Spironolactone Sandoz tablets 50 mg blister No. 30

Instructions Spironolactone Sandoz tablets 50 mg blister No. 30

Composition

active ingredient: spironolactone;

1 tablet contains 50 mg or 100 mg of spironolactone;

Excipients: corn starch, calcium hydrogen phosphate dihydrate, povidone K 25, sodium lauryl sulfate, colloidal anhydrous silicon dioxide, magnesium stearate.

Medical form

Pills.

Main physicochemical properties: round, flat on both sides tablets with smooth edges, white in color with a score on one side.

Pharmacotherapeutic group

Potassium-sparing diuretics. ATX code C03D A01.

Pharmacological properties

Pharmacodynamics

Spironolactone is a competitive aldosterone antagonist. It acts on the distal tubules of the kidneys.

By blocking aldosterone, it suppresses water and Na+ retention and promotes K+ retention, which not only increases Na+ and Cl− excretion and reduces K+ excretion in the urine, but also reduces H+ excretion. As a result, the diuretic effect also has a hypotensive effect.

Pharmacokinetics

Absorption

Spironolactone is rapidly absorbed after oral administration by approximately 73%. Absorption of spironolactone is enhanced when taken with food. As a result, the concentration of the main substance in the blood serum increases by 50 - 100%.

Distribution

The binding of spironolactone and canrenone to blood plasma proteins is 90% (equilibrium dialysis method) or 98% (ultrafiltration method), depending on the method of determination.

Metabolism

After oral administration, spironolactone has a pronounced first-pass effect and is metabolized mainly in the liver and kidneys. Its main metabolites are 7-α-thiospironolactone, canrenone or canrenoate, 7-α-thiomethylspironolactone or 6-β-hydroxy-7-α-thiomethylspironolactone. Compared with the parent compound, the three metabolites listed above have relatively low antimineralocorticoid activity of 26, 68 and 33%, respectively.

After oral administration, the maximum concentration of spironolactone in blood plasma is reached after 1–2 hours, and the maximum concentration of its metabolites after 2–3 hours.

At low doses (50–200 mg), the area under the concentration-time curve of canrenone increases linearly with dose, while higher doses result in lower concentrations, most likely due to enzymatic conversion to metabolites.

Steady-state canrenone concentrations range from 50 to 188 ng/mL and are reached approximately 3 to 8 days after daily administration of spironolactone. In patients with cirrhosis and ascites, this is reached only after 14 days.

Excretion from the body

Spironolactone is excreted primarily in the urine and to a lesser extent in the bile. The proportion of unchanged spironolactone is negligible. Only metabolites are excreted in the urine, mainly canrenone and its glucuronide ester and 6-β-hydroxy-sulfoxide. After a single oral dose of radiolabeled spironolactone, 47–57% is excreted in the urine and 35–41% in the feces within 6 days.

After oral administration of spironolactone, the elimination half-life is 1–2 hours, while the metabolites are eliminated more slowly. The terminal half-life for canrenone is approximately 20 hours, approximately 3 hours for 7-α-thiomethylspironolactone, and approximately 10 hours for 6-β-hydroxy-7-α-thiomethylspironolactone.

Spironolactone and its metabolites cross the placental barrier. Canrenone passes into breast milk.

Indication

- Congestive heart failure in patients who do not respond to treatment with other diuretics, or when potentiation of their effects is necessary.

- Essential arterial hypertension, mainly in the case of hypokalemia (usually in combination with other antihypertensive drugs).

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

- Primary hyperaldosteronism.

- Edema caused by nephrotic syndrome.

- Hypokalemia, if other therapy is not possible.

The drug should be used for the prevention of hypokalemia in patients receiving cardiac glycosides, if other approaches are considered impractical or inappropriate.

Contraindication

- Hypersensitivity to the active substance or any other excipients.

- Use in combination with mitotane, as it may block the action of mitotane.

- Anuria, acute renal failure, severe impairment of nitrogen-excreting renal function (glomerular filtration rate <10 ml/min).

- Severe renal failure accompanied by oliguria or anuria (creatinine clearance below 30 ml/min per 1.73 m2 of body surface area and/or serum creatinine above 1.8 mg/dl).

