Kapoten: instructions for use

Side effects

From the cardiovascular system and blood (hematopoiesis, hemostasis): orthostatic hypotension, tachycardia, peripheral edema.

From the respiratory system: dry cough, bronchospasm, pulmonary edema.

Idiosyncrasy: angioedema of the extremities, face, lips, mucous membranes, tongue, pharynx or larynx is observed when using ACE inhibitors, incl. and captopril.

From the side of water and electrolyte balance: hyperkalemia (most likely in renal failure), hyponatremia (most often with a salt-free diet and simultaneous use of diuretics), proteinuria, increased levels of urea nitrogen in the blood and creatinine, acidosis.

From the hematopoietic system: in rare cases, neutropenia, agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function (creatinine clearance <1.6 mg/dL) in the absence of other complicating factors, neutropenia was observed in 0.02% of cases. Rarely, a positive test for antibodies to nuclear antigen.

From the gastrointestinal tract: taste disturbance (reversible, goes away on its own), dry mouth, aphthous stomatitis, increased activity of liver enzymes, rarely - abdominal pain, diarrhea, gingival hyperplasia, hepatitis, increased levels of hepatic transaminases in the blood plasma and hyperbilirubinemia.

From the skin: rash (mild, maculopapular, disappearing within a few days after reducing the dose), usually accompanied by itching and, in rare cases, increased body temperature; flushing of the face, vesicular and bullous rashes, erythema (including Stevens-Johnson syndrome) and photosensitivity.

From the nervous system and sensory organs: headache, dizziness, ataxia, paresthesia, drowsiness, visual impairment.

Captopril

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, restriction of 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 captopril 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 to 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 disappeared or decreased in severity after taking captopril 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.

Neutropeia/agranulocytosis/thrombocytopeia/anemia

In patients taking ACE inhibitors. cases of neutropenia/agranulocytosis, thrombocytopenia and anemia were noted. 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 procainamide, or a combination of these complicating factors, especially if there are pre-existing renal dysfunction.

In 13% of cases, neutropenia resulted in death. 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.

Due to the fact that the majority of fatal cases of neutropenia due to ACE inhibitors developed in such patients, their white blood cell count should be monitored before starting treatment, in the first 3 months - every 2 weeks, then every 2 months. In all patients, the number of leukocytes in the blood should be monitored monthly in the first 3 months after starting captopril 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/agioedema

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 epinephrine (adrenaline) should be immediately administered subcutaneously and/or the airway should be ensured ( intubation or tracheostomy). In rare cases, during therapy with ACE inhibitors, intestinal edema (angioedema of the intestines) has developed, which is manifested by abdominal pain in combination with or without nausea and vomiting, sometimes without previous angioedema of the face and with normal levels of Cl-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.

An increased risk of angioedema was observed in patients concomitantly taking ACE inhibitors and drugs such as mTOR inhibitors (temsirolimus, sirolimus, everolimus), dipeptidyl peptidase type IV inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin), estramustine, neutral endopeptidase inhibitors (racecadotril). , sacubitril) and tissue plasminogen activators.

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 captopril 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 stopping the inhibitor

ACE 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 taken into account 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 cotrimoxazole [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 it is necessary to simultaneously use captopril and the drugs listed above containing potassium or increasing the potassium content in the blood plasma, 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.

Interaction

Diuretics, ganglion blockers, adrenergic blockers enhance the hypotensive effect of Capoten. Potassium-sparing diuretics (triamterene, amiloride, spironolactone) or potassium dietary supplements may lead to a marked increase in serum potassium concentrations. Indomethacin (and other NSAIDs), as well as clonidine, may reduce the antihypertensive effect of Capoten. Allopurinol and procainamide in combination with Capoten may cause neutropenia and/or Stevens-Johnson syndrome (the causal relationship is unclear). Immunosuppressants (azathioprine, cyclophosphamide) increase the risk of developing hematological disorders when used together with Capoten. Probenecid reduces the excretion of captopril through the kidneys. The simultaneous use of lithium salts and ACE inhibitors may lead to an increase in the concentration of lithium in the blood serum. This increases the risk of side and toxic effects of lithium drugs.

Adverse reactions

The instructions mention possible negative manifestations in response to treatment with Capoten. Patients may experience:

• anorexia, increased potassium levels;
• decrease in eosinophils, platelets, agranulocytes;
• uniformly or periodically changing accelerated heartbeat, decreased blood pressure;
• hot flashes, pale skin, swelling of peripheral areas;
• dry nonproductive cough, shortness of breath, bronchospasm, swelling of the lung tissue;
• attacks of dizziness, cephalalgia, drowsiness, circulatory disorders, problems with skin sensitivity;
• decreased visual acuity, increased dryness of the oral mucosa;
• dyspeptic disorders, stomatitis, glossitis, gastrointestinal ulcerations, discomfort in the abdominal area;
• liver dysfunction, hepatitis, jaundice, cholestasis;
• obsessive itching, dermatological rash, focal baldness, urticaria;
• swelling of the face, arms and legs, tongue, larynx, pharynx;
• painful sensations in muscles and joints;
• renal dysfunction, decreased urine production, increased urge to urinate;
• gynecomastia, sexual impotence;
• soreness in the chest area, asthenia, rapid onset of fatigue.

