Spironolactonum

General characteristics. Structure:

Active agent: Spironolactonum - 25 mg; Excipients: potato starch – 13,2 mg, коповидон (коллидон VA-64) – 3,7 mg, calcium stearate (calcium stearate) – 1,2 mg, talc – 3,6 mg, кросповидон (коллидон CL-M) – 5,4 mg, cellulose microcrystallic - to 120 mg.

Pharmacological properties:

Pharmacodynamics. Kaliysberegayushchy diuretic which effect is caused by antagonism from aldosteronomas (a mineralokortikosteroidny adrenal hormone). Aldosteronum promotes the return absorption of ions of sodium in renal tubules and strengthens removal of potassium ions. Spironolactonum - the competitive antagonist of Aldosteronum on influence on distal departments of nephron (competes for places of binding on cytoplasmatic proteinaceous receptors, reduces synthesis пермеаз in Aldosteronum - the dependent site of collective tubules and distal tubules), increases removal of ions of sodium, chlorine and water and reduces removal of potassium ions and urea, reduces acidity of urine. Strengthening of a diuresis causes anti-hypertensive effect which is changeable. The diuretic effect is shown for 2-5 day of treatment. 

Pharmacokinetics. Absorption - full. Bioavailability - 100%. The maximum concentration at daily reception of 100 mg within 15 days - 80 ng/ml, time necessary for achievement of the maximum concentration after the next morning reception - 2.6 h. After absorption it is metabolized in a liver to several active sulfur-containing metabolites, including a kanrenon whose maximum concentration is defined by 2-4 h. Communication with proteins of plasma - 98% (a kanrenona - 90%). Badly gets into bodies and fabrics, but gets through a placental barrier, and канренон - into breast milk. Distribution volume - 0.05 l/kg. An elimination half-life - 13-24 h. It is removed by kidneys (50% - in the form of metabolites, 10% - in not changed look), partially – through intestines. Removal of a kanrenon (mainly kidneys) two-phase, an elimination half-life in the first phase - 3-2 h, in the second - 12-96 h. At cirrhosis and chronic heart failure the elimination half-life increases without cumulation signs (its probability increases against the background of 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 of a diuretikamiya 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 dose adjustment.
At an idiopathic hyper aldosteronism of 100 - 400 mg/days.
At the expressed hyper aldosteronism and a hypopotassemia the daily dose makes 300 mg (at most 400 mg) for 2-3 receptions, at improvement of a state the dose is gradually reduced to 25 mg/days.
At the hypopotassemia and a hypomagnesiemia caused by therapy by diuretics drug appoint in a dose 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.
At diagnosis and treatment of primary hyper aldosteronism and quality of diagnostic means at short diagnostic test drug is appointed within 4 days on 400 mg/days, having distributed a daily dose in stages 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 drug is appointed 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.
After the diagnosis of a hyper aldosteronism is established by means of more exact diagnostic methods, as a short course of preoperative therapy of primary hyper aldosteronism drug it is necessary to accept 100 – 400 mg in a daily dose, having divided on 1 – 4 reception during the entire period of preparation for surgery. If operation is not shown, then drug is used for carrying out a long maintenance therapy, at the same time the smallest effective dose which is selected individually for each patient is used.
At treatment of hypostases against the background of a nephrotic syndrome a daily dose for adults sostavlyaet100-200 mg. Influence of Spironolactonum on the main pathological process and therefore use of this drug is recommended only in cases when other types of therapy are inefficient is not revealed.
At an edematous syndrome against the background of chronic heart failure drug is appointed 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. The maximum daily dose makes 200 mg.
At hypostases against the background of cirrhosis the daily dose for adults usually makes      100 mg if the ratio of ions of sodium and potassium (Na+/K+) in urine exceeds 1,0. If a ratio less than 1,0, then a daily dose it is usually equal to 200-400 mg. The maintenance dose is selected individually.
At hypostases at children the initial dose makes 1-3,3 mg/kg of body weight or 30-90мг/м2/сут in 1-4 receptions. In 5 days carry out dose adjustment and in need of it increase by 3 times in comparison with initial.

