Spironolactone

Package leaflet (information for patients)

Tradename
Spironolactone

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Spironolactone 50 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil ® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Diuretic potassium-sparing agent

Pharmacological properties
Pharmacodynamics
Spironolactone is a potassium-sparing diuretic, a specific long-acting aldosterone antagonist ( mineralocorticosteroid hormone of the adrenal cortex). In the distal nephron, Spironolactone prevents sodium and water retention by aldosterone and suppresses the potassium-excreting effect of aldosterone. 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 urine acidity.
The maximum effect is observed 7 hours after ingestion and lasts at least 24 hours. The hypotensive effect of the drug is due to the presence of a diuretic effect, which is variable: the diuretic effect appears on days 2-5 of treatment.
Pharmacokinetics
Spironolactone is well absorbed after oral administration and is mainly metabolized into active metabolites: sulfur-containing metabolites (80%) and partially canrenone (20%). The plasma half-life of Spironolactone is short (1.3 hours), the half-life of active metabolites is longer (from 2.8 to 11.2 hours). Excretion of metabolites occurs mainly through the urine, a small part is excreted in the feces. Spironolactone and its metabolites cross the placenta and ekskre tiruyutsya breast milk.
After administration of 100 mg of Spironolactone per day for 15 days on an non-fasting basis in healthy volunteers, Tmax was reached in 2.6 hours, Cmax was approximately 80ng / ml and Ti / 2 was approximately 1.4 hours. For 7-alpha- ( thiomethyl ) spironolactone and canrenone - Tmax 3.2 hours and 4.3 hours, Cmax was 391ng / ml and 181ng / ml and T1 / 213.8 hours aca and 16.5 hours, respectively.
The effect on the kidneys of a single dose of Spironolactone reaches its peak after 7 hours and the activity persists for at least 24 hours.

Indications for use
Edema in chronic heart failure, cirrhosis of the liver (especially with the simultaneous presence of hypokalemia and hyperaldosteronism ), with nephrotic syndrome.
Edema in the II and III trimesters of pregnancy.
Arterial hypertension, incl. with aldosterone-producing adrenal adenoma (as part of combination therapy).
Primary hyperaldosteronism. Aldosterone- producing adrenal adenoma (long-term maintenance therapy in case of contraindication to surgical treatment or in case of refusal). Di agnostic hyperaldosteronism.
Hypokalemia and its prevention in the treatment of saluretics.
Polycystic ovary syndrome, premenstrual syndrome.

Method of administration and dosage
Set individually depending on the severity of violations of water and electrolyte metabolism and hormonal status.
With edematous syndrome - 100-200 mg / day (less often - 300 mg / day ) in 2-3 doses (usually in combination with a "loop" or / and thiazide diuretic) daily for 14-21 days. Dose adjustments should be made taking into account the values of the plasma potassium concentration. If necessary, courses are repeated every 10-14 days. With pronounced hyperaldosteronism and reduced potassium content in plasma - 300 mg / day in 2-3 doses.

Side effects
From the digestive system: nausea, vomiting, abdominal pain, gastritis, ulceration and bleeding in the gastrointestinal tract, intestinal colic, diarrhea or constipation.
From the side of the central nervous system: dizziness, drowsiness, lethargy, headache, lethargy, ataxia.
Metabolism: increasing concentrations of urea, hypercreatininemia, hyperuricemia, impaired water-salt exchange and AAR (metabolic gipohlo remichesky acidosis or alkalosis).
From the hematopoietic system: megaloblastosis, agranulocytosis, thrombocytopenia.
From the endocrine system: with prolonged use - gynecomastia, erectile dysfunction in men; in women - dysmenorrhea, amenorrhea, metrorrhagia in menopause, hirsutism, coarsening of the voice, tenderness of the mammary glands, carcinoma of the mammary gland.
Allergic reactions: urticaria, maculopapular and erythematous rashes, drug fever, itching.
Others: muscle spasms, decreased potency.

Contraindication
Disease Addison, hyperkalemia, hypercalcemia, hyponatremia, chronic renal failure, anuria, hepatic failure, diabetes with confirmed or suspected chronic renal failure, diabetic nephropathy, I trimester of pregnancy, metabolic acidosis, menstrual disorders or breast enlargement, increased sensitivity to spironolactone...

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. With hyperkalemia, it is necessary to normalize water-electrolyte metabolism with the help of potassium - excreting diuretics, rapid parenteral administration of a dextrose solution (5-20% solutions) with insulin at the rate of 0.25-0.5 U per 1 g of dextrose; if necessary, re-administration of dextrose is possible.

