Captopril: when prescribed, special instructions

"Captopril": main characteristics

The drug is a light-colored tablet with a characteristic odor. It is also available in the form of capsules of a similar composition. The active ingredient is captopril (1 tablet contains 25 mg). The therapeutic effect is based on inhibition of the action of the ACE enzyme.

Available in cardboard packaging of 10 tablets. Store at room temperature (no more than 25 degrees) and moderate humidity. The shelf life is 4 years from the date of issue. Dispensed from pharmacies only with a prescription.

What does Capril help with: indications for use

The drug is indicated for use in the presence of chronic and acute diseases of the cardiovascular system:

• mild to moderate high blood pressure;
• insufficient heart function (impaired functioning of the left ventricle);
• myocardial infarction (taken during the first 24 hours, as well as as long-term prophylaxis);
• diabetic nephropathy type 1.

The effect of "Capril" is due to the fact that the active substance reduces the synthesis of angiotensin II, which leads to severe vasoconstriction. Due to this, the potassium content in the blood plasma increases. In this case, the drug reduces blood pressure without affecting the pulse.

Captopril-Sandoz tablets 25 mg No. 40

Compound

Active substance: captopril 25 mg.
Excipients: microcrystalline cellulose 70 mg, corn starch 10 mg, lactose monohydrate 50 mg, stearic acid 5 mg.

Pharmacokinetics

Absorption is rapid, accounting for about 75% of the dose taken. Eating reduces bioavailability by 30-40%. Binds to plasma proteins - 25-30%, mainly with albumin. Less than 0.002% of the taken dose of captopril is secreted into breast milk and does not penetrate the blood-brain barrier.

Metabolized in the liver to form the disulfide dimer of captopril and captopril-cysteine ​​sulfide. Metabolites are pharmacologically inactive. The half-life of captopril is approximately 2-3 hours.

About 95% is excreted by the kidneys during the first day, of which 40-50% is unchanged, the rest - in the form of metabolites. 4 hours after a single dose, the urine contains about 38% unchanged captopril and 28% in the form of metabolites, after 6 hours - only in the form of metabolites; in daily urine - 38% unchanged captopril and 62% in the form of metabolites.

As a result of the accumulation of captopril and its metabolites in the kidneys, their function may be impaired. The half-life for renal failure is 3.5 - 32 hours. Cumulates in chronic renal failure. Therefore, in patients with impaired renal function, the dose of the drug should be reduced and/or the interval between doses should be increased.

Indications for use

• Arterial hypertension, incl. renovascular;
• chronic heart failure (as part of complex therapy);
• dysfunction of the left ventricle after myocardial infarction in a clinically stable condition;
• diabetic nephropathy due to type 1 diabetes mellitus (with albuminuria more than 30 mg/day).

Contraindications

• Hypersensitivity to captopril, other components of the drug or other ACE inhibitors (including a history);
• hereditary angioedema or idiopathic edema; angioedema (against the background of previous therapy with other ACE inhibitors in history);
• severe renal dysfunction, azotemia, hyperkalemia, bilateral renal artery stenosis or stenosis of a single kidney with progressive azotemia, condition after kidney transplantation, primary hyperaldosteronism;
• pregnancy;
• breastfeeding period;
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption;
• simultaneous use of ACE inhibitors (including captopril) or angiotensin II receptor antagonists with aliskiren and aliskiren-containing drugs in patients with type 2 diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2) ( see section “Interaction with other drugs”);
• age under 18 years (efficacy and safety have not been established).

With caution:
Hypertrophic obstructive cardiomyopathy, connective tissue diseases (especially systemic lupus erythematosus or scleroderma), suppression of bone marrow circulation (risk of developing neutropenia and agranulocytosis), cerebrovascular diseases, coronary heart disease, diabetes mellitus (increased risk of developing hyperkalemia), dietary restriction salts, conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting in patients on hemodialysis), mitral valve stenosis, aortic stenosis and similar changes that impede the outflow of blood from the left ventricle of the heart, a history of angioedema, disorder liver function, chronic renal failure, bilateral renal artery stenosis or solitary renal artery stenosis, black patients, surgery/general anesthesia, hemodialysis using high-flux membranes (eg, AN69®), desensitization therapy, low-density lipoprotein (LDL) apheresis, taking potassium-sparing diuretics, potassium supplements, potassium-containing salt and lithium substitutes, renovascular hypertension, old age.

Directions for use and doses

Orally 1 hour before meals. The dosage regimen is prescribed individually.

For arterial hypertension, treatment begins with the lowest effective dose of 12.5 mg 2 times a day. You should pay attention to the tolerability of the first dose within 1 hour. If arterial hypotension develops, the patient should be transferred to a horizontal position (such a reaction to the first dose should not serve as an obstacle to further therapy). If necessary, gradually increase the dose (with an interval of 2-4 weeks) until the optimal effect is achieved.

For mild or moderate arterial hypertension, the usual maintenance dose is 25 mg 2 times a day; the maximum dose can be increased to 50 mg 3 times a day. The maximum daily dose is 150 mg. In elderly patients, the initial dose is 6.25 mg 2 times a day.

