Captopril

Instruction manual

For medical use of the drug

Captopril

(captopril)

Structure:

Active ingredient: captopril;

1 tablet contains captopril 25 mg (0.025 g);

excipients: potato starch, lactose monohydrate, microcrystalline cellulose, povidone, magnesium stearate, anhydrous colloidal silicon dioxide.

Dosage form.

Tablets.

Basic physical and chemical properties: tablets of white or almost white color, with a flat surface, risk and chamfer, with a specific smell.

Pharmacotherapeutic group.

Inhibitors of angiotensin-converting enzyme (APF).

Code ATX C09A A01.

Pharmacological properties.

Pharmacodynamics

Captopril, an angiotensin converting enzyme (ACE) inhibitor, reduces the concentration of angiotensin II and aldosterone in the blood, and prevents the inactivation of endogenous vasodilators, bradykinin and prostaglandin E₂. As a result, blood pressure, total peripheral vascular resistance, post- and preload on the heart, pressure in the pulmonary circulation and pulmonary vascular resistance gradually decrease, cardiac output increases without changing the heart rate, left ventricular hypertrophy decreases (with prolonged therapy), tolerance increases to physical activity.

The antihypertensive effect is manifested 15-60 minutes after ingestion, reaching a maximum after 60-90 minutes, and lasts 6-12 hours. The duration of the antihypertensive effect depends on the dose and reaches optimal values ​​within a few weeks with continuous use. In patients with moderate arterial hypertension, captopril when used in doses of 25-50 mg 2 times a day increases the quality and life expectancy, improves overall well-being, sleep and emotional state. In patients with arterial hypertension in combination with diabetes mellitus reduces the frequency of cardiovascular complications. It exhibits angioprotective properties in relation to the vessels of the microvasculature, increases the diameter of large peripheral arteries (from 13% to 21%), slows down the progression of renal failure in diabetic nephropathy.

Pharmacokinetics

Quickly and completely absorbed from the gastrointestinal tract, the minimum absorption is 60-75%. When taken on an empty stomach, the maximum concentration in the blood is reached after 30-90 minutes. It undergoes biotransformation in the liver. Passes through the histohematological barriers, with the exception of the blood-brain barrier, passes through the placenta and into breast milk (the concentration reaches about 1% of the level in the mother’s blood). The elimination half-life is 2-3 hours, in patients with chronic heart and kidney failure it increases to 3.5-32 hours. It is excreted mainly by the kidneys (2/3 of the dose excreted within 4 hours, more than 95% of the dose within 24 hours) in the form of metabolites and unchanged (40-50%). Cumulates in chronic renal failure.

Clinical characteristics.

Indications.

• Arterial hypertension. heart failure. captopril is prescribed for the treatment of chronic heart failure with a decrease in systolic ventricular function, as well as in combination with diuretics and, if necessary, digitalis and beta-blockers. myocardial infarction: for short-term (4 weeks) treatment, captopril may be administered within 24 hours after myocardial infarction to patients with a stable condition; for the long-term prevention of symptomatic heart failure, the drug is indicated for patients with a clinically stable state with asymptomatic left ventricular dysfunction (ejection fraction ≤ 40%). diabetic nephropathy in patients with type I diabetes mellitus, which is manifested by macroproteinuria.

Contraindications

• Hypersensitivity to captopril or to excipients of the drug, as well as to other APF inhibitors; a case of angioneurotic edema with the use of APF inhibitors in history; narrowing of the mouth of the aorta or mitral stenosis, the presence of other obstacles to the outflow of blood from the left ventricle of the heart; hypertrophic cardiomyopathy with low cardiac output; primary hyperaldosteronism; hyperkalemia severe renal impairment; bilateral narrowing of the renal arteries or narrowing of the artery of a single kidney; condition after a kidney transplant; congenital (idiopathic) angioedema; porphyria; pregnancy or pregnancy planning (see section "use during pregnancy or lactation"). lactation period (see the section "use during pregnancy or lactation"); the simultaneous use of captopril with drugs containing aliskiren, in patients with diabetes mellitus or in patients with renal failure (glomerular filtration rate 2).

Interaction with other drugs and other types of interactions.

