Captopril-STI tablets 50 mg

Instructions for use of Captopril-STI tablets 50 mg

Brand name of the drug: Captopril-STI

International nonproprietary name: Captopril

Dosage form: tablets

Composition per one tablet:

Description:

Round, biconvex, white or almost white tablets with a score line and a characteristic odor. Slight marbling is allowed.

Pharmacotherapeutic group: angiotensin-converting enzyme inhibitor (ACE inhibitor).

ATC code: C09AA01

Pharmacological action

Pharmacodynamics:

The drug Captopril-STI is an angiotensin-converting enzyme (ACE) inhibitor. It suppresses the formation of angiotensin II and eliminates its vasoconstrictive effect on arterial and venous vessels.

Reduces total peripheral vascular resistance, reduces afterload, lowers blood pressure. Reduces preload, reduces pressure in the right atrium and the pulmonary circulation. Reduces aldosterone secretion in the adrenal glands. The maximum antihypertensive effect is observed within 60-90 minutes after oral administration. The degree of blood pressure reduction is the same in the "standing" and "lying" positions.

The efficacy and safety of captopril in children have not been established. Limited experience with the use of captopril in children has been described in the literature. Children, especially newborns, may be more susceptible to hemodynamic side effects. Cases of excessive, prolonged, and unpredictable increases in blood pressure, as well as related complications, including oliguria and convulsions, have been reported.

Pharmacokinetics:

After oral administration, the bioavailability of captopril is 60-70%. Concurrent food intake slows absorption by 30-40%. Plasma protein binding is 25-30%. Half-life is 2-3 hours. The drug is excreted from the body primarily by the kidneys, up to 50% unchanged.

Indications for use:

Arterial hypertension, including renovascular; chronic heart failure (as part of combination therapy); left ventricular dysfunction after myocardial infarction in clinically stable condition; diabetic nephropathy in type 1 diabetes mellitus (with albuminuria greater than 30 mg/day).

Contraindications:

Hypersensitivity to captopril or other ACE inhibitors; angioedema (in history associated with ACE inhibitor therapy or hereditary); severe impairment of liver and/or kidney function; hyperkalemia; bilateral renal artery stenosis, stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, aortic orifice stenosis and similar changes obstructing blood outflow from the left ventricle, pregnancy, lactation, age under 18 years (efficacy and safety not established).

Rare hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Concomitant use with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate or severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m² body surface area.

Concomitant use with angiotensin II receptor antagonists (ARBs) in patients with diabetic nephropathy is contraindicated.

Concomitant use with neutral endopeptidase inhibitors (e.g., drugs containing sacubitril) due to a high risk of angioedema.

With caution:

Severe autoimmune connective tissue diseases (including systemic lupus erythematosus, scleroderma), bone marrow depression (risk of neutropenia and agranulocytosis), cerebral ischemia, diabetes mellitus (increased risk of hyperkalemia), patients on hemodialysis, sodium-restricted diet, primary hyperaldosteronism, coronary artery disease, conditions accompanied by a decrease in circulating blood volume (including vomiting, diarrhea), elderly age (dose adjustment required).

Use during pregnancy and breastfeeding:

The use of Captopril-STI is contraindicated during pregnancy.

Captopril-STI should not be used in the first trimester of pregnancy. Appropriate controlled studies on the use of ACE inhibitors in pregnant women have not been conducted. The available limited data on the drug's effects in the first trimester of pregnancy indicate that the use of ACE inhibitors does not lead to fetal malformations associated with fetotoxicity. Epidemiological data on the risk of teratogenicity after exposure to ACE inhibitors in the first trimester of pregnancy have not been conclusive, but some increased risk cannot be ruled out. If ACE inhibitor use is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive therapy with an established safety profile for use during pregnancy.

It is known that prolonged exposure of the fetus to ACE inhibitors in the second and third trimesters of pregnancy can lead to impaired development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (such as renal failure, arterial hypotension, hyperkalemia). If the patient received Captopril-STI during the second and third trimester of pregnancy, an ultrasound examination is recommended to assess the condition of the fetal skull bones and renal function.

The use of ACE inhibitors during pregnancy can cause developmental disorders (including arterial hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure) and fetal death. If pregnancy is confirmed, the use of Captopril-STI should be discontinued as soon as possible.

Approximately 1% of the administered dose of captopril is found in breast milk. Due to the risk of developing serious adverse reactions in the child, breastfeeding should be discontinued or therapy with Captopril-STI should be canceled in the mother during breastfeeding.

Dosage and administration:

Orally, one hour before meals. The dosage regimen is set individually.

