Composition, form of production and packaging
Tablets are white or white with a creamy shade of color, oval, biconvex, with a notch on one side and squeezed out the word "SQUIBB" and the numbers "50/25" on the other side, having a bevelled edge, with a sulphide-like odor; slight marmorage is allowed.
1 tab.
captopril 50 mg
hydrochlorothiazide 25 mg
Excipients: microcrystalline cellulose - 118.5 mg, pregelatinized starch (corn) - 30 mg, stearic acid - 6 mg, magnesium stearate - 0.3 mg, lactose - 70.2 mg.
14 pcs. - packings cellular planimetric (2) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Combined drug, has antihypertensive and diuretic effect.
Captopril is an ACE inhibitor. Reduces the formation of angiotensin II from angiotensin I, reduces the release of aldosterone. Reduces blood pressure, OPSS, afterload, preload. Expands arteries more than veins. 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 aggregation of platelets.
Hydrochlorothiazide - a thiazide diuretic of medium strength, reduces the reabsorption of sodium ions at the level of the cortical segment of the Henle loop. Does not affect the acid-base state. Reduces blood pressure by changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictors (epinephrine, norepinephrine) and increasing the depressor effect on autonomic ganglia (to a lesser extent, by reducing the bcc). Enhances the hypotensive effect of captopril.
Diuretic effect is observed after 2 hours and reaches a maximum after 4 hours after ingestion. The action lasts for 6-12 hours.
PHARMACOKINETICS
Captopril
When ingestion is rapidly absorbed from the gastrointestinal tract, C max in the blood plasma is observed about 1 hour after ingestion. Bioavailability of captopril is 60-70%. Simultaneous food intake slows the absorption of the drug by 30-40%. Binding to plasma proteins is 25-30%. Рў 1/2 2-3 hours. The drug is excreted from the body mainly by the kidneys, up to 50% unchanged, the rest - in the form of metabolites.
Hydrochlorothiazide
When ingested relatively quickly absorbed. T 1/2 in plasma is 2.5 h when taken on an empty stomach by healthy volunteers. It is excreted by the kidneys, 95% of the dose is unchanged.
INDICATIONS
- Arterial hypertension (patients who are shown combined therapy).
DOSING MODE
The drug is taken orally 1 tablet. 1 time / day. Tablets should be taken 1 hour before meals.
SIDE EFFECT
The frequency of adverse reactions is classified as follows: 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 tachyarrhythmia, chest pains, angina, palpitations, myocardial infarction, orthostatic hypotension, syncope, peripheral edema, excessive decrease in blood pressure, Raynaud's syndrome, "tides" of 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.
Allergic reactions: often - skin itching, with or without rashes, sometimes accompanied by fever and arthralgia, rashes on the skin; infrequently - vascular swelling of the skin and subcutaneous tissue; rarely - angioedema of the intestine; very rarely - urticaria, Stevens-Johnson syndrome, erythema multiforme, photosensitivity, erythroderma, reversible pemphigoid reactions, bullous pemphigus, exfoliative dermatitis, allergic alveolitis, eosinophilic pneumonia, angioedema, extremities, face, lips, mucous membranes, tongue, throat and larynx including those with a fatal outcome).
From the side of the central nervous system: often - drowsiness, dizziness; rarely - headache, ataxia, paresthesia; very rarely - confusion, depression, cerebral blood flow disorders, including stroke and syncope, blurred vision.
On the part of the hematopoiesis system: very rarely - neutropenia, agranulocytosis, pancytopenia, lymphadenopathy, eosinophilia, thrombocytopenia, anemia (including aplastic and hemolytic forms), increase of antinuclear antibody titers, 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; rarely - stomatitis, aphthous stomatitis, anorexia; very rarely - glossitis, stomach ulcer, pancreatitis, gingival hyperplasia, impaired liver function and cholestasis (including jaundice), increased activity of liver enzymes, hepatitis (including necrosis), and hyperbilirubinemia.
From the musculoskeletal system: very rarely - myalgia, arthralgia, myasthenia gravis.