- Hyperkalemia (blood potassium levels > 5.0 mmol/L).

- Hyponatremia.

- Addison's disease.

- Hypovolemia or dehydration.

- Concomitant use of eplerenone or other potassium-sparing diuretics

- Pregnancy or breastfeeding.

- ACE inhibitors or AT1 receptor blockers in combination.

Interaction with other medicinal products and other types of interactions

The concomitant use of spironolactone and potassium-containing solutions (e.g. potassium chloride), ACE inhibitors (e.g. captopril, enalapril), heparin and low molecular weight heparin, angiotensin-II receptor antagonists (e.g. candesartan, valsartan), aldosterone blockers or potassium-sparing diuretics (triamterene, amiloride) should be avoided, as this may lead to an increase in serum potassium and the development of severe, and possibly life-threatening, hyperkalemia.

Concomitant use of ACE inhibitors, loop diuretics and spironolactone may lead to the development of acute renal failure.

Concomitant use of trimethoprim/sulfamethoxazole (cotrimoxazole) and spironolactone may lead to clinically significant hyperkalemia.

Spironolactone should not be used in combination with mitotane, as it may block the effects of mitotane.

In the case of additional intake of drugs to lower blood pressure, a significant decrease in blood pressure may be observed.

Other diuretics: increased diuresis and significant decrease in blood pressure.

Cholestyramine, ammonium chloride: increased risk of hyperkalemia and hyperchloremic metabolic acidosis).

Immunosuppressants (tacrolimus and cyclosporine): increased risk of hyperkalemia.

Tricyclic antidepressants and antipsychotics may enhance the hypotensive effect of Spironolactone Sandoz®.

Antihypertensive drugs (especially ganglioblockers): Excessive hypotension may occur. Therefore, the dose of antihypertensive drugs may be reduced when Spironolactone Sandoz® is added to the therapeutic regimen, with subsequent adjustments if necessary.

Alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension caused by spironolactone.

Pressor amines (norepinephrine): Spironolactone reduces their effect. This should be taken into account when performing local or general anesthesia with these drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid, indomethacin and mefenamic acid: increased risk of hyperkalemia with concomitant reduction of the diuretic, natriuretic and antihypertensive effects of spironolactone. In patients who develop hypovolemia or dehydration during spironolactone therapy, concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause acute renal failure.

Glucocorticosteroids, adrenocorticotropic hormone (ACTH): paradoxical increase in potassium excretion.

Digoxin: Spironolactone may increase the half-life of digoxin, which may lead to an increase in its serum levels and the development of glycoside intoxication.

Lithium preparations should not be administered concomitantly with diuretics, as they reduce renal clearance of lithium and may increase the risk of toxicity.

Carbenoxolone may cause sodium retention and thus reduce the effectiveness of spironolactone, and a mutual reduction in the effectiveness of the drugs is possible. The use of large amounts of licorice has an effect similar to the action of carbenoxolone.

Carbamazepine: when taken simultaneously with spironolactone, may cause the development of clinically significant hyponatremia.

Terfenadine, when used simultaneously with spironolactone, increases the risk of ventricular arrhythmia due to hypokalemia and imbalance of other electrolytes.

Coumarin derivatives: their effect is weakened.

Triptorelin, buserelin, gonadorelin: their effects are enhanced.

Neomycin may delay the absorption of spironolactone.

Antipyrine: Spironolactone accelerates the metabolism of antipyrine.

Inhaled analgesics: a severe decrease in blood pressure may occur.

Impact on laboratory test results: an impact on the process of determining digoxin concentration by radioimmunoassay methods may be expected.

Hyperkalemic metabolic acidosis has been reported with cholestyramine.

The simultaneous use of spironolactone and ACE inhibitors (such as captopril, enalapril) is associated with the risk of a significant decrease in blood pressure, which may progress to shock, and with the risk of worsening of renal function, which in isolated cases may lead to acute renal failure. In order to avoid the possible development of arterial hypotension at the beginning of treatment, the use of diuretics should be discontinued 2-3 days before starting therapy with ACE inhibitors.

Spironolactone binds to the androgen receptor and may increase prostate-specific antigen (PSA) levels in prostate cancer patients treated with abiraterone. Use with abiraterone is not recommended.