Precautions
With the use of Spironolactone, a temporary increase in the level of urea nitrogen in the blood serum is possible, especially with reduced renal function and hyperkalemia. It is also possible to develop hyperchloremic metabolic acidosis. When prescribing Spironolactone to patients with impaired renal and liver function, elderly patients, regular monitoring of serum electrolytes and renal function is necessary.
Hyperkalemia can develop in patients with impaired renal function or in patients with excessive potassium intake and lead to the development of fatal arrhythmias. In the case of hyperkalemia, Spironolactone should be discontinued and active measures taken to reduce serum potassium to normal levels. Simultaneous application of spironolactone to other potassium-sparing diuretic, an angiotensin converting enzyme (ACE) inhibitors, non-steroidal anti-inflammatory agents, antagonists of angiotensin II, aldosterone blockers, heparin, low molecular weight heparins or other drugs that contribute to the development of hyperkalemia, and in circumstances where it may be hyperkalemia (additives potassium, a diet rich in potassium, or salt substitutes containing potassium) can lead to severe hyperkalemia.
Hyperkalemia in Patients with Severe Heart Failure
Hyperkalemia can be fatal. Careful monitoring and regulation of the level of potassium in the blood is necessary in the case of prescribing Spironolactone to patients with severe heart failure. Prescription of other potassium-sparing diuretics should be avoided. Potassium supplementation should be avoided in patients with serum potassium> 3.5 mEq / L. It is recommended to monitor the level of potassium and creatinine for one week after starting or increasing the dose of Spironolactone, then monthly for the first 3 months, then quarterly for a year, then every 6 months. If the serum potassium level is more than 5 mEq / L or the serum creatinine level is more than 4 mg / dL, treatment should be discontinued.
In connection with the drug-lactose is not recommended for patients with congenital galactose intolerance, lack lactase yl ma labsorbtsiey glucose-galactose.
Despite the absence of a direct effect on carbohydrate metabolism, the presence of diabetes mellitus, especially with diabetic nephropathy, requires special care when prescribing Spironolactone due to the possibility of developing hyperkalemia.
During treatment with Spironolactone, alcohol consumption is contraindicated, and you should avoid eating foods rich in potassium.
Application in children
The drug is not recommended for children under 6 years of age.

Interaction with other medicinal products
While the use of antihypertensive drugs is potentiated hypotensive effect spiro nolaktona.
With simultaneous use with ACE inhibitors, hyperkalemia may develop (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, which leads to a retention of potassium in the body against the background of limiting the excretion of potassium.
With simultaneous use with potassium preparations, other potassium-sparing diuretics, substitutes for table salt and dietary supplements containing potassium, hyperkalemia may develop.
With simultaneous use with salicylates, the diuretic effect of spironolactone decreases due to the blockage of canrenone excretion by the kidneys.
Indomethacin and mefenamic acid inhibit renal excretion of canrenone.
With simultaneous use, the hypoprothrombinemic effect of oral anticoagulants decreases.
When used simultaneously with digitoxin, it is possible to both increase and decrease the effects of digitoxin.
With the simultaneous use of spironolactone inhibits the excretion of digoxin by the kidneys and probably decreases its volume of distribution. This can cause increased concentra radio digoxin in the blood plasma.
With simultaneous use with candesartan, losartan, eprosartan, there is a risk of hyperkalemia.
While the use of colestyramine this incident au hypochloremic alkalosis.
With simultaneous use with lithium carbonate, an increase in the concentration of lithium in the blood plasma is possible.
With simultaneous use with norepinephrine, it is possible to reduce the sensitivity of blood vessels to norepinephrine.
With simultaneous use, the effect of triptorelin, buserelin, gonadorelin is enhanced.

Special instructions
Use with caution in AV blockade (the possibility of strengthening due to the development of hyperkalemia ), decompensated liver cirrhosis, surgical interventions, taking drugs that cause gynecomastia, when taking local and general anesthetics, in elderly patients.
Against the background of the use of spironolactone, drugs containing potassium, as well as other diuretics that cause potassium retention in the body, should not be prescribed. It should avoid the use of spironolactone with carbenoxolone ohm causing sodium retention.
During the treatment period, periodic determination of the content of electrolytes and urea in the blood should be carried out.
When using spironolactone in combination with other diuretic or antihypertensive drugs, it is recommended to reduce the dose of the latter. When spironolactone is used simultaneously with digoxin, it may be necessary to reduce both the saturating and maintenance dose of the latter.

Pregnancy and elbowing
The use of Spironolactone is contraindicated during pregnancy and during breastfeeding.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect.

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
On prescription.

Packaging
Spironolactone 50 mg Tablets. There are 25 tablets in a blister. 4 blisters are packed in a cardboard box together with an enclosed leaflet.