Captopril

General characteristics. Structure:

Active ingredient: 12,5 mg, 25 mg or 50 mg of captopril in 1 tablet.

Excipients: lactose, starch potato or corn, cellulose microcrystallic, povidone low-molecular, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Inhibitor of an angiotensin-converting enzyme. Reduces formation of Iiiz angiotensin of angiotensin I. Decrease in content of Iivedet angiotensin to direct reduction of allocation of Aldosteronum. At the same time the general peripheric vascular resistance, arterial pressure, post-and preload of heart decreases. Expands arteries more than veins. Causes reduction of degradation of bradikinin (one of effects of APF) and increase in synthesis of prostaglandin. The hypotensive effect does not depend on activity of a renin of plasma, the lowering of arterial pressure is noted at the normal and even reduced level of hormone that is caused by influence on fabric a renin - angiotenzinovy systems. Strengthens a coronary and renal blood stream.

At prolonged use reduces expressiveness of a hypertrophy of a myocardium and walls of arteries of resistive type. Improves blood supply of an ischemic myocardium. Reduces aggregation of thrombocytes. Promotes decrease in maintenance of Na + at patients with heart failure.

In high doses (500 mg/days) shows angioprotektorny properties concerning vessels of a microcirculator bed and allows to slow down progressing of a chronic renal failure at a diabetic nefroangiopatiya. The lowering of arterial pressure, unlike direct vazodilatator (a gidralazin, a minoksidil and so forth) is not followed by reflex tachycardia and leads to decrease in need of a myocardium for oxygen. At heart failure in an adequate dose does not influence the size of arterial pressure. The maximum lowering of arterial pressure after intake is observed in 60-90 min. Duration of hypotensive effect дозозависимо also reaches optimum values within several weeks.
 
Pharmacokinetics. Absorption – bystry, reaches 75% (meal lowers by 30-40%), bioavailability - 35-40% (effect of "the first passing" through a liver). Communication with proteins of a blood plasma (it is preferential with albumine) - 25-30%; the maximum concentration in a blood plasma (114 ng/ml) at oral administration – 30-90 min. Through a blood-brain barrier and a placental barrier gets badly (less than 1%).

The dimeasure of captopril and captopril-tsisteindisulfida is metabolized in a liver with education disulfide. Metabolites pharmacological are inactive. The elimination half-life makes 3 h. Other part in the form of metabolites is removed by kidneys of 95% (40-50% in an invariable look). Cosecretes with maternal milk. In 4 hours after a single dose inside contains in urine the 38th %neizmenenny captopril and 28% in the form of metabolites, in 6 hours – only in the form of metabolites; in daily urine - 38% of not changed captopril and 62% in the form of metabolites.

Elimination half-life at the broken renal function – 3,5-32 h Kumuliruyet at a chronic renal failure.

Indications to use:

Arterial hypertension, including renovascular; chronic heart failure (as a part of complex therapy); dysfunction of a left ventricle after the postponed myocardial infarction at clinically stable state; a diabetic nephropathy against the background of a diabetes mellitus of the I type (at an albuminuria more than 30 mg/days).

Route of administration and doses:

Captopril is appointed inside in 1 hour prior to food. The mode of dosing is set individually.

At arterial hypertension treatment there begin with the smallest effective dose 12,5 mg 2 times a day (seldom 6,25 mg 2 times a day). It is necessary to pay attention to portability of the first dose within the first hour. If at the same time arterial hypotension developed, the patient should be transferred to horizontal position (such reaction to the first dose should not serve as an obstacle to further therapy). If necessary the dose gradually (at an interval of 2-4 weeks) is increased before achievement of optimum effect. At soft or moderate arterial hypertension the usual maintenance dose makes 25 mg 2 times a day; the maximum dose – 50 mg 2 times a day. At heavy arterial hypertension the maximum dose – 50 mg 3 times a day. The maximum daily dose – 150 mg.

At elderly patients the initial dose makes 6,25 mg 2 times a day.

At heart failure appoint together with diuretics and/or in a combination with foxglove drugs (in order to avoid initial excessive decrease in the ABP, before purpose of captopril diuretic is cancelled or reduce a dose). The initial dose makes 6,25 mg or 12,5 mg 3 times a day, if necessary the dose is increased to 25 mg by 3 times a day. The maximum daily dose makes 150 mg.

