Instructions Spironolactone film-coated tablets 25 mg blister No. 50
Composition
active ingredient spironolactone;
1 tablet contains 25 mg, 50 mg or 100 mg of spironolactone;
excipients:
25 mg and 100 mg tablets: calcium sulfate dihydrate, corn starch, povidone 30, magnesium stearate, mint flavoring, Opadry White 03F180011 [hypromellose, macrogol 8000, titanium dioxide (E 171)], iron oxide yellow (E 172);
50 mg tablets: calcium sulfate dihydrate, corn starch, povidone 30, magnesium stearate, mint flavoring, Opadry White 03F180011 [hypromellose, macrogol 8000, titanium dioxide (E 171)].
Dosage form
Film-coated tablets.
Main physicochemical properties:
25 mg and 100 mg tablets: film-coated tablets, pale yellow to yellow in color, straight solid cylinders with convex end surfaces;
50 mg tablets: film-coated tablets, white or almost white, straight solid cylinders with convex end surfaces.
Pharmacotherapeutic group
Drugs affecting the cardiovascular system. Diuretics. Aldosterone antagonists and other potassium-sparing drugs. Aldosterone antagonists. Spironolactone.
ATX code C03D A01.
Pharmacological properties
Pharmacodynamics
Spironolactone is a specific aldosterone antagonist that acts primarily by competitively binding to receptors at the aldosterone-dependent site of sodium-potassium exchange in the distal renal tubule. Spironolactone acts as a potassium-sparing diuretic, causing increased excretion of sodium and water while conserving potassium and magnesium.
By acting on the distal parts of the renal tubules, spironolactone enhances the effect of conventional diuretics, which act mainly in the proximal part, thereby increasing the influx of sodium into the distal part. Under the influence of aldosterone, sodium is reabsorbed in the distal segment of the tubule in exchange for potassium, thus reducing diuresis. Diuretics themselves can affect the metabolism of glucose and uric acid. The diuretic effect of spironolactone begins gradually and reaches a maximum on the 3rd day. After the end of therapy, the diuretic effect persists for another 2–3 days.
Pharmacokinetics.
Absorption
Food increases the bioavailability of spironolactone by increasing absorption and possibly decreasing the metabolism of spironolactone as it passes through the body.
Bioavailability is > 90%.
After administration of 100 mg of spironolactone daily for 15 days to healthy volunteers after a meal, the tmax was 2.6 hours, Cmax was 80 ng/ml, and t1/2 was 1.4 hours. For the metabolite 7-alpha-(thiomethyl)-spironolactone, the tmax was 3.2 hours, Cmax was 391 ng/ml, and t1/2 was 13.8 hours, and for canrenone, the tmax was 4.3 hours, Cmax was 181 ng/ml, and t1/2 was 16.5 hours.
Distribution
The binding of spironolactone and canrenone to blood plasma proteins is over 90%.
Metabolism
After oral administration, spironolactone is rapidly and completely metabolized.
The two main active metabolites of spironolactone are canrenone and 7-alpha-(thiomethyl)-spironolactone.
Excretion from the body
Spironolactone and its metabolites are excreted mainly in the urine and to a lesser extent in the bile and feces.
Spironolactone and its metabolites cross the placental barrier. Canrenone passes into breast milk.
Indication
Essential hypertension
Spironolactone should be prescribed together with other antihypertensive agents when conventional agents are ineffective or cause undesirable effects.
Hypertension
With increased aldosterone secretion, hypokalemia and metabolic alkalosis.
Edema in heart failure
Especially in patients receiving digitalis therapy and in patients at risk of diuretic-induced hypokalemia.
Liver cirrhosis with ascites
This condition is often associated with very high levels of aldosterone.
Nephrotic syndrome
When conventional measures, such as limiting water and salt intake, and therapy with conventional diuretics do not produce the desired result.
Idiopathic edema
In the presence of secondary aldosteronism.
