Veroshpilakton

General characteristics. Structure:

Active ingredient: 0,025 g of Spironolactonum in 1 tablet.

Excipients: magnesium stearate, lactose (sugar milk), potato starch, silicon dioxide colloid (aerosil), talc.

Pharmacological properties:

Pharmacodynamics. Spironolactonum is kaliysberegayushchy diuretic, the specific antagonist of Aldosteronum of the prolonged action (a mineralokortikosteroidny adrenal hormone). In distal departments of nephron Spironolactonum interferes with a delay of aldosteronomas of sodium of water and suppresses kaliyvyvodyashchy effect of Aldosteronum, reduces synthesis пермеаз in Aldosteronum - the dependent site of collective tubules and distal tubules. Contacting Aldosteronum receptors, increases excretion of ions of sodium, chlorine and water with urine, reduces removal of potassium ions and urea, reduces acidity of urine.

The maximum effect is observed in 7 hours after intake and not less than 24 p last. Hypotensive effect of drug is caused by existence of diuretic effect which is changeable: the diuretic effect is shown for 2-5 day of treatment.

Pharmacokinetics. At intake it is quickly and completely soaked up from digestive tract and turns into active metabolites: the metabolite containing sulfur (80%) and partially канренон (20%). The maximum concentration (Cmax) of a kanrenon in a blood plasma is reached in 2-4 h, its communication with proteins of a blood plasma of 90%.

Communication with proteins of a blood plasma about 98% (a kanrenona – 90%).

After daily reception of 100 mg of Spironolactonum within 15 days of Cmax reaches 80 mg/ml, time of achievement of Cmax after the next morning reception – 2-6 h.

Spironolactonum badly gets into bodies and fabrics, at the same time itself and its metabolites get through a placental barrier, and канкреон – into breast milk. Distribution volume – 0,05 l/kg. An elimination half-life (T1/2) of Spironolactonum of 13-24 h, active metabolites – to 15 h.

It is removed by kidneys: 50% – in the form of metabolites, 10% – in an invariable look and partially – fecal masses. Removal of a kanrenon (mainly kidneys) two-phase, T1/2 in the first phase – 2-3 h, in the second – 12-96 h.

At cirrhosis and heart failure duration of an elimination half-life increases without signs of cumulation which probability is higher at a chronic renal failure and a hyperpotassemia.

Indications to use:

- essential hypertensia (as a part of a combination therapy);
- an edematous syndrome at chronic heart failure (it can be applied in the form of monotherapy and in a combination with standard therapy);
- states at which the secondary hyper aldosteronism, including the cirrhosis which is followed by ascites and/or hypostases, a nephrotic syndrome, and also other states which are followed by hypostases can be found;
- a hypopotassemia/hypomagnesiemia (as supportive application for its prevention during treatment by diuretics and at impossibility of use of other ways of correction of level of potassium);
- primary hyper aldosteronism (Conn's syndrome) – for a short preoperative course of treatment;
- for establishment of the diagnosis of primary hyper aldosteronism.

Route of administration and doses:

Inside.

At essential hypertensia. The daily dose for adults usually makes 50-100 mg once and can be increased to 200 mg, at the same time it is necessary to increase a dose gradually, 1 time in 2 weeks. To achieve the adequate response to therapy, drug it is necessary to accept not less than 2 weeks. If necessary carry out correction of a dose.

At an idiopathic hyper aldosteronism of 100-400 mg/days. At the expressed hyper aldosteronism and a hypopotassemia of 300 mg/days (at most 400 mg) for 2-3 receptions, at improvement of a state the dose is gradually reduced to 25 mg/days.

Hypopotassemia/hypomagnesiemia. At the hypopotassemia and/or a hypomagnesiemia caused by therapy by diuretics appoint drug in a dose of 25-100 mg/days, once or in stages. The maximum daily dose of 400 mg if peroral drugs of potassium or other methods of completion of its deficit are inefficient.

