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

Excipients: lactose monohydrate (milk sugar) 68.6 mg, microcrystalline cellulose 71.0 mg, magnesium stearate 2.0 mg, talc 6.0 mg, silicon dioxide colloid (aerosil) 0.4 mg, crospovidone (kollidone CL-M, kollidone CL) 2.0 mg.

Description:TOfungal tablets white or almost white with a characteristic odor, flat-cylindrical shape with a facet and a risk. Presence of "marble" is admissible.

Pharmacotherapeutic group:ACE inhibitor

ATX: & nbsp

C.09.A.A.01 Captopril

Pharmacodynamics:

An angiotensin-converting enzyme (ACE) inhibitor of the first generation, containing a sulfhydryl group (SHgroup). Has antihypertensive effect. Inhibiting ACE, reduces the conversion of angiotensin I into angiotensin II and eliminates its vasoconstrictive effect on arterial and venous vessels.As a result of a decrease in angiotensin II concentration, a secondary increase in renin plasma activity occurs (by eliminating the negative feedback during the release of renin), which leads to a direct reduction in the secretion of aldosterone by the adrenal cortex. This reduces the overall peripheral vascular resistance (OPSS) and blood pressure (BP), resistance in the pulmonary vessels, reduce post-and preload on the heart. Increases the minute volume of the heart and tolerance to physical activity.

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 antihypertensive effect does not depend on the plasma renin activity, the decrease in blood pressure is noted with normal and even decreased activity of the hormone, which is due to the effect on the tissue renin-angiotensin-aldosterone system (RAAS). Strengthens coronary and renal blood flow. With prolonged use reduces the severity of myocardial hypertrophy and the walls of arteries of the resistive type, prevents the progression of heart failure and slows the development of dilatation of the left ventricle.

Improves the blood supply of the ischemic myocardium. Reduces the aggregation of platelets. Helps reduce sodium ions in patients with heart failure.

Reduces the tone of arterioles carrying out the glomeruli of the kidneys, thereby improving intramedular hemodynamics, and interferes with the development of diabetic nephropathy.

At doses of 50 mg / day shows angioprotective properties in relation 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 AD.

The maximum decrease in blood pressure is observed after 60-90 minutes after ingestion. The duration of the antihypertensive effect depends on the dose of the drug taken and reaches optimal values within a few weeks of therapy.

The withdrawal of captopril should not occur dramatically, as this can cause a significant increase in blood pressure.

Pharmacokinetics:

Absorption - fast, is about 75% of the dose (with simultaneous intake with food, the absorption of the drug is reduced by 30-40%), bioavailability is 35-40% (the effect of "primary passage" through the liver). The connection with blood plasma proteins (mainly with albumins) is 25-30%. Time to reach the maximum concentration in the blood plasma (C_mOh =114 ng / ml) with oral administration - 30-90 min. Less than 0.002% of the accepted dose of captopril is secreted with breast milk. Through the blood-brain barrier and placental barrier penetrates slightly (less than 1%).

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

The half-life of captopril is about 2-3 hours. About 95% is excreted by the kidneys during the first day, 40-50% of them in unchanged form, the rest - in the form of metabolites. In daily urine, 38% of unchanged captopril and 62% - in the form of metabolites.

Cumulates in chronic kidney failure. Half-life with renal failure is 3.5-32 hours, so patients with impaired renal function should reduce the dose and / or increase the interval between doses.

Indications:

- Arterial hypertension (including renovascular);

- xheart failure (as part of complex therapy);

- Mr.left heart failure after a myocardial infarction with a clinically stable condition;

- dIabetic nephropathy against type 1 diabetes mellitus (for albuminuria more than 30 mg / day).

