Instructions Spilacton film-coated tablets 25 mg blister No. 20
Composition
active ingredient: spironolactone;
1 film-coated tablet contains 25 mg, 50 mg or 100 mg of spironolactone;
excipients: corn starch; colloidal anhydrous silicon dioxide; povidone KZ0; calcium hydrogen phosphate, dihydrate; magnesium stearate;
film coating:
25 mg tablets: Opadry II Yellow 85F220095 [polyvinyl alcohol; titanium dioxide (E 171); macrogol; talc; iron oxide yellow (E 172); tartrazine aluminum lake (E 102); sunset yellow FCF aluminum lake (E 110)];
50 mg tablets: Opadry II Orange 85F230047 [polyvinyl alcohol; titanium dioxide (E 171); macrogol; talc; iron oxide yellow (E 172); iron oxide red (E 172)];
100 mg tablets: Opadry II Orange 85F230020 [polyvinyl alcohol; titanium dioxide (E 171); macrogol; talc; iron oxide yellow (E 172); iron oxide red (E 172)].
Dosage form
Film-coated tablets.
Main physicochemical properties:
25 mg tablets: round, biconvex, film-coated tablets from light yellow to yellow, with a breakline on one side;
50 mg tablets: round, biconvex, film-coated tablets from light orange to orange, with a breakline on one side;
100 mg tablets: round biconvex tablets, film-coated, yellowish-orange, with a breakline on one side.
Pharmacotherapeutic group
Potassium-sparing diuretics. ATX code C03D A01.
Pharmacological properties
Pharmacodynamics.
Spironolactone is a competitive aldosterone antagonist. It increases sodium excretion while decreasing potassium excretion in the distal renal tubules. It has a gradual and long-lasting effect.
Pharmacokinetics.
Spironolactone is well absorbed after oral administration and is mainly metabolized to form active metabolites: sulfur-containing (80%) and partially canrenone (20%).
The half-life (T1/2) of spironolactone is short (1.3 hours), the half-life (T1/2) of the active metabolites is longer (from 2.8 to 11.2 hours). Metabolites are excreted mainly by the kidneys, the rest is excreted through the intestines. Spironolactone and its metabolites penetrate the placenta and into breast milk.
When spironolactone was administered 100 mg daily for 15 days to healthy volunteers in the fed state, Tmax was 2.6 hours, Cmax was 80 ng/ml and T1/2 was approximately 1.4 hours. For 7-alpha-(thiomethyl)-spironolactone and canrenone, Tmax was 3.2 and 4.3 hours, Cmax was 391 ng/ml and 181 ng/ml and T1/2 was 13.8 hours and 16.5 hours, respectively.
The renal effect of a single dose of spironolactone reaches its peak after 7 hours, and the activity persists for at least 24 hours.
Indication
- Congestive heart failure.
- Cirrhosis of the liver, accompanied by edema and ascites.
- Malignant ascites.
- Nephrotic syndrome.
- Primary hyperaldosteronism — diagnosis and treatment.
Treatment of children should only be carried out under the supervision of a pediatrician. Data on use in children are limited.
Contraindication
- Hypersensitivity to the active substance and/or excipients of the medicinal product.
- Acute renal failure, severe impairment of nitrogen-excreting kidney function, anuria.
- Addison's disease.
- Hyperkalemia.
- Hyponatremia.
- Moderate or severe renal impairment in children.
- Concomitant use with eplerenone or other potassium-sparing diuretics and potassium supplements - due to the risk of hyperkalemia.
- Breastfeeding period.
Interaction with other medicinal products and other types of interactions
In case of simultaneous use of spironolactone:
With other potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin II receptor antagonists, aldosterone blockers, heparin, low molecular weight heparins, potassium supplements, with other drugs or foods that can cause an increase in plasma potassium levels - the risk of developing severe hyperkalemia. In addition, the simultaneous use of spironolactone with trimethoprim/sulfamethoxazole may lead to the development of clinically significant hyperkalemia.
With digoxin - an increase in the half-life of digoxin. Spironolactone may also affect the process of determining the concentration of digoxin in the blood plasma. When using these drugs simultaneously, the body's response to digoxin should be monitored by methods that do not depend on the use of spironolactone. The patient's condition should be carefully monitored and, if necessary, the dosage of digoxin should be adjusted.
