Pharmacological properties

Pharmacodynamics. active ingredient of medicament — Spironolactonum — the competitive antagonist of Aldosteronum influencing distal tubules of kidneys. owing to blockade of Aldosteronum suppresses a delay of water and ions of na + and promotes deduction of ions of k+ that not only increases excretion of ions of na + and cl– and reduces excretion of ions of k + with urine, but also reduces excretion of ions of h+. as a result of it the diuretic effect has also hypotensive effect.

Pharmacokinetics. After intake, medicament is quickly and completely absorbed in a digestive tract. The bioavailability is 92–99% and increases at reception with food.

C _max Spironolactonum in blood plasma is reached in 2.6 h and makes 80 ng/ml. Linking with proteins of blood plasma makes ≈90%. The t _½ makes 1.3 h

Spironolactonum is metabolized in a liver. Its active metabolites are 7α-тиометилспиронолактон and kanrenon. Antialdosteronovy action defines kanrenon which makes ≈50% of all metabolites of Spironolactonum. Indicators of the C _max in blood plasma and time of its achievement: for 7α-тиометилспиронолактона — 391 ng/ml, 3.2 h, for a kanrenon — 181 ng/ml, 4.3 h. The t _½ makes 13.8 and 16.5 h respectively. Spironolactonum and its metabolites get into a placenta and into breast milk.

allocates from an organism in the form of metabolites mainly by a renal ekskrektion, a small part — with a stake. The cumulative effect is characteristic of Spironolactonum.

Indication

Primary hyper aldosteronism.

Stagnant heart failure at inefficiency or intolerance of other diuretics, or in need of increase in their efficiency.

Essentsialnaya AG, mainly at a hypopotassemia, usually in a combination with other antihypertensive drugs.

Cirrhosis which is followed by hypostases and/or ascites.

Hypostases caused by a nephrotic syndrome.

Hypopotassemia — in case of impossibility of use of other therapy.

Prevention of a hypopotassemia for the patients accepting cardiac glycosides in case other ways of therapy are considered as inexpedient or inappropriate.

Use

to take the Drug inside to adults and children. in general the daily dose of medicament is appointed in 1 or 2 receptions after a meal. the daily dose for 1 reception or the first administration of medicament at double use is recommended in the morning.

, in certain cases can reach several years, at the same time use of medicament in a minimal effective dose on condition of constant control of electrolytic composition of blood plasma and indicators of function of kidneys is necessary.

Adult

Primary hyper aldosteronism. At a preparation for surgery medicament is used in a dose 100–400 mg/days

in case of impossibility of operational treatment can use medicament it is long as maintenance therapy in the smallest effective dose which is defined individually.

In this case an initial dose is admissible to be reduced each 14 days to achievement of a minimal effective dose. At long-term treatment it is recommended to use medicament in a combination with other diuretics for reduction of severity of side effects.

Stagnant heart failure, hypostases caused by a nephrotic syndrome. Drug is used in an initial dose 100 mg/days in 1 or 2 receptions. The daily dose can also fluctuate ranging from 25 up to 200 mg.

When assigning can use medicament in higher doses it in a combination with other diuretics operating in proximal departments of renal tubules. In this case it is necessary to carry out Spironolactonum dose adjustment.

Essentsialnaya AG. Drug is used in an initial dose 50–100 mg/days in 1 or 2 inclusion in combinations with other antihypertensive drugs. Treatment it is necessary to continue not less than 2 weeks as by the end of this period the maximum antihypertensive effect is reached. Further dose adjustment individual depending on the reached effect.

Cirrhosis which is followed by ascites and/or hypostases. If a ratio of Na ⁺ / K ⁺ in urine 1, use medicament in an initial dose 100 mg/days. The maximum daily dose — 100 mg/days. If this ratio 1, medicament use in a dose 200 mg/days, at the same time the maximum daily dose — 400 mg/days

Hypopotassemia. Drug is used in a dose 25–100 mg/days to patients at whom not enough nutritional supplements with potassium or other methods of kaliyzamestitelny therapy.

Children. Drug is used in a dose 1–3 mg/kg of body weight a day in 1 or 2 receptions. At maintenance therapy in a combination with other diuretics the daily dose makes 1–2 mg/kg of body weight.

In need of medicament use to children under 3 years a tablet should crush, dissolve and allow to be drunk to the child in the form of suspension.

Patients of advanced age. Drug is recommended to use in lower doses with the subsequent gradual increase to achievement of the maximum effect. It is necessary to take into account that at this category of patients hepatic and renal disturbances which can influence metabolism and removal of medicament take place.

Contraindication

Hypersensitivity to active ingredient or other components of drug.

OPN, significant disturbance of azotovydelitelny function of kidneys (glomerular filtration rate of 10 ml/min.), anury.

Hyperpotassemia, hyponatremia.

Addison's Disease.

Simultaneous use with kaliysberegayushchy diuretics and medicaments of potassium because of a possibility of development of a hyperpotassemia.