At dysfunctions of a left ventricle after the postponed myocardial infarction at the patients who are in clinically stable state, use of captopril can be begun in 3 days after a myocardial infarction. The initial dose makes 6,25 mg/days, then the daily dose can be increased to 37,5-75 mg for 2-3 receptions (depending on portability of drug). If necessary the dose is gradually increased to the maximum daily dose – 150 mg/days.

At development of arterial hypotension the dose decline can be required. The subsequent attempts of use of the maximum daily dose of 150 mg have to be based on portability patients of Captopril.

At a diabetic nephropathy appoint in a daily dose 75-100 mg/days for 2-3 receptions. At insulin-dependent diabetes with a microalbuminuria (release of albumine of 30-300 mg a day) the dose of drug makes 50 mg 2 times a day. At the general clearance of protein more than 500 mg a day drug is effective in a dose of 25 mg 3 times a day.

At moderate degree of a renal failure (KK – not less than 30 ml/min. / 1,73 sq.m) captopril can appoint 75 - 100 mg/days in a dose. At more expressed degree of a renal failure (KK – less than 30 ml/min. / 1,73 sq.m) the initial dose has to make no more than 12,5 mg/days; further, if necessary, the captopril dose is gradually raised through rather long intervals of time, but use smaller, than in case of treatment of arterial hypertension, a daily dose of drug.

If necessary in addition appoint loopback diuretics, but not diuretics of a thiazide row.

Features of use:

Before the beginning, and also it is regular in the course of treatment by Captopril, it is necessary to control function of kidneys. At patients with chronic heart failure apply under careful medical control.

Against the background of prolonged use of Captopril approximately at 20% of patients stable increase in urea and creatinine of blood serum more than for 20%, in comparison with norm or a reference value is observed. Less than at 5% of patients, especially at heavy nefropatiya, the termination of treatment because of growth of concentration of creatine is required.

At patients with arterial hypertension, at Captopril use, the expressed arterial hypotension is observed only in rare instances; the probability of development of this state increases at deficit of loss of liquid and salts (for example, after intensive treatment by diuretics), at patients with heart failure or being on dialysis. The possibility of a sharp lowering of arterial pressure can be minimized at preliminary cancellation (in 4-7 days) diuretic or increase in intake of sodium of chloride (approximately in a week prior to reception), or by purpose of captopril in an initiation of treatment in small doses (6.25-12.5 mg/days). At therapy in out-patient conditions to warn the patient about possible emergence of symptoms of an infection demanding control medical examination, clinic - laboratory inspection.

In the first 3 months of therapy monthly control number of leukocytes of blood, further - 1 time in 3 months; at patients with autoimmune diseases in the first 3 months – in each 2 weeks, then – each 2 months. If the number of leukocytes are lower 4000/mkl, performing the general blood test is shown, below 1000/mkl – administration of drug is stopped. At emergence of the first symptoms of consecutive infection against the background of a myeloid hypoplasia it is necessary to carry out immediately developed blood test.

It is necessary to exclude the independent termination of administration of drug and independent significant increase in intensity of exercise stresses. In certain cases, against the background of use of APF inhibitors, including captopril, increase in potassium concentration in blood serum is observed. The risk of development of a hyperpotassemia at use of APF inhibitors is increased at the patients with a renal failure and a diabetes mellitus and also accepting the kaliysberegayushchy diuretics, drugs of potassium or other drugs causing increase in potassium concentration in blood (for example, heparin). It is necessary to avoid simultaneous use of kaliysberegayushchy diuretics and drugs of potassium. When carrying out a hemodialysis at the patients receiving Captopril it is necessary to avoid use of dialysis membranes with high-permeability (for example, AN69) as in such cases the risk of development of anaphylactoid reactions increases. In case of development of a Quincke's disease drug is cancelled and carry out careful medical observation and symptomatic therapy.

At reception of Captopril false positive reaction can be observed in the analysis of urine on acetone.

During treatment it is necessary to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions since dizziness, especially after reception of an initial dose is possible.

With care appoint the patient who is on a low-salt or electrolyte-deficient diet (the increased risk of development of arterial hypotension) and a hyperpotassemia.

