Possibilities of using a new generation of centrally acting drugs in the treatment of arterial hypertension

pharmachologic effect

Capozide is a diuretic and antihypertensive drug .

Hydrochlorothiazide , which is part of the drug, is a thiazide diuretic of moderate potency and is capable of reducing the reabsorption of sodium neons at the level of the cortical segment of the loop of Henlev. Lowers blood pressure by changing the reactivity of the vascular wall, reducing the pressor effect of substances with a vasoconstrictor effect ( norepinephrine and epinephrine ) and increasing the depressor effect on the autonomic ganglia. Does not affect the acid-base state.

Captopril is an ACE inhibitor and reduces the release of aldosterone and the formation of angiotensin I and angiotensin II. It has an enhancing effect on renal and coronary blood flow, and also reduces blood pressure, preload, and afterload. Arteries dilate to a greater extent than veins. Long-term use reduces platelet aggregation, increases blood supply to ischemic myocardium, and reduces the severity of hypertrophy of arterial walls and resistive myocardium.

Contraindications

Capozide should not be taken if:

• hypersensitivity to the contents of tablets, sulfonamide , thiazide diuretics;
• under 18 years of age;
• pregnancy and lactation ;
• primary hyperaldosteronism ;
• severe disturbances in kidney function;
• severe liver disorders ( hepatic coma , precomatose state);
• tachycardia;
• arterial hypotension;
• cardiogenic shock;
• chronic heart failure ;
• condition after renal transplantation;
• stenosis of the artery of a single kidney or bilateral stenosis of the renal arteries;
• hypertrophic obstructive cardiomyopathy ;
• mitral stenosis ;
• aortic stenosis ;
• angioedema (history of taking ACE inhibitors).

Should be used with caution when:

• simultaneous administration of lithium, procainamide, allopurinol, immunosuppressants, cytostatics, corticosteroids;
• old age (over 65 years);
• periarteritis nodosa , scleroderma and SLE ;
• collagenosis , gout , hypercalcemia , hypovolemia , hyponatremia , hypokalemia , proteinuria ;
• moderate renal dysfunction.

Capozid®

The drug Capozide should not be used to relieve a hypertensive crisis. The use of the drug Capozide in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use.

Hydrochlorothiazide

Renal dysfunction

In patients with impaired renal function, hydrochlorothiazide may cause azotemia. In case of renal failure, accumulation of hydrochlorothiazide is possible.

In patients with reduced renal function, periodic monitoring of creatinine clearance is necessary. If renal dysfunction progresses and/or oliguria (anuria) occurs, the drug Capozide should be discontinued.

Liver dysfunction

When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. In patients with severe liver failure or hepatic encephalopathy, the use of thiazides is contraindicated. In patients with mild to moderate hepatic impairment and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even slight changes in fluid and electrolyte balance and serum ammonium accumulation can cause hepatic coma. If symptoms of encephalopathy occur, the drug Capozide should be stopped immediately.

Water-electrolyte balance and metabolic disorders

Thiazide diuretics (including hydrochlorothiazide) can cause a decrease in the volume of circulating fluid (hypovolemia) and disturbances in water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of fluid and electrolyte imbalance are dry mouth, thirst, weakness, lethargy, fatigue, drowsiness, restlessness, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia and gastrointestinal disorders (such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with long-term course treatment), clinical symptoms of water-electrolyte imbalance should be identified and blood electrolyte levels should be regularly monitored.

Sodium

All diuretics can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in chlorine ions can lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine the content of sodium ions in the blood plasma before starting treatment and regularly monitor this indicator while taking drugs containing hydrochlorothiazide.

Potassium

When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in the potassium content in the blood plasma and the development of hypokalemia (potassium concentration less than 3.4 mmol/l). Hypokalemia increases the risk of developing heart rhythm disturbances (including severe arrhythmias) and enhances the toxic effect of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic ventricular tachycardia of the torsade de pointes type, which can be fatal.

Hypokalemia poses the greatest danger to the following groups of patients: elderly people, patients simultaneously receiving therapy with antiarrhythmic and non-antiarrhythmic drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type or increase the duration of the QT interval on the ECG, patients with impaired liver function, coronary heart disease , chronic heart failure. In addition, patients with an increased QT interval are at increased risk. It does not matter whether this increase is caused by congenital causes or the effect of drugs.

