Captopril - instructions for use, dose, side effects, contraindications

Angiotensin-converting enzyme inhibitor. Reduces the formation of angiotensin II from angiotensin I. Reduction in angiotensin II leads to a direct reduction in the release of aldosterone. This reduces the overall peripheral vascular resistance, blood pressure, post- and preload on the heart. Expands arteries more than veins.It causes a decrease in the degradation of bradykinin (one of the effects of ACE) and an increase in the synthesis of prostaglandin.

The hypotensive effect does not depend on the plasma renin activity, the decrease in arterial pressure is noted at a normal and even lowered level of the hormone, which is due to the effect on tissue renin-angiotensin systems. Strengthens coronary and renal blood flow.

With prolonged use reduces the severity of myocardial hypertrophy and the walls of arteries of resistive type. Improves the blood supply of the ischemic myocardium. Reduces the aggregation of platelets. Promotes content reduction Na+ in patients with heart failure.

In large doses (500 mg / day), it shows angioprotective properties with respect to the vessels of the microcirculatory bed and allows slowing the progression of chronic renal failure in diabetic nephroangiopathy.

Reduction of blood pressure in contrast to direct vasodilators (hydralazine, minoxidil, etc.) is not accompanied by reflex tachycardia and leads to a decrease in myocardial oxygen demand. With heart failure in an adequate dose does not affect the value of blood pressure.

The maximum decrease in blood pressure after ingestion is observed after 60-90 minutes. The duration of the hypotensive effect is dose-dependent and reaches optimal values within a few weeks.

Pharmacokinetics:

Absorption - fast, reaches 75% (food intake decreases by 30-40%), bioavailability - 35-40% (the effect of "first pass" through the liver). Connection with blood plasma proteins (mainly with albumins) - 25-30%; the maximum concentration in the blood plasma (114 ng / ml) with oral intake - 30-90 min. Through the blood-brain barrier and placental barrier penetrates poorly (less than 1%).

Metabolized in the liver with the formation of disulfide dimer captopril and captopril-cysteine disulfide. Metabolites are pharmacologically inactive.

The half-life of - 3 hours excreted by the kidneys 95% (40-50% unchanged), the rest in the form of metabolites.. It is secreted with mother's milk. After 4 hours after a single oral urine contained 38% captopril unchanged and 28% as metabolites through 6h - only as metabolites; in daily urine - 38% of unchanged Captopril and 62% - in the form of metabolites.

The half-life period for impaired renal function is 3.5-32 hours. Cumulates in chronic renal failure.

Indications:

Arterial hypertension, incl. Renovascular; chronic heart failure (as part of complex therapy); a violation of the function of the left ventricle after a previous myocardial infarction in a clinically stable state; Diabetic nephropathy against type I diabetes mellitus (for albuminuria more than 30 mg / day).

Contraindications:

Hypersensitivity to the drug and other ACE inhibitors, angioedema (with ACE inhibitors, including history), severe renal or hepatic dysfunction, hyperkalaemia, bilateral renal artery stenosis or arterial stenosis of a single kidney with progressive azotemia, condition after transplantation kidneys, stenosis of the aortic aorta and similar changes that hinder the outflow of blood, pregnancy, lactation, age 18 years.

Carefully:Severe autoimmune diseases (especially SLE or scleroderma), oppression of bone marrow hematopoiesis (risk of neutropenia and agranulocytosis), coronary insufficiency, cerebral ischemia, diabetes mellitus (increased risk of hyperkalemia), patients on hemodialysis, sodium-restricted diet, primary hyperaldosteronism, cardiac ischemia, conditions, accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), elderly age.

Dosing and Administration:

Captopril is administered orally 1 hour before meals. The dosage regimen is set individually.

