Captopril

General characteristics. Structure:

Active ingredient: 1 tablet contains captopril in terms of 100%     veshchestvo25mg;

excipients: potato starch; lactose, monohydrate; povidone; calcium stearate; silicon dioxide colloid anhydrous.

Pharmacological properties:

Pharmacodynamics. Captopril – the first synthetic inhibitor of an angiotensin-converting enzyme (APF) which found application in medical practice. Blocking transformation of angiotensin I into angiotensin II, captopril has vasodilating effect, thanking kotoromuumenshat the general peripheric vascular resistance (afterload), pressure of "jamming" in pulmonary capillaries (preloading) and resistance in pulmonary vessels; increases the minute volume of heart and tolerance to loading. At prolonged use captopril reduces expressiveness of a hypertrophy of a myocardium of a left ventricle, prevents progressing of heart failure and slows down development of dilatation of a left ventricle. Reduces a tone of the taking-out arterioles of balls of kidneys, thereby improving an intraglomerular hemodynamics, and interferes with development of a diabetic nephropathy.

Pharmacokinetics. At use inside drug quickly and almost completely (not less than 75%) is soaked up from digestive tract. In the presence of food bioavailability decreases by 30-40%. The maximum concentration in a blood plasma is reached in 30-90 minutes. Linkng with proteins, is preferential with albumine, makes 25-30%. Passes through gistogematichesky barriers, except for a blood-brain barrier, gets through a placenta. It is metabolized in a liver. The elimination half-life makes less than 3 hours and increases at a renal failure. It is excreted preferential by kidneys both in the form of metabolites, and in not changed look (to 50%). Within 24 hours 95% of the soaked-up drug are removed. The maximum lowering of arterial pressure after intake is observed in 60-90 minutes. Duration of hypotensive effect of a dozozavisim also reaches optimum values within several weeks.

Main physical and chemical properties: tablets of white or almost white color with a flat surface, with one or two risks, with a facet.

Indications to use:

Arterial hypertension.
heart failure. Captopril is appointed for treatment of chronic heart failure with decrease in systolic function of ventricles, and also in a combination with diuretics and, if necessary, sdigitalisom and beta-blockers.
myocardial infarction: for short-term (4 weeks) treatments purpose of captopril for 24 hours after the postponed myocardial infarction to patients with a stable state is possible;
for long prevention of symptomatic heart failure drug is shown to patients with clinically stable state with asymptomatic dysfunction of a left ventricle (fraction of emission ≤ 40%). A diabetic nephropathy at patients with a diabetes mellitus of the I type which is shown by a macroproteinuria.

Route of administration and doses:

Kaptoprilprinimat inside to, in time to an iliposla of meal. It is necessary to accept drug regularly, at the same time every day. If reception of a tablet is missed, it should be accepted as soon as possible; however if there were several hours before reception of the following dose, then the following dose is recommended to be accepted according to the schedule and to miss reception of the passed dose. It is not necessary to accept         2 doses of captopril at the same time.

Arterial hypertension. The recommended initial dose of captopril makes on 12,5-25 mg 2 times a day. In 2-4 weeks of treatment it is possible to carry out titration of a dose, depending on the reached arterial pressure, to 100-150 mg a day, a razdelennoyn 2 receptions. Captopril can be applied separately or with other anti-hypertensive drugs, especially with thiazide diuretics. The mode of dosing of 1 times a day can be applied when such accompanying anti-hypertensive drug as thiazide diuretic is added.

With a superactivity system renin-angiotensin-aldosteronovoy (a hypovolemia, renovascular hypertensia, dekompensirovanny heart failure) therapy it is desirable for patients to begin 6,25 mg or 12,5 mg with a single dose. The beginning of such treatment should be spent under careful medical control with the subsequent administration of drug 2 times a day. The dosage can be increased gradually to 50 mg or 100 mg in 1 or 2 receptions.