In all the cases described above, it is necessary to avoid the risk of developing hypokalemia and regularly monitor the potassium content in the blood plasma. The first measurement of the content of potassium ions in the blood must be carried out within the first week from the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia can be corrected by using potassium-containing medications or eating foods rich in potassium (dried fruits, fruits, vegetables).

Calcium

Thiazide diuretics may reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in plasma calcium levels. In some patients, with long-term use of thiazide diuretics, pathological changes in the parathyroid glands were observed with hypercalcemia and hyperphosphatemia, but without the typical complications of hyperparathyroidism (nephrolithiasis, decreased bone mineral density, peptic ulcer). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism.

Because of their effect on calcium metabolism, thiazides may interfere with laboratory parameters of parathyroid function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued before testing parathyroid function.

Magnesium

Thiazides have been found to increase renal excretion of magnesium, which can lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.

Glucose

Treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with manifest or latent diabetes mellitus, it is necessary to regularly monitor the concentration of glucose in the blood. Dosage adjustment of hypoglycemic medications may be required.

Uric acid

In patients with gout, the frequency of attacks may increase or the course of gout may worsen. Careful monitoring of patients with gout and impaired uric acid metabolism (hyperuricemia) is necessary.

Lipids

When using hydrochlorothiazide, the concentration of cholesterol and triglycerides in the blood plasma may increase.

Acute myopia/secondary angle-closure glaucoma

Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include: sudden loss of visual acuity or eye pain, usually occurring within hours to weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to irreversible vision loss. If symptoms appear, you should stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma are: a history of an allergic reaction to sulfonamides or penicillin.

Immune system disorders

There are reports that thiazide diuretics (including hydrochlorothiazide) may cause exacerbation or progression of systemic lupus erythematosus, as well as lupus-like reactions.

In patients receiving thiazide diuretics, hypersensitivity reactions may occur even in the absence of a history of allergic reactions or bronchial asthma.

Photosensitivity

There is information about cases of the development of photosensitivity reactions when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued. If continued use of the diuretic is necessary, the skin should be protected from exposure to sunlight or artificial ultraviolet rays.

Athletes

Hydrochlorothiazide may give a positive result during doping control in athletes.

Other

In patients with severe atherosclerosis of the cerebral and coronary arteries, hydrochlorothiazide should be used with extreme caution.

Thiazide diuretics can reduce the amount of iodine bound to plasma proteins without causing signs of thyroid dysfunction.

Non-melanoma skin cancer

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of nonmelanoma skin cancer (NMSC) basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide.

Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.

Any suspicious skin changes should be reported to your doctor immediately. Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment.

In patients with a history of non-melanoma skin cancer, it is recommended to reconsider the use of hydrochlorothiazide.

Captopril

Arterial hypotension

In patients with arterial hypertension, when using captopril, severe arterial hypotension is observed only in rare cases. The likelihood of developing this condition increases with increased fluid loss and hyponatremia (for example, after intensive treatment with diuretics, restriction of sodium intake, in patients on dialysis, and in patients with diarrhea or vomiting).

Captopril should be prescribed with caution to patients on a low-salt or salt-free diet. Circulating blood volume and blood sodium levels should be adjusted before captopril is prescribed. The possibility of a sharp decrease in blood pressure can be minimized by first withdrawing (4-7 days before) the diuretic or increasing sodium chloride intake (about a week before starting treatment), or by prescribing low doses of captopril at the beginning of treatment (6.25-12 .5 mg/day). Renal function should be regularly monitored before and during treatment with captopril.

Excessive reduction in blood pressure due to antihypertensive medications may increase the risk of myocardial infarction or stroke in patients with coronary heart disease or cerebrovascular disease. If arterial hypotension develops, the patient should take a horizontal position with legs elevated. Intravenous administration of 0.9% sodium chloride solution may be required.

Aortic or mitral stenosis/hypertrophic obstructive cardiomyopathy

Like all drugs that have a vasodilating effect, ACE inhibitors should be used with extreme caution in patients with left ventricular outflow tract obstruction. In case of hemodynamically significant obstruction, the use of captopril is not recommended.

Renal dysfunction

Some patients with kidney disease, especially those with severe renal artery stenosis, experience increases in serum urea nitrogen and creatinine concentrations after lowering blood pressure. This increase is usually reversible when captopril therapy is discontinued. In these cases, it may be necessary to reduce the dose of captopril and/or discontinue the diuretic.

