Composition, form of production and packaging
Tablets from white to white with a creamy shade of color, square with rounded edges, biconvex with a crosswise notching on one side and squeezed out the word "SQUIBB" and the number "452" - on the other, with a characteristic odor; slight marmorage is allowed.
captopril 25 mg
Excipients: microcrystalline cellulose - 40 mg, corn starch - 7 mg, stearic acid - 3 mg, lactose monohydrate - 25 mg.
10 pieces. - blisters (4) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
ACE inhibitor. Suppresses the formation of angiotensin II and eliminates its vasoconstrictive effect on arterial and venous vessels.
Reduces OPSS, postnagruzku, reduces blood pressure. Reduces preload, reduces pressure in the right atrium and a small circle of circulation.
Reduces the secretion of aldosterone in the adrenal glands.
The maximum hypotensive effect is observed within 60-90 minutes after ingestion. The degree of decrease in blood pressure is the same in the patient's standing and lying position.
The efficacy and safety of captopril in children are not established. The literature describes the limited experience of using captopril in children. Children, especially newborns, may be more prone to developing hemodynamic side effects. There have been cases of development of excessive, prolonged and unpredictable increase in blood pressure, as well as complications related to it, including oliguria and seizures.
When ingested quickly absorbed from the digestive tract. C max in blood plasma is achieved approximately 1 hour after administration. Bioavailability of captopril is 60-70%. Simultaneous food intake slows the absorption of the drug by 30-40%.
Binding to blood proteins is 25-30%.
T 1/2 is 2-3 hours. The drug is excreted from the body mainly with urine, up to 50% unchanged, the rest - in the form of metabolites.
- arterial hypertension, incl. Renovascular;
- chronic heart failure (as part of combination therapy);
- violations of the function of the left ventricle after a previous myocardial infarction in a clinically stable state;
- Diabetic nephropathy in the background of type 1 diabetes mellitus (for albuminuria> 30 mg / day).
The drug is taken orally for 1 hour before meals. The dosage regimen is set individually.
With arterial hypertension, the initial dose is 12.5 mg (1/2 table 25 mg) 2 times / day. If necessary, increase the dose gradually (with an interval of 2-4 weeks) until the optimal effect is achieved. With mild and moderate arterial hypertension, the maintenance dose is 25 mg 2 times / day; the maximum dose is 50 mg 2 times / day. Insevere arterial hypertension, the initial dose is 12.5 mg (1/2 table 25 mg) 2 times / day. The dose is gradually increased to a maximum daily dose of 150 mg (50 mg 3 times / day).
In chronic heart failure, the initial daily dose is 6.25 mg (1/4 table 25 mg) 3 times / day. If necessary, increase the dose gradually (at intervals of not less than 2 weeks). The maintenance dose is 25 mg 2-3 times / day. The maximum daily dose is 150 mg. If before the appointment of the drug Kapoten В® therapy with diuretics was carried out, it is necessary to exclude the presence of a marked decrease in the content of electrolytes and bcc.
In cases of violations of left ventricular function after a previous myocardial infarction in patients in a clinically stable state, the use of the Kapoten В® preparation can begin as early as 3 days after myocardial infarction. The initial dose is 6.25 mg / day (1/4 table 25 mg), then the daily dose can be increased to 37.5-75 mg for 2-3 doses (depending on the drug tolerability) up to a maximum of 150 mg / day.
With diabetic nephropathy the drug is prescribed in a dose of 75-100 mg, divided into 2-3 doses. In type 1 diabetes mellitus with microalbuminuria (albumin clearance 30-300 mg / day) the dose of the drug is 50 mg 2 times / day. With proteinuria more than 500 mg / day the drug is effective at a dose of 25 mg 3 times / day.
Patients with impaired renal function of moderate degree (CK-30 ml / min / 1.73 m 2 ) Kapoten В® are prescribed in a dose of 75-100 mg / day. In severe disorders of kidney function (CC <30 ml / min / 1.73 m 2 ), the initial dose is no more than 12.5 mg / day (1/2 table 25 mg). In the future, if necessary, the dose is gradually increased (with sufficiently large intervals), but use a smaller, than usual, daily dose of the drug.
For elderly patients, the dose is selected individually. It is recommended to start treatment with a dose of 6.25 mg (1/4 table, 25 mg) 2 times / day and, if possible, maintain it at this level.