From the urinary system: infrequently - violations of the kidneys (including kidney failure), polyuria, oliguria, frequent urination, nephrotic syndrome.
On the part of the reproductive system and breast: very rarely - impotence, gynecomastia.
Other: often - alopecia; infrequently - pain in the chest, increased fatigue, deterioration of well-being.
Laboratory indicators: often - eosinophilia; very rarely - proteinuria, hyperkalemia, hyponatremia (including symptomatic), increased urea nitrogen, bilirubin and creatinine in the blood, a decrease in hematocrit, a decrease in hemoglobin, leukocytes, platelets.
CONTRAINDICATIONS
- angionevrotichesky edema hereditary or idiopathic (in the anamnesis on the background of administration of ACE inhibitors);
stenosis of the aortic aperture;
- mitral stenosis;
- hypertrophic obstructive cardiomyopathy;
- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;
- condition after kidney transplantation;
- Chronic heart failure;
- cardiogenic shock;
- arterial hypotension;
- hepatic insufficiency of a serious degree (precomatous condition, hepatic coma);
- Severe renal insufficiency (serum creatinine> 1.8 mg / dl or KK <20-30 ml / min, anuria);
- primary hyperaldosteronism;
- simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or impaired renal function (GFR <60 ml / min);
- Pregnancy;
- the period of lactation (breastfeeding);
- age under 18 years (efficiency and safety not established);
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
- Hypersensitivity to the components of the drug, other ACE inhibitors, thiazide diuretics, sulfonamide derivatives (cross-allergic reactions possible).
With caution:
- violations of the liver, progressive liver disease;
- renal failure of moderate severity (CK 30-60 ml / min);
- proteinuria (more than 1 g / day),
- hypokalemia (not corrected by drugs);
- hyponatremia;
- hypovolemia;
- hypercalcemia;
- gout, hyperuricemia;
- systemic connective tissue diseases and other autoimmune diseases (including systemic lupus erythematosus, scleroderma, nodular periarteritis);
- Older age (over 65 years);
- simultaneous use of drugs that suppress the protective reactions of the body (glucocorticoids, cytotoxic drugs, immunosuppressants), allopurinol, procainamide;
- surgical intervention / general anesthesia;
- use of Negroid race in patients;
- hemodialysis using high-strength membranes (for example, AN69 В® );
- simultaneous desensitizing therapy;
- simultaneous use of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes;
- simultaneous use of lithium preparations;
- acute myopia and secondary closed angle glaucoma.
PREGNANCY AND LACTATION
The use of the drug Kapozid В® is contraindicated in pregnancy.
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 Kapozid 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 hydrochlorothiazide in pregnancy is not recommended because it can worsen perfusion of the placenta and cause fetal / newborn jaundice, thrombocytopenia, a disturbance of the water-electrolyte balance, and possibly other unwanted reactions observed in adults.
The use of ACE inhibitors in pregnancy can cause developmental disorders and fetal death. When establishing the fact of pregnancy, the use of the preparation Kapozid В® should be stopped as soon as possible.
Captopril and hydrochlorothiazide after ingestion of a breastfeeding woman are found in breast milk. Because of the risk of serious adverse reactions in the child caused by both active substances, breastfeeding should be discontinued or therapy with Capposid В® taken from the mother for the period of breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe renal insufficiency (serum creatinine> 1.8 mg / dl or KK <20-30 ml / min, anuria).
With caution should prescribe the drug for renal failure of moderate severity (KK 30-60 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in hepatic failure of severe degree (precomatosis, hepatic coma).
With caution should prescribe the drug for violations of liver function, progressive liver diseases.
APPLICATION FOR CHILDREN
The drug is contraindicated in children and adolescents under the age of 18 years.
APPLICATION IN ELDERLY PATIENTS
Caution should be used to appoint Capozid В® to elderly patients (over 65 years of age).
SPECIAL INSTRUCTIONS
At the beginning of treatment, there may be an excessive decrease in blood pressure, especially in patients with chronic heart failure, severe arterial hypertension (including renal genesis) and / or renal insufficiency. Before the start of treatment, it is necessary to compensate for the deficiency of sodium ions and to normalize BCC (to reduce the dose of previously prescribed diuretics or, in some cases, completely to cancel them), and to determine the indicators of kidney function.
