Verospilactone (Spironolactone)

Instructions for Verospilactone

Composition Verospilactone:

Each tablet contains 0,025 g of the active substance Spironolactone.
Excipients:
magnesium stearate,
lactose (milk sugar),
potato starch,
colloidal silicon dioxide (aerosil),
talc.

Pharmacodynamics Verospilactone:

Spironolactone is a potassium-sparing diuretic, a specific long-acting aldosterone antagonist (mineralocorticosteroid hormone of the adrenal cortex). In the distal parts of the nephron, Spironolactoneinterferes with the retention of sodium by water by aldosterone and suppresses the potassium-excreting effect of aldosterone, reduces the synthesis of permeases in the aldosterone-dependent portion of the collecting tubules and distal tubules. By binding to aldosterone receptors, it increases the excretion of sodium, chlorine and water ions in the urine, reduces the excretion of potassium and urea ions, and reduces the acidity of urine.

The maximum effect is observed 7 hours after ingestion and lasts at least 24 hours. The antihypertensive effect of the drug Verospilactone is due to the presence of a diuretic effect, which is unstable: the diuretic Verospilactone effect manifests itself on the 2nd-5th day of treatment.

Pharmacokinetics Verospilactone:

When taken orally, it is rapidly and completely absorbed from the gastrointestinal tract and turns into active metabolites: a metabolite containing sulfur (80%) and partially canrenone (20%). The maximum concentration (Cmax) of canrenone in blood plasma is reached after 2-4 hours, its connection with plasma proteins is 90%. Communication with blood plasma proteins is about 98% (canrenone - 90%). After daily intake of 100 mg of Spironolactone for 15 days, Cmax reaches 80 mg / ml, the time to reach Cmax after the next morning dose is 2-6 hours.

Spironolactone penetrates poorly into organs and tissues, while itself and its metabolites penetrate through the placental barrier, and cancreon - into breast milk. Distribution volume - 0,05 l / kg. The half-life (T1 / 2) of Spironolactone is 13-24 hours, of active metabolites - up to 15 hours. It is excreted by the kidneys: 50% - in the form of metabolites, 10% - unchanged and partially - fecal masses.

Excretion of canrenone (mainly by the kidneys) is two-phase, T1 / 2 in the first phase - 2-3 hours, in the second - 12-96 hours. With cirrhosis of the liver and heart failure, the half-life increases without signs of cumulation, the probability of which is higher in chronic renal failure and hyperkalemia. 

Side effects Verospilactone:

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 central nervous system: ataxia, lethargy, dizziness, headache, drowsiness, lethargy, confusion, muscle spasm. From the hematopoietic system: leukopenia (including agranulocytosis), thrombocytopenia. From the endocrine system: coarsening of the voice, in men - gynecomastia (the likelihood of development depends on the dose, duration of treatment and, usually, is reversible); decreased potency and erection; in women - menstrual irregularities; dysmenorrhea, amenorrhea, menorrhagia in the menopause, hirsutism, pain in the area of the mammary glands, breast carcinoma (the presence of a connection with the drug has not been established). Spironolactone

Metabolic disorders: hypercreatininemia, increased urea concentration, impaired water-salt metabolism (hyperkalemia, hyponatremia) and acid-base balance (metabolic hyperchloremic acidosis or alkalosis), hyperuricemia. With the use of Veroshpilactone, gynecomastia can develop. The likelihood of gynecomastia depends on the dose of the drug and on the duration of therapy. Spironolactone

In this case, gynecomastia is usually reversible, and after discontinuation of the drug Verospilactone disappears, and only in rare cases, the mammary gland remains somewhat enlarged. 

Allergic reactions on Verospilactone/Spironolactone: urticaria, rarely maculopapular and erythematous rash, drug fever, pruritus. From the skin: alopecia, hypertrichosis. From the urinary system: acute renal failure. From the musculoskeletal system

Special conditions Verospilactone:

A temporary increase in serum urea nitrogen level is possible, especially with decreased kidney function and hyperkalemia. Possible reversible hyperchloremic metabolic acidosis. In diseases of the kidneys and liver, as well as in old age, regular monitoring of serum electrolytes and kidney function is necessary.

The drug Verospilactone 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. When treating with non-steroidal anti-inflammatory drugs Verospilactone, kidney function and electrolyte levels in the blood should be monitored.

Potassium-rich foods should be avoided. During treatment, alcohol is contraindicated. Influence on the ability to drive vehicles and other mechanisms: In the initial period of treatment, it is forbidden to drive a car and engage in activities that require an increased concentration of attention and speed of psychomotor reactions. The duration of the restrictions is set individually.