If necessary, additionally prescribed "loop" diuretics, and not diuretics thiazide series.
Determination of the frequency of adverse reactions: often (? 1/100, <1/10); infrequently (? 1/1000, <1/100), rarely (? 1/10 000, <1/1000), very rarely (<1/10 000).
From the cardiovascular system: infrequently - tachycardia or arrhythmia, angina, palpitations, orthostatic arterial hypotension, excessive lowering of blood pressure, Raynaud's syndrome, flushing of the blood to the skin of the face, pallor; very rarely - cardiac arrest, cardiogenic shock.
From the respiratory system: often - dry, unproductive cough, shortness of breath; very rarely - bronchospasm, eosinophilic pneumonitis, rhinitis, pulmonary edema.
From the skin and subcutaneous tissues: often - skin itching, with or without rashes, rashes on the skin, alopecia.
Allergic reactions: infrequently - angioedema of the extremities, face, lips, mucous membranes, tongue, pharynx and larynx; rarely - angioedema of the intestine; very rarely - hives, Stevens-Johnson syndrome, erythema multiforme, photosensitivity, erythroderma, pemphigoid reactions, exfoliative dermatitis, allergic alveolitis, eosinophilic pneumonia.
From the nervous system: often - drowsiness, dizziness, insomnia; infrequently - headache, paresthesia; rarely - ataxia; very rarely - confusion, depression, cerebral blood flow disorders, including stroke and syncope, blurred vision.
From the hemopoietic system: very rarely - neutropenia, agranulocytosis, pancytopenia, lymphadenopathy, eosinophilia, thrombocytopenia, anemia (including aplastic and hemolytic forms).
On the part of the immune system: very rarely - an increase in the titer of antinuclear antibodies, autoimmune diseases.
On the part of the digestive system: often - nausea, vomiting, irritation of the gastric mucosa, abdominal pain, diarrhea, constipation, taste disturbance, dryness of the oral mucosa, dyspepsia; infrequently - anorexia; rarely - stomatitis, aphthous stomatitis; very rarely - glossitis, stomach ulcer, pancreatitis, gingival hyperplasia, impaired liver function and cholestasis (including jaundice), increased activity of liver enzymes, hepatitis (including rare cases of hepatonecrosis), hyperbilirubinemia.
From the osteomuscular system: very rarely - myalgia, arthralgia.
From the urinary system: rarely - violations of the kidneys (including kidney failure), polyuria, oliguria, frequent urination; very rarely - nephrotic syndrome.
From the side of the reproductive system: very rarely - impotence, gynecomastia.
Other: infrequent - peripheral edema, chest pain, fatigue, a feeling of general malaise, asthenia; rarely - hyperthermia.
Laboratory indicators: very rarely - proteinuria, eosinophilia, hyperkalemia, hyponatremia, increased urea nitrogen, bilirubin and creatinine in the blood, a decrease in hematocrit, a decrease in hemoglobin, leukocytes, platelets, hypoglycemia.
- angioedema (Quincke's edema) in an anamnesis associated with the use of ACE inhibitors;
- hereditary / idiopathic angioedema;
- severe renal dysfunction;
severe hepatic impairment;
- refractory hyperkalemia;
- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney with progressive azotemia;
- condition after kidney transplantation;
- Stenosis of the aortic aorta and similar obstructive changes that hinder the outflow of blood from the left ventricle;
- simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or impaired renal function (GFR less than 60 ml / min);
- lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome;
- the period of lactation (breastfeeding);
- age under 18 years (efficiency and safety not established);
- Hypersensitivity to the components of the drug and other ACE inhibitors.
With caution should prescribe the drug in severe autoimmune diseases of connective tissue (including SLE, scleroderma); oppression of bone marrow hematopoiesis (risk of neutropenia and agranulocytosis); ischemia of the brain; diabetes mellitus (increased risk of hyperkalemia); primary hyperaldosteronism; IHD; Conditions accompanied by a decrease in BCC (including vomiting, diarrhea); arterial hypotension; violations of kidney and / or liver function; chronic heart failure; surgical intervention / general anesthesia; patients on hemodialysis; patients who follow a diet with reduced sodium intake; when carrying out hemodialysis using high-strength membranes (for example, AN69 В® ), desensitizing therapy, apheresis of LDL; simultaneous application of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes, lithium preparations, immunosuppressants, allopurinol, procainamide (risk of neutropenia, agranulocytosis); elderly patients (dose adjustment required); patients Negroid race.