Features of use:

Perhaps temporary increase in level of an urea nitrogen in blood serum, especially at depression of 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 on ability to manage vehicles and mechanisms
 In an initial stage of treatment it is forbidden to manage vehicles and to be engaged in other potentially dangerous 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 the alimentary system: nausea, vomiting, abdominal pain, gastritis, ulcerations and bleedings of digestive tract, intestinal colic, diarrhea or lock, abnormal liver function.
From a nervous system: dizziness; drowsiness, lethargy, headache, block, ataxy, muscular spasms, confusion of consciousness.
From endocrine system: at prolonged use – a gynecomastia, disturbance of an erection at men, decrease in a potentiality; women have a dysmenorrhea, an amenorrhea, the rorragiya in a climacteric, a hirsutism, a hypertrichosis, voice coarsening, morbidity of mammary glands, a carcinoma of a mammary gland mt. Read here about Inspr's drug with which it is possible to replace Spironolactonum for men.
From an urinary system: increase in concentration of urea, giperkreatininemiya, hyperuricemia, acute renal failure.
From a metabolism: disturbance of water and electrolytic exchange and acid-base state (metabolic gipokhloremichesky acidosis or alkalosis).
From bodies of a hemopoiesis: мегалобластоз, agranulocytosis, thrombocytopenia.
Allergic reactions: small tortoiseshell, makulopapulezny and эритематознаясыпь, medicinal fever, itch.
Dermatological reactions: alopecia.
Others: spasms of gastrocnemius muscles, muscular spasm.

Interaction with other medicines:

Reduces effect of anticoagulants, indirect anticoagulants (heparin, derivative coumarin, an indandion) and toxicity of cardiac glycosides (as normalization of level of potassium in blood interferes with toxicity development).
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 therefore 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 (derivative a benzotiazina, 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 of antiotenzinprevrashchayushchy increases
 enzyme (acidosis), antagonists of an antiotenzin of II, Aldosteronum blockers, indometacin, cyclosporine.
Salicylates, indometacin reduce diuretic effect.
Ammonium chloride, Colestyraminum promote development of a giperkaliyemichesky metabolic acidosis.
Fludrokortizon causes paradoxical strengthening of canalicular secretion of potassium.
Reduces effect of Mitotanum.
Strengthens effect of a triptorelin, buzerelin, ganadorelin.

Contraindications:

- Addison's disease;
- hyperpotassemia;
- hyponatremia;
- heavy chronic renal failure (clearance of creatinine less than 10 ml/min.);
- anury;
- lactose intolerance, deficit of lactase, syndrome of glyukozo-galaktozny malabsorption;
- pregnancy;
- period of a lactation (breastfeeding);
- children's age up to 3 years;
- hypersensitivity to any of drug components. 
Use at pregnancy Use of drug during pregnancy and a lactation is contraindicated.

Overdose:

Symptoms: nausea, vomiting, dizziness, a lowering of arterial pressure, diarrhea, skin rash, a hyperpotassemia (paresthesias, a myasthenia, arrhythmias), a hyponatremia (dryness in an oral cavity, thirst, drowsiness), a hypercalcemia, dehydration, increase in concentration of urea.
Treatment: gastric lavage, symptomatic therapy 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 solution of a dextrose  (5-20% solutions) with insulin at the rate of 0.25-0.5 PIECES on 1 g of a dextrose; if necessary perhaps repeated introduction of a dextrose. In hard cases carry out a hemodialysis.

Storage conditions:

In the dry, protected from light place, at a temperature no more than 25 °C. To store in the places unavailable to children. 
Period of validity of 5 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

In 1 tablet of Spironolactonum of 25 mg or 100 mg, packaging contains 20 tablets.