Dosage form:
Round, flat-cylindrical tablets of white or white with a yellowish tint, with a risk on one side and a chamfer on both sides, with a characteristic odor.
Composition:
Per tablet:
Active ingredient: spironolactone 25.0 mg
Excipients:
Lactose Monohydrate (Milk Sugar) 117.0 mg
Corn starch 50.0 mg
Povidone-K25 5.0 mg
Silicon Colloidal Dioxide 1.0 mg
Magnesium Stearate 2.0 mg
Pharmacodynamics:
Potassium-sparing diuretic, the effect of which is due to the antagonism of aldosterone (mineralocorticosteroid hormone of the adrenal cortex). Aldosterone promotes the reverse absorption of sodium ions in the renal tubules and enhances the excretion of potassium ions.
Spironolactone is a competitive aldosterone antagonist in influencing the distal nephron (competes for binding sites on cytoplasmic protein receptors, reduces the synthesis of permeases in the aldosterone-dependent portion of the collecting tubules and distal tubules), increases the excretion of sodium, chlorine and water ions and reduces the excretion of potassium ions and urine and urine ions reduces the acidity of urine.
Increased diuresis causes an antihypertensive effect, which is unstable. The diuretic effect is manifested on 2-5 days of treatment.
Indications:
Essentsial'naya gipertenziya (v sostave kombinirovannoy terapii); - otechnyy sindrom pri khronicheskoy serdechnoy nedostatochnosti (mozhet primenyat'sya v monoterapii i v sostave kombinirovannoy terapii); - sostoyaniya, pri kotorykh mozhet obnaruzhivat'sya vtorichnyy giperal'dosteronizm, vklyuchaya tsirroz pecheni, soprovozhdayushchiysya astsitom i/ili otekami, nefroticheskiy sindrom, a takzhe drugiye sostoyaniya, soprovozhdayushchiyesya otekami; - gipokaliyemiya/gipomagniyemiya (v kachestve vspomogatel'nogo sredstva dlya yeye profilaktiki vo vremya lecheniya diuretikami pri nevozmozhnosti primeneniya drugikh sposobov korrektsii soderzhaniya kaliya); - pervichnyy giperal'dosteronizm (sindrom Konna) - dlya korotkogo predoperatsionnogo kursa lecheniya; - dlya ustanovleniya diagnoza pervichnogo giperal'dosteronizma; - tyazhelaya khronicheskaya serdechnaya nedostatochnost' (III-IV funktsional'nyy klass po klassifikatsii NYHA) na fone standartnoy terapii
Pharmacokinetics:
When taken orally, it is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is 100%. The maximum concentration with daily intake of 100 mg for 15 days is 80 ng / mg, the time required to reach the maximum concentration after the next morning intake is 2.6 hours. After absorption, several active sulfur-containing metabolites are metabolized in the liver (80%), including canrenone (20%), the maximum concentration of which is determined 2-4 hours after ingestion. Communication with blood plasma proteins - 98% (canrenone - 90%).
It penetrates poorly into organs and tissues, but penetrates the placental barrier, and canrenone - into breast milk. Distribution volume - 0,05 l / kg. It is excreted by the kidneys (50% in the form of metabolites, 10% in unchanged form), partially through the intestines. The elimination of canrenone (mainly by the kidneys) is two-phase, the half-life in the first phase is 2-3 hours, in the second 12-96 hours. With cirrhosis and chronic heart failure, the half-life increases without signs of cumulation (its probability increases against the background of chronic renal failure and hyperkalemia). The half-life is 13-24 hours
Side effects:
From the digestive system: nausea, vomiting, diarrhea, ulceration and bleeding of the gastrointestinal tract, gastritis, intestinal colic, abdominal pain, diarrhea or constipation, impaired liver function.
From the nervous system: ataxia, lethargy, dizziness, headache, drowsiness, lethargy, confusion, muscle spasm.
From the endocrine system: with prolonged use - gynecomastia, erectile dysfunction in men, decreased potency; in women - dysmenorrhea, amenorrhea, menorrhagia in the menopause, hirsutism, hypertrichosis, coarsening of the voice, pain in the area of the mammary glands, carcinoma of the mammary gland.
From the urinary system: acute renal failure.
From the hemopoietic organs: agranulocytosis, thrombocytopenia, megaloblastosis. Allergic reactions: drug fever, urticaria, maculopapular and erythematous rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.
From the skin: alopecia, itching.
On the part of laboratory indicators: increased urea concentration, hypercreatininemia, hyperuricemia, impaired water-electrolyte metabolism and acid-base state (metabolic hypochloremic acidosis or alkalosis). Other: spasms of the calf muscles, muscle spasm.