PREGNANCY AND LACTATION
The use of the drug Kapoten В® is contraindicated in pregnancy.
The drug Kapoten В® 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 data suggesting a risk of teratogenicity after exposure to ACE inhibitors in the first trimester of pregnancy were not convincing, but some increase in risk can not be ruled out. If the use of an ACE inhibitor is considered necessary, patients planning a pregnancy should be transferred to alternative antihypertensive therapy that has an established safety profile for use in pregnancy.
It is known that prolonged exposure to ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to disruption of its development (decreased kidney function, oligohydramnion, delayed ossification of the skull bones) and development of complications in the newborn (such as kidney failure, arterial hypotension, hyperkalemia) . If the patient received the preparation Kapoten В® in the II and III trimesters of pregnancy, it is recommended to perform an ultrasound examination to assess the condition of the bones of the skull and the function of the kidneys of the fetus.
The use of ACE inhibitors in pregnancy can cause developmental disorders (including arterial hypotension, neonatal hypoplasia of the skull bones, anuria, reversible or irreversible renal failure) and fetal death. When establishing the fact of pregnancy, the drug Kapoten В® should be discontinued as soon as possible.
Approximately 1% of the accepted dose of captopril is found in breast milk. In connection with the risk of developing serious adverse reactions in the child, breastfeeding should be stopped or treatment with Kapoten В® taken from the mother during the period of breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated use of the drug in severe violations of kidney function.
With caution should prescribe the drug for violations of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated use of the drug in severe violations of liver function.
With caution should prescribe the drug for violations of liver function.
APPLICATION FOR CHILDREN
Contraindicated use of the drug in patients under the age of 18 years (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
With caution should prescribe the drug to elderly patients (dose adjustment is required).
Before the onset, and also regularly during the treatment with the drug Kapoten В® , kidney function should be monitored. In patients with chronic heart failure, Kapoten В® should be used under close medical supervision.
With the use of ACE inhibitors, a characteristic non-productive cough is observed, which stops after the abolition of therapy with ACE inhibitors.
In rare cases, with the use of ACE inhibitors, there is a syndrome that begins with the appearance of cholestatic jaundice, which turns into lightning-fast hepatonecrosis, sometimes with a lethal outcome. The mechanism of development of this syndrome is unknown. If a patient receiving ACE inhibitor therapy develops jaundice or a marked increase in hepatic enzyme activity, discontinue treatment with ACE inhibitors and establish patient monitoring.
In some patients with kidney disease, especially with severe renal artery stenosis, there is an increase in the concentrations of urea nitrogen and creatinine in the serum after lowering blood pressure. This increase is usually reversible after discontinuation of therapy with Kapoten В® . In these cases, it may be necessary to reduce the dose of Kapoten В® and / or to cancel the diuretic.
Against the backdrop of prolonged use of the drug Kapoten В®, approximately 20% of patients have an increase in the concentration of urea and serum creatinine by more than 20% compared to the norm or baseline. Less than 5% of patients, especially in severe nephropathies, require discontinuation of treatment due to increased creatinine concentrations.
It is not recommended to use a double blockade of RAAS caused by simultaneous administration of ACE inhibitors and angiotensin II receptor antagonists or aliskiren and aliskiren containing drugs, as it was associated with an increased incidence of side effects such as hypotension, hyperkalemia, and decreased renal function (including acute renal failure). If simultaneous use of ACE inhibitors and angiotensin II receptor antagonists (double blockade of RAAS) is necessary, the treatment should be performed under the supervision of a physician and in the constant monitoring of kidney function, the content of electrolytes in the blood, and blood pressure.
The combined use of ACE inhibitors and angiotensin II receptor antagonists in patients with diabetic nephropathy is not recommended.
In patients with hypertension with the use of the drug Kapoten В®, severe arterial hypotension is observed only in rare cases; the likelihood of developing this condition increases with increased loss of fluid and salts (eg, after intensive treatment with diuretics), in patients with heart failure or who are on dialysis. The possibility of a sharp decrease in blood pressure can be minimized by first canceling (for 4-7 days) a diuretic or increasing the intake of sodium chloride (about a week before the start of the intake) or by prescribing the drug Kapoten В® at the start of treatment at low doses (6.25-12.5 mg / day).
With caution, the drug is prescribed for patients who follow a diet with a reduced sodium content or a salt-free diet (an increased risk of hypotension and hyperkalemia).