Potassium-sparing diuretics or potassium supplements. APF inhibitors reduce the loss of potassium caused by the use of diuretics. potassium-sparing diuretics (e.g. spironolactone, triamteren, or amiloride), potassium supplements, or salt substitutes containing potassium can lead to hyperkalemia. with simultaneous administration through existing hypokalemia, they should be used with great care and with frequent monitoring of serum potassium concentration.

Diuretics (thiazide or loop diuretics). Preliminary treatment with diuretics in high doses can lead to a decrease in BCC and an increase in the risk of significant hypotension (see. "Features of use"). The antihypertensive effect can be reduced by stopping the intake of the diuretic, increasing the intake of salt and liquid, or by starting therapy with a low dose of captopril. However, no clinically significant interactions with hydrochlorothiazide or furosemide have been identified.

Other antihypertensive drugs. The simultaneous administration of captopril with other antihypertensive drugs (for example, beta-blockers and calcium channel blockers of prolonged action) is safe, and concomitant use of drugs can increase the hypotensive effect of captopril. Care should be taken to treat nitroglycerin, other nitrates, or other vasoconstrictor drugs.

Treatment of acute myocardial infarction. For patients with myocardial infarction, captopril can be taken simultaneously with acetylsalicylic acid (in cardiac doses), antiplatelet agents, beta-blockers and / or nitrates.

Lithium. The simultaneous use of ACE inhibitors and lithium can cause a temporary increase in serum lithium levels and lithium intoxication. The simultaneous use of ACE inhibitors and thiazide diuretics can further increase serum lithium levels and increase the risk of lithium intoxication. Therefore, the simultaneous administration of captopril with lithium is not recommended. If such a combination of drugs is necessary, then careful monitoring of serum lithium levels should be carried out.

Tricyclic antidepressants / antipsychotics. Concomitant use of certain tricyclic antidepressants and antipsychotics with ACE inhibitors can lead to an additional decrease in blood pressure (see section "Features of use"). Postural hypotension may occur.

Allopurinol, procainamide, cytostatic or immunosuppressive drugs. Their simultaneous use with ACE inhibitors can lead to an increased risk of leukopenia, especially when the latter were used in doses exceeding the recommended ones.

Nonsteroidal anti-inflammatory drugs (NSAIDs).It is described that ACE and NSAIDs have an additional effect on increasing serum potassium levels, which can lead to impaired renal function. Usually this effect is reversible. Acute renal failure is rarely possible, especially in patients with impaired renal function, for example, elderly patients or patients with dehydration. Prolonged administration of NSAIDs may reduce the antihypertensive effect of ACE inhibitors.

Sympathomimetics. May reduce the antihypertensive effect of ACE inhibitors, therefore, patient blood pressure should be carefully monitored.

Antidiabetic drugs. ACE inhibitors, including captopril, can enhance the antiglycemic effect of insulin and other oral antidiabetic drugs (sulfonylureas) in patients with diabetes mellitus. This effect occurs very rarely, but when it occurs, there is a need to reduce the dose of antidiabetic drugs with simultaneous treatment with ACE inhibitors.

Clinical chemical analysis: captopril may lead to a false-positive urine test for acetone.

Features of the application.

Double blockade of raas: it is obvious that the combined use of apf inhibitors, angiotensin ii receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and leads to a decrease in renal function (including acute renal failure). therefore, double blockade of the renin-angiotensin-aldosterone system (raas) by the combined use of apf inhibitors, angiotensin ii receptor blockers or aliskiren is not recommended.

If therapy with double blockade is absolutely necessary, it should be carried out under the supervision of a doctor with frequent verification of renal function, electrolyte levels and blood pressure.

ACE inhibitors and angiotensin II receptor blockers cannot be used simultaneously in patients with diabetic nephropathy.

Arterial hypotension. Arterial hypotension is rarely possible in patients with arterial hypertension who have a decrease in blood volume and / or a decrease in the amount of sodium due to diuretic therapy, limited intake of dietary salt, and also due to diarrhea, vomiting, or hemodialysis. Before prescribing ACE inhibitors, the volume of circulating blood (BCC) should be adjusted, as well as the question of the appointment of the minimum effective optimal dose of the drug.

Patients with heart failure are also at risk for symptomatic hypotension with ACE inhibitors. Therefore, it is recommended that these patients be prescribed captopril with a low initial dose. An increase in the dose of ACE inhibitors and diuretics should be carried out under the supervision of a doctor.