Heart failure. An initial dose – 6,25-12,5 mg 2 or 3 times a day. Titration to a maintenance dose (75-150 mg a day) should be carried out on the basis of reaction of the patient (data of objective inspection and portability of drug) in response to treatment. The dose should be increased gradually, bucketed at least 1 time in 2 weeks, for the purpose of assessment of reaction of the patient in response to treatment. The maximum daily dose makes 150 mg, divided into 2 receptions.

Myocardial infarction. Short-term treatment. Purpose of drug in the first 24 hours after a myocardial infarction is carried out according to the following scheme: the initial dose makes     6,25 mg, in 2 hours appoint 12,5 mg and in 12 hours accept 25 more mg of captopril. From the next day within 4 weeks captopril should be accepted in the dose 100 mg a day divided into 2 receptions. At the end of 4 weeks treatment it is necessary to make repeated assessment of a condition of the patient for making decision on treatment at a stage after the postponed myocardial infarction.

Prolonged treatment. If reception of captopril did not begin within the first 24 hours of a stage of an acute myocardial infarction, it is recommended to begin treatment during the period between     the 3rd and 16th days after a heart attack, with the moment when necessary conditions of treatment (a stable hemodynamics and treatment of any residual ischemia) are provided. Treatment should be begun in hospital under strict control (in particular, arterial pressure) until achievement of a dose of 75 mg a day. The initial dose of drug has to be low (see the section "Features of Use"), in particular, if the patient has normal or low pressure at the beginning of therapy. Treatment it is necessary to begin 6,25 mg with a dose, then to pass to a dose 12,5 mg 3 times a day for 2 days, then – on a dose of 25 mg         3 times a day in the absence of side hemodynamic reactions. The recommended dose for effective cardioprotection throughout prolonged treatment makes 75-150 mg daily which is divided into 2 or 3 receptions. In case of symptomatic hypotension, as well as at heart failure, the dose of diuretics and/or other vasodilating drugs can be reduced for achievement of a stable dose of captopril. If necessary the dose of captopril can be regulated depending on clinical reaction of the patient. Captopril can be applied in a combination with other types of treatment of a myocardial infarction, for example with thrombolytic drugs, beta-blockers and acetylsalicylic acid.

Diabetic to a nefropatiya of patients with a diabetes mellitus of the I type. Captopril apply in a dose 75-100 mg a day in 2 receptions. If necessary combine with other anti-hypertensive drugs.

Renal failure. As captopril is generally removed by kidneys, at a renal failure it is necessary or to lower a drug dose, to libouvelichit an interval between its reception. In case the accompanying therapy is required by diuretics, it is necessary to give preference to loopback diuretics (furosemide), but not thiazide.

The scheme below, dosing of captopril for prevention of its cumulation in an organism is recommended to patients with a renal failure.

Clearance of creatinine (ml/min. / 1,73 sq.m)  Initial daily dose (mg)  Maximum daily dose (mg)
 
            >                                                                                   40 25-50 150
 
                                                                                                 21-40 25 100
 
                                                                  10-20 12,5                               75
 
            <                                                         10 6,25                             37,5

 

Children. Efficiency and safety of use of captopril to children is studied insufficiently. It is necessary to apply captopril to children subcareful observation of the doctor. The recommended initial dose – 0,3 mg/kg of body weight. For special groups of patients (to children with a renal failure, the premature newborn, the newborn and to babies in connection with immaturity of an urinary system) the initial dose has to make 0,15 mg/kg of body weight. Usually captopril is appointed to children by 3 times a day, but the interval between introduction needs to be selected individually, depending on reaction to administration of drug.

Patients of advanced age. As well as at treatment by other anti-hypertensive drugs, it is necessary to begin therapy with captopril with a dose of 6,25 mg 2 times a day as at elderly patients disturbance both functions of kidneys, and functions of other bodies and systems is possible. The dose should be titrated depending on reaction of arterial pressure upon drug, at the same time to appoint such minimum dose which can adequately control pressure.