With long-term use of captopril, approximately 20% of patients experience an increase in serum urea and creatinine concentrations by more than 20% compared with normal or baseline values.

In less than 5% of patients, especially with severe nephropathy, treatment discontinuation is required due to an increase in creatinine concentration.

Renovascular hypertension

Patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney have an increased risk of developing arterial hypotension and renal failure when using ACE inhibitors. Renal failure may initially manifest itself as only slight changes in plasma creatinine levels. The use of captopril in such patients is not recommended.

Kidney transplant

There is no experience with the use of captopril in patients who have recently undergone transplantation. Therefore, the use of captopril in such patients is not recommended.

Proteinuria

When using captopril, 0.7% of patients had proteinuria more than 1000 mg per day. In 90% of cases, proteinuria occurred in patients with impaired renal function, as well as when using high doses of captopril (more than 150 mg per day). Approximately 20% of patients with proteinuria developed nephrotic syndrome. In most cases, proteinuria disappeared or decreased in severity after taking captopril within 6 months, regardless of whether the drug was stopped or not. Renal function tests (blood urea nitrogen and creatinine concentrations) in patients with proteinuria were almost always within normal limits. In patients with kidney disease, the protein content in the urine should be determined before starting treatment and periodically throughout the course of therapy.

Liver dysfunction

In rare cases, the use of ACE inhibitors has been accompanied by the development of a syndrome that begins with the appearance of cholestatic jaundice or hepatitis and progresses to fulminant liver necrosis, sometimes with death. The mechanism of development of this syndrome is unknown. If a patient receiving ACE inhibitor therapy develops jaundice or a significant increase in liver enzyme activity, captopril treatment should be discontinued and appropriate adjuvant therapy should be instituted. The patient should be under appropriate supervision.

Neutropenia/agranulocytosis/thrombocytopenia/anemia

Cases of neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients taking ACE inhibitors. In patients with normal renal function and in the absence of other disorders, neutropenia is rare. In renal failure, simultaneous administration of captopril and allopurinol led to neutropenia.

Captopril should be used with extreme caution in patients with systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc.) taking immunosuppressants, allopurinol or procainamide, or a combination of these complicating factors, especially if there are pre-existing renal dysfunction.

In 13% of cases with neutropenia, death was observed. In almost all cases, death was observed in patients with connective tissue diseases, renal or heart failure, while taking immunosuppressants, or a combination of both of these factors.

Due to the fact that the majority of fatal cases of neutropenia due to ACE inhibitors developed in such patients, their white blood cell count should be monitored before starting treatment, in the first 3 months - every 2 weeks, then every 2 months. In all patients, the white blood cell count should be monitored monthly for the first 3 months after starting captopril therapy, then every 2 months. If the number of leukocytes is below 4000/μl, a repeat general blood test is indicated; below 1000/μl, the drug is stopped while monitoring the patient continues. Typically, restoration of the number of neutrophils occurs within 2 weeks after discontinuation of captopril.

Some patients developed serious infectious diseases, which in some cases did not respond to intensive antibiotic therapy. When using captopril in patients with a high risk of neutropenia/agranulocytosis, regular monitoring of the number of leukocytes in the blood is recommended. Patients should be warned to seek immediate medical attention if any signs of an infectious disease (eg, fever, sore throat) occur.

Hypersensitivity reactions/angioedema

Rare cases of angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx have been observed with the use of ACE inhibitors, including captopril.

Angioedema may develop at any time during treatment.

If angioedema develops, you should immediately stop taking captopril and carefully monitor the patient's condition until symptoms disappear completely.

If the swelling is localized to the face, no special treatment is usually required (antihistamines can be used to reduce the severity of symptoms). Even in cases where only swelling of the tongue is observed without the development of respiratory distress syndrome, patients may require long-term observation, since therapy with antihistamines and corticosteroids may not be sufficient.

Angioedema, associated with swelling of the larynx and tongue, can be fatal in very rare cases. If the swelling spreads to the tongue, pharynx or larynx and there is a threat of developing airway obstruction, 0.3-0.5 ml of a 0.1% solution of epinephrine (adrenaline) should be immediately administered subcutaneously and/or ensure airway patency ( intubation or tracheostomy).

