Instructions for Spironolactone
Dosage form Spironolactone:
Capsules - hard, gelatin, No. 0, white. The contents of the capsules is a mixture of powder and granules, white or almost white with a cream tint, almost odorless or with a slight specific smell.
Composition Spironolactone:
1 capsule contains: Active ingredient: Spironolactone 100 mg
Excipients - until the contents of the capsule are obtained: 450 mg of lactose monohydrate 260.0 mg of corn starch 85.0 mg of magnesium stearate 5.0 mg Spironolactone
The composition of the capsule shell: Hard gelatin capsules No. 0 Case and cap: titanium dioxide, medical gelatin.
Pharmacodynamics Spironolactone:
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, spironolactone prevents the retention of sodium and water by aldosterone and suppresses the potassium-eliminating 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. Increased diuresis is due to the presence of a diuretic effect, which is unstable. The diuretic effect is manifested on 2-5 days of treatment.
Pharmacokinetics Spironolactone:
Absorption and distribution: When taken orally, it is rapidly and completely absorbed from the gastrointestinal tract (GIT). It binds to plasma proteins by approximately 98% (canrenone - 90%). The maximum concentration (Cmax) of canrenone is achieved 2-4 hours after administration. After daily intake of 100 mg of spironolactone for 15 days, Cmax reaches 80 ng / ml, the time to reach Cmax after the next morning intake is 2-6 hours. Distribution volume is 0.05 l / kg.
Spironolactone penetrates poorly into organs and tissues, while he and his metabolites penetrate through the placental barrier, and canrenone - into breast milk. Metabolism: Spironolactone is converted into active metabolites: a metabolite containing sulfur (80%) and partially canrenone. Excretion: It is excreted by the kidneys (50% - in the form of metabolites, 10% - unchanged) and partially through the intestine. Spironolactone
The elimination half-life (T1 / 2) of spironolactone is 13-24 hours, of active metabolites - up to 15 hours. The elimination of canrenone (mainly by the kidneys) is two-phase, T1 / 2 in the first phase is 2-3 hours, in the second 12-96 hours. Special patient groups With cirrhosis of the liver and chronic heart failure, the half-life period increases without signs of cumulation, the probability of which is higher with chronic renal failure and hyperkalemia.
Side effects Spironolactone:
Violations of the blood and lymphatic system Agranulocytosis, thrombocytopenia, megaloblastosis, eosinophilia. Violations of the immune system Urticaria. Violations of the endocrine system Coarsening of the voice, violation of the menstrual cycle, dysmenorrhea, amenorrhea, metrorrhagia in the menopause, hirsutism. Disorders of the nervous system Ataxia, lethargy, dizziness, headache, drowsiness, lethargy, confusion, muscle spasm. Disorders of the respiratory system, chest organs and mediastinum Dyspnea.
Disorders of the gastrointestinal tract Nausea, vomiting, diarrhea, ulceration and bleeding from the gastrointestinal tract, gastritis, intestinal colic, abdominal pain, constipation. Violations of the liver and biliary tract Disorders of the liver.
Disorders of the skin and subcutaneous tissues Hypertrichosis, pruritus, maculopapular and erythematous rashes, Steven-Johnson syndrome, toxic epidermal necrolysis. Violations of the musculoskeletal and connective tissue Cramps of the calf muscles, osteomalacia.
Disorders from the kidneys and urinary tract Acute renal failure. Disorders from the reproductive system and mammary glands In men - gynecomastia (the likelihood of developing depends on the dose, duration of treatment and, usually, is reversible, and after discontinuation of the drug disappears, and only in rare cases the breast remains slightly enlarged); sexual dysfunction; Spironolactone
In women - pain in the area of the mammary glands, breast carcinoma (the presence of a connection with the drug has not been established). General disorders and disorders at the injection site Alopecia, drug fever. Laboratory and instrumental data Hyperuricemia, hypercreatinemia, increased urea concentration, violation of the water-electrolyte balance (hyperkalemia, hyponatremia) and the acid-base state (metabolic hyperchloremic acidosis or alkalosis).
Special conditions Spironolactone:
A temporary increase in serum urea nitrogen is possible, especially with decreased renal function and hyperkalemia. Reversible hyperchloremic acidosis is possible.
In cases of impaired renal and hepatic function, as well as in old age, regular monitoring of serum electrolytes and renal function is necessary.
The drug Spironolactone 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.
With simultaneous treatment with non-steroidal anti-inflammatory drugs, kidney function and electrolyte levels in the blood should be monitored. Avoid eating potassium-rich foods.
During treatment, alcohol is contraindicated. Influence on the ability to drive vehicles, mechanisms An adverse effect of spironolactone on the ability to drive vehicles and mechanical means has not been identified.
However, it is known that the drug SPYRONOLACTONE can cause dizziness and drowsiness, as a result of which during its application it is necessary to exercise caution when performing work requiring increased attention and when driving vehicles.
Indications Spironolactone:
Essential hypertension Spironolactone (as part of combination therapy). Edema syndrome in chronic heart failure (can be used in monotherapy and in combination with standard therapy).
Conditions in which secondary hyperaldosteronism can be detected, including cirrhosis, accompanied by ascites and / or edema, nephrotic syndrome, as well as other conditions accompanied by edema.