An excessive decrease in blood pressure in patients with cerebrovascular and coronary heart disease increases the risk of myocardial infarction and stroke. In the event of hypotension, the patient must be given a horizontal position (put on his back), and if necessary, increase the BCC by introducing a 0.9% sodium chloride solution.

Renovascular hypertension. There is an increased risk of hypotension and renal failure when patients with bilateral renal artery stenosis or with single kidney stenosis take ACE inhibitors. In this case, it is possible to stop renal function with slight fluctuations in the level of serum creatinine, therefore, such patients are recommended to start treatment with small doses of captopril and under the close supervision of a doctor, and during treatment, dose titration and constantly monitor renal function.

Impaired renal function. Patients with impaired renal function (creatinine clearance ≤ 40 ml / min) require individual dose selection (see"Dosage and administration"). When using captopril, such patients should constantly monitor the level of potassium and creatinine in the blood serum.

Angioneurotic edema. Rarely, during treatment with ACE inhibitors, in particular during the first weeks of treatment, the development of angioedema of the extremities, face, lips, mucous membranes, tongue, larynx and / or glottis is possible. However, extremely rarely angioedema can develop due to prolonged treatment with ACE inhibitors. In such cases, treatment should be discontinued immediately. Angioedema of the tongue, glottis and / or larynx can be fatal, therefore, immediate relief of such reactions should be immediately followed by hospitalization and observation for at least 12-24 hours until the symptoms disappear completely.

Cough. There have been reports of coughing during treatment with ACE inhibitors. The cough was characterized as continuous, dry, unproductive, which stops after discontinuation of therapy.

Liver failure. ACE inhibitors in rare cases have been associated with a syndrome that begins with cholestatic jaundice, progresses to sudden necrotic hepatitis and sometimes leads to death. The mechanism of development of this syndrome remains incomprehensible. Therefore, if jaundice or an increase in liver enzymes occurs during treatment with ACE inhibitors, treatment should be stopped immediately and the patients condition carefully monitored.

Hyperkalemia The risk of hyperkalemia is increased in patients with kidney failure, diabetes mellitus, those who are taking potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium or other drugs that can cause hyperkalemia (for example, heparin). If the simultaneous use of these drugs is considered necessary, it is recommended to regularly monitor the level of potassium in the blood serum.

Aortic or mitral valve stenosis / hypertrophic cardiomyopathy. ACE inhibitors should be taken with caution in patients with stenosis of the aorta or mitral valve and obstruction of the excretory tract of the left ventricle. It is necessary to avoid taking captopril during the development of cardiogenic shock and significant hemodynamic disturbances.

Lithium. A combination of lithium and captopril is not recommended (see section "Interaction with other drugs and other types of interactions").

Neutropenia / agranulocytosis. There have been reports of neutropenia / agranulocytosis, thrombocytopenia and anemia in patients taking ACE inhibitors. In patients with normal renal function and without other aggravating factors, neutropenia occurs rarely. Captopril should be used with caution in patients with vascular lesions in collagenoses (e.g. systemic lupus erythematosus, scleroderma), with concomitant therapy with antidepressants, allopurinol or procainamide, or with a combination of these factors, especially if there are already impaired renal function. Some of these patients may develop a severe infection that sometimes does not respond to intensive antibiotic therapy. If captopril is necessary for such patients, it is recommended to monitor the number of leukocytes in the blood and check the detailed blood test before treatment, every 2 weeks during the first 3 months of treatment and periodically thereafter. Patients should be instructed on the need to immediately inform the doctor about any signs of infection (for example, sore throat, fever) and a subsequent blood test with a developed white blood cell formula. Captopril and other concomitant medication (see “Interaction with other drugs and other types of interactions”) should be discontinued immediately if neutropenia is detected or suspected (neutrophils less than 1000 / mm³).

In most patients, the number of neutrophils quickly returns to normal after stopping captopril.

Proteinuria Proteinuria can occur in patients with impaired renal function or when using high doses of ACE inhibitors. Total urine protein of more than 1 g per day is observed in approximately 0.7% of patients taking captopril. Most of these patients had evidence of a previous kidney disease or were taking relatively high doses of captopril (more than 150 mg per day), or both of these factors are present. Nephrotic syndrome is observed in 1/5 of patients with proteinuria. In most cases, proteinuria decreases or disappears within 6 months, regardless of captopril. In patients with proteinuria, such parameters of renal function as the level of urea and creatinine in the blood serum rarely change.

