Spironolactone

Pharmacological properties

the active substance of the drug is spironolactone, a competitive aldosterone antagonist that affects the distal tubules of the kidneys. due to blockade, aldosterone suppresses the retention of water and na + ions and promotes the retention of k + ions, which not only increases the excretion of na + and cl– ions and reduces the excretion of k + ions in the urine, but also reduces the excretion of h + ions. as a result of this, the diuretic effect also has a hypotensive effect.

Pharmacokinetics After oral administration, the drug is rapidly and completely absorbed in the digestive tract. Bioavailability is 92–99% and increases when taken with food.

C_max spironolactone in blood plasma is reached after 2.6 hours and amounts to 80 ng / ml. Binding to plasma proteins is ≈90%. T_½ 1.3 hours

Spironolactone is metabolized in the liver. Its active metabolites are 7α-thiomethylspironolactone and canrenone. The antialdosterone effect determines canrenone, which accounts for ≈50% of all spironolactone metabolites. Indicators C_max in blood plasma and time of its achievement: for 7α-thiomethylspironolactone - 391 ng / ml, 3.2 hours, for canrenone - 181 ng / ml, 4.3 hours._½ is 13.8 and 16.5 hours, respectively. Spironolactone and its metabolites enter the placenta and breast milk.

It is excreted in the form of metabolites mainly by renal excretion, a small part - with feces. Spironolactone is characterized by a cumulative effect.

Indications

Primary hyperaldosteronism.

Congestive heart failure with inefficiency or intolerance of other diuretics, or if necessary, increase their effectiveness.

Essential hypertension, mainly with hypokalemia, usually in combination with other antihypertensive drugs.

Cirrhosis of the liver, accompanied by edema and / or ascites.

Edema due to nephrotic syndrome.

Hypokalemia - if it is impossible to use another therapy.

Prevention of hypokalemia for patients taking cardiac glycosides, in the case when other methods of therapy are considered inappropriate or inappropriate.

Application

The drug is taken orally for adults and children. In general, the daily dose is prescribed in 1 or 2 doses after meals. the daily dose for 1 dose or the first dose of the drug with double use is recommended in the morning.

The duration of the course of treatment is individual, in some cases it can reach several years, while it is necessary to use the drug in the minimum effective dose, subject to constant monitoring of the electrolyte composition of blood plasma and indicators of renal function.

Adults

Primary hyperaldosteronism. In preparation for surgery, the drug is used in a dose of 100-400 mg / day.

In case of impossibility of surgical treatment, the drug can be used for a long time as maintenance therapy in the lowest effective dose, which is determined individually.

In this case, every 14 days it is permissible to reduce the initial dose until the minimum effective dose is reached. With prolonged treatment, it is recommended to use the drug in combination with other diuretics to reduce the severity of side effects.

Congestive heart failure, edema due to nephrotic syndrome. The drug is used in an initial dose of 100 mg / day in 1 or 2 doses. The daily dose can also range from 25 to 200 mg.

When prescribing the drug in higher doses, it can be used in combination with other diuretics acting in the proximal renal tubules. In this case, a dose adjustment of spironolactone should be carried out.

Essential hypertension. The drug is used in an initial dose of 50-100 mg / day in 1 or 2 doses in combination with other antihypertensive drugs.Treatment should be continued for at least 2 weeks, since by the end of this period the maximum antihypertensive effect is achieved. Further dose adjustment is individual, depending on the effect achieved.

Cirrhosis of the liver, accompanied by ascites and / or edema. If the ratio of Na⁺/ K⁺ in urine 1, the drug is used in an initial dose of 100 mg / day. The maximum daily dose is 100 mg / day. If this ratio is 1, the drug is used in a dose of 200 mg / day, while the maximum daily dose is 400 mg / day.

Hypokalemia. The drug is used at a dose of 25-100 mg / day for patients who have insufficient nutritional supplements with potassium or other methods of potassium replacement therapy.

Children. The drug is used in a dose of 1-3 mg / kg of body weight per day in 1 or 2 doses. With maintenance therapy in combination with other diuretics, the daily dose is 1-2 mg / kg of body weight.

If it is necessary to use the drug for children under 3 years of age, the tablet should be crushed, dissolved and given to the child in the form of a suspension.

Elderly patients. The drug is recommended for use in lower doses, followed by a gradual increase to achieve maximum effect. It should be borne in mind that in this category of patients there are hepatic and renal disorders that can affect the metabolism and excretion of the drug.

Contraindications

Hypersensitivity to the active substance or other components of the drug.

Acute renal failure, severe impaired renal excretory function of the kidneys (glomerular filtration rate of 10 ml / min), anuria.

Hyperkalemia, hyponatremia.

Addisons disease.

Concomitant use with potassium-sparing diuretics and potassium preparations due to the possibility of developing hyperkalemia.

Side effects

From the cardiovascular system: arterial hypotension, arrhythmia (in patients with renal failure and those receiving potassium preparations), vasculitis.

From the blood and lymphatic systems: leukopenia (including agranulocytosis), thrombocytopenia, megaloblastic or aplastic anemia, eosinophilia.