Primary hyperaldosteronism
Diagnosis and therapy.
Contraindication
The use of spironolactone is contraindicated:
- in acute renal failure;
- in severe renal failure (creatinine clearance < 30 ml/min);
- with anuria;
- with Addison's disease;
- with hyperkalemia;
- with hyponatremia;
- in case of simultaneous use of eplerenone;
- with hypersensitivity to spironolactone or to any of the excipients included in the medicinal product;
- during pregnancy or breastfeeding.
Interaction with other medicinal products and other types of interactions
Spironolactone may potentiate the effects of other diuretics and antihypertensive agents. Therefore, their doses may need to be reduced when spironolactone is used.
Noradrenaline and adrenaline: Spironolactone reduces vascular sensitivity to noradrenaline and adrenaline. This should be taken into account when performing local or general anesthesia with these drugs.
Digoxin: Spironolactone may prolong the half-life of digoxin, so the dose of digoxin should be reduced when co-administered. In addition, the patient should be closely monitored to prevent digitalis toxicity.
Effect of the drug on laboratory test results: may affect the process of determining the concentration of digoxin in blood plasma by radioimmunological methods and cause falsely elevated values, as well as interfere with the determination of cortisol.
Nonsteroidal anti-inflammatory drugs (NSAIDs): In some patients, NSAIDs (e.g., aspirin, indomethacin, and mefenamic acid) may reduce the diuretic, natriuretic, and antihypertensive effects of diuretics by inhibiting intrarenal prostaglandin synthesis, and have been shown to reduce the diuretic effect of spironolactone. The risk of hyperkalemia is increased when NSAIDs and spironolactone are used concomitantly.
Antipyrine: Spironolactone stimulates the metabolism of antipyrine.
ACE inhibitors and furosemide: Acute renal failure may occur with the simultaneous use of spironolactone, ACE inhibitors and furosemide.
Ammonium chloride, cholestyramine: Hyperkalemic metabolic acidosis has been reported with concomitant administration of spironolactone with ammonium chloride or cholestyramine.
Carbenoxolone: Concomitant use of spironolactone and carbenoxolone may reduce the effectiveness of both drugs.
Neomycin may slow the absorption of spironolactone.
Abiraterone: When used concomitantly, spironolactone binds to the androgen receptor and may increase prostate-specific antigen (PSA) levels in prostate cancer patients treated with abiraterone. Use with abiraterone is not recommended.
Application features
During treatment with spironolactone, the concomitant use of potassium supplements, high-potassium diets, other potassium-sparing diuretics, potassium-containing salt substitutes, ACE inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin II antagonists, aldosterone receptor antagonists, heparin or low molecular weight heparins, trimethoprim and other drugs or conditions that cause hyperkalemia may lead to severe hyperkalemia, especially in the presence of renal failure.
Reversible hyperchloremic metabolic acidosis, usually associated with hyperkalemia, has been observed in some patients with decompensated cirrhosis, even with normal renal function.
Caution should be exercised in patients prone to acidosis and/or hyperkalemia due to underlying disease (e.g. diabetes mellitus).
Periodic determination of serum electrolytes and renal function is indicated, especially in elderly patients and/or patients with pre-existing renal or hepatic insufficiency due to the possibility of developing hyperkalemia, hyponatremia, and transient increases in blood urea nitrogen (BUN).
In addition, caution is required in case of mild renal impairment (serum creatinine from 1.2 mg/100 ml to 1.8 mg/100 ml or creatinine clearance from 30 mg/min to 60 ml/min), hypotension and hypovolemia.
It is necessary to avoid losing weight too quickly.
Hyperkalemia in patients with severe heart failure
Hyperkalemia can be life-threatening. In patients with severe heart failure, serum potassium levels should be monitored.