In case of chronic heart failure, it is prescribed together with other diuretics and/or in combination with digitalis preparations (to avoid an initial excessive decrease in blood pressure, before prescribing the drug, stop taking the diuretic or reduce the dose). The initial dose is 6.25 mg or 12.5 mg 3 times a day, the dose is increased if necessary. The average maintenance dose is 25 mg 2-3 times a day, and the maximum is 150 mg per day.

In cases of symptomatic hypotension due to heart failure, doses of diuretics and/or other concomitantly prescribed vasodilators may be reduced to achieve a sustained captopril dose effect.

In cases of left ventricular dysfunction after myocardial infarction in patients who are in a clinically stable condition, the use of captopril 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 the tolerability of the drug) up to a maximum of 150 mg per day. Captopril may be prescribed in combination with other drugs in the treatment of myocardial infarction, such as thrombolytic agents, beta blockers and acetylsalicylic acid.

For patients with type I diabetes mellitus complicated by nephropathy, the recommended daily dose of captopril is 75-100 mg in 2-3 doses. If further reduction in blood pressure is necessary, captopril can be prescribed in combination with other drugs.

In patients with impaired renal function, the dose of captopril should be adjusted: the dose of the drug should be reduced or the dosage intervals should be increased. If necessary, loop diuretics are additionally prescribed rather than thiazide diuretics.

In elderly patients, captopril should be prescribed at an initial dose of 6.25 mg twice daily to prevent impairment of renal function. It is recommended that the dose of captopril be adjusted continuously depending on the patient's therapeutic response and maintained at the lowest possible level.

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of the reach of children.

Best before date

Dosage 6.25 mg/25 mg/50 mg: 3 years.

Dosage 12.5 mg/100 mg: 5 years. Do not use after the expiration date stated on the package.

special instructions

Before starting, and regularly during treatment with Captopril Sandoz®, blood pressure and renal function should be regularly monitored.
In patients with chronic heart failure, the drug is used under close medical supervision. Arterial hypotension

In patients with arterial hypertension when using the drug Captopril Sandoz®, severe arterial hypotension is observed only in rare cases; the likelihood of developing this condition increases with a decrease in circulating blood volume and an imbalance in water and electrolyte balance (for example, after treatment with high doses of diuretics), in patients with chronic heart failure or on hemodialysis. The possibility of a sharp decrease in blood pressure can be minimized by prior withdrawal (4-7 days) of the diuretic or replenishment of circulating blood volume (about a week before use), or by using the drug Captopril Sandoz® in small doses (6.25-12 .5 mg/day) at the beginning of treatment.

When using antihypertensive drugs, a pronounced decrease in blood pressure in patients with cerebrovascular accidents and cardiovascular diseases may increase the risk of myocardial infarction or stroke. If arterial hypotension has developed, the patient should be placed in a supine position with legs elevated. Sometimes it may be necessary to replenish the volume of circulating blood.

Renovascular hypertension

There is an increased risk of hypotension and renal failure in patients with bilateral renal artery stenosis or solitary renal artery stenosis when using ACE inhibitors.

Impaired renal function can occur with moderate changes in serum creatinine concentrations. In such patients, therapy should be initiated under close medical supervision with low doses, carefully titrated and with monitoring of renal function. The use of ACE inhibitors - including captopril - with aliskiren should be avoided in patients with severe renal impairment (GFR less than 60 ml/min/1.73 m).

Proteinuria

In patients, especially with impaired renal function or in combination with relatively high doses of ACE inhibitors, taking Captopril Sandoz®, proteinuria may occur. In most cases, proteinuria decreased or disappeared within 6 weeks, regardless of whether captopril treatment was continued or not. Renal function parameters such as residual blood nitrogen and creatinine rarely changed in patients with proteinuria.

Hyperkalemia

In some cases, when using the drug Captopril Sandoz®, an increase in potassium levels in the blood serum is observed. The risk of developing hyperkalemia when using ACE inhibitors is increased in patients with renal failure and diabetes mellitus, as well as those taking potassium-sparing diuretics, potassium supplements and other drugs that cause an increase in potassium levels in the blood (for example, heparin). The simultaneous use of potassium-sparing diuretics and potassium supplements should be avoided. Use with caution in patients on a low-salt or salt-free diet (increased risk of developing arterial hypotension) and hyperkalemia.

Neutropenia/agranulocytosis

In the first 3 months of therapy, the number of leukocytes in the blood is monitored monthly, then once every 3 months. Neutropenia/agranulocytosis, anemia and thrombocytopenia have been reported in patients taking ACE inhibitors, including captopril. In patients with normal renal function and no other complicating factors, neutropenia rarely occurs. The drug Captopril Sandoz® should be used with great caution in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy (allopurinol or procainamide), especially with existing renal impairment. In such patients, a clinical blood test is monitored every 2 weeks in the first 3 months, then every 2 months. If the number of leukocytes is below 4.0 x 109/l, a general blood test is indicated once a week; below 1.0 x 109/l, the use of Captopril Sandoz® is discontinued. These patients may develop severe infections that do not respond to intensive antibiotic therapy. During treatment, all patients should be instructed that if signs of infection occur (eg, sore throat, fever), they should notify their physician and have a complete blood count with a white blood cell count performed. In most patients, the white blood cell count quickly returns to normal when captopril treatment is stopped.