Indications Verospilactone:

Essential hypertension (as part of combination therapy); edema syndrome in chronic heart failure (can be used as monotherapy and in combination with standard therapy); conditions in which secondary hyperaldosteronism can be detected, including cirrhosis of the liver, accompanied by ascites and / or edema, nephrotic syndrome, as well as other conditions accompanied by edema; hypokalemia / hypomagnesemia (as an adjuvant

For its prevention during treatment with diuretics and when it is impossible to use other methods of correcting the level of potassium); - primary typeraldosteronism (Conn syndrome). - for a short preoperative course of treatment; to establish a diagnosis of primary hyperaldosteronism. Verospilactone

Contraindications Verospilactone:

Hypersensitivity to any of the components of the drug Verospilactone, Addison's disease, hyperkalemia, hyponatremia, severe renal failure (creatinine clearance less than 10 ml / min), anuria, pregnancy, lactation. Children's age (up to 3 years), due to the solid dosage form Spironolactone.

With caution: Hypercalcemia, metabolic acidosis, atrioventricular block (hyperkalemia enhances it), diabetes mellitus (with confirmed or suspected chronic renal failure), diabetic nephropathy, surgical interventions, taking medications that cause gynecomastia, local and general anesthesia, old age menstrual irregularities, enlargement of the mammary glands, liver failure.

Drug Interactions Verospilactone:

Reduces the effect of anticoagulants, indirect anticoagulants (heparin, coumarin derivatives, indandinone) and toxicity of cardiac glycosides (since normalization of potassium levels in the blood prevents toxicity). Enhances the metabolism of phenazole (antipyrine). Reduces the sensitivity of blood vessels to noepinephrine (requires caution when conducting anesthesia), increases the half-life of digoxin - intoxication is possible - digoxin.

Enhances the toxic effect of lithium due to reduced clearance. Accelerates the metabolism and excretion of carbenoxolone. Carbenoxolone promotes sodium retention with Spironolactone. Glucocorticosteroid drugs Verospilactone and diuretics (benzothiadiazine derivatives, furosemide, ethacrylic acid) enhance and accelerate the diuretic and natriuretic effects. Enhances the effect of diuretic and antihypertensive drugs Verospilactone.

Nonsteroidal anti-inflammatory drugs Verospilactone reduce the diuretic and natriuretic effects, the risk of developing hyperkalemia increases. Glucocorticosteroid drugs enhance the diuretic Verospilactone and natriuretic effect with 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 P antagonists, blockers of aldeoterone, indomethacin, cyclosporin.

Salicylates, indomethacin reduce the diuretic Spironolactone effect. Ammonium chloride, colestyramine contribute to the development of hyperkalemic metabolic acidosis. Fludrocortisone causes a paradoxical increase in the tubular section of potassium. Reduces the effect of mitotan. Enhances the effect of triptorelin, buserelin, gonadorelin.

Dosage Verospilactone:

Inside. 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, adjust the dose.

With idiopathic hyperaldosteronism 100-400 mg / day. With severe hyperaldosteronism and hypokalemia 300 mg / day (maximum 400 mg) for 2-3 doses, with improvement, the dose is gradually reduced to 25 mg / day. Hypokalemia / hypomagnesemia In case of 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 treatment of primary hyperaldosteronism As a diagnostic tool for a short diagnostic test: 400 mg / day for 4 days, distributed into several doses per day. With an increase in the concentration of potassium in the blood while taking the drug and a decrease after cancellation it can be assumed the presence of primary hyperaldosteronism. With a long diagnostic test: 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, Veroshpilactone should be taken 100-400 mg / day, divided into 1-4 doses per day during the entire period of preparation for a surgical operation. If the operation is not indicated, then Veroshpilactone is used for long-term maintenance therapy, while the lowest effective dose is used, which is selected individually for each patient. Edema on the background of nephrotic syndrome The daily dose for adults is usually 100-200 mg / day. No effect of Veroshpilactone on the main pathological process was detected, and therefore the use of this drug is recommended only in cases where other types of therapy are ineffective. With edematous syndrome against 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 on the background of 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. Edema in children The initial dose Verospilactone is 1-3.3 mg / kg body weight or 30-90 mg / m2 / day. In 1-4 doses. After 5 days, the dose Spironolactone is adjusted and, if necessary, increased by 3 times compared to the original.

Overdose Verospilactone:

Symptoms:

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

Treatment on Verospilactone:

• gastric lavage
• symptomatic treatment of dehydration and arterial hypotension. 
• With hyperkalemia, it is necessary to normalize the water-electrolyte metabolism using potassium-releasing diuretics, rapid parenteral administration of 5-20% dextrose solution with insulin at the rate of 0.25-0.5 PIECES per 1 g of dextrose; 
• if necessary, you can Verospilactone re-enter. In severe cases, hemodialysis is performed.
• Verospilactone