For patients who have had kidney disease, a protein analysis should be performed in the urine (test-band analysis of the first portion of morning urine) before and periodically after treatment.

Anaphylactoid reactions during desensitization by an allergen from hymenoptera venom can occur in patients while taking ACE inhibitors, which in rare cases can be life-threatening. Such reactions can be avoided by temporarily discontinuing therapy with ACE inhibitors before each desensitization, but the reactions can occur again with random repeated antigenic stimulation of the drug. Therefore, it is recommended to treat ACE inhibitors with caution in patients undergoing such desensitization procedures.

There have been reports of anaphylactoid reactions in patients during dialysis using membranes with high permeability / apheresis of LDL with dextrin sulfate. For such patients, a decision should be made on the use of a different type of dialysis, membrane or another group of drugs.

Surgical intervention / anesthesia. In patients with serious surgery, arterial hypotension may occur with anesthesia. With a decrease in blood pressure, replenishment of the bcc is recommended.

Diabetes. In patients with diabetes who take oral antidiabetic drugs or insulin, the level of blood glycemia should be carefully monitored during the first month of the joint use of ACE inhibitors.

Ethnic features. Like other ACE inhibitors, captopril is a less effective antihypertensive drug for patients of the Negroid race, possibly due to the greater prevalence of low-root essential hypertension.

Use during pregnancy or lactation.

Pregnancy. the drug is contraindicated for pregnant women or women who plan to become pregnant. if pregnancy is confirmed during treatment with this drug, its use should be stopped immediately and replaced with another drug approved for use by pregnant women.

The epidemiological findings regarding the risk of teratogenicity under the influence of angiotensin-converting enzyme inhibitors during the first trimester of pregnancy are mixed. Some increase in risk cannot be ruled out. If the continuation of therapy with angiotensin-converting enzyme inhibitors is not considered necessary, patients who are planning a pregnancy should be transferred to alternative antihypertensive treatment, which has an approved safety profile for use during pregnancy.

It is known that the use of angiotensin-converting enzyme inhibitors during the II and III trimester of pregnancy can cause fetotoxicity (decreased renal function, oligohydramniosis, retardation of ossification of the skull) and neonatal toxicity (renal failure, hypotension, hyperkalemia).

If the use of an ACE inhibitor occurred in the second trimester of pregnancy, it is recommended to conduct an ultrasound examination of kidney and skull function.

Babies whose mothers were taking ACE inhibitors should be carefully monitored for arterial hypotension (also see the sections “Contraindications” and “Features of use”).

The period of breastfeeding. Captopril is contraindicated during lactation.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

During the treatment period, caution is required when driving and carrying out potentially dangerous activities that require concentration and increased speed of psychomotor reactions, as dizziness and drowsiness are possible, especially at the beginning of therapy.

Dosage and administration.

Captopril taken orally before, during or after a meal. You should take the drug regularly at the same time every day. if you have missed taking the pill, you should take it as soon as possible, however, if several hours are left before the next dose, then the next dose is recommended to be taken on schedule and not to take the missed dose. 2 doses of captopril should not be taken at the same time.

Arterial hypertension. The recommended initial dose is 25-50 mg daily in 2 doses per day. After 2-4 weeks of treatment, dose titration can be carried out depending on the achieved blood pressure, up to 100-150 mg per day, divided into 2 doses. Captopril can be used alone or with other antihypertensive drugs, especially with thiazide diuretics. The dosage regimen once a day can be used when a concomitant antihypertensive drug such as a thiazide diuretic is added.

For patients with increased activity of the renin-angiotensin-aldosterone system (hypovolemia, renovascular hypertension, decompensated heart failure), it is advisable to start therapy with a single dose of * 6.25 mg * or 12.5 mg. The beginning of such treatment should be carried out under close medical supervision with subsequent use of the drug 2 times a day. The dosage can be gradually increased to 50 mg or 100 mg per day in 1 or 2 doses.