Anaphylactoid reactions

Patients taking the drug Captopril Sandoz® against the background of desensitizing therapy with hymenoptera venom, etc., have an increased risk of developing anaphylactoid reactions. This can be avoided if you first temporarily stop taking the drug.

When performing hemodialysis in patients receiving Captopril Sandoz®, the use of high permeability dialysis membranes (for example, AN69®) should be avoided, since in such cases the risk of developing anaphylactoid reactions increases.

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis using dextran sulfate. To prevent anaphylactoid reactions, ACE inhibitor therapy should be discontinued before each LPNHT apheresis procedure using high-flux membranes.

Angioedema

In patients taking the drug Captopril Sandoz®, when abdominal pain occurs, it is necessary to differentiate it from intestinal angioedema.

If angioedema develops, the drug is discontinued and careful medical supervision is provided. If the swelling is localized on the face, special treatment is usually not required (antihistamines can be used to reduce the severity of symptoms); in the event that the swelling spreads to the tongue, pharynx or larynx and there is a threat of developing airway obstruction and a threat to the patient’s life, epinephrine (adrenaline) should be immediately administered subcutaneously (0.5 ml in a dilution of 1:1000), and also make sure that airway patency. It is recommended to stop taking ACE inhibitors, including Captopril Sandoz®, 12 hours before surgery, warning the surgeon-anesthesiologist about the use of ACE inhibitors.

Cough

The development of a non-productive, prolonged cough when using ACE inhibitors is reversible and resolves after discontinuation of treatment.

Diabetes

In patients with diabetes mellitus taking oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of treatment with Captopril Sandoz®.

Liver dysfunction

During therapy with ACE inhibitors, several cases of liver dysfunction with cholestatic jaundice, fulminant liver necrosis (in some cases) with a fatal outcome have been reported.

If, during therapy with Captopril Sandoz®, jaundice develops or the activity of “liver” transaminases increases, Captopril Sandoz® should be discontinued immediately; the patient should be closely monitored and, if necessary, receive appropriate therapy.

Hypokalemia

The simultaneous use of an ACE inhibitor and a thiazide diuretic does not exclude the possibility of hypokalemia. It is recommended to regularly monitor potassium levels in the blood.

Surgery/anesthesia

Hypotension may occur in patients undergoing major surgery or during the use of anesthetics known to lower blood pressure. If arterial hypotension occurs, it is recommended to replenish the circulating blood volume.

Ethnic differences

ACE inhibitors, including the drug Captopril Sandoz®, have a less pronounced antihypertensive effect in patients of the Black race, which is apparently due to the frequent occurrence of low renin activity in this group of patients.

Laboratory data

Captopril may cause a false-positive urine acetone test.

Description

Angiotensin-converting enzyme inhibitor.

Use in children

Contraindicated under 18 years of age (efficacy and safety have not been established).

Pharmacodynamics

Angiotensin-converting enzyme inhibitor.
Reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. At the same time, total peripheral vascular resistance, blood pressure, post- and preload on the heart decrease. Dilates arteries more than veins. Causes a decrease in the degradation of bradykinin (one of the effects of angiotensin-converting enzyme) and an increase in prostaglandin synthesis. The hypotensive effect does not depend on the activity of plasma renin; a decrease in blood pressure is observed with normal and even reduced levels of the hormone, which is due to the effect on the tissue renin-angiotensin system. Strengthens coronary and renal blood flow. With long-term use, it reduces the severity of hypertrophy of the myocardium and the walls of resistive arteries. Improves blood supply to ischemic myocardium. Reduces platelet aggregation. Helps reduce the content of sodium ions in patients with heart failure. A decrease in blood pressure, unlike direct vasodilators (hydralazine, minoxidil, etc.), is not accompanied by reflex tachycardia and leads to a decrease in myocardial oxygen demand. In case of heart failure in an adequate dose, it does not affect blood pressure. The maximum reduction in blood pressure after oral administration is observed after 60-90 minutes.

The duration of the hypotensive effect is dose-dependent and reaches optimal values ​​within several weeks.

Temporary withdrawal of captopril should not occur abruptly, as this may cause a significant increase in blood pressure.

Side effects

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, < 1/100), rare (≥1/10000, <1/1000) and very rare (<1/10000); frequency unknown - based on available data, it was not possible to determine the frequency of occurrence.

From the blood and lymphatic system: very rarely: neutropenia; agranulocytosis; pancytopenia, especially in patients with impaired renal function; anemia (including aplastic, hemolytic), thrombocytopenia, lymphadenopathy, eosinophilia, autoimmune diseases and/or increased titer for antinuclear antibodies.

Metabolism and nutrition: rarely: anorexia; very rarely: hyperkalemia, hypoglycemia.