In rare cases, during therapy with ACE inhibitors, intestinal edema (angioedema of the intestines) has developed, which is manifested by abdominal pain in combination with or without nausea and vomiting, sometimes without previous angioedema of the face and with normal Cl-esterase levels. Diagnosis is made using abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after stopping the ACE inhibitors. The possibility of developing intestinal edema must be taken into account when carrying out the differential diagnosis of abdominal pain in patients taking ACE inhibitors.

Patients with a history of angioedema not associated with ACE inhibitors may be at greater risk of developing angioedema during ACE inhibitor therapy.

In representatives of the Negroid race, cases of the development of angioedema when using ACE inhibitors were observed with a higher frequency compared to representatives of other races.

An increased risk of developing angioneurotic edema was observed in patients simultaneously taking ACE inhibitors and drugs such as mTOR inhibitors (temsirolimus, sirolimus, everolimus), dipeptidyl peptidase type IV inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin), estramustine, neutral endopeptidase inhibitors ( racecadotril, sacubitril) and tissue plasminogen activators.

Anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom

In rare cases, during therapy with ACE inhibitors, life-threatening anaphylactoid reactions were observed in patients undergoing desensitization with an allergen from the venom of Hymenoptera. In such patients, these reactions were prevented by temporarily stopping ACE inhibitor therapy before desensitization began. The use of captopril should be avoided in patients receiving bee venom immunotherapy.

Anaphylactoid reactions during low-density lipoprotein apheresis (LDL apheresis)

Life-threatening anaphylactoid reactions have rarely been observed in patients taking ACE inhibitors during LDL apheresis using dextran sulfate. The development of these reactions can be prevented by temporarily discontinuing the ACE inhibitor before each LDL apheresis procedure.

Hemodialysis using high-flow membranes

When performing hemodialysis in patients receiving ACE inhibitors, the use of high-flow polyacrylonitrile dialysis membranes (for example, AN69®) should be avoided, since in such cases the risk of developing anaphylactoid reactions increases. In such cases, it is necessary to use a different type of dialysis membrane or use antihypertensive drugs of other classes.

Diabetes

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored while using ACE inhibitors.

Patients taking oral hypoglycemic agents or insulin should be informed before starting the use of ACE inhibitors of the need to regularly monitor blood glucose concentrations (hypoglycemia), especially during the first month of simultaneous use of these drugs.

Cough

When taking ACE inhibitors, a characteristic cough is often observed. As a rule, the cough is non-productive, constant and stops after discontinuation of the drug. Cough associated with the use of ACE inhibitors should be considered in the differential diagnosis of dry cough.

Surgery/general anesthesia

During major surgical operations, as well as when using general anesthesia agents that have an antihypertensive effect, patients taking ACE inhibitors may experience an excessive decrease in blood pressure (since captopril blocks the formation of angiotensin II, caused by compensatory release of renin). In such cases, to correct low blood pressure, measures aimed at increasing the volume of circulating blood are used.

Hyperkalemia

In some cases, against the background of the use of ACE inhibitors, incl. captopril, an increase in serum potassium levels is observed.

Risk factors for the development of hyperkalemia are renal failure, old age (over 65 years), diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene or amiloride), as well as potassium preparations, potassium-containing table salt substitutes and other drugs that increase the level of potassium in the blood plasma (such as heparin, tacrolimus, cyclosporine; drugs containing co-trimoxazole [trimethoprim + sulfamethoxazole]).

The use of potassium supplements, potassium-sparing diuretics, or potassium-containing table salt substitutes, especially in patients with impaired renal function, can lead to a significant increase in serum potassium levels. Hyperkalemia can cause serious heart rhythm disturbances, sometimes fatal. It is recommended to avoid the simultaneous use of potassium-sparing diuretics and potassium supplements. If simultaneous use of captopril and the above-listed potassium-containing or potassium-increasing drugs in the blood plasma is necessary, caution should be exercised and the potassium content in the blood serum should be regularly monitored.

Hypokalemia

When using AIF inhibitors simultaneously with thiazide diuretics, the risk of hypokalemia cannot be excluded. Therefore, in such cases, regular monitoring of potassium levels in the blood should be carried out during therapy.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

The simultaneous use of drugs from different groups that act on the RAAS is not recommended (double blockade of the RAAS), since it has been associated with an increased incidence of side effects such as arterial hypotension, hyperkalemia, and decreased renal function (including acute renal failure).