To ensure the dosage regimens indicated below, if it is necessary to use captopril at a dose of 6.25 mg, captopril preparations from other manufacturers in the dosage form "25 mg tablets" with a cross score or "12.5 mg tablets" with a score should be prescribed.

For arterial hypertension, the drug is prescribed at an initial dose of 12.5 mg 2 times a day. If necessary, the dose is gradually increased (at intervals of 2-4 weeks) to achieve the optimal effect. For mild to moderate arterial hypertension, the usual maintenance dose is 25 mg 2 times a day; the maximum dose is 50 mg 2 times a day. For severe arterial hypertension, the initial dose is 12.5 mg 2 times a day. The dose is gradually increased to a maximum daily dose of 150 mg (50 mg 3 times a day).

For the treatment of chronic heart failure, Captopril-STI is prescribed in cases where the use of diuretics does not provide an adequate effect. The initial daily dose is 6.25 mg 3 times a day. Subsequently, if necessary, the dose is gradually increased (at intervals of at least 2 weeks). The average maintenance dose is 25 mg 2-3 times a day, and the maximum is 150 mg per day.

For left ventricular dysfunction after myocardial infarction in patients who are clinically stable, the use of Captopril-STI can be started as early as 3 days after myocardial infarction. The initial dose is 6.25 mg per day, then the daily dose can be increased to 37.5-75 mg in 2-3 doses (depending on drug tolerance) up to a maximum of 150 mg per day.

For diabetic nephropathy, Captopril-STI is prescribed at a dose of 75-100 mg, divided into 2-3 doses. For insulin-dependent diabetes with microalbuminuria (albumin excretion 30-300 mg per day), the drug dose is 50 mg 2 times a day. With total protein clearance of more than 500 mg per day, the drug is effective at a dose of 25 mg 3 times a day.

For patients with impaired renal function with moderate renal impairment (creatinine clearance (CrCl) not less than 30 ml/min/1.73 m²), Captopril-STI can be prescribed at a dose of 75-100 mg/day. With more severe renal impairment (CrCl less than 30 ml/min/1.73 m²), the initial dose should be no more than 12.5 mg/day; subsequently, if necessary, with sufficiently long intervals, the dose of Captopril-STI is gradually increased, but a lower than usual daily dose of the drug is used.

In elderly patients, the dose of the drug is selected individually; it is recommended to start therapy with a dose of 6.25 mg 2 times a day and, if possible, maintain it at this level.

If necessary, loop diuretics are additionally prescribed, rather than thiazide diuretics.

Side effects:

The frequency of adverse reactions is understood as: common – ≥ 1/100, <1/10; uncommon – ≥ 1/1000, <1/100; rare – ≥ 1/10000, < 1/1000; very rare –< 1/10000.

From the cardiovascular system:

uncommon – tachycardia or arrhythmia, angina pectoris, palpitations, orthostatic arterial hypotension, peripheral edema, marked decrease in blood pressure, Raynaud's syndrome, facial flushing, pallor; very rare – cardiac arrest, cardiogenic shock.

From the respiratory system:

common – dry non-productive cough, shortness of breath; very rare – bronchospasm, eosinophilic pneumonitis, rhinitis, pulmonary edema.

Allergic reactions:

common – skin itching, with or without rash, skin rash, alopecia;

uncommon – angioedema of the extremities, face, lips, mucous membranes, tongue, pharynx and larynx;

rare – intestinal angioedema;

very rare – urticaria, Stevens-Johnson syndrome, multiforme erythema, photosensitivity, erythroderma, pemphigoid reactions, exfoliative dermatitis, allergic alveolitis, eosinophilic pneumonia.

From the central nervous system:

common – drowsiness, dizziness, insomnia;

uncommon – headache, paresthesia;

rare – ataxia;

very rare – confusion, depression, cerebrovascular accidents, including stroke and syncope, blurred vision.

From the hematopoietic organs:

very rare – neutropenia, agranulocytosis, pancytopenia, lymphadenopathy, eosinophilia, thrombocytopenia, anemia (including aplastic and hemolytic forms), increased titer of antinuclear antibodies, autoimmune diseases.

From the digestive system:

common – nausea, vomiting, gastric mucosal irritation, abdominal pain, diarrhea, constipation, taste disturbance, dry oral mucosa, dyspepsia;

uncommon – anorexia;

rare – stomatitis, aphthous stomatitis;

very rare – glossitis, gastric ulcer, pancreatitis, gingival hyperplasia, impaired liver function and cholestasis (including jaundice), increased activity of liver enzymes, hepatitis (including rare cases of hepatonecrosis), hyperbilirubinemia.