Special conditions:
Vozmozhno vremennoye povysheniye kontsentratsii azota mocheviny v syvorotke krovi, osobenno pri snizhennoy funktsii pochek i giperkaliyemii. Vozmozhen obratimyy giperkhloremicheskiy metabolicheskiy atsidoz.
Pri narusheniyakh funktsii pochek i pecheni, a takzhe v pozhilom vozraste, neobkhodim regulyarnyy kontrol' pokazateley elektrolitov syvorotki krovi i funktsii pochek. Preparat zatrudnyayet opredeleniye digoksina, kortizola i adrenalina v krovi. Nesmotrya na otsutstviye pryamogo vozdeystviya na uglevodnyy obmen, nalichiye sakharnogo diabeta, osobenno s diabeticheskoy nefropatiyey, trebuyet osoboy ostorozhnosti iz-za vozmozhnosti razvitiya giperkaliyemii.
Pri lechenii nesteroidnymi protivovospalitel'nymi preparatami sleduyet kontrolirovat' funktsiyu pochek i pokazateli elektrolitov krovi. Sleduyet izbegat' upotrebleniya pishchi, bogatoy kaliyem. Vo vremya lecheniya upotrebleniye alkogolya protivopokazano. Vliyaniye preparata na sposobnost' k upravleniyu transportnymi sredstvami i drugimi mekhanizmami:
V nachal'nom periode lecheniya zapreshchayetsya upravlyat' transportnymi sredstvami i zanimat'sya drugimi potentsial'no opasnymi vidami deyatel'nosti, trebuyushchimi povyshennoy kontsentratsii vnimaniya i bystroty psikhomotornykh reaktsiy. Dlitel'nost' ogranicheniy ustanavlivayetsya v individual'nom poryadke.
1256/5000
Special conditions:
A temporary increase in the concentration of urea nitrogen in the blood serum is possible, especially with reduced renal function and hyperkalemia. Possible reversible hyperchloremic metabolic acidosis.
In cases of impaired renal and hepatic function, as well as in old age, regular monitoring of serum electrolytes and renal function is necessary. The drug makes it difficult to determine digoxin, cortisol and adrenaline in the blood. Despite the absence of a direct effect on carbohydrate metabolism, the presence of diabetes mellitus, especially with diabetic nephropathy, requires special care because of the possibility of developing hyperkalemia.
In the treatment of non-steroidal anti-inflammatory drugs, kidney function and blood electrolyte counts should be monitored. Avoid eating potassium-rich foods. During treatment, alcohol is contraindicated. The effect of the drug on the ability to drive vehicles and other mechanisms:
In the initial period of treatment, it is forbidden to drive vehicles and engage in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions. The duration of the restrictions is set individually.
Contraindications:
- Hypersensitivity to spironolactone and any of the components of the drug.
- Addison's disease;
- hyperkalemia; - hyponatremia; - severe renal failure (creatinine clearance less than 10 ml / min); - anuria; - Lactose deficiency, lactase intolerance, glucose-galactose malabsorption syndrome;
- pregnancy;
- lactation (breastfeeding);
- children's age up to 3 years (solid dosage form); - the simultaneous use of eplerenone and other potassium-sparing diuretics, potassium preparations (risk of hyperkalemia).
With caution: Atrioventricular block (the possibility of strengthening in connection with the development of hyperkalemia);
diabetes mellitus (with confirmed or suspected chronic renal failure); diabetic nephropathy; dysmenorrhea; hypercalcemia; metabolic acidosis; liver failure, cirrhosis; surgical interventions; gynecomastia and the simultaneous administration of drugs that cause gynecomastia; local and general anesthesia; elderly age. Pregnancy and lactation:
The use of the drug during pregnancy and during breastfeeding is contraindicated.
If necessary, use during lactation, breastfeeding should be discontinued.
Drug Interactions:
Reduces the effect of anticoagulants, indirect anticoagulants (heparin, coumarin derivatives, indandion) and toxicity of cardiac glycosides (since normalization of potassium in the blood prevents the development of toxicity).
Enhances the metabolism of phenazole (antipyrine). Reduces vascular sensitivity to norepinephrine (requires caution when conducting anesthesia). Increases the half-life of digoxin - digoxin intoxication is possible.
Enhances the toxic effect of lithium due to a decrease in its clearance.
Accelerates the metabolism and excretion of carbenoxolone. Carbenoxolone promotes sodium retention with spironolactone. Glucocorticosteroid drugs and diuretics (benzothiazine derivatives, furosemide, ethacrylic acid) enhance and accelerate the diuretic and natriuretic effect.
Enhances the effect of diuretic and antihypertensive drugs. Nonsteroidal anti-inflammatory drugs reduce diuretic and natriuretic effects, the risk of developing hyperkalemia increases.