Excessive reduction in blood pressure can occur in patients during major surgical operations, as well as in the use of anesthetics that have an antihypertensive effect.In such cases, measures to increase the BCC are used to correct the lowered blood pressure.
Excessive reduction in blood pressure due to the use of antihypertensive drugs may increase the risk of myocardial infarction or stroke in patients with IHD or cerebrovascular disease. When developing arterial hypotension, the patient should be moved to a horizontal position with a low head. A 0.9% solution of sodium chloride may be required.
Caution should be exercised when using ACE inhibitors in patients with mitral / aortic stenosis / hypertrophic obstructive cardiomyopathy; in the case of cardiogenic shock and hemodynamically significant obstruction, the use of the drug is not recommended.
In patients taking ACE inhibitors, there was neutropenia / agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function and in the absence of other disorders, neutropenia is rare. With renal failure, simultaneous use of the drug Kapoten В® and allopurinol led to neutropenia.
The drug Kapoten В® should be used very carefully in patients with autoimmune connective tissue diseases, in those taking immunosuppressors, allopurinol and procainamide, especially if there is an existing renal impairment. Due to the fact that the majority of lethal cases of neutropenia against the background of the use of ACE inhibitors developed in such patients, it is necessary to monitor the number of blood leukocytes before treatment, in the first 3 months - every 2 weeks, then every 2 months.
All patients should be monitored monthly for the number of leukocytes in the blood in the first 3 months after initiation of therapy with Kapoten В® , then every 2 months. If the number of counts below 4000 / L, shown holding a total re-analysis of blood, less than 1000 / l - the drug is stopped, continuing monitoring of the patient. Typically, the reduction in neutrophils occurs within 2 weeks after discontinuation of the drug Capoten В® . In 13% of cases of neutropenia noted fatal. In almost all cases, lethal neutropenia noted in patients with connective tissue disorders, renal or heart failure, in patients receiving immunosuppressive or a combination of both these factors.
With the use of ACE inhibitors can be marked proteinuria, mainly in patients with impaired renal function, as well as use of the drug at high doses. In most cases, proteinuria when applying the drug Capoten В®disappeared or the degree of its severity decreased for 6 months regardless of whether stop taking the drug or not. Indicators of renal function (the concentration of blood urea nitrogen and creatinine) in patients with proteinuria were almost always within normal limits. Patients with kidney disease should determine the content of protein in the urine before treatment and periodically during the course of therapy. In some cases, treatment with ACE inhibitors, including drug Capoten В®, There is an increase potassium in the blood serum. The risk of hyperkalemia when using ACE inhibitors elevated in patients with renal insufficiency and diabetes, as well as host potassium-sparing diuretics, potassium supplements or other drugs that cause an increase in the potassium content of the blood (e.g., heparin). It should avoid the simultaneous use of potassium sparing diuretics and drugs. Furthermore, when using ACE inhibitors simultaneously with thiazide diuretics there is a risk of hypokalemia, so in such cases it is necessary to regularly monitor the content of potassium in the blood during treatment.
In hemodialysis in patients treated with ACE inhibitors should be avoided dialysis membranes with high permeability (e.g., N69 В®), Since in such cases increases the risk of anaphylactoid reactions. Anaphylactoid reactions were observed in patients who underwent LDL apheresis procedure using the dextran sulfate. The application of any other antihypertensive drugs class, or another type of dialysis membranes should be considered.
In rare cases, the therapy of ACE inhibitors occurred life-threatening anaphylactoid reactions in patients undergoing desensitization course with poison Hymenoptera (bees, wasps). In such patients, these reactions could be prevented by temporary discontinuation of therapy with an ACE inhibitor. It should be particularly careful in the case of such patients desensitization.
In the case of angioedema drug overturned and perform careful medical supervision until complete disappearance of symptoms. Angioneurotic edema of the larynx may be fatal. If localized swelling of the face, special treatment is not usually required (antihistamines may be employed to reduce the severity of symptoms); in the event that swelling spread on the tongue, pharynx or larynx and there is threat to the development of airway obstruction, should immediately enter epinephrine (adrenaline) p / (0.3-0.5 ml at a dilution of 1: 1000). In rare cases, patients after receiving ACE inhibitors bowel angioneurotic edema was observed, which was accompanied by pain in the abdomen (nausea and vomiting, or without them),sometimes - at normal activity of the C-1 esterase and without prior facial edema. bowel swelling should be included into the spectrum of differential diagnosis of patients with complaints of pain in the abdominal cavity during the use of ACE inhibitors.