Application features

Careful monitoring of the condition must be established:

- patients with moderate renal impairment (creatinine clearance 30–60 ml/min and/or serum creatinine within 1.2–1.8 mg/dl);

- patients with diathesis, acidosis and/or hyperkalemia caused by an underlying disease (e.g. in the case of diabetes mellitus).

- patients with arterial hypotension.

Spironolactone may increase the risk of hyperkalemia in patients with diabetic nephropathy.

Hyperkalemia can be life-threatening. In patients with severe heart failure, serum potassium should be monitored. Potassium-sparing diuretics should be avoided. Patients with serum potassium levels exceeding 3.5 mmol/l should avoid oral potassium supplements. Monitoring of potassium and creatinine levels is recommended 1 week after initiation of treatment or dose increase, then monthly for the first 3 months, then 4 times a year for 1 year, and then every 6 months. If serum potassium exceeds 5 mmol/l or serum creatinine exceeds 4 mg/dl, treatment should be discontinued or interrupted.

Spironolactone therapy may cause a transient increase in serum urea nitrogen, especially in patients with pre-existing renal impairment and hyperkalemia. Spironolactone may cause reversible hyperchloremic metabolic acidosis. Therefore, in patients with renal and hepatic impairment, as well as in the elderly, biochemical parameters of renal function and electrolyte balance should be regularly monitored.

Spironolactone should be used with extreme caution in patients with porphyria, as many drugs provoke exacerbation of porphyria.

During treatment with spironolactone, alcohol consumption is prohibited.

It is necessary to avoid prolonged unjustified use of the drug, since, according to published data, prolonged use of spironolactone in animals at maximum doses contributed to the development of carcinoma and myeloid leukemia.

The concomitant use of spironolactone and potassium-sparing diuretics (e.g. triamterene, amiloride), potassium-containing solutions or ACE inhibitors may lead to life-threatening hyperkalemia. Therefore, the use of these drugs is not recommended.

In case of severe renal insufficiency (glomerular filtration rate below 30 ml/min and/or serum creatinine above 1.8 ml/dl), spironolactone is not only ineffective, but even harmful, as the glomerular filtration rate will continue to decline.

In case of impaired renal function (serum creatinine level is within 1.2–1.8 mg/dl and creatinine clearance is within 60–30 ml/min) and concomitant use of drugs that may increase blood potassium levels, spironolactone therapy should be carried out with regular monitoring of blood potassium levels.

During treatment with spironolactone, serum electrolyte balance (mainly potassium, sodium, calcium, bicarbonate), serum creatinine, urea and uric acid, which are normally excreted in the urine, as well as acid-base status should be regularly monitored.

Weight loss caused by increased urination should not exceed 1 kg/day, regardless of the volume of urine excreted.

Pseudo-Bartter syndrome with edema may occur as a result of chronic diuretic abuse. Edema is a manifestation of increased renin, resulting in secondary hyperaldosteronism.

Spironolactone may interfere with the results of some diagnostic tests (e.g., serum digoxin concentration by radioimmunoassay (RIA), plasma cortisol, and epinephrine).

With intensive urination or a very rapid decrease in blood pressure at the beginning of treatment, complaints of circulatory disorders such as intracranial pressure, dizziness, visual disturbances and decreased ability to concentrate may occur.

No negative effect on carbohydrate metabolism was observed when using spironolactone.

Patients should drink sufficient fluids during treatment with spironolactone.

The use of Spironolactone Sandoz may cause a false-positive doping control result.

Incorrect use of Spironolactone Sandoz as a doping agent can harm your health.

Spironolactone Sandoz® 50 mg tablets contain 5 mg sodium lauryl sulfate, and 100 mg tablets contain 6 mg sodium lauryl sulfate. Caution should be exercised when used in patients on a controlled sodium diet.

Children and adolescents

If potassium levels in children and adolescents exceed the normal range, spironolactone should be reduced or discontinued, and electrolyte levels should be monitored more closely.

Information for patients with diabetes

1 tablet contains less than 0.01 bread units.

Use during pregnancy or breastfeeding

Spironolactone should not be used during pregnancy or breastfeeding.