Features of use:

Arterial hypotension. Developing of arterial hypotension at patients with arterial hypertension at whom the reduced volume of blood and/or decrease in amount of sodium owing to therapy by diuretics, the limited use of edible salt, and also owing to diarrhea, vomiting or a hemodialysis is observed is seldom possible. Before purpose of APF inhibitors it is necessary to modify the volume of the circulating blood (VCB), and also to resolve an issue of purpose of the lowest effective optimum dose of drug.

Patients with cordial to a nedostatochnostyyutakzha are in risk group of developing of symptomatic hypotension at use of APF inhibitors. Therefore these patients are recommended to appoint captopril from a boleenizky initial dose. Increase in a dose of APF inhibitors and diuretics should be carried out under careful observation of the doctor.

The excessive lowering of arterial pressure at patients with cerebrovascular and coronary heart disease increases risk of developing of a myocardial infarction and stroke. In case of developing of hypotonia the patient needs to give horizontal position (to put on a back), and if necessary – to increase OTsK due to introduction of 0,9% of solution of sodium of chloride.

Renovascular hypertensia. There is an increased risk of developing of hypotonia and renal failure when patients with a bilateral stenosis of renal arteries or with a stenosis of the only kidney accept APF inhibitors. In this case the termination of function of kidneys with insignificant fluctuations of an indicator of level of creatinine in blood serum therefore such patients are recommended to begin treatment with small doses of captopril and under careful observation of the doctor is possible, and during treatment to carry out titration of a dose and to monitor constantly function of kidneys.

Renal failure. Patients with a renal failure (clearance of creatinine ≤ 40 ml/min.) demand individual selection of a dose (see the section "Route of Administration and Doses"). During captopril reception such patients should control constantly the level of potassium and creatinine in blood serum.

Quincke's disease. Seldom at treatment by APF inhibitors, in particular for the first weeks of treatment, development of a Quincke's disease of extremities, persons, lips, mucous membranes, language, a throat and/or a glottis is possible. However extremely seldom Quincke's disease can develop owing to prolonged treatment by APF inhibitors. In such cases it is necessary to stop treatment immediately. The Anginevrotichesky paraglossa, a glottis and/or a throat can be deadly therefore it is necessary to carry out immediately urgent stopping of such reactions with further hospitalization and observation not less than 12-24 hours before total disappearance of symptoms.

Cough. Messages on developing of cough were during treatment APF inhibitors. Cough was characterized as continuous, dry, unproductive which stops after therapy cancellation.

Liver failure. APF inhibitors in rare instances were associated with a syndrome which begins with cholestatic jaundice, progresses to sudden necrotic hepatitis and sometimes leads to a lethal outcome. The mechanism of development of this syndrome remains not clear. Therefore if during treatment jaundice or increase in enzymes of a liver arises APF inhibitors, then treatment should be stopped immediately and to watch carefully a condition of the patient.

Hyperpotassemia. The risk of emergence of a hyperpotassemia is increased at patients with a renal failure, a diabetes mellitus, at those who at the same time accept kaliysberegayushchy diuretics, additives with potassium or the salt substitutes containing potassium or other drugs which can cause a hyperpotassemia (for example heparin). If the concomitant use of above-mentioned drugs is considered necessary, it is regularly recommended to check potassium level in blood serum.

Stenosis of an aorta or mitral valve / hypertrophic cardiomyopathy. APF inhibitors should be taken with caution to patients with a stenosis of an aorta or the mitral valve and obstruction of an output path of a left ventricle. It is necessary to avoid reception of captopril at development of cardiogenic shock and considerable hemodynamic disturbances.

Lithium. The combination of lithium and captopril is not recommended (see the section "Interaction with Other Medicines and Other Types of Interactions").