From the nervous system: often: taste disturbances, sleep disturbances, dizziness; rarely: drowsiness, headache, paresthesia, asthenia; very rare: depression, cerebrovascular disorders, including stroke, fainting, impaired consciousness.

From the organ of vision: very rarely: visual acuity disturbances.

From the cardiovascular system: infrequently: tachycardia, tachyarrhythmia, palpitations, angina pectoris, arrhythmia, orthostatic hypotension, Raynaud's syndrome, flushing of the face, pallor, peripheral edema; very rare: cardiogenic shock, cardiac arrest.

From the respiratory system, chest and mediastinal organs: often: dry, irritating (non-productive) cough, shortness of breath; very rarely: bronchospasm, rhinitis, allergic alveolitis, eosinophilic pneumonia.

From the digestive system: often: dryness of the oral mucosa, nausea, vomiting, abdominal pain, diarrhea, constipation; rarely: stomatitis, aphthous ulcers of the inner surface of the mucous membrane of the cheeks and tongue, anorexia; very rare: glossitis, peptic ulcer, pancreatitis, liver dysfunction, cholestasis, jaundice, hepatitis, liver necrosis, increased activity of liver enzymes, increased bilirubin concentration in the blood serum, angioedema of the intestinal mucosa.

From the skin and subcutaneous tissues often: itching of the skin with or without rashes, skin rash (maculopapular, less often vesicular or bullous), baldness; very rare: urticaria, Stevens-Johnson syndrome, erythema multiforme, photosensitivity, exfoliative dermatitis, pemphigoid reactions.

From the musculoskeletal system: very rarely: myalgia, arthralgia.

From the genitourinary system: rarely: impaired renal function, acute renal failure, polyuria, oliguria, increased frequency of urination; very rare: nephrotic syndrome, impotence, gynecomastia.

General and administration site disorders: uncommon: chest pain, fatigue, weakness/very rare: fever.

Laboratory indicators: very rarely: proteinuria, hyperkalemia, hyponatremia, increased concentrations of urea nitrogen and creatinine in the blood plasma; increased activity of “liver” transaminases, increased serum bilirubin concentration, decreased hemoglobin, hematocrit, increased erythrocyte sedimentation rate (ESR), metabolic acidosis.

Other: frequency unknown: symptom complex including facial flushing, nausea, vomiting and decreased blood pressure.

Use during pregnancy and breastfeeding

The use of Captopril Sandoz® during pregnancy is contraindicated.
The use of ACE inhibitors during pregnancy can lead to morbidity and death of the fetus and/or newborn. Long-term use of captopril in the second and third trimesters is toxic to the fetus (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and newborns (neonatal renal failure, arterial hypotension, hyperkalemia).

In addition, the use of ACE inhibitors in the first trimester of pregnancy is associated with a potentially increased risk of developing congenital defects in the fetus.

If pregnancy occurs while using Captopril Sandoz®, use of the drug should be discontinued as soon as possible and fetal development should be monitored regularly.

Women planning pregnancy should not use ACE inhibitors (including captopril). Women of childbearing age should be aware of the potential dangers of using ACE inhibitors (including captopril). Approximately 1% of a given dose of captopril is found in breast milk. Due to the risk of serious adverse reactions in the child, breastfeeding should be stopped or therapy with Captopril Sandoz® should be discontinued in the mother during the period of breastfeeding.

If the patient received the drug during the second and third trimesters of pregnancy, it is recommended to conduct an ultrasound examination to assess the condition of the skull bones and fetal kidney function. If the use of an ACE inhibitor is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive therapy that has an established safety profile for use during pregnancy.

Interaction

Double blockade of the RAAS. The simultaneous use of ACE inhibitors with other drugs that affect the RAAS, including angiotensin II receptor antagonists (ARA II) and aliskiren, leads to an increased incidence of cases of a pronounced decrease in blood pressure, hyperkalemia, and renal dysfunction (including acute renal failure).
It is necessary to monitor blood pressure, renal function, and plasma electrolyte levels when using captopril with other drugs that affect the RAAS. The simultaneous use of ACE inhibitors (including captopril) with aliskiren and aliskiren-containing drugs should be avoided in patients with severe renal impairment (GFR less than 60 ml/min/1.73 m2). The simultaneous use of ACE inhibitors (including captopril) with aliskiren and aliskiren-containing drugs is contraindicated in patients with type 2 diabetes mellitus. Combined use with potassium-sparing diuretics, potassium preparations, potassium supplements, salt substitutes (contain significant amounts of potassium ions) increases the risk of developing hyperkalemia. If it is necessary to use them simultaneously with captopril, plasma potassium levels should be monitored.

When using high doses of diuretics (thiazide diuretics, loop diuretics) simultaneously with captopril, due to the reduced circulating blood volume, the risk of arterial hypotension increases, especially at the beginning of captopril therapy.