Diagnosis treatment of primary hyper aldosteronism. As diagnostic means at short diagnostic test: within 4 days on 400 mg/days, having distributed on several receptions in day. At increase in potassium concentration in blood during administration of drug and decrease after cancellation it is possible to assume it existence of primary hyper aldosteronism.

At long diagnostic test: in the same dose within 3-4 weeks. At achievement of correction of a hypopotassemia and arterial hypertension it is possible to assume existence of primary hyper aldosteronism.

Short course of preoperative therapy of primary hyper aldosteronism. After the diagnosis of a hyper aldosteronism is established by means of more exact diagnostic methods, Veroshpilakton it is necessary to accept 100-400 mg/days, having divided into 1-4 receptions a day during the entire period of preparation for surgery. If operation is not shown, then Veroshpilakton is applied to carrying out a long maintenance therapy, at the same time the smallest effective dose which is selected individually for each patient is used.

Hypostases against the background of a nephrotic syndrome. The daily dose for adults usually makes 100-200 mg/days. Veroshpilakton's influence on the main pathological process and therefore use of this drug is recommended only when other types of therapy are inefficient is not revealed.

At an edematous syndrome against the background of chronic heart failure daily, within 5 days on 100-200 mg/days in 2-3 receptions, in a combination with "loopback" or thiazide diuretic. Depending on effect, the daily dose is reduced to 25 mg. The maintenance dose is selected individually. Maximum dose of 200 mg/days.

Hypostases against the background of cirrhosis. If in urine the ratio of ions of sodium and potassium (Na+/K+) is exceeded 1,0, then the daily dose for adults usually makes 100 mg. If a ratio less than 1,0, then a daily dose for adults it is usually equal to 200-400 mg. The maintenance dose is selected individually.

Hypostases at children. The initial dose makes 1-3,3 mg/kg of body weight or 30-90 mg/sq.m/days. In 1-4 receptions. In 5 days the dose is adjusted and if necessary increased by 3 times in comparison with initial.

Features of use:

Perhaps temporary increase in level of an urea nitrogen in blood serum, especially at reduced function of kidneys and a hyperpotassemia. The reversible giperkhloremichesky metabolic acidosis is possible.

At diseases of kidneys and a liver, and also at advanced age regular control of electrolytes of blood serum and function of kidneys is necessary.

Drug complicates definition of digoxin, cortisol and adrenaline in blood.

Despite the lack of direct impact on carbohydrate metabolism, existence of a diabetes mellitus, especially with a diabetic nephropathy, demands extra care because of a possibility of development of a hyperpotassemia.

At treatment by non-steroidal anti-inflammatory drugs it is necessary to control function of kidneys and level of electrolytes in blood.

It is necessary to avoid the food rich with potassium.

During treatment alcohol intake is contraindicated.

Influence of drug on ability to drive the car and mechanisms on which work is connected with the increased risk of traumatism. In an initial stage of treatment it is forbidden to drive the car and to be engaged in the types of activity demanding the increased concentration of attention and speed of psychomotor reactions. Duration of restrictions is established in an individual order.

Side effects:

From digestive tract: nausea, vomiting, diarrhea, ulcerations and bleedings from digestive tract, gastritis, intestinal colic, an abdominal pain, a lock.

From a liver: abnormal liver function.

From the central nervous system: ataxy, block, dizziness, headache, drowsiness, lethargy, confusion of consciousness, muscular spasm.

From the hemopoietic system: a leukopenia (including an agranulocytosis), thrombocytopenia.

From endocrine system: voice coarsening, men have a gynecomastia (the probability of development depends on a dose, duration of treatment and, usually, has reversible character); decrease in a potentiality and erection; women have a disturbance of a menstrual cycle; a dysmenorrhea, an amenorrhea, a metrorrhagia in a climacteric, a hirsutism, pains in mammary glands, a carcinoma of a mammary gland (existence of communication with administration of drug is not established).

Metabolic disturbances: giperkreatininemiya, increase in concentration of urea, disturbance of a water salt metabolism (hyperpotassemia, hyponatremia) and acid-base balance (metabolic giperkhloremichesky acidosis or alkalosis), hyperuricemia.