Neutropenia/agranulocytosis. Patients who accepted APF inhibitors had messages on emergence of a neutropenia/agranulocytosis, thrombocytopenia and anemia. At patients with normal function of kidneys and without other burdening factors the neutropenia arises seldom. Captopril should be applied carefully to patients with defeat of vessels at collagenoses (for example a system lupus erythematosus, a scleroderma), with the accompanying therapy by antidepressants, Allopyrinolum or procaineamide or at a combination of these factors, especially if there is already a renal failure. At some of such patients the serious infection which sometimes does not react to an intensive care antibiotics can develop. If to such patients apply captopril, then it is recommended to carry out control of quantity of leukocytes to blood and to check the developed blood count prior to treatment, every 2 week within the first 3 months of treatment and periodically after that. For patients the doctor should instruct concerning need of the immediate message on any symptoms of an infection (for example about a throat inflammation, fever) and the subsequent blood test with the developed leukocytic formula. Captopril and other accompanying drug (see the section "Interaction with Other Medicines and Other Types of Interactions") should be cancelled immediately if it is found or the neutropenia is suspected (neutrophils less than 1000/mm3).

At most of patients the quantity of neutrophils quickly is returned to norm after the captopril reception termination.

Proteinuria. The proteinuria can arise at patients with a renal failure or at reception of high doses of APF inhibitors. Crude protein in urine more than 1 g in a day is observed approximately at 0,7% of the patients accepting captopril. Most of these patients have the previous disease of kidneys or accepted rather high doses of captopril (more than 150 mg a day) or both of these factors take place. The nephrotic syndrome is observed at 1/5 patients with a proteinuria. In most cases the proteinuria decreases or disappears within 6 months irrespective of captopril reception. At patients with a proteinuria such parameters of function of kidneys as level of urea and creatinine in blood serum seldom change.

For the patients who had diseases of kidneys it is necessary to carry out the analysis of protein in urine (the test and strip analysis of the first portion of morning urine) before an initiation of treatment and periodically after it.

Anaphylactoid реакцииво time of performing desensitization by allergen from poison of hymenopterous insects can arise at patients at a concomitant use of APF inhibitors that in rare instances can pose a threat for life. Such reactions can be avoided by the temporary termination of therapy by APF inhibitors before each desensitization, but reactions can arise again at an accidental repeated antigen challenge drug. Therefore patients who undergo such procedures of desensitization are recommended to carry out with care therapy by APF inhibitors.

Patients of anaphylactoid reactions had messages on emergence during dialysis using membranes with high permeability / афереза lipoproteins low плотностис a dextrin sulfate. For such patients it is necessary to make the decision on use of other type of dialysis, a membrane or drugs of other group.

Surgical intervention / anesthesia. Patients with serious surgical intervention at use of anesthesia can have an arterial hypotension. At a lowering of arterial pressure it is recommended пополнениеОЦК.

Diabetes mellitus. At the patients with a diabetes mellitus accepting peroral antidiabetic drugs or insulin within the first month accompanying применениея APF inhibitors it is necessary to control carefully glycemia level in blood.

Ethnic features. As well as other APF inhibitors, captopril is less effective anti-hypertensive drug for patients of negroidniy race, perhaps, because of bigger prevalence of lowrenine essentsialnoyarterialny hypertensia.

Способностьвлиять on speed of response at upravleniiavtotransporty or work with other mechanisms. Care at control of vehicles is necessary or when performing other work requiring special attention as reduction in the rate of reaction, especially in an initiation of treatment is possible or when changing a drug dosing, and also at simultaneous alcohol intake. These effects are shown individually and depend on features of an organism of the patient.

Side effects:

From cardiovascular system: tachycardia, tachyarrhythmia, stenocardia, arterial hypotension, Reynaud's syndrome, inflows, pallor of the person, cardiac standstill, cardiogenic shock.

From respiratory system, bodies of a thorax and a mediastinum: the dry, irritating (unproductive) cough and an asthma. Dry cough usually passes through several weeks after the treatment termination by captopril. Also the bronchospasm, rhinitis, an allergic alveolitis / eosinophilic pneumonia can be observed.