Contraindications:

- Hypersensitivity to captopril, other components of the drug or other ACE inhibitors (including in the history);

- hereditary and / or idiopathic angioedema, an angioedema in the anamnesis (against the background of previous therapy with other ACE inhibitors);

- severe renal dysfunction, refractory hyperkalemia, bilateral stenosis of the renal arteries, stenosis of a single kidney with progressive azotemia, condition after kidney transplantation, primary hyperaldosteronism;

- severe violations of liver function;

- pregnancy;

- the period of breastfeeding;

- age under 18 years (effectiveness and safety not established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

- simultaneous use of ACE inhibitors (including captopril) with aliskiren and aliskiren-containing drugs in patients with type 2 diabetes or renal dysfunction (glomerular filtration rate (GFR) of less than 60 ml / min / 1.73 m² surface area of the body) (see section "Interaction with other drugs").

Carefully:

Hypertrophic obstructive cardiomyopathy, connective tissue diseases (especially systemic lupus erythematosus or scleroderma), oppression of bone marrow hematopoiesis (risk of developing neutropenia and agranulocytosis), cerebrovascular disease, coronary heart disease, diabetes (increased risk of hyperkalemia), diet with restriction of table salt, , accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting, in patients on hemodialysis), mitral stenosis, aortic minutes stenosis and similar changes impeding the outflow of blood from the left ventricle of the heart, the liver, chronic renal failure, surgery / general anesthesia, using vysokoprotochnyh hemodialysis membranes (e.g. AN69®), desensitizing therapy, low-density lipoprotein apheresis (LDL), potassium-sparing diuretics, potassium, potassium-containing salt and lithium substitutions, hyperkalemia, renovascular hypertension, in patients of the Negroid race, in elderly patients (dose adjustment is required).

Pregnancy and lactation:

The use of the drug Captopril-AKOS during pregnancy is contraindicated.

The drug Captopril-AKOS should not be used in the first trimester of pregnancy. Appropriate controlled trials of the use of ACE inhibitors in pregnant women have not been conducted. Available limited data on the effect of the drug in the first trimester of pregnancy suggest that the use of ACE inhibitors does not lead to fetal malformations associated with fetotoxicity. Epidemiological evidence of a risk of teratogenicity after the effects of ACE inhibitors in the first trimester was not convincing, but some increase in risk can not be ruled out.

The use of ACE inhibitors in pregnancy can lead to the incidence and death of the fetus and / or newborn. Long-term use of captopril in II and III trimester is toxic to the fetus (decreased kidney function, low blood pressure, delayed ossification of the skull bones) and newborns (neonatal kidney failure, arterial hypotension, hyperkalemia).

In addition, the use of ACE inhibitors in the first trimester of pregnancy is associated with a potentially increased risk of congenital fetal defects.

Women planning a pregnancy should not use ACE inhibitors (including Captopril-AKOS). Women of childbearing age should be aware of the potential dangers of using ACE inhibitors (including Captopril-AKOS).

If the pregnancy occurred during the use of the drug Captopril-AKOS, the drug should be stopped as soon as possible and regularly monitor the development of the fetus.

If the patient received the drug during the second and third trimester of pregnancy, it is recommended that an ultrasound be performed to assess the condition of the skull bones and the function of the kidneys of the fetus.

If the use of an ACE inhibitor is considered necessary, patients planning a pregnancy should be transferred to alternative antihypertensive therapy,having an established safety profile for use during pregnancy.

Approximately 1% of the accepted dose of the drug Captopril-AKOS is found in breast milk. In connection with the risk of developing serious adverse reactions in the child, breastfeeding should be stopped or the drug should be withdrawn from the mother for the period of breastfeeding.

Dosing and Administration:

Inside for 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 twice a day (for this dosing regimen it is necessary to apply captopril in tablets of 25 mg with the risk of other manufacturers). Pay attention to the tolerability of the first dose during the first hour. If the arterial hypotension develops, the patient should be transferred to the "lying" position with raised legs (this reaction to the first dose should not be 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 a mild to moderate degree arterial hypertension the usual maintenance dose is 25 mg (1/2 tablets 50 mg) twice a day; the maximum dose is 50 mg twice a day.

With severe degree of hypertension the maximum daily dose of the drug Captopril-AKOS - 150 mg (50 mg 3 times per day).

