced to 25 mg * 1 time in 2 days. Ascites and edema due to liver cirrhosis If the ratio of sodium and potassium ions in urine exceeds 1.0, then the daily dose of the drug should be 100 mg. If the specified ratio is less than 1.0, then 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.caused by liver cirrhosis If the ratio of sodium and potassium ions in urine exceeds 1.0, then the daily dose of the drug should be 100 mg. If the specified ratio is less than 1.0, then 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.caused by liver cirrhosis If the ratio of sodium and potassium ions in urine exceeds 1.0, then the daily dose of the drug should be 100 mg. If the specified ratio is less than 1.0, then 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 preparations or other potassium-sparing methods is insufficient.

Primary hyperaldosteronism

For diagnostic purposes

1. Long-term test: spironolactone is taken at 400 mg / day for 3-4 weeks. When the correction of hypokalemia and arterial hypertension is achieved, the presence of primary hyperaldosteronism can be assumed.

2. Short test: Spironolactone is taken at 400 mg / day for 4 days.

With an increase in serum potassium while taking spironolactone and a decrease after its cancellation, one can assume the presence of primary hyperaldosteronism.

Treatment

In preparation for surgical treatment, spironolactone is used in doses from 100 to 400 mg / day. If surgery is not indicated, spironolactone can 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, the drug Veroshpiron is recommended to be used in combination with other diuretics. Special groups of patients In children over 3 years of age and adolescents under 18 years of age, the initial dose of the drug is 1-3 mg / kg of body weight / day in 2-4 doses. When carrying out maintenance therapy or while using it with other diuretics, the dose of Veroshpiron should be reduced to 1-2 mg / kg of body weight *.In elderly patients, drug treatment 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 mild to moderate renal impairment and liver dysfunction, 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 the section 'Special instructions').when using the drug in elderly patients, the risk of developing hyperkalemia should be taken into account (see the section 'Special instructions').when using the drug in elderly patients, the risk of developing hyperkalemia should be taken into account (see the section 'Special instructions').

* Doses below 50 mg cannot be obtained when taking the drug Veroshpiron in the dosage form of capsules, so you should take the drug Veroshpiron in the dosage form of a tablet of 25 mg.

spironolactone

hypersensitivity to the active substance or any of the components of the drug; Addison's disease; hyperkalemia; hyponatremia; severe renal failure (GFR less than 10 ml / min / 1.73 m2); acute renal failure, anuria; heart failure (GFR <30 ml / min / 1.73 m2 or serum creatinine concentration more than 220 ?mol / l); concomitant use with eplerenone or other potassium-sparing diuretics; lactase deficiency, lactose intolerance, glucose-galactose malabsorption; pregnancy; lactation period (breastfeeding); children under 3 years of age (solid dosage form).

With care: hypercalcemia, metabolic acidosis, AV blockade (hyperkalemia contributes to its strengthening); renal failure; diabetic nephropathy; diabetes mellitus (in patients with confirmed or suspected chronic renal failure); taking medications that cause hyperkalemia; local and general anesthesia; elderly age; liver failure; cirrhosis of the liver; porphyria.

pharmachologic effect

Spironolactone is a potassium-sparing diuretic, a specific long-acting aldosterone antagonist (a mineralocorticoid hormone of the adrenal cortex). In the distal nephron, spironolactone prevents the retention of sodium and water by aldosterone and inhibits the potassium-excreting effect of aldosterone. By binding to aldosterone receptors, it increases the excretion of sodium, chlorine and water ions in the urine, reduces the excretion of potassium and urea ions, and reduces the acidity of urine. The antihypertensive effect of the drug is due to the presence of a diuretic effect. Renal activity after a single dose of spironolactone reaches a peak after 7 hours and persists for at least 24 hours.

Pharmacokinetics

Absorption and distribution

When taken orally, it is rapidly and completely absorbed from the gastrointestinal tract. Actively binds to blood plasma proteins (approximately 90%). After taking spironolactone at a dose of 100 mg / day for 15 days, healthy volunteers Tmax of the drug in plasma and Cmax of spironolactone were 2.6 h and 80 ng / ml, respectively. For the metabolites of 7-alpha-thiomethylspironolactone and canrenone, the Tmax was 3.2 h and 4.3 h, the Cmax 391 ng / ml and 181 ng / ml, respectively. Spironolactone and its metabolites cross the placental barrier and into breast milk. Metabolism and excretion Spironolactone is rapidly metabolized in the human body. The pharmacologically active metabolites of spironolactone are 7-alpha-thiomethylspironolactone and canrenone. Despite the fact that T1 / 2 of unchanged spironolactone from the blood has a short duration (1.3 hours),T1 / 2 of active metabolites is longer (in the range from 2.8 to 11.2 hours). Metabolites are excreted mainly by the kidneys, small amounts of them are excreted through the intestines. After taking spironolactone at a dose of 100 mg / day for 15 days by healthy volunteers, T1 / 2 of spironolactone was about 1.4 hours, and T1 / 2 of the metabolites of 7-alpha-thiomethylspironolactone and canrenone - 13.8 hours and 16.5 hours, respectively.