The simultaneous use of ACE inhibitors with medicinal products containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. Concomitant use of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

In cases where the simultaneous administration of two drugs acting on the RAAS is necessary, their use should be carried out under the supervision of a physician with extreme caution and with regular monitoring of renal function, blood pressure and electrolyte levels in the blood plasma.

The simultaneous use of captopril and drugs containing lithium is not recommended due to the risk of potentiating the toxicity of the latter.

Ethnic differences

ACE inhibitors are less effective in blacks than in Caucasians, which may be due to the higher prevalence of low renin activity in blacks.

Other

When taking captopril, a false-positive urine test for acetone may occur.

Side effects

Side effects are as follows:

• Miscellaneous: progression of myopia , impotence.
• Metabolism: hyperuricemia , hyperglycemia , hyperlipidemia , hypermagnesemia.
• Urinary system: pollakiuria , glucosuria , oliguria , polyuria , proteinuria , in rare cases - hyponatremia , increased levels of potassium, creatinine and urea ions in the blood serum, with prolonged use - nephritis and impaired renal function.
• Hematopoietic system: increased titer of antinuclear antibodies, eosinophilia , neutropenia , leukopenia , thrombocytopenia , decreased hematocrit, anemia (including hemolytic and aplastic forms).
• Central and peripheral nervous systems: paresthesia , tremor , blurred vision, tinnitus, dizziness , ataxia , convulsions , sleep disturbances , depression , weakness , drowsiness , depression , fatigue and headache.
• Digestive system: hyperbilirubinemia , increased activity of liver transaminases, cholestatic jaundice , hepatitis , hemorrhagic pancreatitis , acute cholecystitis , decreased appetite, abdominal pain, epigastric discomfort, diarrhea or constipation , nausea and vomiting , with prolonged use - taste disturbance and gum hyperplasia .
• Dermatology: toxic epidermal necrolysis ( Lyell's syndrome ), Stevens-Johnson syndrome , exfoliative dermatitis erythema multiforme , exanthema (skin rash). These skin changes may be accompanied by the development of vasculitis , pain in the joints and muscles, and a rise in temperature. In rare cases onycholysis , alopecia , photosensitivity , and psoriasis-like skin changes are possible.
• Allergic reactions: angioedema of the tongue and/or pharynx, larynx, mucous membranes, lips, face and limbs, in rare cases - urticaria.
• Respiratory system: laryngitis , rhinitis , sinusitis , respiratory failure , dry cough , bronchospasm.
• Water-electrolyte metabolism: thirst , dry mouth, in rare cases – decreased formation of tear fluid.
• Cardiovascular system: severe arterial hypotension with symptoms of weakness and dizziness , swelling of the legs, palpitations, tachycardia , headache , dizziness , feeling of heat, “flushes” of blood to the skin of the face.

Capozide

Use during pregnancy and breastfeeding

The use of Kaposide® is contraindicated during pregnancy.
Epidemiological data demonstrating a risk of teratogenicity after exposure to ACE inhibitors in the first trimester of pregnancy have not been convincing, but some increased risk cannot be excluded. If the use of an ACE inhibitor is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive therapy that has an established safety profile for use in pregnancy. It is known that long-term exposure of the fetus to ACE inhibitors in the second and third trimesters of pregnancy can lead to disruption of its development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (such as renal failure, arterial hypotension, hyperkalemia) . If the patient received the drug Capozide® in the second and third trimesters of pregnancy, it is recommended to conduct an ultrasound examination to assess the condition of the skull bones and fetal kidney function.

The use of hydrochlorothiazide during pregnancy is not recommended as it may impair placental perfusion and cause fetal/neonatal jaundice, thrombocytopenia, fluid and electrolyte imbalance and possibly other adverse reactions observed in adults.

The use of ACE inhibitors during pregnancy can cause developmental disorders and fetal death. If pregnancy is established, the use of the drug Capozide should be discontinued as soon as possible.

Captopril and hydrochlorothiazide are found in breast milk after oral administration by a nursing woman. Due to the risk of serious adverse reactions in the child caused by both active substances, breastfeeding should be stopped or therapy with Capozide® should be discontinued in the mother during the period of breastfeeding.