With chronic heart failure prescribe along with diuretics and / or in combination with cardiac glycosides (to avoid initial excessive reduction in blood pressure, prior to prescribing the drug is canceled taking a diuretic or reducing the dose).

The initial daily dose is 6.25 mg (for this dosing regimen it is necessary to apply captopril in tablets of 12.5 mg with a risk or in tablets of 25 mg with a cross-like risk of other manufacturers) 3 times a day, then, if necessary, increase the dose gradually (at intervals of not less than 2 weeks).

The average maintenance dose is 25 mg (1/2 tablets 50 mg) 2-3 times a day, and the maximum dose is 150 mg per day.

In case of symptomatic arterial hypotension in heart failure, the dose of diuretics and / or other concomitantly prescribed vasodilators can be reduced to achieve a steady effect of the drug Captopril-ACOS.

In cases of violations of left ventricular function after a previous myocardial infarction in patients in a clinically stable state, the use of the drug Captopril-ACOS can begin as early as 3 days after myocardial infarction.

The initial dose is 6.25 mg per day (for this dosing regimen it is necessary to apply captopril in tablets of 12.5 mg with a risk or in tablets of 25 mg with a cross-like risk from other manufacturers). If necessary, the dose gradually, within a few weeks, is increased to 75 mg per day in 2-3 doses (depending on the drug tolerability) up to a maximum daily dose of 150 mg (50 mg 3 times a 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 the patient's tolerability of the drug.

With diabetic nephropathy the preparation of Captopril-AKOS is prescribed in a dose of 75-100 mg per day in 2-3 doses. With insulin-dependent diabetes (type 1) with microalbuminuria (albumin release 30-300 mg per day), the dose of the drug is 50 mg twice a day. With a total protein clearance of more than 500 mg per day, the drug is effective at a dose of 25 mg (1/2 tablets 50 mg) 3 times a day.

With a moderate degree of impaired renal function (GFR - not less than 30 ml / min / 1.73 m²) drug Captopril-AKOS can be prescribed in a dose of 75-100 mg per day.

With a more pronounced degree of impaired renal function (GFR less than 30 ml / min / 1.73 m²) the initial dose should be no more than 12.5 mg per day (for this dosing regimen it is necessary to apply captopril in tablets of 25 mg with the risk of other manufacturers); in the future, if necessary, the dose is gradually increased at sufficiently long intervals, but use a daily dose of the drug less than in the case of the treatment of arterial hypertension.

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

Recommended scheme for correction of doses of the drug Captopril-AKOS in patients with impaired renal function

Glomerular filtration rate (ml / min / 1.73 m²)	The initial daily dose (mg)	The maximum daily dose (mg)
40	25-50	150
21-40	25	100
10-20	12,5	75
< 10	6,25	37,5

In elderly patients the initial dose is 6.25 mg twice a day (this dosing regimen should be used captopril in tablets of 12.5 mg with a risk or in tablets of 25 mg with a cross-like risk from other manufacturers) and, if possible, is maintained at this level to prevent impaired renal function.The dose of the drug is recommended to be adjusted constantly depending on the patient's therapeutic response and maintained at the lowest possible level.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often (≥ 1/10); often (≥ 1/100, <1/10); infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10000, <1/1000); very rarely (<1/10000), including individual messages; frequency (frequency can not be calculated from available data).

From the central nervous system: often - a disorder of taste, sleep disorders, dizziness, drowsiness; rarely - headache, paresthesia, asthenia; very rarely - depression, cerebrovascular disorders, including stroke, syncope, impaired consciousness.

From the skin: often - skin itching with rashes and without rashes, skin rash (maculopapular, less often - vesicular or bullous nature), baldness; very rarely - hives, Stevens-Johnson syndrome, erythema multiforme, photosensitivity, erythroderma, exfoliative dermatitis, pemphigoid reactions.

From the genitourinary system: rarely - renal failure, acute renal failure, polyuria, oliguria, increased frequency of urination; very rarely - nephrotic syndrome, sexual dysfunction, gynecomastia.