Side effect

Adverse reactions are most often due to the competitive antagonism of spironolactone in relation to aldosterone (which leads to increased potassium excretion), as well as the antiandrogenic effect of spironolactone. Usually, after you stop taking spironolactone, the undesirable effects disappear. Adverse reactions are presented in accordance with systemic organ classes according to MedDRA and with an indication of the frequency of occurrence: very often (? 1/10); often (from? 1/100 to <1/10); infrequently (from? 1/1000 to <1/100); rarely (from? 1/10000 to <1/1000); very rare (<1/10000), frequency unknown (cannot be estimated from available data). From the hematopoietic system: very rarely - thrombocytopenia, agranulocytosis, eosinophilia. From the immune system: rarely - hypersensitivity. From the endocrine system: very rarely - hirsutism.From the side of metabolism: very often - hyperkalemia (in patients with renal insufficiency and in patients receiving potassium supplements at the same time); often - hyperkalemia (in elderly patients, with diabetes mellitus and in patients taking ACE inhibitors at the same time); rarely - hyponatremia, dehydration, porphyria; frequency unknown - hyperchloremic acidosis. Mental disorders: infrequently - confusion. From the nervous system: infrequently - drowsiness (in patients with liver cirrhosis), headache; very rarely - paralysis, paraplegia. From the side of the cardiovascular system: very often - arrhythmias (in patients with renal insufficiency and in patients receiving potassium preparations simultaneously with spironolactone); very rarely - vasculitis; frequency unknown - excessive decrease in blood pressure. From the respiratory system:very rarely - a change in the tone of the voice. From the digestive system: often - nausea, vomiting; rarely - gastritis, ulcer, stomach bleeding, stomach pain, diarrhea; very rarely - hepatitis. On the part of the skin and subcutaneous tissues: rarely - rash, urticaria; very rarely - alopecia, eczema, erythema annulus, lupus-like skin changes; frequency unknown - bullous pemphigoid (usually with prolonged use). From the musculoskeletal system: very rarely - osteomalacia. From the urinary system: very rarely - acute renal failure. From the genitals and breast: very often - decreased libido, erectile dysfunction, gynecomastia (in men), breast tenderness, chest pain (in men), breast enlargement, menstrual irregularities (in women);often - infertility (when using the drug in high doses (450 mg / day)).

Others: infrequently - asthenia, fatigue. Laboratory and instrumental data: very rarely - an increase in the concentration of urea in the blood serum, an increase in the concentration of creatinine in the blood serum; the frequency is unknown - an increase in the content of glycosylated hemoglobin (HbA1c). If any of the adverse reactions specified in the instructions are aggravated or any other adverse reactions not specified in the instructions are noted, the patient should be informed about this by the attending physician.

Application during pregnancy and lactation

Pregnancy

Spironolactone has an antiandrogenic effect in humans. Spironolactone and its metabolites cross the placental barrier. The use of spironolactone during pregnancy is contraindicated. Breastfeeding period Spironolactone metabolites pass into breast milk. If it is necessary to use spironolactone, breastfeeding should be interrupted and another method of feeding the baby should be used.

Application for violations of liver function

The drug should be prescribed with caution in liver failure, liver cirrhosis.

Application for impaired renal function

The drug should be prescribed with caution in renal failure and diabetic nephropathy. The drug is contraindicated in severe renal failure (GFR less than 10 ml / min / 1.73 m2), acute renal failure, anuria. Application in children

The use of the drug in children under 3 years of age is contraindicated.

Use in elderly patients

The drug should be prescribed with caution to elderly patients.