Glucocorticosteroid drugs enhance the diuretic and natriuric effect in case of hypoalbuminemia and / or hyponatremia. The risk of hyperkalemia increases when taken with potassium preparations, potassium supplements and potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (acidosis), angiotensin II receptor antagonists, aldosterone blockers, indomethacin, cyclosporin. Salicylates, indomethacin reduce the diuretic effect. Ammonium chloride, colestyramine contribute to the development of hyperkalemic metabolic acidosis. Fludrocortisone causes a paradoxical increase in tubular secretion of potassium. Reduces the effect of mitotan.
Enhances the effect of triptorelin, buserelin, gonadorelin. Ethanol, barbiturates, narcotic substances increase orthostatic hypotension.
Dosage:
Inside. At the same time as eating. With essential hypertension: The daily dose for adults is usually 50-100 mg once and can be increased to 200 mg, and the dose should be increased gradually, once every 2 weeks. To achieve an adequate response to therapy, the drug must be taken for at least 2 weeks.
If necessary, carry out dose adjustment. With idiopathic hyperaldosteronism: 100-400 mg / day. With severe hyperaldosteronism and hypokalemia: The daily dose is 300 mg / day (maximum 400 mg) for 2-3 doses, with improvement, the dose is gradually reduced to 25 mg / day. With hypokalemia and / or hypomagnesemia caused by diuretic therapy: Prescribe the drug at a dose of 25-100 mg / day once or in several doses.
The maximum daily dose is 400 mg if potassium preparations for oral administration or other methods of replenishing its deficiency are ineffective. In the diagnosis and treatment of primary hyperaldosteronism as a diagnostic tool for a short diagnostic test:
The drug is prescribed for 4 days at 400 mg / day, distributing the daily dose in several doses per day. With an increase in potassium in the blood while taking the drug and a decrease after discontinuing it, we can assume the presence of primary hyperaldosteronism. With a long diagnostic test:
The drug is prescribed in the same dose for 3-4 weeks. When correcting hypokalemia and arterial hypertension, primary hyperaldosteronism can be assumed. Short course of preoperative therapy of primary hyperaldosteronism: After the diagnosis of hyperaldosteronism is established using more accurate diagnostic methods, Spironolactone should be taken 100-400 mg / day. dividing by 1-4 doses per day during the entire period of preparation for surgical intervention. If the operation is not indicated, then Spironolactone is used for long-term maintenance therapy, while the lowest effective dose is applied, which is selected individually for each patient. Edema on the background of nephrotic syndrome:
The daily dose for adults is usually 100-200 mg. No effect of spironolactone on the main pathological process was revealed, and therefore the use of this drug is recommended only in cases where other types of therapy are ineffective. With edematous syndrome against a background of chronic heart failure: The drug is prescribed daily, for 5 days, 100-200 mg / day in 2-3 doses.
Depending on the effect, the daily dose is reduced to 25 mg. The maintenance dose is selected individually. The maximum dose is 200 mg / day. Edema with cirrhosis: If in the urine the ratio of sodium and potassium ions (Na + / K +) exceeds 1.0, then the daily dose for adults is usually 100 mg. If the ratio is less than 1.0, then the daily dose for adults is usually 200-400 mg. The maintenance dose is selected individually.
For edema in children: The initial dose is 1-3.3 mg / kg body weight or 30-90 mg / m2 / day. in 1-4 doses. After 5 days, the dose is adjusted and, if necessary, increased by 3 times compared to the original. Use in elderly patients: It is recommended to start treatment with a minimum dose and titrate it until the maximum dose is achieved under the control of liver / kidney function.
Severe chronic heart failure (NYHA Class III-IV functional class) with standard therapy: Treatment begins with 25 mg once a day if serum potassium is less than 5.0 mEq / L and blood creatinine is less than 2.5 mg / l Patients who tolerate a dose of 25 mg 1 time / day can increase the dose to 50 mg 1 time / day.
Treatment is carried out under the control of potassium and blood creatinine levels one week after the start of therapy or an increase in the dose, then monthly for the first 3 months, then quarterly for a year, and then every 6 months.
Overdose:
Symptoms: nausea, vomiting, dizziness, decreased blood pressure, diarrhea, skin rash, hyperkalemia (paresthesia, myasthenia gravis, arrhythmias, weakness), hyponatremia (dry mouth, thirst, drowsiness), hypercalcemia, dehydration, increased urea concentration.
Treatment: gastric lavage, symptomatic therapy of dehydration and arterial hypotension. With hyperkalemia, it is necessary to normalize water-electrolyte metabolism using potassium-excreting diuretics, rapid parenteral administration of a solution of dextrose (glucose) (5-20% solutions) with insulin at the rate of 0.25-0.5 PIECES per 1 g of dextrose (glucose); if necessary, reintroduction of dextrose (glucose) is possible. In severe cases, hemodialysis is performed.