From the side of the nervous system and psyche: headache, drowsiness, dizziness, ataxia, paralysis, paraplegia, lethargy, lethargy, confusion.

From the respiratory system, chest and mediastinal organs: a change in the timbre of the voice.

From the digestive tract: nausea, vomiting, decreased appetite, abdominal and stomach pain, diarrhea, constipation, intestinal colic, gastritis, gastric and duodenal ulcer, gastric bleeding.

From the digestive system: hepatitis, impaired liver function.

From the urinary system: acute renal failure.

From the musculoskeletal system and connective tissue: osteomalacia, muscle spasm, muscle cramps of the lower extremities.

From the side of metabolism and metabolism: hyperkalemia, hyponatremia, hypercreatininemia, increased levels of urea in the blood plasma, hyperuricemia, porphyria, metabolic hyperchloremic acidosis or alkalosis, dehydration.

From the endocrine system: hirsutism.

On the part of the reproductive system and mammary glands: decreased libido, erectile dysfunction, gynecomastia, menstrual irregularities, dysmenorrhea, amenorrhea, metrorrhagia during menopause, swelling and pain in the mammary glands in women, infertility (when used in high doses - 450 mg / day ), a benign tumor of the mammary gland.

From the immune system, skin and subcutaneous tissue: hypersensitivity reactions, including: rash, itching, urticaria, drug fever; hypertrichosis, alopecia, lupus-like syndrome, hyperemia, ring-shaped erythema, eczema, Stevens-Johnson syndrome.

General: asthenia, fatigue.

special instructions

The use of the drug, especially in patients with impaired renal function, can lead to a transient increase in urea nitrogen in the blood plasma and hyperkalemia, which can lead to the development of cardiac arrhythmias and reversible hyperchloremic metabolic acidosis. the drug is used with caution in patients with impaired renal, hepatic, and elderly patients. should periodically determine the level of electrolytes in blood plasma and indicators of renal function. in case of hyperkalemia, treatment should be discontinued.

The drug is used with caution in patients in whom existing diseases can cause the development of acidosis and / or hyperkalemia.

The drug is used with caution in patients with diabetes mellitus, especially in the presence of diabetic nephropathy.

Spironolactone therapy may interfere with the determination of cortisol, epinephrine and digoxin concentrations (by radioimmunological methods).

Avoid prolonged unreasonable use of the drug, because, according to the literature, the prolonged use of spironolactone in animals at maximum doses contributed to the development of carcinoma and myeloid leukemia.

During the use of the drug should not drink alcohol.

The drug contains lactose, therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome cannot use the drug.

Use during pregnancy and lactation. The drug is contraindicated during pregnancy and lactation.

Children. The drug is used in pediatric practice as prescribed by a doctor.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. During the initial period of treatment, the duration of which is individual, driving is contraindicated or work with other mechanisms.

Interactions

With the simultaneous use of the drug with other drugs, it is possible:

with antihypertensive agents (especially ganglioblockers, nicardipine, nimodipine) - an excessive decrease in blood pressure; with simultaneous use, the dose of antihypertensive agents should be reduced with its subsequent correction if necessary;

with ammonium chloride, cholestyramine - an increased risk of developing hyperkalemia and hyperchloremic metabolic acidosis;

with potassium-sparing diuretics, potassium preparations, ACE inhibitors, angiotensin II receptor blockers, aldosterone receptor blockers, anticholinesterase agents, tacrolimus, cyclosporine - increased risk of hyperkalemia; simultaneous use with potassium-sparing diuretics and potassium preparations is contraindicated because of the possibility of developing hyperkalemia;

with other diuretics - increased diuretic effect;

with NSAIDs - an increased risk of developing hyperkalemia and renal failure with a concomitant decrease in the diuretic, natriuretic and antihypertensive effects of spironolactone; with simultaneous use with acetylsalicylic acid, the synthesis of prostaglandins is also suppressed, with antipyrine, the metabolism of the drug in the liver is enhanced;

with glucocorticoids, ACTH - increased diuretic, natriuretic action of spironolactone and a paradoxical increase in potassium excretion;

with α- and β-adrenergic agonists, carbenoxolone - weakening of the action of spironolactone;

with antipsychotics, tricyclic antidepressants - increased action of spironolactone;

with barbiturates, narcotic drugs, ethanol - orthostatic hypotension;

with terfenadine - an increased risk of ventricular arrhythmias due to hypokalemia and an imbalance of other electrolytes;

with carbamazepine - increased risk of hyponatremia;

with digoxin - increased risk of glycoside intoxication due to lengthening of its T_½;

with lithium preparations - increased risk of intoxication due to a decrease in renal clearance of lithium; do not use these drugs at the same time;

with indirect anticoagulants (coumarin derivatives), mitotan, pressor amines (epinephrine), cardiac glycosides - weakening of the action of the latter;

with triptorelin, buserelin, gonadorelin - increased action of the latter.

Overdose

Symptoms: drowsiness / fatigue, confusion, electrolyte disturbances.

Treatment: symptomatic therapy. Water-electrolyte and acid-base balance should be maintained: the appointment of diuretics that remove potassium, parenteral administration of glucose with insulin, in severe cases - hemodialysis. There is no specific antidote.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.