Verospilactone^® (Capsules) Instructions for Use

Marketing Authorization Holder

Aliym, JSC (Russia)

Contact Information

ALIUM JSC (Russia)

ATC Code

C03DA01 (Spironolactone)

Active Substance

Spironolactone (Rec.INN registered by WHO)

Dosage Forms

	Verospilactone®	Capsules 25 mg: 10, 14, 15, 20, 28, 30, 40, 42, 45 or 60 pcs.
		Capsules 50 mg: 10, 14, 15, 20, 28, 30, 40, 42, 45 or 60 pcs.
		Capsules 100 mg: 10, 14, 15, 20, 28, 30, 40, 42, 45 or 60 pcs.
		Tablets 25 mg: 10, 15, 20, 30, 40, 45, 60 or 90 pcs.

Dosage Form, Packaging, and Composition

Tablets white or white with a yellowish, brownish, or pinkish tint, round, flat-cylindrical, with a score on one side, with a bevel, almost odorless or with a weak specific odor.

Excipients: magnesium stearate, lactose monohydrate, potato starch, colloidal silicon dioxide (aerosil), talc.

10 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
15 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
20 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
30 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.

Capsules hard gelatin, size No. 3, with a white body and cap; capsule contents – powder white or white with a yellowish tint.

Excipients: lactose monohydrate, potato starch, sodium lauryl sulfate, colloidal silicon dioxide (aerosil), talc, magnesium stearate.

Composition of the capsule body and cap titanium dioxide, gelatin.

10 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
14 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
15 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
20 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.

Capsules hard gelatin, size No. 3, with a white body and a blue cap; capsule contents – powder white or white with a yellowish tint.

Excipients: lactose monohydrate, potato starch, sodium lauryl sulfate, colloidal silicon dioxide (aerosil), talc, magnesium stearate.

Composition of the capsule body titanium dioxide, gelatin.
Composition of the capsule cap titanium dioxide, patent blue dye, brilliant black dye, gelatin.

10 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
14 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
15 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
20 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.

Capsules hard gelatin, size No. 1, with a blue body and cap; capsule contents – powder white or white with a yellowish tint.

Excipients: lactose monohydrate, potato starch, sodium lauryl sulfate, colloidal silicon dioxide (aerosil), talc, magnesium stearate.

Composition of the capsule body and cap titanium dioxide, patent blue dye, gelatin.

10 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
14 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
15 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.
20 pcs. – contour cell packaging (1, 2, 3) – cardboard packs.

Clinical-Pharmacological Group

Potassium-sparing diuretic

Pharmacotherapeutic Group

Diuretics, potassium-sparing diuretics, aldosterone antagonists

Pharmacological Action

Spironolactone is a potassium-sparing diuretic, a specific long-acting antagonist of aldosterone (a mineralocorticoid hormone of the adrenal cortex).

In the distal parts of the nephron, Spironolactone prevents the retention of sodium and water by aldosterone and suppresses the potassium-excreting effect of aldosterone, reducing the synthesis of permeases in the aldosterone-dependent section of the collecting ducts and distal tubules.

By binding to aldosterone receptors, it increases the excretion of sodium, chloride, and water ions in the urine, reduces the excretion of potassium ions and urea, and decreases urine acidity.

The maximum effect is observed 7 hours after oral administration and lasts for at least 24 hours.

The hypotensive effect of the drug is due to the presence of a diuretic effect, which is inconsistent: the diuretic effect appears on the 2nd-5th day of treatment.

Pharmacokinetics

Absorption and Distribution

When taken orally, it is rapidly and completely absorbed from the gastrointestinal tract.

The maximum concentration C_max of canrenone in blood plasma is reached 2-4 hours after administration.

It binds to blood plasma proteins by approximately 98% (canrenone – 90%). The volume of distribution (V_d) is 0.05 l/kg.

After daily administration of spironolactone at a dose of 100 mg for 15 days, C_max is 80 ng/ml, the time to reach C_max after the next morning dose is 2-6 hours.

Spironolactone poorly penetrates into organs and tissues, while it and its metabolites penetrate the placental barrier, and canrenone passes into breast milk.

Metabolism

Spironolactone is converted into active metabolites: a sulfur-containing metabolite (80%) and partially canrenon (20%).

Excretion

It is excreted by the kidneys: 50% as metabolites, 10% unchanged, and partially through the intestines.

The half-life (T_1/2) of spironolactone is 13-24 hours, of active metabolites – up to 15 hours.

The excretion of canrenone (mainly by the kidneys) is biphasic, T_1/2 in the first phase is 2-3 hours, in the second phase – 12-96 hours.