From a digestive tract: nausea, vomiting, irritation of a stomach, an abdominal pain, diarrhea, a lock, dryness in a mouth, stomatitis/emergence of aphthous ulcers, a glossitis, a round ulcer, pancreatitis.

From gepatobiliarny system: an abnormal liver function, a cholestasia, including jaundice, hepatitis, including necrotizing hepatitis, increase in level of enzymes of a liver and bilirubin. The abnormal liver function usually passes after the treatment termination by captopril.

Neurologic frustration: taste disturbance, dizziness, drowsiness, a headache, paresthesias, cerebrovascular manifestations, an ataxy, including a stroke and a loss of consciousness.

From system of blood and lymphatic system: a leukopenia, a neutropenia/agranulocytosis, a pancytopenia (in particular at patients with a renal failure), anemia (including aplastic and hemolitic), thrombocytopenia, a lymphadenopathy, an eosinophilia.

From immune system: autoimmune diseases and/or positive test for antinuclear antibodies.

Disturbances of metabolism and process of digestion: anorexia, acidosis, hypoglycemia.

Mental disorders: sleep disorders, confusion of consciousness, depression.

From organs of sight: sight misting.

From skin and hypodermic cellulose: an itch, rash, an alopecia, a Quincke's disease (see the section "Features of Use"), a small tortoiseshell, Stephens-Johnson's syndrome, a polymorphic erythema, photosensitivity, an erythrosis, pemfigoidny reactions and exfoliative dermatitis.

From a musculoskeletal system and connecting fabric: mialgiya, arthralgia.

From urinary tract: a renal failure, including a renal failure, a polyuria, an oliguria and a frequent urination, a nephrotic syndrome.

From reproductive system: impotence, gynecomastia.

General disturbances: stethalgia, increased fatigue, weakness, fever.

From laboratory indicators: a proteinuria, a hyperpotassemia, a hyponatremia (it is most often observed at observance of an electrolyte-deficient diet with a concomitant use of diuretics), the increased level of urea, creatinine and bilirubin in blood serum, and also decrease in level of hemoglobin, a hematocrit and increase in a blood sedimentation rate, a leukopenia, thrombocytopenia, the raised caption of antinuclear antibodies. Captopril can cause false positive result of the analysis of urine on acetone.

Interaction with other medicines:

Kaliysberegayushchy diuretics or nutritional supplements with potassium. APF inhibitors reduce the potassium loss caused by reception of diuretics. Kaliysberegayushchy diuretics (for example Spironolactonum, Triamterenum or amiloride), or the salt substitutes containing potassium can lead additives with potassium to a hyperpotassemia. At co-administration         on prichineimeyushcheysyagipokaliyemiiy it is necessary to apply carefully and with frequent monitoring of potassium concentration in blood serum.

Diuretics (thiazide or loopback diuretics). The previous treatment by diuretics in high doses can lead to decrease in OTsK and povysheniyurisk of development of considerable hypotonia (see the section "Features of Use"). The hypotonic effect can be reduced by cancellation of reception of diuretic, increase in consumption of salt and liquid or having begun therapy with a low dose of captopril. However no odnogoklinicheska of significant interaction with a hydrochlorothiazide or furosemide is revealed.

Other anti-hypertensive drugs. The concomitant use of captopril with other anti-hypertensive drugs (for example beta-blockers and blockers of calcium channels of the prolonged action) is safe, and the accompanying reception of such drugs can increase hypotensive effect of captopril. It is necessary to carry out with care treatment by nitroglycerine, other nitrates or other vasoconstrictive drugs.

Treatment of an acute myocardial infarction. Captopril can be accepted along with acetylsalicylic acid (in cardiological doses), trombolitika, beta-blockers and/or nitrates to patients with a myocardial infarction.

Lithium. Simultaneous use of APF inhibitors and lithium can bring to временномуповышениюуровня a lity in blood serum and intoxication lithium. The accompanying reception of APF inhibitors and thiazide diuretics can increase in addition lithium levels in blood serum and increase risk of intoxication lithium. Therefore the concomitant use of captopril with lithium is not recommended. If such combination is necessary for the patient, it is necessary to carry out careful monitoring of level of lithium in blood serum.