With arterial hypertension treatment is started with the lowest effective dose of 12.5 mg 2 times a day (rarely with 6.25 mg 2 times a day). Pay attention to the tolerability of the first dose during the first hour. If at the same time arterial hypotension develops, the patient should be transferred to a horizontal position (this reaction to the first dose should not serve as an obstacle to further therapy). If necessary, the dose gradually (with an interval of 2-4 weeks) is increased to achieve the optimal effect. With mild or moderate arterial hypertension, the usual maintenance dose is 25 mg 2 times a day; the maximum dose is 50 mg twice a day. In severe arterial hypertension, the maximum dose is 50 mg 3 times a day. The maximum daily dose is 150 mg.

In elderly patients the initial dose is 6.25 mg 2 times a day.

With heart failure prescribe along with diuretics and / or in combination with digitalis preparations (in order to avoid an initial excessive decrease in blood pressure, prior to the appointment of captopril the diuretic is canceled or reduced by a dose).The initial dose is 6.25 mg or 12.5 mg 3 times a day, if necessary, increase the dose to 25 mg 3 times a day. The maximum daily dose is 150 mg.

In cases of violations of left ventricular function after a previous myocardial infarction in patients in a clinically stable state, the use of captopril can begin as early as 3 days after myocardial infarction. The initial dose is 6.25 mg / day, then the daily dose can be increased to 37.5-75 mg for 2-3 doses (depending on the tolerability of the drug). If necessary, the dose is gradually increased to a maximum daily dose of 150 mg / day.

With the development of arterial hypotension, a dose reduction may be required. Subsequent attempts to apply a maximum daily dose of 150 mg should be based on tolerability of patients with Captopril.

With diabetic nephropathy prescribe in a daily dose of 75-100 mg / day for 2-3 doses. In insulin-dependent diabetes with microalbuminuria (albumin release 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.

With a moderate degree of impaired renal function (KK - not less than 30 ml / min / 1.73 m 2) captopril can be prescribed in a dose of 75-100 mg / day.With a more pronounced degree of renal dysfunction (CC - less than 30 ml / min / 1.73 m 2), the initial dose should not exceed 12.5 mg / day; In the future, if necessary, the dose of captopril is gradually increased after sufficiently long intervals of time, but use a daily dose of the drug less than in the case of arterial hypertension.

If necessary, additionally prescribed loop diuretics, and not diuretics thiazide series.

Side effects:

From the side of the cardiovascular system: tachycardia, lowering of arterial pressure, orthostatic hypotension, peripheral edema.

From the nervous system: dizziness, headache, fatigue, asthenia, paresthesia.

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

From the urinary system: proteinuria, impaired renal function (increased levels of urea and creatinine in the blood).

From the side of water-electrolyte exchange: hyperkalemia, hyponatremia (most often with salt-free diet and simultaneous intake of diuretics), proteinuria, increased urea nitrogen in the blood, creatinine, acidosis.

On the part of the organs of hematopoiesis: neutropenia, anemia, thrombocytopenia, agranulocytosis.

Allergic reactions: angioedema, tides of blood to the skin of the face, fever, skin rash (maculopapular, less often vesicular or bullous), itching, photosensitivity, bronchospasm, serum sickness, lymphadenopathy, in rare cases - the appearance of antinuclear antibodies in the blood.

From the gastrointestinal tract: a violation of taste, a decrease in appetite, stomatitis, dyspepsia, nausea, abdominal pain, constipation or diarrhea, increased activity of "liver" transaminases, hyperbilirubinemia; signs of hepatocellular injury (hepatitis) and cholestasis (in rare cases); pancreatitis (in isolated cases).

Other: general weakness, swelling of the legs.

Overdose:

Symptoms: a marked decrease in blood pressure, including collapse, myocardial infarction, acute impairment of cerebral circulation, thromboembolic complications.

Treatment: lay the patient with raised lower limbs; measures aimed at restoring blood pressure (increase in the volume of circulating blood, incl.IV infusion of physiological solution), symptomatic therapy.

Possible use of hemodialysis; peritoneal dialysis - ineffective.

Interaction:

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

Increases the bioavailability of propranolol.

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

Hypotensive effect weaken NSAIDs (delay Na+ and decreased synthesis of prostaglandin), especially against a background of low renin concentrations, and estrogens (delay Na+).