In blacks cases of angioedema observed with greater frequency compared to Caucasians.
ACE inhibitors are less effective in blacks than in Caucasians patients that may be associated with a higher prevalence of low activity of renin in blacks.
In patients with diabetes receiving hypoglycemic drugs (hypoglycemic agents for oral or insulin) should carefully monitor their blood glucose levels, especially during the first month of therapy with ACE inhibitors.
During the extensive surgical operations or when used for general anesthesia agents having hypotensive effect in patients treated with ACE inhibitors, may experience excessive reduction in blood pressure. In these cases, you can increase the BCC.
In applying the drug Capoten В® may be a false positive reaction in the analysis of urine for acetone.
Impact on the ability to drive vehicles and manage mechanisms
During the period of treatment should refrain from driving motor vehicles and activities potentially hazardous activities that require high concentration and speed of psychomotor reactions, because dizziness, especially after receiving the initial dose.
Symptoms: sharp decrease in blood pressure, shock, stupor, bradycardia, disturbances of water and electrolyte balance, renal failure.
Treatment: gastric lavage, administration of adsorbents and sodium sulfate for 30 minutes after ingestion, administration of 0.9% sodium chloride or other plasma preparations (pre patient must be placed in a horizontal position with a low headboard, then take measures to fill bcc) Hepatology. When expressed bradycardia or vagal reactions - atropine. It may be considered the use of artificial pacemaker. Peritoneal dialysis is not effective for removing captopril from the body.
In patients receiving diuretics, drug Capoten В® can potentiate the hypotensive action. This effect is also a strict limitation reception of salt (salt-free diet), hemodialysis. Usually excessive blood pressure reduction takes place during the first hour after the first scheduled dose preparation Capoten В® .
Vasodilators (e.g., nitroglycerin) in combination with a drug Capoten В® should be used in the lowest effective doses because of the risk of excessive reduction in blood pressure.
Care must be taken in the combined use of the drug Capoten В®(without or with a diuretic), and drugs affecting the sympathetic nervous system (e.g., ganglionic, alpha-blockers).
When the joint application of the drug Capoten В®and indomethacin (and possibly other NSAIDs, such as acetylsalicylic acid) can be marked reduction in hypotensive action, especially in arterial hypertension accompanied by low activity of renin. In patients with risk factors (old age, hypovolemia, the simultaneous use of diuretics, renal failure) simultaneous use of NSAIDs (including COX-2 inhibitors) and ACE inhibitors (including captopril) can lead to a deterioration of renal function, up to acute renal failure. Typically, renal dysfunction in these cases are reversible. Periodically check renal function in patients taking the drug Capoten В® and NSAIDs.
When therapy with Capoten В®potassium-sparing diuretics (e.g., triamterene, spironolactone, amiloride), potassium supplements, potassium supplements, salt substitutes (contain significant amounts of potassium ions) should only be used when hypokalemia proven since their use increases the risk of hyperkalemia.
With simultaneous use of ACE inhibitors (especially in combination with a diuretic) and lithium preparations may increase lithium content in blood serum, and hence toxicity of drugs lithium. It periodically determine lithium content in the blood serum.
With simultaneous use of insulin and hypoglycemic agents for oral administration, such as derivatives of sulfonylureas, with ACE inhibitors, including CapotenВ®Perhaps an excessive fall in blood glucose levels. It is necessary to monitor blood glucose concentration at the beginning of therapy with Capoten В® and if necessary to adjust the dose of the hypoglycemic drug.
Dual RAAS blockade caused by simultaneous use of ACE and angiotensin II receptor antagonists or aliskiren and aliskirensoderzhaschih drugs was associated with increased incidence of side effects such as arterial hypotension inhibitors, hyperkalemia, decrease in renal function (including acute renal failure).
The use of the drug Capoten В® in patients treated with allopurinol or procainamide, increases the risk of neutropenia and / or Stevens-Johnson syndrome.
Use of the drug Capoten В® in patients receiving immunosuppressive drugs (e.g. azathioprine or tsiklofosfatsin) increases the risk of hematological disorders.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of the reach of children, dry place at a temperature not higher than 25 В° C. Shelf life - 5 years.