Potassium-sparing diuretics should be avoided. Oral potassium supplements should also be avoided in patients with serum potassium levels above 3.5 mmol/L. It is recommended to monitor potassium and creatinine levels one week after initiation of treatment or after dose increases, then monthly for three months, then four times a year for one year, and then every six months. Treatment should be discontinued or interrupted if serum potassium levels exceed 5 mmol/L or if serum creatinine levels exceed 4 mg/dL.
Use during pregnancy or breastfeeding
Pregnancy
Feminization of the genitals of male offspring has been observed in animal studies with the use of spironolactone. Therefore, the drug should not be used during pregnancy unless clearly necessary.
Breast-feeding.
Canrenone, a metabolite of spironolactone, may pass into breast milk. Therefore, it is not recommended to prescribe spironolactone to nursing mothers. If treatment is necessary, breastfeeding should be discontinued.
Ability to influence reaction speed when driving vehicles or other mechanisms
Method of administration and doses
Spironolactone is usually prescribed together with conventional diuretics, since the full effect of spironolactone can be expected no earlier than the 3rd day of treatment. Adults can take the daily dose once or in several doses. The maintenance dose should always be set individually.
Essential hypertension
The usual starting dose for adults is 50–100 mg per day as a single dose or in 2 divided doses during the day, and it is advisable to take spironolactone in combination with other antihypertensive agents. In severe cases, the dose can be increased at intervals of 2 weeks to 200 mg per day. The success of treatment should be assessed no earlier than after 2 weeks, since the effect of spironolactone is often delayed. Individual dosage is then carried out. With long-term treatment with spironolactone, a dose reduction is always indicated.
Adjunctive therapy for hypertension in the presence of increased aldosterone secretion, hypokalemia, and metabolic alkalosis
In combination with other antihypertensive agents, the initial dose is 100 mg per day. If necessary, the dose can be increased to 200 mg per day within 2 weeks.
Edema in heart failure
The usual dose for adults is 100 mg per day. In difficult cases, the dose can be increased to 200 mg per day. After the appearance of diuresis, a dose reduction can be attempted. For maintenance therapy, 25–100 mg per day is usually prescribed (see section “Special instructions” regarding hyperkalemia in patients with severe heart failure).
Liver cirrhosis with ascites
If the ratio of Na/K in the urine is more than 1, then the daily dose is 100 mg. If the ratio is less than 1, then the dose of the drug should be 200–400 mg/day. After weight stabilization, the minimum possible dose should be selected for maintenance therapy to prevent any undesirable effects of diuretic therapy.
Nephrotic syndrome
The usual dose is 100–200 mg per day. Spironolactone has no anti-inflammatory effect and does not affect the underlying disease process. Therefore, spironolactone should be used only in cases where fluid and salt restriction and the use of conventional diuretics are ineffective.
Idiopathic edema
100 mg per day.
Diagnosis and treatment of primary hyperaldosteronism
In patients who follow a normal diet, spironolactone can be used as an initial diagnostic tool when detecting the first signs of primary hyperaldosteronism.
Short-term test
Adults 400 mg spironolactone daily for 4 days. If serum potassium increases with spironolactone and decreases after discontinuation of spironolactone, a diagnosis of primary hyperaldosteronism should be considered.
Long-term test
Adults: 400 mg spironolactone daily for 3–4 weeks. Correction of hypokalemia and hypertension suggests possible primary hyperaldosteronism. After further evaluation establishes the diagnosis of hyperaldosteronism, spironolactone may be given in doses of 100–400 mg daily in preparation for surgery.
In inoperable patients, the dose of spironolactone should be individually titrated to the minimum effective dose.
Hypokalemia
To correct potassium deficiency caused by diuretics or if oral potassium is contraindicated: 25–100 mg per day.
Children.
Edema in children
The initial dose is 1.5–3.0 mg/kg body weight per day in divided doses. The dosage should be adjusted based on response to treatment and tolerability.
A suspension can be prepared by crushing 25 mg Spironolactone tablets and dissolving them in a small amount of glycerin, then dissolving in the syrup. The stability of the suspension is guaranteed for 1 month when stored in the refrigerator.
