Veroshpilactone, tablets 25 mg 20 pcs

Pharmacodynamics

Spironolactone is a potassium-saving diuretic, a specific prolonged aldosterone antagonist (mineralocorticosteroid hormone of the adrenal cortex). In the distal parts of the nephron, spironolactone prevents aldosterone retention of sodium water and suppresses potassium withdrawal effect of aldosterone, reduces the synthesis of permease in aldosterone-dependent part of the collecting tubes and distal tubules. By binding to aldosterone receptors it increases excretion of sodium, chlorine and water ions with urine, decreases excretion of potassium ions and urea, reduces urine acidity.

The maximum effect is observed 7 hours after oral administration and lasts at least 24 hours. The hypotensive effect of the drug is due to the diuretic effect which is not constant: the diuretic effect is seen on the 2nd-5th day of treatment.

Pharmacokinetics

When administered orally, it is quickly and completely absorbed from the gastrointestinal tract and converted to active metabolites: metabolite containing sulfur (80%) and partially canrenone (20%). The maximum concentration (Cmax) of canrenone in blood plasma is reached after 2-4 hours, its binding to plasma proteins is 90%. Binding with blood plasma proteins is about 98% (canrenone 90%).

After daily administration of 100 mg of spironolactone for 15 days, the Cmax reaches 80 mg/mL, the time to reach Cmax after another morning administration is 2-6 hours. Spironolactone penetrates poorly into organs and tissues, with itself and its metabolites penetrating the placental barrier and cancreon into breast milk. The volume of distribution is 0.05 l/kg. The half-life (T½) of spironolactone is 13-24 hours, active metabolites – up to 15 hours.

Extracted by the kidneys: 50% – as metabolites, 10% – unchanged and partially – in feces. Excretion of canrenone (mainly by kidneys) is biphasic, T½ in the first phase is 2-3 hours, in the second phase – 12-96 hours.

In liver cirrhosis and heart failure, the duration of half-life is prolonged without signs of cumulation, which is more likely in chronic renal failure and hyperkalemia.

Indications

Active ingredient

Composition

1 tablet contains

the active ingredient:

spironolactone – 0.025 g

excipients:

magnesium stearate,

lactose (milk sugar),

potato starch,

colloidal silica (aerosil),

talc

How to take, the dosage

Verospilactone is taken orally.

In essential hypertension

The daily dose for adults is usually 50-100 mg once and may be increased up to 200 mg, and the dose should be increased gradually, once every 2 weeks. To achieve an adequate response to therapy, the drug should be taken for at least 2 weeks. Dose adjustment is necessary.

In idiopathic hyperaldosteronism 100-400 mg/day.

In severe hyperaldosteronism and hypokalemia, 300 mg/day (maximum 400 mg) in 2-3 doses; if the condition improves, the dose is gradually reduced to 25 mg/day.

Hypokalemia/hypomagnesemia

In hypokalemia and/or hypomagnesemia caused by therapy with diuretics, the drug is prescribed in 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 potassium deficiency supplementation are ineffective.

Diagnostic treatment of primary hyperaldosteronism

As a diagnostic tool in a short diagnostic test: for 4 days at 400 mg/day, spread over several doses per day. If blood potassium concentration increases while taking the drug and decreases after discontinuation, primary hyperaldosteronism may be suspected.

In the long-term diagnostic test: at the same dose for 3-4 weeks. If correction of hypokalemia and arterial hypertension is achieved, primary hyperaldosteronism can be assumed.

A short course of preoperative therapy for primary hyperaldosteronism

After the diagnosis of hyperaldosteronism is established by more definitive diagnostic methods, Veroshpilactone should be taken at 100-400 mg/day, divided into 1-4 doses per day for the duration of preparation for surgery. If surgery is not indicated, Veroshpilactone is used for long-term supportive therapy, using the lowest effective dose, which is adjusted individually for each patient.

Oedema with nephrotic syndrome

The daily dose for adults is usually 100-200 mg/day. Veroshpilactone has not been found to affect the underlying pathological process, and therefore the use of this drug is recommended only in cases when other therapies are ineffective.

In case of edematous syndrome against the background of chronic heart failure, 100-200 mg/day in 2-3 doses daily for 5 days in combination with “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.

Hepatic cirrhosis edema

If the urinary sodium to potassium ion ratio (Na+/K+) is greater than 1.0, the daily dose for adults is usually 100 mg. If the ratio is less than 1.0, the daily dose for adults is usually 200-400 mg. The maintenance dose is adjusted individually.