The antihypertensive effect of captopril is potentiated when used simultaneously with aldesleukin, alprostadil, beta-blockers, alpha1-blockers, central alpha2-adrenergic agonists, diuretics, cardiotonics, blockers of “slow” calcium channels, minoxidil, muscle relaxants, nitrates and vasodilators. Antidepressants, antipsychotics, anxiolytics and hypnotics can also enhance the antihypertensive effect of captopril.

With long-term use, the antihypertensive effect of captopril is weakened by indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs), incl. selective cyclooxygenase-2 inhibitors (sodium ion retention, decreased prostaglandin synthesis, especially against the background of low renin activity) and estrogens.

NSAIDs and ACE inhibitors have been described to have an additive effect in increasing serum potassium levels while decreasing renal function. These effects are reversible. Rarely, acute renal failure may occur, especially in patients with pre-existing renal impairment, in elderly patients or in those with reduced circulating blood volume (dehydration).

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthetic agents that have an antihypertensive effect.

Slows down the excretion of lithium drugs, increasing the concentration of lithium in the blood. If simultaneous use of captopril and lithium preparations is necessary, serum lithium concentrations should be carefully monitored.

When using captopril while taking allopurinol or procainamide, the risk of developing Stevens-Johnson syndrome and neutropenia increases.

With the simultaneous use of ACE inhibitors and gold preparations (iv sodium aurothiomalate), a symptom complex has been described, including facial flushing, nausea, vomiting and decreased blood pressure.

Sympathomimetics may reduce the antihypertensive effects of captopril.

Insulin and oral hypoglycemic agents increase the risk of hypoglycemia.

Concomitant use of captopril with food or antacids slows down the absorption of captopril in the gastrointestinal tract (GIT).

During therapy with captopril, the use of ethanol is not recommended, since ethanol enhances the antihypertensive effect of captopril.

The antihypertensive effect of captopril is weakened by epoetins, estrogens and combined oral contraceptives, carbenoxolone, glucocorticosteroids and naloxone. Probenecid reduces the renal clearance of captopril and increases its serum concentrations in the blood.

The use of captopril in patients taking immunosuppressants (for example, azathioprine or cyclophosphamide) increases the risk of developing hematological disorders.

Increases the concentration of digoxin in blood plasma by 15-20%.

Increases the bioavailability of propranolol.

Cimetidine, by slowing down metabolism in the liver, increases the concentration of captopril in the blood plasma.

Clonidine reduces the severity of the antihypertensive effect.

Overdose

Symptoms: marked decrease in blood pressure, up to collapse, stupor, bradycardia, water-electrolyte imbalance, acute renal failure, myocardial infarction, acute cerebrovascular accident, thromboembolic complications.

Treatment: gastric lavage, use of absorbent agents no later than 30 minutes after taking the drug; transfer the patient to the “lying” position with raised legs; measures aimed at restoring blood pressure, replenishing the volume of circulating blood (for example, intravenous administration of 0.9% sodium chloride solution).

For bradycardia or severe vagal reactions, atropine should be used. It is possible to use a temporary pacemaker.

Symptomatic therapy: hemodialysis may be used; peritoneal hemodialysis is not effective.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, because Dizziness may occur, especially after taking the initial dose.

Contraindications for use

In some cases, taking the drug is excluded:

• pregnancy period (2nd and 3rd trimester);
• GW period (entirely);
• angioedema;
• hypersensitivity, individual intolerance to captopril or excipients;
• simultaneous use with the drug "Aliskiren" (should be excluded by people suffering from diabetes or having renal failure).

"Captopril": instructions for use

The optimal dosage is determined by the doctor depending on the age, condition of the patient, and concomitant diseases. The maximum daily amount in terms of the weight of the active substance is 150 mg, which corresponds to 6 tablets per day. Also, the dosage depends on the disease:

1. High blood pressure – 25-50 mg per day. The dose can be gradually increased starting from the 3rd week of admission.
2. Heart failure - therapy begins with a dosage of 6.25 to 12.5 mg with a gradual increase to a maximum amount of 150 mg.
3. For myocardial infarction, first take 6.25 mg, then after 2 hours increase to 12.5 mg and after another 12 hours - 25 mg. Starting from the next day, take 100 mg for a month, after which the decision to continue therapy should be made in consultation with the doctor.
4. In case of long-term treatment in the presence of established myocardial infarction, up to 75 mg per day is prescribed. Moreover, the initial dose is 6.25 mg with a gradual increase to 12.5 mg and 25 mg, then from 75 to 150 mg.
5. In the presence of diabetic nephropathy type I, use from 75 to 100 mg.

Elderly people should start taking the medicine with a minimum dose of 6.25 mg. Then the amount is gradually increased. Teenagers under 18 years of age can also start with this amount, but only in consultation with their doctor. Also, "Captopril" can be prescribed to newborns and infants based on the ratio of 0.15 mg of the substance per kilogram of body (also in agreement with the doctor).

Attention!

In all cases, the tablet is placed under the tongue 30-60 minutes before meals. May be taken during or after meals.

Captopril-FPO® (Captopril-FPO®)

Arterial hypotension

In patients with arterial hypertension, when using captopril, severe arterial hypotension is observed only in rare cases. The likelihood of developing this condition increases with increased fluid loss and hyponatremia (for example, after intensive treatment with diuretics, limiting sodium intake, in patients on dialysis, and in patients with diarrhea or vomiting).

