Verospiron, 50 mg capsules, 30 pcs.

Pharmacodynamics

Veroshpiron is a potassium-saving, diuretic. Spironolactone is a potassium-saving diuretic, a specific aldosterone antagonist (mineralocorticosteroid hormone of the adrenal cortex) with prolonged action.

In the distal nephron, spironolactone prevents sodium and water retention by aldosterone and suppresses potassium withdrawal effect of aldosterone, reduces the synthesis of permease in aldosterone-dependent section of the collecting tubes and distal tubules.

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. Increased diuresis is caused by the presence of diuretic effect, which is not constant; diuretic effect appears on the 2nd-5th day of treatment.

Pharmacokinetics

Absorption and distribution

On oral administration it is quickly and completely absorbed from the gastrointestinal tract. It is about 98% bound to plasma proteins (canrenone – 90%). Tmax of canrenone in blood plasma is 2-4 hours. After daily administration of 100 mg of spironolactone for 15 days, Cmax reaches 80 ng/ml, Tmax after another morning dose is 2-6 hours. Vd is 0.05 l/kg.

Metabolism

Spironolactone is converted to active metabolites: metabolite containing sulfur (80%) and partially to canrenone (20%). Spironolactone poorly penetrates into organs and tissues, while it and its metabolites pass through the placental barrier and canrenone into breast milk.

Elimation

Extracted by the kidneys: 50% – as metabolites, 10% – unchanged and partially through the intestine. T1/2 of spironolactone is 13-24 hours, the active metabolites – up to 15 hours.

Extraction of canrenone (mainly by kidneys) is biphasic; T1/2 in the first phase is 2-3 hours, in the second phase – 12-96 hours.

In liver cirrhosis and heart failure: T1/2 duration increases without evidence of cumulation, which is more likely in chronic renal failure and hyperkalemia.

Indications

Liver cirrhosis, Edema, Heart failure, Hypertension (high blood pressure)

Primary hyperaldosteronism (Conn’s syndrome) – for short preoperative treatment.

To establish the diagnosis of primary hyperaldosteronism. Essential hypertension (as part of combination therapy). Edematous syndrome in chronic heart failure (can be used as monotherapy and in combination with standard therapy).

Conditions in which secondary hyperaldosteronism may be found, including liver cirrhosis accompanied by ascites and/or edemas, nephrotic syndrome and other conditions accompanied by edemas.

Hypkalemia/hypomagnesemia (as an adjunct to its prophylaxis during treatment with diuretics and when other methods of correction of potassium levels are not possible).

Active ingredient

Spironolactone

Composition

1 capsule contains:

Active ingredients:

Spironolactone – 50 mg.

Auxiliary substances:

sodium lauryl sulfate – 2.5 mg,

magnesium stearate – 2.5 mg,

corn starch – 42.5 mg,

lactose monohydrate – 127.5 mg.

Composition of the hard gelatin capsule:

Cap – quinoline yellow dye (E104) – 0.48%,

titanium dioxide (E171) – 2%,

gelatin – up to 100%;

casing – titanium dioxide (E171) – 2%,

gelatin – up to 100%.

How to take, the dosage

In essential hypertension, the daily dose for adults is usually 50-100 mg once and may 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 should be taken for at least 2 weeks.

The dose is adjusted if necessary. In idiopathic hyperaldosteronism the drug is prescribed in dose of 100-400 mg/day. In severe hyperaldosteronism and hypokalemia the daily dose is 300 mg (maximum 400 mg) in 2-3 doses; in case of improvement of condition the dose is gradually reduced to 25 mg/day.

In hypokalemia and/or hypomagnesemia caused by therapy with diuretics Veroshpiron is prescribed in a dose of 25-100 mg/day, once or in several doses. Maximum daily dose is 400 mg if oral potassium preparations or other methods of potassium deficiency therapy are ineffective.

In diagnosis and treatment of primary hyperaldosteronism as a diagnostic agent in short diagnostic test Veroshpiron is prescribed for 4 days in 400 mg/day, distributing daily dose in several intakes per day. If blood potassium concentration increases during drug administration and decreases after drug withdrawal, the presence of primary hyperaldosteronism may be assumed. In the long-term diagnostic test, the drug is prescribed in the same dose for 3-4 weeks.

When correction of hypokalemia and arterial hypertension is achieved, the presence of primary hyperaldosteronism may be assumed. Once the diagnosis of hyperaldosteronism has been established by more accurate diagnostic methods, Veroshpiron should be taken at a daily dose of 100-400 mg divided into 1-4 doses as a short course of preoperative therapy for primary hyperaldosteronism throughout the preparation for surgery.

If surgery is not indicated, Veroshpiron is used for long-term maintenance therapy, using the lowest effective dose that is adjusted individually for each patient. In treatment of edema against nephrotic syndrome daily dose for adults is usually 100-200 mg. Spironolactone has not been found to affect the underlying pathological process, and therefore the use of this drug is recommended only in those cases in which other forms of therapy are ineffective.

In case of edematous syndrome due to chronic heart failure, the drug is prescribed daily for 5 days at a dose of 100-200 mg/day in 2-3 times, in combination with “loop” or thiazide diuretic. Depending on the effect, the daily dose is reduced to 25 mg. The maintenance dose is adjusted individually.