From the musculoskeletal system:

very rare – myalgia, arthralgia.

From the urinary system:

rare – renal function impairment (including renal failure), polyuria, oliguria, frequent urination;

very rare – nephrotic syndrome.

From the reproductive organs:

very rare – impotence, gynecomastia.

Other:

uncommon – chest pain, increased fatigue, general malaise, asthenia;

rare – hyperthermia.

Laboratory parameters:

very rare – proteinuria, eosinophilia, hyperkalemia, hyponatremia, increased blood urea nitrogen, bilirubin and creatinine, decreased hematocrit, decreased hemoglobin, leukocytes, platelets, hypoglycemia.

Overdose:

Symptoms: sharp decrease in blood pressure.

Treatment: administration of isotonic sodium chloride solution or other plasma-substituting solutions, hemodialysis.

Drug interactions:

In patients taking diuretics, Captopril-STI may potentiate the antihypertensive effect. Similar action is also exerted by restriction of table salt intake (salt-free diets), hemodialysis. Excessive lowering of blood pressure usually occurs within one hour after taking the first prescribed dose of Captopril-STI.

Vasodilators (e.g., nitroglycerin) in combination with Captopril-STI should be used in the lowest effective doses due to the risk of excessive blood pressure reduction.

Caution should be exercised when co-administering Captopril-STI (with or without a diuretic) and drugs that affect the sympathetic nervous system (e.g., ganglion blockers, alpha-adrenergic blockers). With the combined use of Captopril-STI and indomethacin (and possibly other non-steroidal anti-inflammatory drugs, for example, acetylsalicylic acid), a decrease in the antihypertensive effect may be observed, especially in arterial hypertension accompanied by low renin activity. In patients with risk factors (old age, hypovolemia, concurrent use of diuretics, impaired renal function), simultaneous use of NSAIDs (including cyclooxygenase-2 inhibitors) and ACE inhibitors (including captopril) may lead to worsening of renal function, up to acute renal failure. Usually, renal function impairment in such cases is reversible. Renal function should be periodically monitored in patients taking Captopril-STI and NSAIDs.

During therapy with Captopril-STI, potassium-sparing diuretics (e.g., triamterene, spironolactone, amiloride, eplerenone), potassium preparations, potassium supplements, salt substitutes (contain significant amounts of potassium ions) should be prescribed only for proven hypokalemia, as their use increases the risk of hyperkalemia.

When combined with drugs containing co-trimoxazole (trimethoprim + sulfamethoxazole), the risk of hyperkalemia increases.

With simultaneous use of ACE inhibitors (especially in combination with diuretics) and lithium preparations, an increase in serum lithium concentration and, consequently, the toxicity of lithium preparations is possible. Serum lithium levels should be periodically determined.

ACE inhibitors, including captopril, may potentiate the hypoglycemic effect of insulin and oral hypoglycemic agents such as sulfonylurea derivatives.

Blood glucose concentration should be monitored at the beginning of therapy with Captopril-STI, and if necessary, the dose of the hypoglycemic drug should be adjusted.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) caused by simultaneous intake of ACE inhibitors and angiotensin II receptor antagonists or aliskiren and aliskiren-containing drugs has been associated with an increased incidence of adverse effects such as arterial hypotension, hyperkalemia, and decreased renal function (including acute renal failure).

The use of Captopril-STI in patients taking allopurinol or procainamide increases the risk of developing neutropenia and/or Stevens-Johnson syndrome.

The use of Captopril-STI in patients taking immunosuppressants (e.g., cyclophosphamide or azathioprine) increases the risk of developing hematological disorders.

The risk of angioedema increases with the combined use of ACE inhibitors with the following drugs:

• with mTOR inhibitors (mammalian Target of Rapamycin), e.g., temsirolimus, sirolimus, everolimus;
• with dipeptidyl peptidase type IV (DPP-IV) inhibitors (gliptins), e.g., sitagliptin, saxagliptin, vildagliptin, linagliptin;
• with neutral endopeptidase inhibitors:

1. racecadotril (an enkephalinase inhibitor used to treat acute diarrhea);
2. sacubitril (a neprilysin inhibitor). ACE inhibitors should be prescribed no earlier than 36 hours after withdrawal of drugs containing sacubitril. The use of drugs containing sacubitril is contraindicated in patients receiving ACE inhibitors, and also within 36 hours after ACE inhibitor withdrawal.