Use for liver dysfunction

Contraindicated in severe liver failure (precomatose state, hepatic coma).

The drug should be prescribed with caution in case of liver dysfunction or progressive liver diseases.

Use for renal impairment

Contraindicated in severe renal failure (serum creatinine >1.8 mg/dL or creatinine clearance <20-30 ml/min, anuria).

The drug should be prescribed with caution in case of moderate renal failure (creatinine clearance 30-60 ml/min).

Use in children

The drug is contraindicated in children and adolescents under 18 years of age.

special instructions

At the beginning of treatment, an excessive decrease in blood pressure may be observed, especially in patients with chronic heart failure, severe arterial hypertension (including renal origin) and/or renal failure. Before starting treatment, it is necessary to compensate for the deficiency of sodium ions and normalize the blood volume (reduce the dose of previously prescribed diuretics or, in some cases, completely cancel them), and also determine indicators of kidney function.

Regular monitoring of the concentration of potassium and calcium in the blood serum is necessary (especially in patients receiving treatment with cardiac glycosides, glucocorticoids, often using laxatives, as well as in elderly patients), glucose, uric acid, lipids (cholesterol and triglycerides), urea and creatinine, activity liver enzymes.

Regular monitoring of blood pressure and laboratory parameters is especially necessary in the following cases: in patients with renal failure; patients with severe arterial hypertension (including renal origin); in elderly patients (over 65 years old); in patients with water-electrolyte imbalance and decompensated chronic renal failure; as well as those receiving simultaneously allopurinol, lithium salts, procainamide and drugs that reduce immunity.

When using ACE inhibitors, a characteristic non-productive cough is observed, which ceases after discontinuation of ACE inhibitor therapy.

Some patients with kidney disease, especially those with severe renal artery stenosis, experience increases in serum urea nitrogen and creatinine concentrations after lowering blood pressure. This phenomenon is usually reversible; a decrease in the concentration of urea nitrogen and creatinine in the blood serum is observed after discontinuation of the drug.

In some cases, during the use of ACE inhibitors, an increase in the concentration of potassium in the blood serum is observed. The risk of developing hyperkalemia when using ACE inhibitors is increased in patients with renal failure and diabetes mellitus, as well as those taking potassium-sparing diuretics, potassium supplements or other drugs that cause an increase in the concentration of potassium in the blood (for example, heparin). The simultaneous use of potassium-sparing diuretics and potassium supplements should be avoided. In addition, when using ACE inhibitors simultaneously with thiazide diuretics, the risk of hypokalemia cannot be excluded, therefore, in such cases, regular monitoring of potassium concentrations in the blood during therapy should be carried out.

When performing hemodialysis in patients receiving ACE inhibitors, the use of high-permeability dialysis membranes (for example, AN69) should be avoided, as in such cases the risk of developing anaphylactoid reactions increases. Anaphylactoid reactions have also been observed in patients undergoing LDL apheresis with dextran sulfate. The use of either a different class of antihypertensive drugs or a different type of dialysis membrane should be considered.

If angioedema develops, the drug is discontinued and careful medical observation is carried out until the symptoms disappear completely. Angioedema of the larynx can be fatal. If the swelling is localized on the face, special treatment is usually not required (antihistamines can be prescribed to reduce the severity of symptoms); if the swelling spreads to the tongue, pharynx or larynx and there is a threat of developing airway obstruction, epinephrine (adrenaline) should be immediately administered subcutaneously (0.3-0.5 ml in a dilution of 1:1000). In rare cases, patients after taking ACE inhibitors experienced angioedema of the intestine, which was accompanied by abdominal pain (with or without nausea and vomiting), sometimes with normal values ​​of C1-esterase activity and without previous facial edema. Intestinal edema should be included in the differential diagnosis in patients complaining of abdominal pain while taking ACE inhibitors. In two patients undergoing desensitization with hymenoptera venom, life-threatening anaphylactoid reactions were noted while taking captopril. When the ACE inhibitor was temporarily discontinued in the same patients, anaphylactoid reactions were avoided. Caution should be exercised when performing desensitization in patients taking ACE inhibitors.

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be carefully monitored, especially during the first month of ACE inhibitor therapy.

ACE inhibitors are less effective in blacks than in Caucasians, which may be due to the higher prevalence of low renin activity in blacks.