Heart failure. The initial dose is * 6.25 mg * or 12.5 mg 2 or 3 times a day. Titration to a maintenance dose (75-150 mg per day) should be carried out on the basis of the patients response (objective examination data and drug tolerance) in response to treatment. The dose should be increased gradually, at intervals of at least 1 time in 2 weeks, to evaluate the patients response to treatment. The maximum daily dose is 150 mg, divided into 2 doses.

Myocardial infarction.

Short-term treatment. The drug should be administered in the first 24 hours after myocardial infarction according to the following scheme: the initial dose is * 6.25 mg *, after 2 hours, 12.5 mg should be prescribed, and after 12 hours, take another 25 mg of captopril. From the next day, for 4 weeks, captopril should be taken at a dose of 100 mg per day, divided into 2 doses. At the end of the 4-week treatment, a reassessment of the patients condition should be made to make a decision regarding the treatment at the stage after myocardial infarction.

Long-term treatment. If captopril is not started during the first 24 hours of the stage of acute myocardial infarction, it is recommended to start treatment between the third and sixteenth days after the heart attack from the moment when the necessary treatment conditions are provided (stable hemodynamics and treatment of any residual ischemia). Treatment should be started in the hospital under strict control (in particular, blood pressure) until a dose of 75 mg per day is reached. The initial dose should be low (see "Features of use"), in particular, if the patient has normal or low pressure at the beginning of therapy.Treatment should begin with a dose of * 6.25 mg *, then switch to a dose of 12.5 mg 3 times a day for 2 days, then a dose of 25 mg 3 times a day in the absence of adverse hemodynamic reactions. The recommended dose for effective cardioprotection during long-term treatment is 75-150 mg daily, which should be divided into 2 or 3 doses. In case of symptomatic hypotension, as with heart failure, the dose of diuretics and / or other vasodilator drugs can be reduced to achieve a stable dose of captopril. If necessary, the dose of captopril can be adjusted depending on the clinical response of the patient. Captopril can be used in combination with other treatments for myocardial infarction, for example, with thrombolytic drugs, beta-blockers and acetylsalicylic acid.

Diabetic nephropathy in patients with type I diabetes. Captopril is used in a dose of 75-100 mg per day in 2 divided doses. If necessary, combine with other antihypertensive drugs.

Impaired renal function. Since captopril is mainly excreted by the kidneys, in case of impaired renal function, the dose of the drug should be reduced or the interval between its use should be increased. If concomitant diuretic therapy is required, loop diuretics (furosemide) should be preferred over thiazide ones.

For patients with impaired renal function, the captopril dosage regimen below is recommended to prevent its accumulation in the body.

Children. The efficacy and safety of captopril in children is not well understood. The use of captopril in children should begin under close medical supervision. The initial dose of captopril is 0.3 mg / kg body weight. For special groups of patients (children with renal failure, premature infants, newborns and infants due to the immaturity of the urinary system), the initial dose should be 0.15 mg / kg body weight. Usually captopril can be prescribed to children 3 times a day, but the interval between administration must be selected individually depending on the patients reaction to the administration of the drug.

Elderly patients. As with other antihypertensive drugs, it is necessary to start captopril therapy with a dose of * 6.25 mg * 2 times a day, since elderly patients may have impaired renal function as well as functions of other organs and systems. The dose should be titrated depending on the reaction of blood pressure to the drug, while prescribing such a minimum dose that can adequately control the pressure.

* - Captopril preparations should be used with the possibility of such dosing.

Children.

The efficacy and safety of captopril in children has not been sufficiently studied. the use of captopril in children should be carried out under close medical supervision.

Overdose.

It manifests itself as severe arterial hypotension with the possible development of shock, stupor, bradycardia, electrolyte imbalance and renal failure.

Treatment: the presence of severe arterial hypotension requires discontinuation of the drug. The patient should be given a horizontal position, rinse the stomach and conduct therapy aimed at normalizing blood pressure. With severe symptoms of an overdose, the patient is subject to urgent hospitalization for intensive detoxification methods, including hemodialysis, and measures aimed at increasing the volume of circulating blood, normalizing the functions of the cardiovascular, respiratory and nervous systems, and restoring kidney function. It is necessary to avoid hemodialysis through membranes with high permeability from polyacrylonitrite metal sulfate, (AN69), hemofiltration due to the possibility of anaphylactoid reactions.Peritoneal dialysis is ineffective.

Adverse Reactions

On the part of the cardiovascular