Captopril should be prescribed with caution to patients on a low-salt or salt-free diet. Circulating blood volume and blood sodium levels should be adjusted before captopril is prescribed. The possibility of a sharp decrease in blood pressure can be minimized by first withdrawing (4-7 days before) the diuretic or increasing sodium chloride intake (about a week before starting treatment), or by prescribing low doses of captopril at the beginning of treatment (6.25-12 .5 mg/day). Renal function should be regularly monitored before and during treatment with captopril.

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

In patients with CHF, a transient decrease in blood pressure by more than 20% of the initial value is observed in approximately half of the cases. The degree of reduction in blood pressure is maximum in the early stages of treatment (after taking the first few doses of captopril) and stabilizes within one to two weeks from the start of treatment. Blood pressure usually returns to baseline without a decrease in therapeutic efficacy within two months. In patients with CHF, treatment should begin with low doses of captopril (6.25-12.5 mg/day) under medical supervision. Increasing the dose of captopril should be done with extreme caution. Transient arterial hypotension in itself is not a reason to discontinue treatment. In cases where arterial hypotension becomes stable, the dose should be reduced and/or discontinued use of the diuretic and/or captopril.

Aortic or mitral stenosis/hypertrophic obstructive cardiomyopathy

Like all drugs that have a vasodilating effect, ACE inhibitors should be used with extreme caution in patients with left ventricular outflow tract obstruction. In case of hemodynamically significant obstruction, the use of captopril is not recommended.

Renal dysfunction

Some patients with kidney disease, especially those with severe renal artery stenosis, experience increases in serum urea nitrogen and creatinine concentrations after lowering blood pressure. This increase is usually reversible when captonril therapy is discontinued. In these cases, it may be necessary to reduce the dose of captopril and/or discontinue the diuretic.

With long-term use of captopril, approximately 20% of patients experience an increase in serum urea and creatinine concentrations by more than 20% compared with normal or baseline values.

In less than 5% of patients, especially with severe nephropathy, treatment discontinuation is required due to an increase in creatinine concentration.

Renovascular hypertension

Patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney have an increased risk of developing arterial hypotension and renal failure when using ACE inhibitors. Renal failure may initially manifest itself as only slight changes in plasma creatinine levels. The use of captopril in such patients is not recommended.

Kidney transplant

There is no experience with the use of captopril in patients who have recently undergone kidney transplantation. Therefore, the use of captopril in such patients is not recommended.

Proteinuria

When using captopril, 0.7% of patients had proteinuria more than 1000 mg per day. In 90% of cases, proteinuria occurred in patients with impaired renal function, as well as when using high doses of captopril (more than 150 mg per day). Approximately 20% of patients with proteinuria developed nephrotic syndrome. In most cases, proteinuria while taking captopril disappeared or its severity decreased within 6 months, regardless of whether the drug was stopped or not. Renal function tests (blood urea nitrogen and creatinine concentrations) in patients with proteinuria were almost always within normal limits. In patients with kidney disease, the protein content in the urine should be determined before starting treatment and periodically throughout the course of therapy.

Liver dysfunction

In rare cases, the use of ACE inhibitors has been accompanied by the development of a syndrome that begins with the appearance of cholestatic jaundice or hepatitis and progresses to fulminant liver necrosis, sometimes with death. The mechanism of development of this syndrome is unknown. If a patient receiving ACE inhibitor therapy develops jaundice or a significant increase in liver enzyme activity, captopril treatment should be discontinued and appropriate adjuvant therapy should be instituted. The patient should be under appropriate supervision.

Neutropenia/agranulocytosis/thrombocytopenia/anemia

Cases of neutropenia/agranulocytosis have been reported in patients taking ACE inhibitors. thrombocytopenia and anemia. Neutropenia is rare in patients with normal renal function and no other abnormalities. In renal failure, simultaneous administration of captopril and allopurinol led to neutropenia.

Captopril should be used with extreme caution in patients with systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc.) taking immunosuppressants, allopurinol or irocainamide, or a combination of these complicating factors, especially if there are pre-existing renal dysfunction.

In 13% of cases with neutropenia, death was observed. In almost all cases, death was observed in patients with connective tissue diseases, renal or heart failure, while taking immunosuppressants, or a combination of both of these factors.

Because. that the majority of fatal cases of neutropenia due to ACE inhibitors developed in such patients, their blood leukocyte count should be monitored before starting treatment, in the first 3 months - every 2 weeks, then every 2 months. All patients should have their white blood cell count monitored monthly for the first 3 months after starting capgopril therapy, then every 2 months. If the number of leukocytes is below 4000/μl, a repeat general blood test is indicated; below 1000/μl, the drug is stopped while monitoring the patient continues. Typically, restoration of the number of neutrophils occurs within 2 weeks after discontinuation of captopril.