special instructions

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 are at increased risk of developing hyperkalemia. Taking spironolactone can cause a transient increase in blood urea nitrogen (BUN), especially in the presence of renal impairment and hyperkalemia. Spironolactone can cause reversible hyperchloremic metabolic acidosis. Thus, when using the drug in patients with impaired renal and liver function, as well as in elderly patients, regular monitoring of serum electrolyte levels and renal function is necessary. The simultaneous use of spironolactone with drugs that cause hyperkalemia (for example, other potassium-sparing diuretics, ACE inhibitors,angiotensin II receptor antagonists, aldosterone blockers, heparin, low molecular weight heparin, potassium supplements, potassium-rich diet, intake of potassium-containing salt substitutes) can lead to severe hyperkalemia. Hyperkalemia can be fatal. It is critical to monitor and adjust potassium levels in patients with severe heart failure receiving spironolactone. The drug should not be used in conjunction with other potassium-sparing diuretics. In patients with serum potassium levels above 3.5 mmol / l, the use of potassium preparations is contraindicated. The recommended frequency of monitoring the content of potassium and creatinine: one week after starting the drug or increasing the dose of spironolactone, monthly for the first 3 months, then quarterly for a year;further every 6 months. If the serum potassium content is more than 5 mmol / L or creatinine is more than 350 ?mol / L, you should temporarily or completely stop taking spironolactone. In patients with porphyria, Veroshpiron should be used with extreme caution, since many drugs provoke an exacerbation of porphyria. When taking the drug, alcohol is prohibited. In case of lactose intolerance, it should be taken into account that each capsule of the drug Veroshpiron 50 mg contains 127.5 mg, and the capsule of the drug Veroshpiron 100 mg contains 255 mg of lactose monohydrate. This drug should not be taken by patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome. The capsule of the drug Veroshpiron 100 mg contains the dye sunset yellow E110,which can cause allergic reactions. Influence on the ability to drive vehicles and control mechanisms In the initial period of treatment, it is forbidden to drive vehicles and engage in activities that require increased concentration of attention and speed of psychomotor reactions. The duration of the restrictions is set on an individual basis.

Overdose

Symptoms: drowsiness, confusion, nausea, vomiting, dizziness, diarrhea, maculopapular or erythematous skin rash. Less commonly, hyperkalemia and hyponatremia may occur, especially in patients with renal insufficiency, in patients with severe liver disease, overdose can lead to hepatic coma. Treatment: there is no specific antidote. Gastric lavage, symptomatic treatment of dehydration and restoration of acid-base balance are performed. With hyperkalemia, it is necessary to normalize water-electrolyte metabolism with the help of potassium-excreting diuretics, rapid parenteral administration of a dextrose solution with insulin. In severe cases, hemodialysis is performed. Drug interactions

Simultaneous administration of the drug Veroshpiron with other potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, aldosterone blockers, potassium preparations, as well as adherence to a potassium-rich diet or the use of potassium-containing salt substitutes can lead to the development of severe hyperkalemia. In addition to drugs that reliably cause hyperkalemia, the simultaneous use of a combination of trimethoprim / sulfamethoxazole (co-trimoxazole) with spironolactone can lead to clinically significant hyperkalemia. Concomitant use of other diuretics: increased diuresis. Immunosuppressants, cyclosporine and tacrolimus may increase the risk of hyperkalemia caused by spironolactone. Cholestyramine, ammonium chloride may also increase the risk of developing hyperkalemia and hyperchloremic metabolic acidosis.Tricyclic antidepressants and antipsychotics can enhance the antihypertensive effect of spironolactone. Antihypertensive drugs: spironolactone potentiates the effect of antihypertensive drugs, the dose of which, when taken simultaneously with spironolactone, may need to be reduced and adjusted further 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 impairment. Concomitant use with nitroglycerin, other nitrates or vasodilators can 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 to patients taking spironolactone. NSAIDs: in some patients, taking NSAIDs can reduce the diuretic, natriuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. The 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 in order to achieve the desired effect of the diuretic. GCS, ACTH: the rate of excretion of electrolytes may increase, in particular, hypokalemia may be observed. Digoxin:spironolactone can increase the T1 / 2 of digoxin, which can lead to an increase in the concentration of digoxin in the blood serum and, as a consequence, an increase in its toxicity. When taking spironolactone, you may need to reduce the dose of digoxin. The patient should be carefully monitored to prevent overdose of digoxin or insufficient digitalization. The effect of the drug on the results of laboratory studies: the literature describes several cases of the effect of spironolactone or its metabolites on the digoxin concentration indicator, determined by radioimmunoassay. The clinical significance of this interaction is not yet clear. In a fluorometric assay, spironolactone can interfere with the assay for compounds with similar fluorescence parameters (eg, cortisol, epinephrine). Antipyrine:spironolactone accelerates the metabolism of antipyrine. Lithium preparations: Generally, lithium preparations should not be used in conjunction with diuretics. Diuretics decrease renal clearance of lithium and increase the risk of 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: Concomitant use with spironolactone can lead to severe hyperkalemia. Coumarin derivatives: spironolactone reduces the effectiveness of this group of drugs. Spironolactone can enhance the action of GnRH (gonadotropin-releasing hormone) analogs: triptorelin,buserelin, gonadorelin.

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