Regular concentration of potassium and calcium in the blood serum is required (especially in patients receiving cardiac glycosides, glucocorticoids, often using laxatives, as well as in elderly patients), glucose, uric acid, lipids (cholesterol and triglycerides), urea and creatinine, hepatic enzymes.
Regular monitoring of blood pressure and laboratory indicators is especially necessary in the following cases: in patients with renal insufficiency; patients with arterial hypertension of severe course (including renal genesis); in elderly patients (over 65 years); in patients with disturbances of water-electrolyte balance and decompensated chronic renal insufficiency; as well as receiving simultaneously allopurinol, lithium salts, procainamide and drugs that reduce immunity.
With the use of ACE inhibitors, a characteristic non-productive cough is observed, which stops after the abolition of therapy with ACE inhibitors.
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 phenomenon is usually reversible, a decrease in the concentration of urea nitrogen and creatinine in the serum is observed after the drug is discontinued.
In some cases, with the use of ACE inhibitors, an increase in the serum potassium concentration is observed. The risk of hyperkalemia in the use of ACE inhibitors is increased in patients with renal insufficiency and diabetes mellitus, as well as taking potassium-sparing diuretics, potassium preparations or other drugs that cause an increase in the potassium concentration in the blood (for example, heparin). You should avoid the simultaneous use of potassium-sparing diuretics and potassium preparations. In addition, with the use of ACE inhibitors concomitantly with thiazide diuretics, the risk of hypokalemia is not ruled out, so in such cases regular monitoring of the potassium concentration in the blood during therapy should be carried out.
When hemodialysis in patients receiving ACE inhibitors, the use of dialysis membranes with high permeability (for example, AN69) should be avoided, since in such cases the risk of anaphylactoid reactions increases. Anaphylactoid reactions were also observed in patients who underwent apheresis procedure for LDL with dextran sulfate. Consideration should be given to the use of either antihypertensive drugs of another class, or another type of dialysis membrane.
In the case of angioedema, the drug is withdrawn and carefully monitored until the symptoms disappear completely. Angioneurotic edema of the larynx can lead to death. If the edema is localized on the face, special treatment is usually not required (to reduce the severity of symptoms, you can prescribe antihistamines); if the swelling spreads to the tongue, throat or larynx and there is a threat of developing airway obstruction, epinephrine (epinephrine) should be injected immediately (0.3-0.5 ml at 1: 1000 dilution). In rare cases, angiotoneurotic edema of the intestine was observed in patients after taking ACE inhibitors, which was accompanied by pains in the abdominal cavity (with or without nausea and vomiting), sometimes with normal values ​​of C1-esterase activity and without previous edema of the face.Bowel edema should be included in the spectrum of differential diagnosis in patients with complaints of abdominal pain while taking ACE inhibitors. Life-threatening anaphylactoid reactions were noted in two patients under the procedure of desensitization by Hymenoptera venom against the background of captopril administration.With the temporary withdrawal of the ACE inhibitor, the same patients managed to avoid anaphylactoid reactions. Care should be taken when carrying out desensitization in patients taking ACE inhibitors.
In patients with diabetes mellitus receiving hypoglycemic agents for ingestion or insulin, blood glucose concentration should be carefully monitored, especially during the first month of therapy with ACE inhibitors.
ACE inhibitors are less effective in representatives of the Negroid race than in patients of the European race, which may be due to the greater prevalence of low renin activity in representatives of the Negroid race.
In carrying out extensive surgical interventions or during anesthetic therapy, patients taking ACE inhibitors may experience an excessive BP reduction. In these cases, measures are taken to increase the BCC.
In rare cases, with the intake of ACE inhibitors, a syndrome begins with the appearance of cholestatic jaundice, which changes into lightning-fast hepatonecrosis, sometimes with a fatal 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 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.