At Veroshpilakton's use the gynecomastia can develop. The probability of emergence of a gynecomastia depends on a dose of drug and on therapy duration. At the same time the gynecomastia usually has reversible character, and after drug withdrawal disappears, and only in rare instances chest gland remains a little increased.

Allergic reactions: urticaria, seldom makulopapulezny and erythematic rash, medicinal fever, itch.

From integuments: alopecia, hypertrichosis.

From an urinary system: acute renal failure.

From a musculoskeletal system: spasms of gastrocnemius muscles.

Interaction with other medicines:

Reduces effect of anticoagulants, indirect anticoagulants (heparin, derivative coumarin, an indandinon) and toxicity of cardiac glycosides (since normalization of level of potassium in blood interferes with toxicity).

Strengthens metabolism of a fenazol (antipyrine).

Reduces sensitivity of vessels to a noepinefrin (demands respect for care when carrying out anesthesia), increases a digoxin elimination half-life – intoxication – digoxin is possible.

Strengthens toxic effect of lithium because of decrease in clearance.

Accelerates metabolism and removal of a karbenoksolon.

Karbenoksolon promotes a sodium delay Spironolactonum.

Glucocorticosteroid drugs and diuretics (petrolthiadiazine derivatives, furosemide, Acidum etacrynicum) strengthen and accelerate diuretic and natriuretic effects.

Strengthens effect of diuretic and hypotensive medicines.

Non-steroidal anti-inflammatory drugs reduce diuretic and natriuretic effects, the risk of development of a hyperpotassemia increases.

Glucocorticosteroid drugs strengthen diuretic and natriuretic effect at a hypoalbuminemia and/or a hyponatremia.

The risk of development of a hyperpotassemia at reception with potassium drugs, potassium additives and kaliysberegayushchy diuretics, inhibitors increases angiotensin - the converting enzyme (acidosis), antagonists of angiotensin P, blockers of Aldosteronum, indometacin, cyclosporine.

Salicylates, indometacin reduce diuretic effect.

Ammonium chloride, Colestyraminum promote development of a giperkaliyemichesky metabolic acidosis.

Fludrokortizon causes paradoxical strengthening of canalicular section of potassium.

Reduces effect of Mitotanum.

Strengthens effect of a triptorelin, buserelin, gonadorelin.

Contraindications:

Hypersensitivity to any of drug components, Addison's disease, a hyperpotassemia, a hyponatremia, a heavy renal failure (clearance of creatinine less than 10 ml/min.), an anury, pregnancy, the feeding period a breast. Children's age (up to 3 years), in connection with a firm dosage form.

With care: a hypercalcemia, a metabolic acidosis, an atrioventricular block (the hyperpotassemia promotes its strengthening), a diabetes mellitus (at the confirmed or estimated chronic renal failure), a diabetic nephropathy, surgical interventions, reception of the medicines causing a gynecomastia, local and general anesthesia, advanced age, disturbance of a menstrual cycle, increase in mammary glands, a liver failure.

Overdose:

Symptoms: nausea, vomiting, dizziness, diarrhea, skin rash, a hyperpotassemia (paresthesias, muscular weakness, arrhythmias), a hyponatremia (dryness in a mouth, thirst, drowsiness) a hypercalcemia, dehydration, increase in concentration of urea.

Treatment: gastric lavage, symptomatic treatment of dehydration and arterial hypotension. At a hyperpotassemia it is necessary to normalize water and electrolytic exchange with the help of kaliyvyvodyashchy diuretics, bystry parenteral administration of 5-20% of solution of a dextrose with insulin at the rate of 0,25-0,5 PIECES on 1 g of a dextrose; if necessary it is possible to enter repeatedly. In hard cases carry out a hemodialysis.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 3 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 25 mg. On 10, 15, 20 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2, 3 blister strip packagings with the application instruction place in a pack from a cardboard.