Tricyclic antidepressants / neuroleptics. The accompanying reception of certain tricyclic antidepressants and neuroleptics with APF inhibitors can lead to an additional lowering of arterial pressure (see the section "Features of Use"). Postural hypotension can take place.

Allopyrinolum, procaineamide, cytostatic or immunosuppressive drugs. Their simultaneous use with APF inhibitors can lead to increase in risk of a leukopenia, especially when the last were applied in doses, prevyshayushchikhrekomenduyemy.

Non-steroidal anti-inflammatory drugs (NPVP). It is described that APF and NPVP inhibitors exert additional impact on increase in level of potassium in blood serum that can cause a renal failure. Usually this effect is reversible. The acute renal failure, especially at patients with a renal failure, for example at patients of advanced age or the dehydrated patients can seldom take place. Long introduction of NPVP can reduce anti-hypertensive effect of APF inhibitors.

Sympathomimetics. Can reduce anti-hypertensive effect of APF inhibitors therefore it is necessary to watch carefully indicators of arterial pressure at the patient.

Anti-diabetic drugs. APF inhibitors, including captopril, can strengthen anti-glycemic effect of insulin and other peroral anti-diabetic drugs (sulphonylurea) at the patients sick with a diabetes mellitus. Such effect meets very seldom, but at its emergence need of a dose decline of an antidiabeticheskikhpreparatovpra simultaneous treatment by APF inhibitors appears.

Contraindications:

Hypersensitivity to captopril, to any excipient or to other APF inhibitors;
Quincke's edema (including in the anamnesis, after use of APF inhibitors, hereditary/idiopathic);
bilateral stenosis of renal arteries which influences a hemodynamics, or a stenosis of an artery of the only kidney which is essential to a hemodynamics;
porphyria;
intolerance of a galactose, deficit of lactase, syndrome glucosic галактозной malabsorption;
 ІІ and ІІІ trimester of pregnancy or feeding by a breast.

Use during pregnancy or feeding by a breast.

APF inhibitors are not recommended to be accepted in the I trimester of pregnancy, and in             the II-III trimesters drugs of this group are contraindicated as perhaps toxic influence on a fruit (depression of function of kidneys of a fruit, delay of ossification of bones of a skull, emergence of an oligogidramnion), and at newborns can be observed a renal failure, arterial hypotension, a hyperpotassemia. If use of APF inhibitor happened in ІІ a pregnancy trimester, it is recommended to conduct ultrasonic examination of function of kidneys and a skull. Babies whose mothers accepted APF inhibitors should be controlled carefully regarding arterial hypotension (see also section "Contraindications").

In case of planning of pregnancy or when pregnancy is confirmed, patients need to be transferred to alternative treatment which has the approved profile of safety of use during pregnancy immediately.

Captopril is contraindicated during feeding by a breast.

Children.

Efficiency and safety of captopril for children is studied insufficiently. It is necessary to apply captopril to children under careful observation of the doctor.

Overdose:

It is shown by the expressed arterial hypotension with possible development of shock, stupor, bradycardia, an electrolytic imbalance and a renal failure.

Treatment. For the prevention of absorption of a high dose of captopril it is necessary to wash out as soon as possible a stomach, to give sorbents and sodium sulfate within 30 minutes after captopril reception. In case of symptoms of arterial hypotension the patient should give horizontal position and to immediately carry out correction of volume of plasma and salt balance.

Angiotensin use ІІ is possible. Bradycardia or excessive vagal reactions it is necessary to treat by administration of atropine. It is necessary to consider option of use of a pacemaker. The hemodialysis is effective.

Storage conditions:

Period of validity 3 years. To store in original packaging at a temperature not over 25 ºС. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister, on 2 blisters in a pack.