Overdose
Symptoms
Acute overdose of spironolactone may cause symptoms such as nausea, vomiting, drowsiness, confusion, maculopapular or erythematous rash, diarrhea. Electrolyte imbalance (e.g., hyperkalemia, hyponatremia) or dehydration may occur.
It is also possible to have disturbances in the formation and conduction of impulses in the heart (for example, atrioventricular block, atrial fibrillation, ventricular fibrillation, cardiac arrest) and ECG changes (tall T waves and progressive widening of the QRS complex).
Treatment
Symptomatic and supportive measures should be taken. Induce vomiting or gastric lavage. There is no specific antidote. Treat dehydration, electrolyte imbalance and hypotension with standard measures. Hyperkalemia can be treated with rapid glucose infusion (20–50%) and regular insulin (0.25–0.5 U/g glucose). Potassium-sparing diuretics and ion exchange resins can also be used. Spironolactone should be discontinued and potassium intake should be restricted (including potassium-containing products).
Side effects
The most common adverse reactions in patients treated with spironolactone were hyperkalemia and gynecomastia. All medically significant adverse reactions observed in clinical trials and during post-marketing use of spironolactone are listed below by MedDRA system organ class using the following MedDRA frequency definitions: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
Neoplasms benign, malignant and unspecified (including cysts and polyps): uncommon - in men: benign breast neoplasms.
Blood and lymphatic system disorders: rarely - leukopenia (including agranulocytosis), thrombocytopenia, eosinophilia in patients with liver cirrhosis.
Metabolism and nutrition: uncommon - life-threatening hyperkalemia (see cardiac adverse reactions below), hyponatremia, acidosis (spironolactone may induce or exacerbate hyperchloremic metabolic acidosis), increased urea or increased urinary nitrogen and creatinine, increased uric acid.
Hyponatremia is possible, especially after frequent fluid intake. Electrolyte changes may manifest as cardiac arrhythmias, fatigue, general muscle weakness, muscle tension (e.g., calf cramps), or dizziness.
From the nervous system: often - confusion, dizziness; infrequently - headache, drowsiness, lethargy, ataxia.
Cardiac: often - dangerous hyperkalemia (especially in patients with impaired renal function), which can lead to cardiac arrhythmia and hyperkalemic paralysis.
Vascular disorders: rarely - vasculitis.
Gastrointestinal: often - nausea; infrequently - gastrointestinal disorders such as diarrhea and cramps, vomiting; rarely - gastritis, bleeding from the gastric mucosa, ulcers.
From the liver and biliary tract: rarely - jaundice, hepatitis, hepatotoxicity with increased levels of liver enzymes.
Skin and subcutaneous tissue disorders: common: pruritus, erythematous or maculopapular rash; uncommon: erythema annulare, urticaria, alopecia, hypertrichosis, hirsutism, skin changes similar to lupus erythematosus and lichen planus; frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).
Musculoskeletal and connective tissue disorders: often - muscle cramps of the lower extremities; rarely - osteomalacia.
Renal and urinary disorders: often - acute renal failure.
On the part of the genitals and breast: often - mostly reversible gynecomastia (development depends on the dose and duration of treatment), in men: mastodynia; infrequently - erectile dysfunction, impotence, decreased sperm motility and number, changes in libido, in women: irregular menstruation or amenorrhea, postmenopausal bleeding, mastodynia.
General disorders and administration site conditions: common: malaise; frequency unknown: fever. In some cases, irreversible changes in the voice, such as hoarseness, and in women, also a deepening of the voice pitch, are possible.
Reporting of adverse reactions. Reporting of adverse reactions after registration of a medicinal product is of great importance. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of a medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 30 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister; 2 or 3 or 5 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
Technolog PJSC.
Location of the manufacturer and address of the place of its activity. Ukraine, 20300, Cherkasy region, Uman city, Stara Prorizna street, building 8.