During major surgery or during anesthetic therapy, patients taking ACE inhibitors may experience an excessive decrease in blood pressure. In these cases, measures are taken to increase the BCC.

In rare cases, when taking ACE inhibitors, a syndrome is observed that begins with the appearance of cholestatic jaundice, progressing to fulminant 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 liver enzymes, treatment with ACE inhibitors should be discontinued and the patient should be monitored.

Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients taking ACE inhibitors. Neutropenia is rare in patients with normal renal function and no other abnormalities.

The drug Capozide® should be used very carefully in patients with autoimmune connective tissue diseases, in patients taking immunosuppressants, allopurinol and procainamide, especially in the presence of pre-existing renal dysfunction. Due to the fact that the majority of fatal cases of neutropenia during the use of ACE inhibitors developed in such patients, their leukocyte count should be monitored before starting treatment, in the first 3 months - every 2 weeks, then every 2 months.

In all patients, the number of leukocytes in the blood should be monitored monthly in the first 3 months after starting therapy, then every 2 months. If the number of leukocytes is below 4000/μl, a repeat general blood test is indicated; if below 1000/μl, the drug is stopped while monitoring the patient continues. Typically, recovery in neutrophil numbers occurs within 2 weeks after discontinuation of captopril. In 13% of cases of neutropenia, death was noted. In almost all cases, fatal neutropenia was observed in patients with connective tissue diseases, renal or heart failure, while taking immunosuppressive drugs, or a combination of these factors.

When using ACE inhibitors, proteinuria may occur, mainly in patients with impaired renal function, as well as when using drugs in high doses. In most cases, proteinuria disappeared or decreased in severity after taking captopril within 6 months, regardless of whether the drug was stopped or not. Renal function tests (blood urea nitrogen and creatinine concentrations) in patients with proteinuria were almost always within normal limits. In patients with kidney disease, the concentration of protein in the urine should be determined before starting treatment and periodically throughout the course of therapy.

Sulfonamide derivatives (including hydrochlorothiazide) can cause transient myopia and acute angle-closure glaucoma, risk factors include a history of allergy to sulfonylureas or penicillin. Symptoms (sharp decrease in visual acuity, pain in the eyeball) are usually observed within a few hours to several weeks after the start of treatment. If symptoms appear, you should immediately stop taking the drug; If necessary, medications to correct intraocular pressure should be prescribed.

In all patients taking thiazide diuretics, clinical signs of fluid and electrolyte imbalance (hyponatremia, hypochloride alkalosis, hypokalemia) should be identified. It is especially important to determine the content of electrolytes in the blood serum and urine during excessive prolonged vomiting or during the administration of infusion solutions. Signs of water and electrolyte imbalance may include dry mouth, thirst, weakness, lethargy, confusion, anxiety, muscle pain or cramps, muscle weakness, excessive decrease in blood pressure, oliguria, tachycardia, nausea, vomiting.

Hypokalemia can provoke or enhance the cardiotoxic effect of cardiac glycosides.

The deficiency of chlorine ions is usually mild and does not require correction.

Patients with edema in hot weather may experience hyponatremia caused by an increase in blood volume. Liquid intake should be limited. In cases of life-threatening hyponatremia, sodium chloride solution is prescribed.

Hyperuricemia or gout attacks may occur during therapy with thiazide diuretics; Latent diabetes mellitus may also manifest itself.

Thiazide derivatives can cause a decrease in the concentration of bound iodine in the blood serum without signs of thyroid dysfunction.

While taking thiazide diuretics, the degree of calcium excretion decreases; There have been cases of pathological changes in the parathyroid glands, accompanied by hypercalcemia and hypophosphatemia. Before monitoring parathyroid function, the thiazide diuretic should be discontinued.

While taking thiazide diuretics, there was an increase in the degree of magnesium excretion, which can lead to hypomagnesemia.

The drug Capozide® may cause a false-positive reaction when testing urine for ketone bodies and distort the results of the test with bentiromide.

If fever appears, swollen lymph nodes and/or signs of laryngitis and/or pharyngitis develop, the white blood cell count must be immediately determined.

The use of thiazide diuretics may cause a positive result during doping control.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Interaction

Methenamine sometimes reduces the effects of hydrochlorothiazide by making the urine more alkaline.

Concomitant use with heparin , potassium-sparing diuretics ( Spironolactone, Amiloride and Triateren ) and potassium salts causes the development of hyperkalemia .