The maximum daily dose is 200 mg. In edema against liver cirrhosis the daily dose of Verospiron for adults is usually 100 mg if the ratio of sodium to potassium ions (Na+/K+) in urine is more than 1.0. If the ratio is less than 1.0, the daily dose is usually 200-400 mg. A maintenance dose is chosen individually. In children with edema, the initial dose is 1-3.3 mg/kg body weight or 30-90 mg/m2/day in 1-4 doses. The dose is adjusted after 5 days and, if necessary, it is increased by 3 times of the initial dose.

Interaction

Fludrocortisone causes a paradoxical increase in tubular potassium secretion. Reduces the effect of mitotane. It enhances the effect of triptorelin, buserelin, gonadorelin.

Veroshpiron reduces the effect of anticoagulants, indirect anticoagulants (heparin, coumarin derivatives, indandion) and toxicity of cardiac glycosides (because normalization of blood potassium levels prevents toxicity). Increases metabolism of phenazole. Decreases vascular sensitivity to norepinephrine (requires caution during anesthesia). Increases the T1/2 of digoxin, so digoxin intoxication is possible.

Accelerates the toxic effects of lithium due to decreased lithium clearance. Accelerates the metabolism and excretion of carbenoxolone. Carbenoxolone promotes sodium retention by spironolactone. GCS and diuretics (benzothiazine derivatives, furosemide, etacrynic acid) enhance and accelerate diuretic and natriuretic effects.

Magnifies the effect of diuretic and hypotensive drugs. GCS increases the diuretic and natriuretic effect in case of hypoalbuminemia and/or hyponatremia. There is an increased risk of hyperkalemia when taking Veroshpiron with potassium preparations, potassium supplements and potassium-saving diuretics, ACE inhibitors (acidosis), angiotensin II antagonists, aldosterone blockers, indomethacin, cyclosporine.

Salicylates, indomethacin reduce diuretic effect. Ammonium chloride, colestyramine contribute to hyperkalemic metabolic acidosis.

Special Instructions

Impact on the ability to drive and operate machinery

In the initial period of treatment, it is prohibited to drive vehicles and engage in activities requiring increased concentration and rapid psychomotor reactions. The duration of restrictions is determined on an individual basis.

When using Veroshpiron a temporary increase in serum urea nitrogen levels is possible, especially with reduced renal function and hyperkalemia. Reversible hyperchloremic metabolic acidosis may also develop.

When prescribing Veroshpiron in patients with impaired renal and hepatic function and in elderly patients, regular monitoring of serum electrolytes and renal function is required.

The administration of Verospiron makes it difficult to determine the blood concentrations of digoxin, cortisol and adrenaline. Although there is no direct effect on carbohydrate metabolism, the presence of diabetes mellitus, especially with diabetic nephropathy, requires special caution when prescribing Veroshpiron because of the possibility of developing hyperkalemia.

Key renal function and blood electrolyte levels should be monitored during treatment with NSAIDs while taking Veroshpiron. Consumption of potassium-rich foods should be avoided during treatment with Verospiron.

Alcohol consumption is contraindicated during treatment.

Contraindications

Pregnancy. Lactation period (breastfeeding). Childhood under 3 years of age. Addison’s disease. Hyperkalemia. Hyponatremia. Severe renal insufficiency (CKR less than 10 ml/min). Anuria.

Lactose intolerance, lactase deficiency, glucose/galactose malabsorption syndrome. Hypersensitivity to the ingredients of the drug.

With caution: the drug should be administered in hypercalcemia, metabolic acidosis, AV-blockade (hyperkalemia contributes to its enhancement), diabetes mellitus (with confirmed or suspected chronic renal failure), diabetic nephropathy, Surgical interventions, administration of drugs that cause gynecomastia, local and general anesthesia, menstrual disorders, breast enlargement, liver failure, liver cirrhosis, and elderly patients.

Side effects

Allergic reactions: urticaria; rarely – maculopapular and erythematous rash, drug fever, itching. Dermatological reactions: alopecia, hypertrichosis.

Urinary system disorders: acute renal failure.

Musculoskeletal system: muscle spasm, cramps of the calf muscles.

Digestive system disorders: nausea, vomiting, diarrhea, gastrointestinal ulcers and bleeding, gastritis, intestinal colic, abdominal pain, constipation, liver function disorders.

CNS and peripheral nervous system disorders: ataxia, lethargy, dizziness, headache, somnolence, lethargy, confusion.

Hematopoietic system disorders: agranulocytosis, thrombocytopenia, megaloblastosis.

Mechanical system disorders: hyperuricemia, hypercreatininemia, increased concentration of urea, hyperkalemia, hyponatremia, metabolic hyperchloremic acidosis or alkalosis.

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 and disappears after withdrawal of Veroshpiron, only in rare cases the breast remains slightly enlarged), reduced potency and erections; in women – menstrual disorders, dysmenorrhea, amenorrhea, metrorrhagia in the menopausal period, hirsutism, pain in the breast, mammary carcinoma (the presence of association with taking the drug is not established).

Overdose

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

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

In hyperkalemia it is necessary to normalize water-electrolyte exchange with the help of potassium withdrawal diuretics, rapid parenteral administration of dextrose solution (5-20% solutions) with insulin at the rate of 0.25-0.5 units per 1 g of dextrose; repeated administration of dextrose is possible if necessary. In severe cases hemodialysis is performed.

Pregnancy use

It is contraindicated. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Similarities

Veroshpiron, Veroshpilactone, Spironolactone