Side effects

from a cardiovascular system: arterial hypotension, arrhythmia (at patients with a renal failure and those who receive potassium drugs), a vasculitis.

from the system of blood and lymphatic system: leukopenia (including agranulocytosis), thrombocytopenia, megaloblastny or aplastic anemia, eosinophilia.

from nervous system and mentality: headache, drowsiness, dizziness, ataxy, paralysis, paraplegia, lethargy, block, confusion of consciousness.

from the respiratory system, bodies of a thorax and mediastinum: change of a timbre of a voice.

from a digestive tract: nausea, vomiting, loss of appetite, abdominal and stomach pain, diarrhea, constipation, intestinal colic, gastritis, ulcer of stomach and duodenum, gastric bleeding.

from digestive system: hepatitis, abnormal liver function.

from an urinary system: OPN.

from the musculoskeletal system and connective tissue: osteomalacy, spasm of muscles, myotonia of the lower extremities.

from a metabolism and metabolism: a hyperpotassemia, a hyponatremia, a giperkreatininemiya, increase in level of urea in blood plasma, a hyperuricemia, a porphyria, metabolic giperkhloremichesky acidosis or an alkalosis, dehydration.

from an endocrine system: hirsutism.

from a reproductive system and mammary glands: decrease a libido, erectile dysfunction, a gynecomastia, disturbances of a menstrual cycle, a dysmenorrhea, an amenorrhea, a metrorrhagia in the period of a menopause, swelling and mammary gland pain at women, infertility (at use in high doses — 450 mg/days), a benign tumor of a mammary gland.

from the immune system, skin and hypodermic cellulose: reactions of hypersensitivity, including: rash, itching, urticaria, medicinal fever; a hypertrichosis, an alopecia, a volchanochnopodobny syndrome, hyperaemia, a ring-shaped erythema, eczema, Stephens's syndrome — Johnson.

General: asthenia, increased fatigue.

Special instructions

medicament Use, especially at patients with a renal failure, can lead to tranzitorny increase in content of urea nitrogen in blood plasma and a hyperpotassemia that can lead to development of disturbances of a warm rhythm and a reversible giperkhloremichesky metabolic acidosis. medicament is used with care at patients with a renal failure, a liver and patients of advanced age. it is necessary to determine periodically the level of electrolytes in blood plasma and indicators of function of kidneys. in case of development of a hyperpotassemia the treatment should be stopped.

Drug with care is used at patients in whom the available diseases can cause development of acidosis and/or a hyperpotassemia.

Drug with care is used at patients with diabetes, especially in the presence of a diabetic nephropathy.

Therapy by Spironolactonum can break process of definition of concentration of cortisol, epinephrine and digoxin (radio immunological methods).

Should avoid prolonged unreasonable use of medicament as, according to literature, prolonged use of Spironolactonum at animals in the maximum doses contributed to the development of a carcinoma and myeloid leukemia.

during use of medicament should not take alcoholic drinks.

Drug contains lactose therefore to patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption it is impossible to use drug.

Use during pregnancy and feeding by a breast. Drug is contraindicated during pregnancy and feeding by a breast.

Children. Drug is used in pediatric practice on doctor's orders.

Ability to influence speed of response at control of vehicles or work with other mechanisms. During an initial stage of treatment which duration is individual the control of vehicles or work with other mechanisms are contraindicated.

Interaction

At simultaneous use of medicament with other medicines perhaps:

with antihypertensive medicaments (especially ganglioblokator, nikardipiny, nimodipiny) — excessive decrease in the ABP; at simultaneous use it is necessary to lower a dose of antihypertensive medicaments with the subsequent its correction in case of need;

from ammonium chloride, holestiraminy — increase in risk of development of a hyperpotassemia and a giperkhloremichesky metabolic acidosis;

with kaliysberegayushchy diuretics, potassium drugs, APF inhibitors, blockers of receptors of angiotensin II, blockers of aldosteronovy receptors, antikholinesterazny means, takrolimusy, cyclosporine — increase in risk of development of a hyperpotassemia; simultaneous use with kaliysberegayushchy diuretics and medicaments of potassium contraindicated because of a possibility of development of a hyperpotassemia;

with other diuretics — strengthening of diuretic effect;

with NPVP — increase in risk of development of a hyperpotassemia and a renal failure with the accompanying decrease in diuretic, natriuretic and antihypertensive effect of Spironolactonum; at simultaneous use with acetylsalicylic acid the synthesis of prostaglandins is also suppressed, with antipyrine — metabolism of medicament in a liver amplifies;

with glucocorticoids, AKTG — strengthening of diuretic, natriuretic effect of Spironolactonum and paradoxical strengthening of excretion of potassium;

with α- and β-adrenomimetikam, karbenoksolony — weakening of effect of Spironolactonum;

with antipsychotic means, tricyclic antidepressants — strengthening of effect of Spironolactonum;

with barbiturates, narcotic drugs, ethanol — orthostatic hypotension;

with terfenadiny — increase in risk of developing ventricular arrhythmia owing to a hypopotassemia and an imbalance of other electrolytes;

with carbamazepine — increase in risk of development of a hyponatremia;

with digoxin — increase in risk of developing glikozidny intoxication owing to lengthening of its T _½ ;

with lithium medicaments — increase in risk of developing intoxication owing to decrease in renal clearance of lithium; it is not necessary to use these medicaments at the same time;

with indirect anticoagulants (coumarin derivatives), Mitotanum, pressor amines (epinephrine), cardiac glycosides — weakening of action of the last;

with triptoreliny, busereliny, gonadoreliny — strengthening of action of the last.

Overdose

Symptoms: drowsiness/fatigue, confusion of consciousness, electrolytic disturbances.

Treatment: symptomatic therapy. It is necessary to maintain water and electrolytic and acid-base balance: prescribing of the diuretics removing potassium, parenteral administration of glucose with insulin in hard cases — carrying out a hemodialysis. There is no specific antidote.

Storage conditions

In original packing at a temperature not above 25 °C.