Some patients developed serious infectious diseases, which in some cases did not respond to intensive antibiotic therapy. When using captopril in patients with a high risk of neutropenia/agranulocytosis, regular monitoring of the number of leukocytes in the blood is recommended. Patients should be warned to seek immediate medical attention if any signs of an infectious disease (eg, fever, sore throat) occur.

Hypersensitivity reactions/angioedema

Rare cases of angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx have been observed with the use of ACE inhibitors, including captopril. Angioedema may develop at any time during treatment.

If angioedema develops, you should immediately stop taking captopril and carefully monitor the patient's condition until symptoms disappear completely.

If the swelling is localized to the face, no special treatment is usually required (antihistamines can be used to reduce the severity of symptoms). Even in cases where only swelling of the tongue is observed without the development of respiratory distress syndrome, patients may require long-term observation, since therapy with antihistamines and corticosteroids may not be sufficient.

Angioedema, associated with swelling of the larynx and tongue, can be fatal in very rare cases. If the swelling spreads to the tongue, pharynx or larynx and there is a threat of developing airway obstruction, 0.3-0.5 ml of a 0.1% solution of eninephrine (adrenaline) should be immediately administered subcutaneously and/or ensure airway patency ( intubation or tracheostomy).

In rare cases, during therapy with ACE inhibitors, intestinal edema (angioedema of the intestines) developed, which manifested itself as abdominal pain in combination with nausea and vomiting (or without them), sometimes without previous angioedema of the face and with normal levels of C1-esterase. Diagnosis is made using abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after stopping the ACE inhibitors. The possibility of developing intestinal edema must be taken into account when carrying out the differential diagnosis of abdominal pain in patients taking ACE inhibitors.

Patients with a history of angioedema not associated with ACE inhibitors may be at greater risk of developing angioedema during ACE inhibitor therapy.

In representatives of the Negroid race, cases of the development of angioedema when using ACE inhibitors were observed with a higher frequency compared to representatives of other races.

Anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom

In rare cases, during therapy with ACE inhibitors, life-threatening anaphylactoid reactions were observed in patients undergoing desensitization with an allergen from the venom of Hymenoptera. In such patients, these reactions were prevented by temporarily stopping ACE inhibitor therapy before desensitization began. The use of cantopril should be avoided in patients receiving bee venom immunotherapy.

Anaphylactoid reactions during low-density lipoprotein apheresis (LDL apheresis)

Life-threatening anaphylactoid reactions have rarely been observed in patients taking ACE inhibitors during LDL apheresis using dextran sulfate. The development of these reactions can be prevented by temporarily discontinuing the ACE inhibitor before each LDL apheresis procedure.

Hemodialysis using high-flow membranes

When performing hemodialysis in patients receiving ACE inhibitors, the use of high-flow polyacrylonitrile dialysis membranes (for example, AN69®) should be avoided, since in such cases the risk of developing anaphylactoid reactions increases. In such cases, it is necessary to use a different type of dialysis membrane or use antihypertensive drugs of other classes.

Diabetes

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin while using ACE inhibitors, blood glucose concentrations should be regularly monitored.

Patients taking oral hypoglycemic agents or insulin should be informed before starting the use of ACE inhibitors of the need to regularly monitor blood glucose concentrations (hypoglycemia), especially during the first month of simultaneous use of these drugs.

Cough

When taking ACE inhibitors, a characteristic cough is often observed. As a rule, the cough is non-productive, constant and stops after discontinuation of the drug. Cough associated with the use of ACE inhibitors should be considered in the differential diagnosis of dry cough.

Surgery/general anesthesia

During major surgical operations, as well as when using general anesthesia agents that have an antihypertensive effect, patients taking ACE inhibitors may experience an excessive decrease in blood pressure (since captopril blocks the formation of angiotensin II, caused by compensatory release of renin). In such cases, to correct low blood pressure, measures aimed at increasing the volume of circulating blood are used.

Hyperkalemia

In some cases, against the background of the use of ACE inhibitors. incl. captopril, an increase in serum potassium levels is observed.

Risk factors for the development of hyperkalemia are renal failure, old age (over 65 years), diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene or amiloride), as well as potassium preparations, potassium-containing table salt substitutes and other drugs that increase the level of potassium in the blood plasma (such as heparin, tacrolimus, cyclosporine; drugs containing co-trimoxazole [trimethoprim + sulfamethoxazole]).

The use of potassium supplements, potassium-sparing diuretics, or potassium-containing table salt substitutes, especially in patients with impaired renal function, can lead to a significant increase in serum potassium levels. Hyperkalemia can cause serious heart rhythm disturbances, sometimes fatal.

It is recommended to avoid the simultaneous use of potassium-sparing diuretics and potassium supplements. If simultaneous use of captopril and the above-listed potassium-containing or potassium-increasing drugs in the blood plasma is necessary, caution should be exercised and the potassium content in the blood serum should be regularly monitored.