The occurrence of adverse reactions requires immediate contact with your doctor and replacement of Capoten with an analogue more suitable for the body.

Directions for use and doses

Inside.

Arterial hypertension. Capoten should be used in the lowest effective dose and is selected individually for each patient.

Mild/moderate hypertension. The initial dose is 12.5 mg 2 times a day. The maintenance dose is 25 mg 2 times a day. If necessary, the dose is increased every 2–4 weeks. The usual effective therapeutic dose is 50 mg 2 times a day.

Severe hypertension. The initial dose is 12.5 mg 2 times a day. The dose is gradually increased to a maximum dose of 150 mg (50 mg 3 times a day). When using the drug Capoten simultaneously with other antihypertensive drugs, individual dosage selection is recommended. The maximum daily dose is 150 mg.

Heart failure. Treatment should begin under medical supervision. When using an initial dose of 6.25 mg 3 times a day, the effect of transient hypotension can be minimized as much as possible. The usual maintenance dose is 25 mg 2-3 times a day. If necessary, the dose is increased every 2 weeks. The maximum daily dose is 150 mg.

Myocardial infarction. Treatment can begin as early as 3 days after myocardial infarction. The starting dose is 6.25 mg 3 times a day, gradually increasing to 25 mg 3 times a day over several weeks. If necessary, the dose is gradually increased to a maximum daily dose of 150 mg (50 mg 3 times a day).

If symptomatic hypotension occurs, a dose reduction may be necessary. Capoten can be used together with other drugs, for example, thrombolytics, acetylsalicylic acid and beta-blockers.

Diabetic nephropathy. The recommended daily dose is 75 to 100 mg 2-3 times a day. For insulin-dependent diabetes with microalbuminuria (albumin secretion 30–300 mg per day), the dose of the drug is 50 mg 2 times a day. With a total protein clearance of more than 500 mg per day, the drug is effective at a dose of 25 mg 3 times a day

If necessary, you can additionally prescribe other antihypertensive drugs: diuretics, beta-blockers, centrally acting drugs or vasodilators.

Renal dysfunction. For mild/moderate renal impairment (creatinine Cl - at least 30 ml/min/1.73 m2), the daily dose is from 75 to 100 mg 2-3 times a day. In case of severe renal dysfunction (creatinine Cl - less than 30 ml/min/1.73 m2), the initial dose is no more than 12.5 mg 2 times a day. If the effectiveness is insufficient, the dose is slowly increased every 1–2 weeks until a therapeutic effect occurs, but the maximum daily dose of the drug should be reduced or the interval between doses of the drug should be increased. If necessary, loop diuretics are additionally prescribed rather than thiazide-type diuretics.

For elderly patients, the dose of the drug is selected individually. It is recommended to start treatment with the lowest therapeutic dose and maintain it at this level.

Children. The safety and effectiveness of the drug in children have not been studied.

Indications and contraindications for therapy with Capoten

The instructions for the medication indicate the pathologies for which therapy is permitted. Capoten is used for patients:

• with hypertension;
• chronic heart dysfunction;
• AMI;
• dysfunction of the left ventricle;
• diabetic nephropathy arising against the background of type 1 diabetes mellitus.

Capoten is contraindicated:

• in case of individual intolerance to the component composition;
• registered Quincke's edema, which arose under the influence of ACE;
• kidney and liver dysfunction;
• excess potassium;
• narrowing of the lumens of arterial vessels in the kidneys, conditions after organ transplantation;
• aortic valve stenosis and changes leading to problems with the removal of blood from the left ventricle;
• when treated with Aliskiren or similar medications in patients with severe renal impairment or diabetes mellitus;
• pregnancy, breastfeeding, adolescence;
• lactase deficiency, lactose allergy.

Particular caution when taking Capoten is necessary for patients:

• with hypotension, CHF, ischemic heart disease;
• liver dysfunction, systemic connective tissue lesions;
• disorders of the kidneys, hemodialysis;
• excess potassium, diabetes;
• spontaneous allergic reactions;
• during surgical interventions, general anesthesia, and taking potassium-sparing diuretics.

Doctors' supervision is required for patients over 65 years of age, while taking lithium drugs, and for representatives of the Negroid race.

Precautionary measures

Prescribe with caution to patients with vascular collagenosis due to the increased risk of neutropenia and agranulocytosis.

When prescribing the drug to patients with severe water-electrolyte imbalances, they should be corrected. During treatment with the drug, it is not recommended to take potassium-sparing diuretics and potassium nutritional supplements, especially in patients with impaired renal function.

If, when using captopril, swelling is limited to the face and lips, then the drug should be discontinued and antihistamines should be prescribed. If swelling covers the tongue, pharynx, larynx with a threat of developing airway obstruction, subcutaneous adrenaline (0.5 ml of 0.1% solution) should be administered.

During treatment, a low sodium diet is indicated.