Pharmacokinetics in Special Patient Groups

In liver cirrhosis and heart failure, the duration of T_1/2 increases without signs of accumulation, the probability of which is higher in chronic renal failure and hyperkalemia.

Indications

• Essential hypertension (as part of combination therapy);
• Edematous syndrome in chronic heart failure (can be used in monotherapy and in combination with standard therapy);
• Conditions in which secondary hyperaldosteronism may be detected, including liver cirrhosis accompanied by ascites and/or edema, nephrotic syndrome, as well as other conditions accompanied by edema;
• Hypokalemia/hypomagnesemia (as an auxiliary agent for its prevention during treatment with diuretics and when other methods of potassium correction are not possible);
• Primary hyperaldosteronism (Conn’s syndrome) – for a short preoperative course of treatment;
• For the diagnosis of primary hyperaldosteronism.

ICD codes

Dosage Regimen

Orally.

Essential hypertension

The daily dose for adults is usually 50-100 mg once and can be increased to 200 mg, with the dose increase being gradual, once every 2 weeks.

To achieve an adequate response to therapy, the drug must be taken for at least 2 weeks.

If necessary, the dose is adjusted.

Idiopathic hyperaldosteronism

Prescribed at a dose of 100-400 mg/day.

Severe hyperaldosteronism and hypokalemia

Prescribed 300 mg/day (maximum 400 mg/day) in 2-3 doses, when the condition improves, the dose is gradually reduced to 25 mg/day.

Hypokalemia and/or hypomagnesemia

For hypokalemia and/or hypomagnesemia caused by diuretic therapy, the drug is prescribed at a dose of 25-100 mg/day, once or in several doses.

The maximum daily dose is 400 mg if oral potassium preparations or other methods of replenishing its deficiency are ineffective.

Diagnosis and treatment of primary hyperaldosteronism

As a diagnostic tool for a short diagnostic test for 4 days at 400 mg/day, divided into several doses per day.

If the blood potassium concentration increases during drug administration and decreases after its withdrawal, primary hyperaldosteronism can be suspected.

For a long diagnostic test: at the same dose for 3-4 weeks.

If correction of hypokalemia and arterial hypertension is achieved, primary hyperaldosteronism can be suspected.

Short course of preoperative therapy for primary hyperaldosteronism

After the diagnosis of hyperaldosteronism is established using more precise diagnostic methods, Verospilactone^® should be taken at 100-400 mg/day, divided into 1-4 doses throughout the preparation period for surgery.

If surgery is not indicated, then Verospilactone^® is used for long-term maintenance therapy, using the lowest effective dose, which is selected individually for each patient.

Edema due to nephrotic syndrome

The daily dose for adults is usually 100-200 mg/day.

No effect of spironolactone on the underlying pathological process has been identified, and therefore the use of this drug is recommended only in cases where other types of therapy are ineffective.

Edematous syndrome due to chronic heart failure

Daily, for 5 days, 100-200 mg/day in 2-3 doses, in combination with a “loop” or thiazide diuretic.

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 due to liver cirrhosis

If the ratio of sodium and potassium ions (Na⁺/K⁺) in the urine 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.

Edema in children

The initial dose in children over 3 years is 1-3.3 mg/kg of 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 initial dose.

Adverse Reactions

From the gastrointestinal tract nausea, vomiting, diarrhea, ulceration and bleeding from the gastrointestinal tract, gastritis, intestinal colic, abdominal pain, constipation.

From the liver: impaired liver function.

From the nervous system: ataxia, lethargy, dizziness, headache, drowsiness, lethargy, confusion, muscle spasm.

From the blood and lymphatic system: agranulocytosis, thrombocytopenia, megaloblastosis.

From laboratory parameters: hyperuricemia, hypercreatininemia, increased urea concentration, disturbance of water-electrolyte balance (hyperkalemia, hyponatremia) and acid-base status (metabolic hyperchloremic acidosis or alkalosis).

From the endocrine system: voice coarsening, in men – gynecomastia (the likelihood of development depends on the dose, duration of treatment and is usually reversible, and disappears after drug withdrawal, and only in rare cases the mammary gland remains somewhat enlarged), decreased potency and erection; in women – menstrual cycle disorders, dysmenorrhea, amenorrhea, metrorrhagia in the climacteric period, hirsutism, breast pain, breast carcinoma (a connection with drug use has not been established).

Allergic reactions: urticaria, maculopapular and erythematous rash, drug fever, skin itching, eosinophilia, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the skin and subcutaneous tissues: alopecia, hypertrichosis.

From the kidneys and urinary tract: acute renal failure.

From the musculoskeletal and connective tissue calf muscle cramps.

From the respiratory system: shortness of breath.

If any of the above adverse reactions worsen or other adverse events not listed in the instructions occur, the patient should inform the doctor.