Combination with thiazide diuretics, vasodilators (minoxidil), verapamil, beta-adrenoblockers, tricyclic antidepressants, ethanol enhances antihypertensive effect.

Combined use with potassium-sparing diuretics, potassium preparations, cyclosporine, milk with low salt content (can contain K + up to 60 mmol / l), potassium supplements, salt substitutes (contain significant amounts of K +) increases the risk of hyperkalemia.

Slows the excretion of lithium preparations.

Clonidine reduces the severity of the hypotensive effect.

When captopril is prescribed against the background of taking allopurinol or procainamide, the risk of developing Stevens-Johnson syndrome and immunosuppressive action is increased.

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

Special instructions:

Before the beginning, and also regularly during the treatment with captopril, kidney function should be monitored. Patients with chronic heart failure are treated under close medical supervision.

Against the background of prolonged use of captopril, approximately 20% of patients have a stable increase in serum urea and serum creatinine by more than 20% compared to the norm or the baseline value. Less than 5% of patients, especially in severe nephropathies, require discontinuation of treatment due to increased creatinine concentrations.

In patients with arterial hypertension with captopril, severe arterial hypotension is observed only in rare cases; the likelihood of developing this condition increases with a loss of fluid and salt loss (for example, after intensive treatment with diuretics), in patients with heart failure or who are on dialysis.

The possibility of a sharp drop in blood pressure can be minimized by a preliminary cancellation(for 4-7 days) a diuretic or an increase in the intake of sodium chloride (approximately one week before the start of the intake) or by the administration of captopril at the start of treatment in small doses (6.25-12.5 mg / day).

When therapy in outpatient settings, warn the patient about the possible appearance of symptoms of an infection requiring a follow-up medical examination, a clinical and laboratory examination. In the first 3 months. The therapy monthly controls the number of white blood cells, then - once every 3 months; in patients with autoimmune diseases in the first 3 months - every 2 weeks, then every 2 months. If the number of white blood cells is less than 4000 / mm3, a general blood test is performed, below 1000 / mkl - the drug is stopped. If the first symptoms of a secondary infection occur against a background of myeloid hypoplasia, an extensive blood test should be performed immediately. It is necessary to exclude self-termination of the drug and an independent significant increase in the intensity of physical exertion.

In some cases, against the background of the use of ACE inhibitors, incl. captopril, there is an increase in the concentration of potassium in the blood serum. The risk of developing hyperkalemia with ACE inhibitors is elevated in patients withrenal insufficiency and diabetes mellitus, and also taking potassium-sparing diuretics, potassium preparations or other drugs that cause an increase in the concentration of potassium in the blood (for example, heparin). You should avoid the simultaneous use of potassium-sparing diuretics and potassium preparations.

When conducting hemodialysis in patients receiving captopril, dialysis membranes with high permeability should be avoided (for example, AN69), because in such cases the risk of anaphylactoid reactions increases.

In the case of development of angioedema, the drug is withdrawn and administered careful medical supervision and symptomatic therapy.

When taking captopril, a false positive reaction may be observed when analyzing urine for acetone.

Be wary appoint patients who are on a low-salt or salt-free diet (an increased risk of arterial hypotension) and hyperkalemia.

Effect on the ability to drive transp. cf. and fur:During the period of treatment it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.possibly dizziness, especially after taking the initial dose.

Form release / dosage:

Tablets of 12.5, 25 and 50 mg.

Packaging:For 10 tablets in a contour mesh package or 10, 20, 30 or 40 tablets in a polymer jar.

Each jar, or 1, or 2, or 3, or 4 contour mesh packages together with the instruction for use is placed in a pack of cardboard.

Storage conditions:

Store in a dry place protected from light.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002308 / 01-2003

Date of registration:16.06.2008

Expiration Date:Unlimited

The owner of the registration certificate:PRANAFARM, LLC PRANAFARM, LLC Russia

Manufacturer: & nbsp

PRANAFARM, LLC Russia

Information update date: & nbsp06.12.2017

Illustrated instructions

Instructions

Captopril (Captopril)