Oedema in children

The starting 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 to 3 times the original dose.

Interaction

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

Accelerates metabolism of phenazole (antipyrine).

Decreases vascular sensitivity to noepinephrine (requires caution during anesthesia), increases the half-life of digoxin – possible intoxication – digoxin.

Worsens the toxic effects of lithium due to decreased clearance.

Accelerates metabolism and excretion of carbenoxolone.

Carbenoxolone promotes sodium retention by spironolactone.

Glucocorticosteroid drugs and diuretics (benzothiadiazine derivatives, furosemide, etacrynic acid) enhance and accelerate diuretic and natriuretic effects.

It enhances the effect of diuretic and hypotensive drugs. Nonsteroidal anti-inflammatory drugs reduce diuretic and natriuretic effects, the risk of hyperkalemia increases.

Glucocorticosteroid drugs increase diuretic and natriuretic effects with hypoalbuminemia and/or hyponatremia.

The risk of hyperkalemia increases when taken with potassium preparations, potassium supplements and potassium-saving diuretics, angiotensin-converting enzyme inhibitors (acidosis), angiotensin P antagonists, aldosterone blockers, indomethacin, cyclosporine. Salicylates, indomethacin reduce diuretic effect.

Ammonium chloride, colestyramine contribute to hyperkalemic metabolic acidosis.

Fludrocortisone causes paradoxical enhancement of the tubular section of potassium. Reduces the effect of mitotane.
It enhances the effect of triptorelin, buserelin, gonadorelin.

Special Instructions

Transient elevation of serum urea nitrogen levels may occur, especially with reduced renal function and hyperkalemia. Reversible hyperchloremic metabolic acidosis is possible.

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

The drug makes it difficult to determine digoxin, cortisol and adrenaline in the blood. Although there is no direct effect on carbohydrate metabolism, the presence of diabetes mellitus, especially with diabetic nephropathy, requires special caution due to the possibility of hyperkalemia.
Renal function and blood electrolyte levels should be controlled when treated with nonsteroidal anti-inflammatory drugs.
Foods rich in potassium should be avoided.

Alcohol consumption is contraindicated during treatment.

The effect of the drug on the ability to drive vehicles and mechanisms with increased risk of injury.
During 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 determined on an individual basis.

Contraindications

With caution: Hypercalcemia, metabolic acidosis, atrioventricular block (hypercalemia contributes to its enhancement), diabetes mellitus (with confirmed or suspected chronic renal failure), diabetic nephropathy, surgical interventions, taking drugs that cause gynecomastia, local and general anesthesia, older age, menstrual cycle disorders, enlargement of the breast, liver failure.

Side effects

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

Liver disorders: liver function impairment.

Central nervous system: ataxia, lethargy, dizziness, headache, drowsiness, lethargy, confusion, muscle spasm. Blood system: leukopenia (including agranulocytosis), thrombocytopenia.

Endocrine system disorders: coarsening of the voice, in men – gynecomastia (the probability of development depends on the dose, duration of treatment and is usually reversible); reduced potency and erections; in women – menstrual cycle disorders; dysmenorrhea, amenorrhea, metrorrhea in menopause, hirsutism, breast pain, breast carcinoma (no association with taking the drug is established).

Metabolic disorders: hypercreatininemia, increased concentration of urea, disorders of fluid-salt metabolism (hyperkalemia, hyponatremia) and acid-base balance (metabolic hyperchloremic acidosis or alkalosis), hyperuricemia.

When using Veroshpilactone, gynecomastia may develop. The likelihood of gynecomastia depends on the dose of the drug and the duration of therapy. However, gynecomastia is usually reversible and disappears after withdrawal of the drug, and only in rare cases the pectoral gland remains slightly enlarged.

Allergic reactions: urticaria, rarely maculopapular and erythematous rash, drug fever, itching.

Skin disorders: alopecia, hypertrichosis.
Urinary system disorders: acute renal failure.
Musculoskeletal system disorders: calf cramps.

Overdose

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

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

In hyperkalemia it is necessary to normalize water-electrolyte metabolism with the help of potassium withdrawal diuretics, rapid parenteral administration of 5-20% dextrose solution with insulin at the rate of 0.25-0.5 units per 1 g dextrose; if necessary it can be reintroduced.

In severe cases hemodialysis is performed.

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