• with estramustine;
• with tissue plasminogen activators. Observational studies have shown an increased incidence of angioedema in patients taking ACE inhibitors after using alteplase for thrombolytic therapy of ischemic stroke.

Special instructions:

Renal function should be monitored before starting and regularly during treatment with Captopril-STI. In patients with chronic heart failure, it should be used under careful medical supervision.

A characteristic non-productive cough is observed when taking ACE inhibitors, which stops after discontinuation of ACE inhibitor therapy.

In rare cases, a syndrome beginning with cholestatic jaundice progressing to fulminant hepatonecrosis, sometimes with a fatal outcome, has been observed with the use of ACE inhibitors. The mechanism of development of this syndrome is unknown. If jaundice develops or a marked increase in "liver" enzyme activity is noted in a patient receiving ACE inhibitor therapy, ACE inhibitor treatment should be discontinued and the patient should be monitored.

In some patients with kidney disease, especially with severe renal artery stenosis, an increase in serum urea nitrogen and creatinine concentrations is observed after blood pressure reduction. This increase is usually reversible upon discontinuation of Captopril-STI therapy. In these cases, it may be necessary to reduce the dose of Captopril-STI and/or discontinue the diuretic.

During long-term use of Captopril-STI, approximately 20% of patients experience an increase in serum urea and creatinine concentrations by more than 20% compared to normal or baseline.

In less than 5% of patients, especially with severe nephropathies, treatment discontinuation is required due to increased creatinine levels. The use of dual blockade of the renin-angiotensin-aldosterone system (RAAS) caused by simultaneous intake of ACE inhibitors and angiotensin II receptor antagonists or aliskiren and aliskiren-containing drugs is not recommended, as it has been associated with an increased incidence of adverse effects such as arterial hypotension, hyperkalemia, and decreased renal function (including acute renal failure). If simultaneous use of ACE inhibitors and ARBs (dual RAAS blockade) is necessary, then treatment should be carried out under medical supervision with constant monitoring of renal function, blood electrolyte levels, and blood pressure. Simultaneous use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m² body surface area) and is not recommended in other patients.

Simultaneous use of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

The combined use of ACE inhibitors and angiotensin II receptor antagonists is not recommended in patients with diabetic nephropathy.

In patients with arterial hypertension, marked arterial hypotension is observed only in rare cases when using Captopril-STI; the likelihood of this condition increases with increased loss of fluid and salts (e.g., after intensive diuretic treatment), in patients with heart failure or on dialysis. The possibility of a sharp decrease in blood pressure can be minimized by prior withdrawal (4-7 days before) of the diuretic or by increasing sodium chloride intake (approximately one week before starting), or by prescribing Captopril-STI at the beginning of treatment in small doses (6.25-12.5 mg/day).

Prescribe with caution to patients on a low-sodium or sodium-free diet (increased risk of arterial hypotension) and hyperkalemia. Excessive lowering of blood pressure may be observed in patients during major surgery, as well as when using general anesthetics that have a hypotensive effect. In such cases, measures to increase the volume of circulating blood should be taken to correct the reduced blood pressure.

Excessive lowering of blood pressure due to antihypertensive drugs may increase the risk of myocardial infarction or stroke in patients with coronary artery disease or cerebrovascular disease. If arterial hypotension develops, the patient should assume a horizontal position with legs elevated. Intravenous administration of 0.9% sodium chloride solution may be required.

Caution should be exercised when taking ACE inhibitors in patients with mitral/aortic stenosis/hypertrophic obstructive cardiomyopathy; in case of cardiogenic shock and hemodynamically significant obstruction – use is not recommended.

Neutropenia/agranulocytosis, thrombocytopenia, and anemia have been reported in patients taking ACE inhibitors. In patients with normal renal function and in the absence of other complications, neutropenia is rare. In renal failure, the simultaneous use of Captopril-STI and allopurinol has led to neutropenia.

Captopril-STI should be used with extreme caution in patients with autoimmune connective tissue diseases, in those taking immunosuppressants, allopurinol and procainamide, especially in the presence of pre-existing renal impairment. Since most fatal cases of neutropenia associated with ACE inhibitors occurred in such patients, their white blood cell count should be monitored before starting treatment, every 2 weeks in the first 3 months, then every 2 months.

In all patients, the white blood cell count should be monitored monthly for the first 3 months after starting therapy with Captopril-STI, then every 2 months. If the white blood cell count is below 4000/µL, a complete blood count should be repeated; if below 1000/µL, the drug should be discontinued, continuing to monitor the patient. Usually, neutrophil count recovery occurs within 2 weeks after discontinuation of Captopril-STI. In 13% of neutropenia cases, a fatal outcome was reported. In almost all cases, death occurred in patients with connective tissue diseases, renal or heart failure, while taking immunosuppressants, or a combination of both of these factors.