Hypokalemia

When using ACE inhibitors simultaneously with thiazide diuretics, the risk of hypokalemia cannot be excluded. Therefore, in such cases, regular monitoring of potassium levels in the blood should be carried out during therapy.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

The simultaneous use of drugs from different groups that act on the RAAS is not recommended (double blockade of the RAAS), since it has been associated with an increased incidence of side effects such as arterial hypotension, hyperkalemia, and decreased renal function (including acute renal failure). The simultaneous use of ACE inhibitors with medicinal products 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.

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

In cases where the simultaneous administration of two drugs acting on the RAAS is necessary, their use should be carried out under the supervision of a physician with extreme caution and with regular monitoring of renal function, blood pressure and electrolyte levels in the blood plasma.

Lithium preparations

The simultaneous use of captopril and drugs containing lithium is not recommended due to the risk of potentiating the toxicity of the latter.

Ethnic differences

ACE inhibitors are less effective in blacks than in Caucasians, which may be due to the higher prevalence of low renin activity in blacks.

Other

When taking captopril, a false-positive urine test for acetone may occur.

Side effects

When taking Catopril, side effects may occur from different organ systems - nervous, circulatory, digestive and others. Main manifestations:

• sleep disorders;
• drowsiness;
• pancytopenia;
• problems with taste (reversible);
• nausea, vomiting;
• pain, heaviness in the abdomen;
• diarrhea;
• dizziness;
• dyspnea;
• feeling of dry mouth;
• ulcer of the stomach walls;
• constipation.

The following manifestations are much less common:

• anorexia;

• confusion;
• depressive states;
• headache;
• heartbeat disturbance;
• exacerbation of autoimmune diseases;
• rhinitis;
• bronchospasm;
• eosinophilic pneumonia;
• pancreatitis;
• angioedema;
• nephrotic syndrome;
• impotence;
• febrile conditions.

Attention!

In case of overdose, shock, stupor, bradycardia, and symptoms of renal failure may occur. In this case, urgent gastric lavage and administration of activated charcoal are indicated (30 minutes after the Captopril tablet). In case of emergency, you should seek emergency help.

CAPTOPRIL-FPO

special instructions

In patients with chronic heart failure, it is used under close medical supervision.
Before starting, as well as regularly during treatment with Captopril-FPO®, renal function should be monitored. During long-term use of the drug Captopril-FPO®, approximately 20% of patients experience a stable increase in serum urea and creatinine concentrations by more than 20% compared to the norm or baseline value. In less than 5% of patients, especially with severe nephropathies, discontinuation of treatment is required due to an increase in serum creatinine concentrations.

In patients with arterial hypertension when using the drug Captopril-FPO®, severe arterial hypotension is observed only in rare cases; the likelihood of developing this condition increases with fluid and salt deficiency (including after intensive treatment with diuretics), in patients with chronic heart failure or on dialysis.

The likelihood of a sharp decrease in blood pressure can be minimized by prior withdrawal (4-7 days before) of the diuretic, or by prescribing captopril at the beginning of treatment in small doses (6.25-12.5 mg/day).

During therapy on an outpatient basis, the patient should be warned about the possible appearance of symptoms of infection, requiring a follow-up medical examination and clinical and laboratory examination.

In the first 3 months of therapy, the number of blood leukocytes is monitored monthly, then 4 times every 3 months; in patients with autoimmune diseases in the first 3 months - every 2 weeks, then every 2 months. If the number of leukocytes is below 4000/μl, a general blood test is indicated; below 1000/μl, the drug is stopped. When the first symptoms of a secondary infection occur against the background of myeloid hypoplasia, a detailed blood test should be immediately performed.

In some cases, against the background of the use of ACE inhibitors, incl. captopril, an increase in serum potassium concentration is observed. The risk of developing hyperkalemia when using ACE inhibitors is increased in patients with renal failure and diabetes mellitus, as well as those taking potassium-sparing diuretics, potassium supplements, or other drugs that cause an increase in the concentration of potassium in the blood (for example, heparin). The simultaneous use of potassium-sparing diuretics and potassium supplements should be avoided.

When performing hemodialysis in patients receiving Captopril-FPO®, the use of high permeability dialysis membranes (for example, AN69) should be avoided, since in such cases the risk of developing anaphylactoid reactions increases.

If angioedema develops, the drug is discontinued and careful medical observation and symptomatic therapy are carried out. If swelling is localized on the face, no special treatment is required (antihistamines are used to reduce the severity of symptoms); if swelling spreads to the tongue, pharynx or larynx with a threat of airway obstruction, epinephrine is immediately administered subcutaneously (0.5 ml at a dilution of 1:1000).

When taking Captopril-FPO®, a false-positive reaction may occur in a urine test for acetone.

Caution should be exercised when performing physical exercise or in hot weather (risk of dehydration and excessive reduction in blood pressure due to decreased circulating blood volume).

special instructions

Taking the drug during pregnancy is excluded during the 2nd and 3rd trimester and is undesirable at the initial stage. Therefore, on the eve of planning or immediately after pregnancy is detected, you should switch to other medications in consultation with your doctor. During breastfeeding, the use of the product is completely excluded.

During therapy with Captopril, the ability to drive a car, as well as certain types of activities, may decrease. The onset of such effects depends on the dosage and individual characteristics of the body.