From the side of metabolism: rarely anorexia; very rarely - hyperkalemia, hypoglycemia.

From the musculoskeletal system: very rarely - myalgia, arthralgia.

From the digestive system: often - dryness of the oral mucosa, nausea, vomiting, abdominal pain, diarrhea, constipation; rarely - stomatitis, aphthous ulcers internal mucosal surfaces of the cheeks and tongue, gingival hyperplasia; very rarely - glossitis, peptic ulcer, pancreatitis, impaired liver function, cholestasis, jaundice, hepatitis (including rare cases of gepatonekroz), increased activity of "liver" transaminases, increased bilirubin concentration in blood serum, angioneurotic edema of the intestinal mucosa.

From the hematopoiesis: very rarely - neutropenia, agranulocytosis, pancytopenia, especially in patients with renal dysfunction, anemia (including aplastic, hemolytic), anemia, lymphadenopathy, eosinophilia, autoimmune disease and / or increase in titer antinuclear antibody.

From the respiratory system: often - dry, irritating (unproductive) cough, shortness of breath; very rarely - bronchospasm, rhinitis, allergic alveolitis, eosinophilic pneumonia, pulmonary edema.

From the sense organs: very rarely - a violation of visual acuity.

From the cardiovascular system: infrequently - tachycardia or tachyarrhythmia, palpitations, angina pectoris, orthostatic hypotension, Raynaud's syndrome, "flushes" of blood to the face, pallor, peripheral edema; very rarely - cardiogenic shock, cardiac arrest.

Laboratory indicators: very rarely - proteinuria, eosinophilia, hyperkalemia, hyponatremia, hypoglycemia, increased urea nitrogen and creatinine in the blood plasma, acidosis, hemoglobin and hematocrit decrease, decrease in the number of leukocytes, platelets, increased erythrocyte sedimentation rate (ESR).

Other: infrequently - pain in the chest, increased fatigue, weakness; very rarely - fever; the frequency is unknown - the symptom complex, which includes flushing of the facial skin, nausea, vomiting and lowering of blood pressure.

Overdose:

Symptoms: a pronounced decrease in blood pressure, up to a collapse, shock,stupor, bradycardia, water-electrolyte balance disorders, acute renal failure, myocardial infarction, acute cerebrovascular accident, thromboembolic complications.

Treatment: gastric lavage, administration of adsorbents and sodium sulfate no later than 30 minutes after taking the drug; transfer the patient to the "lying" position with raised legs, take measures aimed at restoring blood pressure, replenishing the volume of circulating blood (for example, intravenous injection of 0.9% sodium chloride solution), symptomatic therapy - epinephrine (epinephrine) - subcutaneously or intravenously, antihistamines, hydrocortisone - intravenously. When bradycardia or expressed vagus reactions should be used atropine. Possible use of hemodialysis; peritoneal hemodialysis is ineffective.

Interaction:

Simultaneous use of ACE inhibitors with other drugs that affect RAAS, including with angiotensin II receptor antagonists (ARA II) and aliskirenom, leads to an increase in the incidence of severe depression of blood pressure, hyperkalemia, impaired renal function (including acute renal failure).It is necessary to monitor blood pressure, kidney function, and the content of plasma electrolytes when using captopril with other drugs that affect RAAS.

Simultaneous use of ACE inhibitors (including captopril) with aliskiren and aliskiren-containing drugs should be avoided in patients with severe renal dysfunction (GFR less than 60 ml / min / 1.73 m² body surface area), with type 2 diabetes mellitus.

Combined application with potassium-sparing diuretics (triamterene, amiloride, spironolactone and its derivative - eplerenone), potassium preparations, potassium supplements, salt substitutes (contain significant amounts of potassium ions) increases the risk of hyperkalemia. If necessary, their simultaneous use with captopril should monitor the plasma content of potassium.

When applying high doses diuretics (thiazide diuretics, loop diuretics) simultaneously with captopril due to a reduced volume of circulating blood, the risk of arterial hypotension increases, especially at the beginning of captopril therapy.

