Spironolactonum

General characteristics. Structure:

Active ingredient: 25 mg of a spirolonolakton in 1 tablet.

Excipients: starch 1500, corn partially prezhelatinizirovanny, silicon dioxide colloid anhydrous, talc, magnesium stearate, lactose monohydrate.

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. Absorption: Spironolactonum not completely, but is quickly enough soaked up from digestive tract and extent of absorption will depend on the particle size and structure and improves after meal. Bioavailability is estimated ranging from 60% to 90%. Time of peak of concentration in plasma – about one hour.

Distribution: though plasma elimination half-life of Spironolactonum in itself short (1,3 h), an elimination half-life of active metabolites is longer (ranging from 2,8 h to 11,2 h). Spironolactonum is estimated as 90% connected with protein of plasma. The distribution volume, extent of accumulation in fabrics and ability to pass a blood-brain barrier are unknown. Spironolactonum or its metabolites can pass a placental barrier, and канренон gets into breast milk. Spironolactonum is known for the slow beginning of action and slow cancellation.

Metabolism: the main biotransformation occurs in a liver where about 80% of the metabolites containing sulfur, such as alpha thiomethylspironolactonum and канренон are metabolized (20%). Many of these metabolites have also diuretic action. Kanrenon, being an active metabolite, has bi-phase plasma elimination half-life about 4-17 h.

Removal: Spironolactonum is removed with urine and excrements in the form of metabolites.

Renal activity from a single dose of Spironolactonum reaches the peak in 7 hours, activity remains, at least, during 24 h.

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:

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.

At a hypopotassemia/hypomagnesiemia, the diuretics caused by therapy, 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, it is necessary to accept Spironolactonum on 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 Spironolactonum 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. Influence of Spironolactonum 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.

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 Norepinephrinum (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 can cause a delay of sodium and, as a result, decrease in efficiency of Spironolactonum. It is necessary to avoid their simultaneous use.

Glucocorticosteroid drugs and diuretics (petrolthiadiazine derivatives, furosemide, Acidum etacrynicum) strengthen and accelerate diuretic and natriuretic effects. Glucocorticosteroid drugs strengthen diuretic and natriuretic effect at a hypoalbuminemia and/or a hyponatremia.

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.

The risk of development of a hyperpotassemia at reception with potassium drugs, potassium additives and kaliysberegayushchy diuretics, inhibitors of angiotenzinkonvertiruyushchy enzyme increases (acidosis), antagonists of angiotensin II, 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.

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:

In the place protected from light and moisture, at a temperature from 15 °C to 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply medicine after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil, in packaging No. 10х2, No. 10х3 together with a leaf insert.