There are insufficient data on the use of spironolactone in pregnant women. In animal experiments, feminization of the genital organs of male offspring and hormonal disorders in male and female offspring have been observed. Antiandrogenic effects have been observed in humans. Therefore, spironolactone is contraindicated during pregnancy.

It is not known whether spironolactone is excreted in breast milk. The pharmacologically active metabolite canrenoate is excreted in breast milk (the breast milk-plasma concentration ratio is 0.7). Therefore, spironolactone is contraindicated during breastfeeding. If treatment is necessary, breastfeeding should be discontinued.

Ability to influence reaction speed when driving vehicles or other mechanisms

During the initial period of spironolactone use, the duration of which is individual, it is forbidden to drive a car or operate machinery that carries an increased risk of injury.

Method of administration and doses

The dose should be determined individually, depending on the severity and degree of hyperaldosteronism.

Primary hyperaldosteronism

In case of diagnosed primary hyperaldosteronism, the drug can be prescribed in preparation for surgery in a daily dose of 100–400 mg. For patients who are not scheduled for surgery, the drug can be used as long-term maintenance therapy in the lowest effective dose, which is determined individually. In the described situation, the initial dose can be reduced every 14 days until the minimum effective dose is reached. In case of long-term use, it is recommended to use it in combination with diuretics of other groups to reduce side effects.

Edema (congestive heart failure, nephrotic syndrome)

Adults: The initial daily dose is 100 mg (25-200 mg) and is administered in 1 or 2 divided doses. In the case of higher doses, Spironolactone Sandoz® can be administered in combination with other groups of diuretics that act in more proximal parts of the renal tubules. In this case, the dosage of Spironolactone Sandoz® should be adjusted.

Cirrhosis of the liver accompanied by ascites or edema

If the ratio of Na+/K+ in the urine is greater than 1, the initial daily and maximum daily doses are 100 mg. If this ratio is less than 1, the initial daily dose is 200 mg, the maximum - 400 mg/day.

The maintenance dose should be determined individually.

Essential hypertension

The initial daily dose, administered in 1 or 2 divided doses, is 50–100 mg, and should be taken in combination with other antihypertensive drugs. Therapy is continued for at least two weeks, since by the end of this period the maximum antihypertensive effect is achieved. Then the dose should be adjusted individually, depending on the effect achieved.

Hypokalemia

Patients who do not receive enough K+ supplements or other methods of potassium replacement therapy should take the drug in a daily dose of 25–100 mg.

Children

The recommended initial dose for children is 1 - 3 mg of spironolactone per 1 kg of body weight in 1 or 2 doses daily for 5 days. If it is necessary to use the drug in children under 3 years of age, the tablet should be crushed, dissolved and given to the child as a suspension.

If treatment is continued, the dose should be reduced while maintaining the achieved effect of the drug.

Elderly patients

It is recommended to start treatment with lower doses and then gradually increase them until the maximum effect is achieved. Existing hepatic and renal disorders should be taken into account, as they affect the metabolism and excretion of the drug.

Spironolactone Sandozâ 100 mg

Due to the high content of the active substance Spironolactone Sandoz® (100 mg) is not suitable for the treatment of children.

Method and duration of application.

The tablets should be swallowed without chewing, with sufficient liquid (e.g. a glass of water).

The duration of treatment depends on the type and severity of the disease. The duration of treatment should be as short as possible. The need for long-term treatment with spironolactone should be reviewed from time to time.

Children

Spironolactone Sandoz, 50 mg tablets can be used in pediatric practice.

Due to the high content of the active substance Spironolactone Sandoz® (100 mg) is not suitable for the treatment of children.

Overdose

Symptoms

Spironolactone overdose may cause symptoms such as drowsiness/lethargy, confusion, nausea, vomiting, dizziness, or diarrhea. Hyponatremia, hypokalemia, or hyperkalemia may occur in some cases, especially in patients with impaired renal function; hepatic coma may occur in patients with severe liver disease, but is unlikely to be associated with acute spironolactone overdose. Hyperkalemia may present with symptoms such as paresthesia, weakness, flaccid paralysis, or muscle spasms and may be clinically difficult to distinguish from hypokalemia. ECG changes are the first specific symptoms of potassium deficiency

Electrolyte disturbances, arrhythmia, cardiac conduction disturbances.