Side effects:

From cardiovascular system: tachycardia, lowering of arterial pressure, orthostatic hypotension, peripheral hypostases.

From a nervous system: dizziness, headache, feeling of fatigue, adynamy, paresthesias.

From respiratory system: dry cough, fluid lungs, bronchospasm.

From an urinary system: a proteinuria, a renal failure (increase in level of urea and creatinine in blood).

From water and electrolytic exchange: a hyperpotassemia, a hyponatremia (it is the most frequent at an electrolyte-deficient diet and a concomitant use of diuretics), a proteinuria, the increased maintenance of an urea nitrogen in blood, creatinine, acidosis.

From bodies of a hemopoiesis: neutropenia, anemia, thrombocytopenia, agranulocytosis.

Allergic reactions: a Quincke's disease, "inflows" of blood to face skin, heat, skin rash (makulo-papular, is more rare – vesicular or violent character), an itch, photosensitivity, a bronchospasm, a serum disease, a limfoadenopatiya, in rare instances – emergence of anti-nuclear antibodies in blood.

From digestive tract: disturbance of flavoring feelings, loss of appetite, stomatitis, dispepsichesky phenomena, nausea, abdominal pains, lock or diarrhea, increase in activity of "hepatic" transaminases, hyperbilirubinemia; signs of hepatocellular damage (hepatitis) and cholestasia (in rare instances); pancreatitis (in isolated cases).

Others: general weakness, hypostases of shins.

Interaction with other medicines:

Increases concentration of digoxin in a blood plasma for 15-20%. Increases bioavailability of propranolol.

Cimetidinum, slowing down metabolism in a liver, increases concentration of captopril in a blood plasma.

The hypotensive effect is weakened by NPVP (Na delay + and decrease in synthesis of prostaglandin), especially against the background of low concentration of a renin, and estrogen (Na+ delay).

Combination with thiazide diuretics, vazodilatator (minoksidit), verapamil, beta adrenoblockers, tricyclic antidepressants, ethanol strengthens hypotensive effect.

The combined use with kaliysberegayushchy diuretics, potassium drugs, cyclosporine, milk with the low content of salts (may contain K+ to 60 mmol/l), potassium additives, salt substitutes (contain significant amounts of K+), increases risk of development of a hyperpotassemia.
Slows down removal of drugs of lithium.

The clonidine reduces expressiveness of hypotensive effect.

At purpose of captopril against the background of reception of Allopyrinolum or procaineamide, the risk of development of a syndrome of Stephens-Johnson and an immunodepressive effect increases. Use of captopril for the patients accepting immunodepressants (for example, Azathioprinum or cyclophosphamide), increases risk of development of hematologic disturbances.

Contraindications:

Hypersensitivity to drug and other ingibator of APF, a Quincke's disease (against the background of use of ingibator of APF, including in the anamnesis), the expressed renal failures or a liver, a hyperpotassemia, a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney with the progressing azotemia, a state after transplantation of a kidney, the stenosis of the mouth of an aorta and similar changes complicating blood outflow, pregnancy, the lactation period, age up to 18 years.

With care to apply: a serious autoimmune illness (especially hard currency or a scleroderma), oppression of a marrowy hemopoiesis (risk of development of a neutropenia and agranulocytosis), coronary insufficiency, brain ischemia, a diabetes mellitus (the risk of development of a hyperpotassemia), the patients who are on a hemodialysis, a diet with sodium restriction, primary hyper aldosteronism, coronary heart disease, states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting is increased), advanced age.

Overdose:

Symptoms: the expressed lowering of arterial pressure, up to a collapse, a myocardial infarction, an acute disorder of cerebral circulation, tromboembolic episodes.

Treatment: to lay the patient with the raised lower extremities; the measures directed to recovery of arterial pressure (increase in volume of the circulating blood, including in/in injection of normal saline solution), symptomatic therapy.

Use of a hemodialysis is possible; peritoneal dialysis – is not effective.

Storage conditions:

List B. To store in the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children. Not to apply after the period of validity specified on packaging. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets on 12,5 mg, 25 mg or 50 mg. On 10 tablets in a blister strip packaging on 10, 20, 30 or 40 tablets in a polymeric can. Each can, either 1, or 2, or 3, or 4 blister strip packagings together with the application instruction place in a pack from a cardboard.