With antihypertensive agents - potentiation of the effect of the latter. The dose of antihypertensive agents should be reduced when adding spironolactone to the therapeutic regimen and the dose of antihypertensive agents should be further adjusted if necessary. In addition, since ACE inhibitors reduce aldosterone synthesis, their regular simultaneous use with spironolactone is not recommended, especially in patients with renal failure.
With nonsteroidal anti-inflammatory drugs (NSAIDs), in particular acetylsalicylic acid, indomethacin and mefenamic acid, there is a decrease in the diuretic activity of spironolactone due to inhibition of intrarenal prostaglandin synthesis.
With norepinephrine - spironolactone reduces the vascular response to norepinephrine. Caution should be exercised when administering anesthesia to patients using spironolactone.
With antipyrine - increased metabolism of the latter.
When performing fluorometric assays, spironolactone may interfere with the evaluation of compounds with similar fluorescence characteristics.
Spironolactone binds to androgen receptors, which may lead to increased prostate-specific antigen (PSA) levels in prostate cancer patients treated with abiraterone. Therefore, concomitant use of these drugs is not recommended.
Application features
Effect on water and electrolyte balance.
During the use of the drug, water and electrolyte balance should be regularly monitored, especially in elderly patients and patients with impaired renal and hepatic function.
In case of impaired kidney function or excessive potassium intake, hyperkalemia may develop, which can lead to cardiac disorders, including fatal ones.
In case of development of hyperkalemia, the use of the drug should be discontinued and, if necessary, measures should be taken to reduce the level of potassium in the blood plasma.
It has also been reported that reversible hyperchloremic metabolic acidosis may occur with the use of spironolactone in some patients with decompensated cirrhosis of the liver due to hyperkalemia, even with normal renal function.
Effect on the urinary system.
Transient increases in blood urea nitrogen have been reported with spironolactone use, especially in patients with impaired renal function.
Use in patients with severe heart failure.
Hyperkalemia in such patients can be life-threatening. It is very important to carefully monitor the level of potassium in the blood plasma during the use of the drug. It is recommended to monitor the level of potassium and creatinine in the blood plasma 1 week after the start of treatment or an increase in the dose of spironolactone, monthly during the first 3 months of therapy, then quarterly for a year, and then every 6 months. Potassium supplements, other potassium-sparing diuretics should not be used in patients with a potassium level above 3.5 mmol/l. In case of an increase in the level of potassium in the blood plasma to 5 mmol/l or creatinine level to 4 mg/dl and above, the drug should be discontinued.
Application to children.
Spironolactone should only be used in children under the supervision of a pediatrician, as available data on its use in this patient population are limited.
Potassium-sparing diuretics, including spironolactone, should be used with caution in children with hypertension and mild renal impairment due to the risk of hyperkalemia. The drug is contraindicated in children with moderate to severe renal impairment.
The medicinal product in the form of 25 mg tablets contains tartrazine aluminum lake (E 102) and sunset yellow FCF aluminum lake (E 110), which may cause allergic reactions.
Use during pregnancy or breastfeeding
Spironolactone and its metabolites cross the placental barrier and are excreted in breast milk.
During pregnancy, the drug should be used when the expected benefit to the mother outweighs the potential risk to the fetus.
If necessary, use of the drug should stop breastfeeding.
When administered to animals, spironolactone caused feminization in male fetuses.
Ability to influence reaction speed when driving vehicles or other mechanisms
Drowsiness and dizziness have been reported with spironolactone. Caution should be exercised during the initial stages of treatment until the patient's response to the drug is established.
Method of administration and doses
Adults.
Congestive heart failure with edema.
To reduce edema, the initial daily dose of the drug is 100 mg once or in 2 doses, but can vary from 25 mg to 200 mg per day. The maintenance dose is determined individually.
Severe heart failure (NYHA [New York Heart Association] class III–IV).
In combination with standard therapy, the recommended initial dose of the drug is 25 mg 1 time per day with a potassium level ≤ 5.0 mg-eq/l and creatinine in the blood plasma ≤ 2.5 mg/dl. With good tolerability of treatment, the dose is increased to 50 mg 1 time per day according to clinical indications. If the drug is poorly tolerated by the patient, the dose is reduced to 25 mg every other day. For recommendations on monitoring the level of potassium and creatinine in the blood plasma, see the section "Features of use".
Cirrhosis of the liver, accompanied by edema and ascites.
If Na+/K+ in urine is more than 1.0, the dose of the drug is 100 mg per day. If Na+/K+ in urine is less than 1.0, the dose of the drug is 200–400 mg per day. The dose of spironolactone is determined individually for each patient.