Proteinuria may occur with the use of ACE inhibitors, mainly in patients with impaired renal function, as well as with the use of high doses of the drugs. In most cases, proteinuria when taking Captopril-STI disappeared or its severity decreased within 6 months, regardless of whether the drug was discontinued or not. Renal function parameters (blood urea nitrogen and creatinine concentrations) in patients with proteinuria were almost always within normal limits. In patients with kidney disease, urine protein content should be determined before starting treatment and periodically during the course of therapy. In some cases, an increase in serum potassium is observed with the use of ACE inhibitors, including Captopril-STI. The risk of hyperkalemia with the use of ACE inhibitors is increased in patients with renal failure and diabetes, as well as those taking potassium-sparing diuretics, potassium preparations, or other drugs that cause an increase in blood potassium levels (e.g., heparin). The simultaneous use of potassium-sparing diuretics and potassium preparations should be avoided. In addition, when using ACE inhibitors simultaneously with thiazide diuretics, the risk of hypokalemia cannot be excluded, so regular monitoring of blood potassium levels should be carried out during therapy.

During hemodialysis in patients receiving ACE inhibitors, the use of high-permeability dialysis membranes (e.g., AN69) should be avoided, as in such cases the risk of anaphylactoid reactions increases. Anaphylactoid reactions have also been observed in patients undergoing low-density lipoprotein apheresis with dextran sulfate. The use of either antihypertensive drugs of another class or another type of dialysis membrane should be considered.

In rare cases, life-threatening anaphylactoid reactions have been observed during ACE inhibitor therapy in patients undergoing desensitization with hymenoptera venom (bees, wasps). In such patients, these reactions were prevented by temporarily discontinuing ACE inhibitor therapy. Particular caution should be exercised when performing desensitization in such patients.

If angioedema occurs, the drug should be discontinued and careful medical observation should be carried out until the symptoms completely disappear. Laryngeal edema can be fatal. If the edema is localized on the face, special treatment is usually not required (antihistamines may be used to reduce the severity of symptoms); if the edema spreads to the tongue, pharynx, or larynx and there is a threat of airway obstruction, epinephrine (adrenaline) should be administered subcutaneously immediately (0.3-0.5 ml in a 1:1000 dilution). In rare cases, intestinal angioedema has been observed in patients after taking ACE inhibitors, which was accompanied by abdominal pain (with or without nausea and vomiting), sometimes with normal C1-esterase activity and without preceding facial edema. Intestinal edema should be included in the differential diagnosis spectrum in patients complaining of abdominal pain while taking ACE inhibitors.

Cases of angioedema have been reported more frequently in black patients compared to Caucasian patients.

In diabetic patients receiving hypoglycemic drugs (oral hypoglycemic agents or insulin), blood glucose levels should be carefully monitored, especially during the first month of ACE inhibitor therapy.

ACE inhibitors are less effective in black patients than in Caucasian patients, which may be associated with a higher prevalence of low renin activity in black patients.

During extensive surgical operations or when using general anesthetics that have a hypotensive effect, excessive lowering of blood pressure may be observed in patients taking ACE inhibitors. In these cases, the volume of circulating blood can be increased.

When taking Captopril-STI, a false-positive urine test for acetone may be observed.

Effect on ability to drive vehicles and mechanisms:

During treatment, one should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as dizziness is possible, especially after taking the initial dose.

Dosage form:

Tablets of 25 mg and 50 mg.

10 tablets in a blister pack made of polyvinyl chloride film and printed lacquered aluminum foil.

2, 3, 4, 5, or 6 blister packs, together with the instructions for use, are placed in a cardboard carton.

Storage conditions:

In a dry place, protected from light, at a temperature not exceeding 25 °C. Keep out of reach of children.

Prescription status:

Dispensed by prescription.

Shelf life:

3 years. Do not use after the expiration date printed on the packaging.

Name and address of the legal entity in whose name the registration certificate is issued / Organization accepting claims:

JSC "AVVA RUS", Russia, 121614, Moscow, Krylatskie Kholmy st., 30, building 9.

Tel/Fax: +7 (495) 956-75-54.

avva.com.ru

Production site address:

JSC "AVVA RUS", Russia, 610044, Kirov region, Kirov, Luganskaya st., 53a.

Tel.: +7 (8332) 25-12-29; +7 (495) 956-75-54.