The preparation Kapozid В® should be used very carefully in patients with autoimmune connective tissue diseases, in patients 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 control the number of 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 the start of therapy, then every 2 months. If the number of white blood cells is less than 4000 / Ојl, a repeated blood test is shown, if below 1000 / ОјL - the drug is stopped, while monitoring the patient. Usually, the recovery of the number of neutrophils occurs within 2 weeks after the withdrawal of captopril. In 13% of cases, neutropenia was 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 said factors.
With the use of ACE inhibitors can be marked proteinuria, mainly in patients with impaired renal function, as well as the use of drugs at high doses. In most cases, proteinuria disappeared with captopril 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 concentration of protein in the urine before treatment and periodically during the course of therapy.
Sulfonamide derivatives (including hydrochlorothiazide) may cause transient myopia and acute angle-closure glaucoma, the risk factors are allergic to penicillin or sulfonylurea drugs history. Symptoms (sudden decrease in visual acuity, pain in the eyeball) is generally observed in a few hours - a few weeks after starting treatment. If you have symptoms, stop taking the drug; if necessary, appoint preparations for intraocular pressure correction.
All patients taking thiazide diuretics should identify clinical signs of water and electrolyte balance (hyponatremia, alkalosis gipohloridny, hypokalemia). It is particularly important to determine the content of electrolytes in serum and urine during prolonged excessive vomiting when administered or infusion solutions. Signs of violations of water-electrolyte balance may be dry mouth, thirst, weakness, lethargy, confusion, anxiety, pain or muscle cramps, muscle weakness, excessive reduction of blood pressure, oliguria, tachycardia, nausea, vomiting.
Hypokalemia can cause or enhance the cardiotoxic action of cardiac glycosides.
A disadvantage of chlorine ions is usually mild and does not require correction.
In patients with edema in hot weather hyponatremia may occur due to an increase in BCC. Fluid intake should be limited. In cases of life-threatening hyponatremia administered sodium chloride solution.
During therapy, thiazide diuretics hyperuricemia may occur, or gout; It can also occur latently flowing diabetes.
Thiazide derivatives can cause a decrease bound iodine concentration in serum with no signs of thyroid disorders.
In patients receiving thiazide diuretics reduced degree of calcium excretion; there have been cases of pathological changes in the parathyroid gland, accompanied by hypercalcemia and hypophosphatemia. Before checking the function of the parathyroid glands to stop taking thiazide diuretics.
In patients receiving thiazide diuretics was an increase in the degree of excretion of magnesium, which can lead to hypomagnesemia.
Preparation Kapozid В® can cause false-positive reaction in the analysis of urine for ketones and distort test results with bentiromidom.
When fever, lymphadenopathy and / or development of symptoms of laryngitis and / or pharyngitis necessary to determine the number of cells immediately.
The use of thiazide diuretics may cause a positive result if the doping control.
Impact on the ability to drive vehicles and manage mechanisms
During the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE
Symptoms: sharp decrease in blood pressure, shock, stupor, bradycardia, disturbance of water and electrolyte balance, renal failure, lethargy (which may progress to coma within a few hours), not accompanied by a violation of water-electrolyte balance and cause only slight suppression of respiratory and cardiac function -sosudistoy systems. May experience irritation and increase the contractile activity of the gastrointestinal tract.
Treatment:measures for elimination of coma or stupor; gastric lavage, administration of adsorbents and sodium sulfate for 30 minutes after ingestion, administration of 0.9% sodium chloride or other plasma solutions hemodialysis. 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.
DRUG INTERACTION
Captopril
in patients receiving diuretics, especially early in therapy, and also in combination with strict limitation sodium intake (salt-free diet) or hemodialysis may sometimes occur an excessive decrease of blood pressure, which usually occurs within the first hour after the first scheduled dose Kapozid preparation В® . Should be monitored condition of the patient within 1 h after the first dose. If there is an excessive reduction in blood pressure, the patient should be translated in a horizontal position with a low headboard and enter / in 0.9% sodium chloride solution if needed. Transient excessive reduction of blood pressure is not a contraindication to further treatment, which may continue after the normalization of blood pressure by increasing the BCC.
Vasodilators (e.g., nitroglycerin) in combination with a preparation Kapozid В® should be used in the lowest effective doses because of the risk of excessive reduction in blood pressure.