Hypokalemia / hypomagnesemia (as an aid to its prevention during treatment with diuretics and when it is impossible to use other methods of correction of potassium content). Primary hyperaldosteronism (Conn's syndrome) - for a short preoperative course of treatment. To establish a diagnosis of primary hyperaldosteronism
Contraindications Spironolactone:
Hypersensitivity to the components of the drug, Addison’s disease, hyperkalemia, hyponatremia, severe renal failure (creatinine clearance less than 10 ml / min), anuria, simultaneous use of eplerenone and other potassium-sparing diuretics, potassium preparations, pregnancy and lactation, children under 3 years of age (due to the solid dosage form), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose).
Precautions Hypercalcemia, metabolic acidosis; atrioventricular block (hyperkalemia contributes to its strengthening); diabetic nephropathy, diabetes mellitus (with confirmed or suspected renal failure); surgical interventions during local and general anesthesia; gynecomastia; taking drugs that cause gynecomastia; liver failure, cirrhosis; menstrual irregularities; elderly age.
Use during pregnancy and the period of breastfeeding. The use of the drug SPIRONOLACTONE is contraindicated in pregnancy and during 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 breastfeeding, breast-feeding should be discontinued.
Drug Interactions:
Reduces the effect of anticoagulants, indirect anticoagulants (heparin, coumarin derivatives, indandion) and toxicity of cardiac glycosides (since normalization of potassium in the blood prevents the development of toxicity).
Enhances the metabolism of phenazone (antipyrine). Reduces the sensitivity of blood vessels to norepinephrine (norepinephrine) (requires caution when conducting anesthesia), increases the half-life of digoxin - digoxin intoxication is possible.
Enhances the toxic effect of lithium due to reduced clearance. Perhaps enhances the action of non-depolarizing muscle relaxants (e.g. tubocurarine). Accelerates the metabolism and excretion of carbenoxolone. Carbenoxolone promotes sodium retention with spironolactone. Glucocorticosteroid drugs and diuretics (thiazides and thiazide-like, furosemide, ethacrylic acid) enhance and accelerate the diuretic and natriuretic effects.
Enhances the effect of diuretic and antihypertensive drugs. Nonsteroidal anti-inflammatory drugs reduce diuretic and natriuretic effects, the risk of developing hyperkalemia increases. Alcohol (ethanol), barbiturates, narcotic substances increase orthostatic hypotension. Glucocorticosteroid drugs enhance the diuretic and natriuretic effect in case of hypoalbuminemia and / or hyponatremia.
The risk of developing hyperkalemia increases when taken with potassium preparations, potassium supplements and potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors (acidosis), angiotensin II receptor antagonists, aldosterone, indomethacin, cyclosporin blockers. Spironolactone
Salicylates, indomethacin reduce the diuretic effect. Ammonium chloride, colestyramine contribute to the development of hyperkalemic metabolic acidosis. Fludrocortisone causes a paradoxical increase in tubular secretion of potassium. Reduces the effect of mitotan. Enhances the effect of triptorelin, buserelin, gonadorelin.
Dosage Spironolactone:
Inside. To ensure the following dosage regimens, if it is necessary to use spironolactone in a dose of 25 mg, preparations of other manufacturers in the dosage form of “tablets” or “capsules” in a dosage of 25 mg should be prescribed. 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. Spironolactone
To achieve an adequate response to therapy, the drug must be taken for at least 2 weeks. If necessary, adjust the dose. Idiopathic hyperaldosteronism The drug is prescribed in a dose of 100-400 mg / day. Severe hyperaldosteronism and hypokalemia
The drug is prescribed in a dose of 300 mg / day (maximum 400 mg / day) for 2-3 doses; with improvement, the dose is gradually reduced to 25 mg / day. Hypokalemia and / or 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 potassium preparations for oral administration or other methods of replenishing its deficiency are ineffective. Diagnosis and 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. Spironolactone
With an increase in potassium in the blood while taking the drug and a decrease after withdrawal, it can be assumed that there is 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, the drug SPIRONOLACTON should be taken at 100-400 mg / day, divided into 1-4 doses per day during the entire period of preparation for surgical intervention.
If surgery is not indicated, then the drug SPIRONOLACTON is used for long-term maintenance therapy, while the lowest effective dose is applied, 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 spironolactone 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.
Edema 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. Swelling against cirrhosis If the ratio of sodium and potassium ions (Na + / K +) in 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 older than 3 years is 1.0-3.3 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 by 3 times compared to the original.
Use in elderly patients It is recommended to start treatment with a minimum dose and titrate it until the maximum dose is achieved under the control of liver / kidney function.
Overdose Spironolactone:
Symptoms: nausea, vomiting, dizziness, diarrhea, skin rash, hyperkalemia (paresthesia, muscle weakness, arrhythmias), hyponatremia (dry oral mucosa, thirst, drowsiness) hypercalcemia, dehydration, increased urea concentration. Treatment: gastric lavage, symptomatic treatment of dehydration.
With hyperkalemia, it is necessary to normalize the water-electrolyte balance using potassium-excreting diuretics, rapid parenteral administration of 5-20% dextrose (glucose) solution with insulin at the rate of 0.25-0.5 PIECES per 1 g of dextrose (glucose); if necessary, you can re-enter. In severe cases, hemodialysis is performed.