Treatment of hyperkalemia

Symptomatic, there is no specific antidote. Water-electrolyte and acid-base balance should be maintained by prescribing potassium-sparing diuretics; parenteral administration of glucose with insulin, and in difficult cases, hemodialysis.

Treatment of hyponatremia

1M sodium chloride solution or, in case of simultaneous acidosis, 1M sodium bicarbonate solution should be administered as an additive to the carrier solution.

Adverse reactions

Adverse reactions are a consequence of competitive antagonism of aldosterone, which increases potassium excretion, and the antiandrogenic effect of spironolactone.

Adverse reactions are listed by system organ class according to the MedDRA Medical Dictionary of Regulatory Activities using the following MedDRA frequency definitions:

very common (≥ 1/10)

common (≥ 1/100 to < 1/10)

uncommon (≥ 1/1000 to < 1/100)

isolated (1/10,000 to < 1/1,000)

unknown frequency (cannot be estimated from the available data).

1 In patients with renal insufficiency and those receiving potassium supplements.

2 In elderly patients, diabetics, and those receiving ACE inhibitors.

3 In patients with cirrhosis of the liver.

4 In patients with renal failure and those receiving potassium supplements.

5 When using high doses (450 mg per day).

6 In some cases.

7 Dose-dependent.

Metabolism and digestive disorders

Life-threatening hyperkalemia may occur with spironolactone, especially in patients with impaired renal function. This may cause symptoms such as muscle paralysis (hyperkalemic paralysis) and arrhythmia. Therefore, additional potassium supplements, other potassium-sparing diuretics, or a potassium-rich diet should be avoided.

In case of impaired renal function, disturbances of water and electrolyte balance (hyponatremia, hypomagnesemia, hyperchloremia, hypercalcemia) may occur due to increased excretion of water and electrolytes.

As a result of excessive diuresis, patients may develop hypovolemia and hyponatremia. Hyponatremia may occur mainly after excessive water intake while taking spironolactone. As a result of electrolyte imbalance in the blood, loss of appetite, dry mouth, thirst, vomiting, headache or flushing, asthenia, vertigo, drowsiness, fatigue, visual disturbances, apathy, confusion, myasthenia gravis, myospasm (cramps in the back of the legs), as well as arrhythmia and circulatory disorders (see adverse reactions "Cardiac disorders"). In this regard, it is necessary to compensate for unwanted fluid loss (e.g. due to vomiting, diarrhea, hyperhidrosis).

Serum electrolyte balance (especially potassium, sodium and calcium) should be checked regularly.

At the beginning of therapy and during long-term use of spironolactone, serum potassium levels should be monitored at regular intervals to prevent the development of excess potassium in the blood.

Acid-base disturbances are possible. Spironolactone may cause or exacerbate hyperchloremic metabolic acidosis.

Reversible increases in the concentration of nitrogenous compounds normally excreted in the urine (urea, creatinine) have been reported infrequently.

Hyperuricemia has been reported frequently during spironolactone therapy, which may precipitate acute gout in susceptible patients.

Serum urea, creatinine and uric acid concentrations, as well as acid-base balance and water-electrolyte balance, should be monitored regularly during spironolactone therapy.

Cardiac disorders

Excessive diuresis due to hypovolemia may result in headache, vertigo, visual disturbances, dry mouth, and thirst, as well as orthostatic dysregulation or a sudden drop in blood pressure that progresses to vascular insufficiency.

In case of excessive diuresis, dehydration and as a result of hypovolemia, a decrease in plasma volume is possible, as a result of which elderly patients may experience an increased risk of developing thrombosis and embolism.

Serum creatinine and urea concentrations may increase with spironolactone. Increased urine output may worsen or exacerbate existing conditions in patients with urinary tract obstruction.

Expiration date

2 years.

Storage conditions

No special storage conditions are required.

Keep out of reach of children.

Packaging

10 tablets in a blister; 2 or 3 or 6 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

Salutas Pharma GmbH/Salutas Pharma GmbH.

Location of the manufacturer and address of its place of business

Otto-von-Guericke-Allee 1, 39179, Barleben, Germany.