The antihypertensive effect of captopril is potentiated when used simultaneously with alddesleykin, alprostadil, beta-blockers, alpha₁adrenoblockers, central alpha₂adrenomimetics, diuretics, cardiotonics, blockers of "slow" calcium channels, minoxidil, muscle relaxants, nitrates and vasodilators.

Antidepressants, antipsychotics, anxiolytics and hypnotics can also enhance the antihypertensive effect of captopril.

With prolonged use, the antihypertensive effect of captopril weakens indomethacin and others nonsteroidal anti-inflammatory drugs (NSAIDs), incl. selective inhibitors of cyclooxygenase-2 (sodium ion delay, a decrease in the synthesis of prostaglandins, especially against a background of low renin activity), and estrogens.

It has been described that NSAIDs and ACE inhibitors have an additive effect on the increase in serum potassium content, while reducing the renal function. These effects are reversible. Rarely, acute renal failure may occur, especially in patients with a previous impairment of renal function, in elderly patients or with reduced circulating blood volume (with dehydration).

The use of ACE inhibitors in patients undergoing surgery using general anesthesia, can lead to a marked decrease in blood pressure, especially when using funds for general anesthesia that have antihypertensive effects.

Slows down the excretion lithium preparations, increasing the concentration of lithium in the blood. If concomitant use of captopril and lithium preparations is necessary, the serum concentration of lithium should be carefully monitored.

When using captopril on the background of admission allopurinol or procainamide the risk of Stevens-Johnson syndrome and / or neutropenia increases.

With simultaneous application ACE inhibitors and preparations of gold (in / in sodium aurotomy malate) describes a symptom complex, which includes flushing of the facial skin, nausea, vomiting and a decrease in blood pressure.

Sympathomimetics can reduce the antihypertensive effect of captopril.

Insulin and hypoglycemic agents for intravenous useIncrease the risk of developing hypoglycemia.

Simultaneous reception of captopril with food or antacids slows the absorption of captopril in the digestive tract.

During therapy with captopril, the use of ethanol, because the ethanol enhances the antihypertensive effect of captopril.

The antihypertensive effect of captopril is weakened epoetins, estrogens and combined oral contraceptives, carbenoxolone, glucocorticosteroids and naloxone.

Probenecid reduces renal clearance of captopril and increases its serum concentrations in the blood.

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

Captopril increases concentration digoxin in blood plasma by 15-20%.

Increases bioavailability propranolol.

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

Clonidine reduces the severity of antihypertensive effect.

Special instructions:

Before and during the treatment with Captopril-AKOS, regular monitoring of blood pressure and kidney function should be carried out regularly. In patients with chronic heart failure, the drug is used under close medical supervision.

Arterial hypotension

In patients with arterial hypertension with the use of the drug Captopril-AKOS, severe arterial hypotension is observed only in rare cases, the probability of developing this condition increases with a decrease in the volume of circulating blood and a violation of the water-electrolyte balance (for example, after intensive treatment with diuretics), in patients with chronic cardiac deficiency or on hemodialysis. The possibility of a sharp decrease in blood pressure can be minimized by first canceling (for 4-7 days) a diuretic or replenishing the volume of circulating blood (about a week before the start of the procedure), or with the use of Captopril-AKOS in small doses at the beginning of treatment (6 , 25-12.5 mg / day). The pronounced decrease in blood pressure with the use of antihypertensive drugs in patients with impaired cerebral circulation, with cardiovascular diseases may increase the risk of myocardial infarction or stroke. With the development of arterial hypotension the patient should take a horizontal position with raised legs. Sometimes it may be necessary to replenish the volume of circulating blood.

Renovascular hypertension

There is an increased risk of hypertension and renal failure in patients with bilateral renal artery stenosis of a single kidney using ACE inhibitors. Violation of kidney function can occur with a moderate change in the concentration of creatinine in the blood serum. In such patients, therapy should be started under close medical supervision from small doses, carefully titrating and controlling kidney function.

The use of ACE inhibitors (including the drug Captopril-AKOS) with aliskiren should be avoided in patients with severe renal failure (GFR less than 60 ml / min / 1.73 m² surface area of the body).