The usual dose of the drug is 100–200 mg per day. In severe cases, the dose can be gradually increased to 400 mg per day. Based on the dynamics of the development of edematous syndrome, the maintenance dose is determined individually.
Nephrotic syndrome.
The usual dose of the drug is 100–200 mg per day. Spironolactone does not affect the underlying pathological process. Its use is recommended only if treatment with glucocorticosteroids is ineffective.
Diagnosis and treatment of primary hyperaldosteronism.
Spironolactone can be used as a baseline diagnostic test to determine primary hyperaldosteronism in patients on a standard diet.
Long test: spironolactone is prescribed at a dose of 400 mg per day for 3–4 weeks. Correction of hypokalemia and arterial hypertension suggests a diagnosis of primary hyperaldosteronism.
Short test: Spironolactone is given at a daily dose of 400 mg for 4 days. If potassium levels increase during spironolactone use and decrease upon discontinuation, a presumptive diagnosis of primary hyperaldosteronism should be considered.
After the diagnosis of hyperaldosteronism is confirmed by more precise testing procedures, the drug can be used at a dose of 100–400 mg/day in preparation for surgery.
Elderly patients.
It is recommended to start treatment with the drug at low doses with subsequent titration to achieve maximum effect. Caution should be exercised in severe hepatic and renal insufficiency, which alter the metabolism and excretion of spironolactone.
Children.
The initial daily dose of the drug is 1-3 mg / kg body weight in several doses. The dosage should be adjusted based on the response to treatment and tolerability of the drug.
Children.
The use of the drug in children should only be carried out under the guidance of a pediatrician, as the available data on the use in this category of patients is limited.
Side effects
Adverse reactions are classified according to the frequency of occurrence in the following categories: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1000 and < 1/100), rare (≥ 1/10000 and < 1/1000), very rare (< 1/10000), unknown (frequency cannot be estimated from the available data).
Neoplasms benign, malignant and unspecified (including cysts and polyps):
infrequently - benign breast tumors (in men).
Blood and lymphatic system disorders:
not known - leukopenia, agranulocytosis, thrombocytopenia.
Metabolism and nutrition:
very often - hyperkalemia; infrequently - electrolyte imbalance.
From the psyche:
often - confusion; not known - change in libido.
From the nervous system:
often - dizziness.
From the digestive tract:
often - nausea; not known - gastrointestinal disorders.
From the hepatobiliary system:
uncommon - liver dysfunction.
On the part of the immune system, skin and subcutaneous tissue:
often - itching, rash; infrequently - urticaria; unknown - hypersensitivity reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), alopecia, hypertrichosis, pemphigoid.
Musculoskeletal and connective tissue disorders:
often - spasms of the calf muscles.
From the kidneys and urinary tract:
often - acute renal failure.
From the reproductive system and mammary glands:
often - menstrual disorders, breast tenderness (in men); infrequently - breast tenderness (in women).
On the part of the body as a whole and reactions at the injection site:
often - malaise.
When using spironolactone, gynecomastia may develop. Its occurrence depends on the dose and duration of treatment. As a rule, gynecomastia is transient and disappears after discontinuation of the drug. In rare cases, some enlargement of the mammary glands may persist.
Reporting of suspected adverse reactions.
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Overdose
Symptoms.
Symptoms of acute spironolactone overdose include drowsiness, confusion, nausea, vomiting, dizziness, and diarrhea. Hyponatremia or hyperkalemia may develop. Hyperkalemia may present with paresthesia, weakness, flaccid paralysis, or muscle spasms and may be difficult to distinguish clinically from hypokalemia. Electrocardiographic changes are the earliest specific signs of potassium metabolism disorders.
Treatment.
The drug should be discontinued. Supportive care, including electrolyte and fluid balance, is recommended. Hyperkalemia can be treated by limiting potassium intake, using potassium-sparing diuretics, ion exchange resins, and parenteral administration of glucose with insulin. No specific antidote has been identified.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in the original packaging and out of the reach of children.
Packaging
10 tablets in a blister. 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
WORLD MEDICINE ILACH SAN. VE TIJ. A. Sh. /
WORLD MEDICINE ILAC SAN. VE TIC. AS
Location of the manufacturer and address of its place of business.
15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey / 15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.
Applicant.
LLC "WORLD MEDICINE", Ukraine /
WORLD MEDICINE, LLC, Ukraine.