Caution must be exercised when using the drug co Kapozid В® and drugs affecting the sympathetic nervous system (e.g., ganglionic, alpha-blockers).
In therapy preparations containing captopril, 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.
The drug KapozidВ® increases the concentration of digoxin in plasma is 15-20%, increases the bioavailability of propranolol.
The risk of immunosuppressive action is increased by the combined use with procainamide, and drugs that block tubular secretion (reducing the number of leukocytes and granulocytes).
Increases neurotoxicity salicylates, enhances the action of non-depolarizing muscle relaxants such as a competitive action of ethanol.
Decreases excretion quinidine, reduces the effect of hypoglycemic drugs for oral administration, norepinephrine, epinephrine and protivopodagricakih preparations.
It increases the side effects of cardiac glycosides, especially with concomitant administration with drugs that increase the excretion of potassium and magnesium ions and / or delay of calcium ions (e.g., diuretics, adrenocortical hormones, laxatives, amphotericin B, carbenoxolone, penicillin G, salicylates).
Dual RAAS blockade caused by simultaneous use of ACE and angiotensin II receptor blockers 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).
Cimetidine, captopril slowing metabolism in the liver, increases its concentration in plasma.
hydrochlorothiazide
Indomethacin, and other NSAIDs, including COX-2 inhibitors and salt can reduce the antihypertensive effect of the drug, especially in arterial hypertension accompanied by low activity of renin, as well as reduce the absorbability of hydrochlorothiazide. In patients with risk factors (old age, hypovolemia, 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 Kapozid В® and NSAIDs.
Hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants, agents for a general anesthetic used in surgery (e.g. tubocurarine chloride and gallamine triethiodide) and may require dose adjustments of these medications. Recommended monitoring and possible correction of fluid and electrolyte balance before surgery.
Hydrochlorothiazide reduces the effect is applied for therapeutic purposes pressor amines (e.g., norepinephrine) in respect of the arteries, but not completely prevent it.
Anesthetic and means for premedication should be applied at as low doses as possible. If possible, hydrochlorothiazide should be discontinued one week prior to surgery.
The combination with nitrates, thiazide diuretics, verapamil, beta-blockers and other antihypertensive drugs, MAO inhibitors, ganglioblokatorami, and tricyclic antidepressants, hypnotics and ethanol increases the severity of the hypotensive effect.
With simultaneous use of the ACE inhibitor with drugs lithium deceleration can take place removal of lithium ions, increase the concentration of lithium in blood serum and, as a consequence, increasing the damaging effect on the heart and CNS. Also, hydrochlorothiazide Lithium also increases the risk of toxicity. In applying such a combination therapy should be regularly monitored lithium concentrations in serum.
Drugs that bind to the protein rapidly, increase the diuretic effect. It may require correction dose anticoagulants, probenecid and sulfinpyrazone as hydrochlorothiazide can inhibit their action.
Hyperuricemic effect of hydrochlorothiazide exhibits, however may require correction antiurikozuricheskih preparations while the application.
Diazoxide amplifies hyperglycemic, hyperuricemic and antihypertensive effect of thiazide diuretics, however should control the concentration of uric acid and glucose in serum.
With simultaneous use of hypoglycemic agents for oral administration may require insulin and an increase in their doses, because hydrochlorothiazide increases the concentration of glucose in the blood.
With simultaneous use of methyldopa may develop haemolysis of red blood cells.
Cholestyramine and colestipol hydrochloride can delay or reduce the absorption of hydrochlorothiazide.
Potassium salts, potassium-sparing diuretics (triamterene, amiloride and spironolactone) and heparin contribute to the development of hyperkalemia.
Methenamine can reduce the effect of hydrochlorothiazide due to raise the pH of urine.
Carbamazepine increases the risk of symptomatic hyponatremia during concomitant use with hydrochlorothiazide.
The combined application of calcium salts and thiazides in serum calcium concentration may be increased due to the slowing its excretion. Necessary to monitor the concentration of calcium in the blood serum and correction of the dose if necessary.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.