Impaired renal function

In patients with renal insufficiency or when taking high doses of ACE inhibitors (including the drug Captopril-AKOS), proteinuria can be observed. In most cases, proteinuria decreased or disappeared within 6 weeks, regardless of whether treatment continued with the drug Captopril-AKOS or not. Parameters of renal function, such as residual blood nitrogen and creatinine in patients with proteinuria rarely changed.Patients with kidney disease should determine the protein content in the urine before starting therapy and periodically throughout the course of therapy.

Hyperkalemia

In some cases, when using the drug Captopril-AKOS, an increase in the potassium content in the blood serum is observed. The risk of development of hyperkalemia when using ACE inhibitors elevated in patients with renal insufficiency and diabetes, as well as host potassium-sparing diuretics, potassium supplements, and other agents that cause an increase in the potassium content of the blood (e.g., heparin). You should avoid the simultaneous use of potassium-sparing diuretics and potassium preparations. With caution apply in patients on a low-salt or salt-free diet (an increased risk of hypotension and hyperkalemia).

Neutropenia / agranulocytosis

In the first 3 months of therapy, the number of leukocytes in the blood is monitored monthly, then - once in 3 months. Neutropenia / agranulocytosis, thrombocytopenia and anemia have been reported in patients treated with ACE inhibitors, including Kaptopril- ICCO. In patients with normal renal function and the absence of other complicating factors, neutropenia occurs rarely.Captopril-AKOS should be used with great care in patients with connective tissue diseases receiving immunosuppressive therapy simultaneously (allopurinol or procainamide), especially with existing impairments of kidney function. Such patients in the first 3 months are monitored by a clinical blood test every 2 weeks, then every 2 months. If the number of white blood cells is below 4.0 x 10⁹ / l, shows a general blood test, below 1.0 x 10⁹ / l - the drug is stopped. Such patients can develop severe infections that are not amenable to intensive antibiotic therapy. During treatment, all patients should be instructed that if there are signs of infection (eg, sore throat, fever) should inform your doctor and perform a complete blood count with leukocyte counting. In most patients, the number of white blood cells upon discontinuation of treatment with the drug Captopril-AKOS quickly returns to normal.

Anaphylactoid reactions

Patients taking captopril-ICCO on the background of desensitizing therapy Hymenoptera venom, etc., are at increased risk of anaphylactoid

If, against the background of therapy with the drug Captopril-LKO, jaundice develops or the activity of "liver" transaminases increases, the drug should be immediately discontinued; the patient should be under close supervision and, if necessary, receive appropriate therapy.

Hypokalemia

The simultaneous use of an ACE inhibitor and a thiazide diuretic does not exclude the possibility of hypokalemia. It is recommended to regularly monitor the potassium content in the blood.

Surgery / anesthesia

Arterial hypotension can occur in patients who have undergone extensive surgical interventions or during the use of anesthetics, which are known to lower blood pressure. When arterial hypotension occurs, it is recommended that the volume of circulating blood be replenished.

Ethnic differences

ACE inhibitors, including Captopril-ACOS, have a less pronounced antihypertensive effect in patients of the Negroid race, which is likely due to the frequent occurrence of low renin activity in this group of patients. Laboratory data

Captopril-AKOS may cause a false-positive urine test for acetone.

Effect on the ability to drive transp. cf. and fur:

During the treatment period 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, since dizziness is possible, especially after taking the initial dose.

Form release / dosage:Tablets, 50 mg.

Packaging:

For 10, 20 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

10, 20, 30, 40, 50, 60, 80, 100 tablets in cans of polymer made of polypropylene, low-density polyethylene, sealed with lids tightened with the control of the first opening or caps screwed on.

One jar or 1, 2, 3, 4, 5 contour squares with instructions for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-003594

Date of registration:04.05.2016

Expiration Date:04.05.2021

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp07.12.2017

Illustrated instructions

Instructions

Captopril-AKOS (Captopril-AKOS)