Contraindications

• Hypersensitivity to any component of the drug;
• Addison’s disease;
• Hyperkalemia;
• Hyponatremia;
• Severe renal failure (creatinine clearance less than 10 ml/min);
• Anuria;
• Pregnancy;
• Lactation period (breastfeeding);
• Children under 3 years of age (for the solid dosage form);
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (because the drug contains lactose monohydrate).

With caution hypercalcemia, metabolic acidosis, AV block (hyperkalemia contributes to its enhancement); diabetes mellitus (with confirmed or suspected chronic renal failure); diabetic nephropathy; surgical interventions, during anesthesia; taking medications that cause gynecomastia; local and general anesthesia; elderly age; menstrual cycle disorders, breast enlargement; hepatic insufficiency, liver cirrhosis.

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy and breastfeeding.

Spironolactone and its metabolites can penetrate the placental barrier.

Spironolactone metabolites are found in breast milk. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution: hepatic insufficiency, liver cirrhosis.

Use in Renal Impairment

Contraindication: severe renal failure (creatinine clearance less than 10 ml/min).

Pediatric Use

Contraindication: children under 3 years of age (for the solid dosage form).

Geriatric Use

With caution: elderly age.

Special Precautions

A temporary increase in blood urea nitrogen levels is possible, especially with reduced renal function and hyperkalemia.

Reversible hyperchloremic metabolic acidosis is possible.

In case of impaired renal and liver function, as well as in elderly patients, regular monitoring of serum electrolytes and renal function is necessary.

The drug complicates the determination of 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 caution due to the possibility of developing hyperkalemia.

During simultaneous treatment with NSAIDs, renal function and blood electrolyte levels should be monitored.

Consumption of food rich in potassium should be avoided.

Alcohol consumption is contraindicated during treatment.

Effect on the ability to drive vehicles and mechanisms

In the initial period of treatment, it is prohibited to drive vehicles and engage in activities requiring increased concentration and speed of psychomotor reactions. The duration of restrictions is set individually.

Overdose

Symptoms: nausea, vomiting, dizziness, diarrhea, skin rash, hyperkalemia (paresthesia, muscle weakness, arrhythmias), hyponatremia (dry mouth, thirst, drowsiness) hypercalcemia, dehydration, increased urea concentration.

Treatment: gastric lavage, symptomatic treatment of dehydration and arterial hypotension.

In case of hyperkalemia, it is necessary to normalize the water-electrolyte balance with the help of potassium-excreting diuretics, rapid parenteral administration of a 5-20% dextrose (glucose) solution with insulin at the rate of 0.25-0.5 units per 1 g of dextrose (glucose); if necessary, it can be repeated.

In severe cases, hemodialysis is performed.

Drug Interactions

Reduces the effect of anticoagulants, indirect anticoagulants (heparin, coumarin derivatives, indandione) and the toxicity of cardiac glycosides (because normalization of blood potassium levels prevents the development of toxicity).

Enhances the metabolism of phenazone (antipyrine).

Reduces vascular sensitivity to norepinephrine (caution is required during anesthesia), increases the T_1/2 of digoxin – digoxin intoxication is possible.

Enhances the toxic effect of lithium due to reduced clearance.

May enhance the effect of non-depolarizing muscle relaxants (e.g., tubocurarine).

Accelerates the metabolism and excretion of carbenoxolone.

Carbenoxolone promotes sodium retention by spironolactone.

Corticosteroids and diuretics (thiazides and thiazide-like, furosemide, ethacrynic acid) enhance and accelerate the diuretic and natriuretic effects.

Enhances the effect of diuretic and antihypertensive drugs.

NSAIDs reduce the diuretic and natriuretic effects and increase the risk of hyperkalemia.

Alcohol (ethanol), barbiturates, and narcotic substances enhance orthostatic hypotension.

Corticosteroids enhance the diuretic and natriuretic effect in cases of hypoalbuminemia and/or hyponatremia.

The risk of hyperkalemia increases when taken with potassium preparations, potassium supplements, and potassium-sparing diuretics, ACE inhibitors (acidosis), angiotensin II receptor antagonists, aldosterone blockers, indomethacin, and cyclosporine.

Salicylates and indomethacin reduce the diuretic effect of spironolactone.

Ammonium chloride and cholestyramine contribute to the development of hyperkalemic metabolic acidosis.

Fludrocortisone causes a paradoxical increase in tubular potassium secretion.

Spironolactone reduces the effect of mitotane.

It enhances the effects of triptorelin, buserelin, and gonadorelin.

Storage Conditions

The drug should be stored out of the reach of children, in a dry place, protected from light, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life of the tablets is 3 years, and of the capsules is 2 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.