Colestipol hydrochloride and cholestyramine delay or reduce the absorption of hydrochlorothiazide.

Concomitant use with Methyldopa leads to the development of hemolysis of red blood cells; with diazoxide increases the antihypertensive, hyperuricemic and hyperglycemic effects of hydrochlorothiazide; with Indomethacin , COX inhibitors and table salt reduces the antihypertensive effect of the drug and reduces the absorption of hydrochlorothiazide.

Simultaneous use with drugs that intensively bind to proteins enhances the diuretic effect; lithium preparations slow down the excretion of lithium ions, which increases the damaging effect on the central nervous system and heart; ethanol , hypnotics , tricyclic antidepressants , ganglion blockers , MAO inhibitors , beta-blockers , Verapamil , thiazide diuretics , nitrates increases the hypotensive effect.

Hydrochlorothiazide enhances the effect of drugs for initiating anesthetics and anesthesia, which are used in surgical practice ( gallamin triethiodide , tubocurarine chloride ).

Cimetidine slows down the metabolism of captopril in the liver, thereby increasing its plasma levels.

The drug increases the side effects of cardiac glycosides, especially when administered simultaneously with salicylates , penicillin G , carbenoxolone , amphotericin B , laxatives, adrenal hormones and diuretics; reduces the effect of anti-gout drugs, epinephrine, norepinephrine, oral hypoglycemic drugs, reduces the excretion of quinidine.

Capozide increases plasma digoxin of propranolol .

Capozide tablets 50mg/25mg No. 28

pharmachologic effect
The combined drug has a hypotensive and diuretic effect. Captopril is an ACE inhibitor, reduces the formation of angiotensin II from angiotensin I, reduces the release of aldosterone, reduces peripheral vascular resistance, blood pressure, post- and preload. Dilates arteries more than veins. Strengthens coronary and renal blood flow. With long-term use, hypertrophy of the myocardium and the walls of resistive arteries decreases; improves blood supply to ischemic myocardium; reduces platelet aggregation. Hydrochlorothiazide is a moderate-strength thiazide diuretic that reduces Na+ reabsorption at the level of the cortical segment of the loop of Henle. Does not affect CBS. Lowers blood pressure by changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictors (epinephrine, norepinephrine) and enhancing the depressor effect on the autonomic ganglia (to a lesser extent, due to a decrease in the volume of blood volume). Strengthens the hypotensive effect of captopril.

Indications Capozide

Arterial hypertension.

Contraindications Capozide

Hypersensitivity to captopril, thiazide-type diuretics, sulfonamides (cross-allergic reactions are possible), angioedema (history of taking angiotensin-converting enzyme inhibitors), aortic stenosis, mitral stenosis, IGSS, bilateral renal artery stenosis, renal artery stenosis of a solitary kidney , kidney transplantation (history), heart failure, cardiogenic shock, arterial hypotension, tachycardia, severe liver failure (precoma or coma); severe renal failure (serum creatinine more than 1.8 mg/100 ml or creatinine clearance less than 20-30 ml/min, anuria), primary hyperaldosteronism, pregnancy, lactation. With caution (with careful monitoring): moderate renal failure (serum creatinine up to 1.8 mg/100 ml or with creatinine clearance 30-60 ml/min), with increased protein excretion in the urine (more than 1 g/day), hypokalemia (not corrected with medication ); hyponatremia, hypovolemia, hypercalcemia, gout, systemic connective tissue diseases and other immune diseases (including SLE, scleroderma, periarteritis nodosa), old age (over 65 years), simultaneous administration of drugs that suppress the body's defense reactions (GCS, cytostatics, immunosuppressants), allopurinol, procainamide and Li+ drugs.

Dosage regimen Capozide

Orally, regardless of food intake, 1 tablet 1 time per day. In the future, if necessary, the dose can be increased to 2 tablets per day, or reduced to the minimum effective.

Side effects of Capozide

"Rushes" of blood to the skin of the face, fever, dizziness, headache, tachycardia, palpitations, swelling of the legs, a pronounced decrease in blood pressure (including orthostatic) with symptoms of dizziness, feelings of weakness, blurred vision, in rare cases - fainting, tachycardia, palpitations, with a sharp or prolonged excessive decrease in blood pressure - transient cerebrovascular accident, stroke, myocardial infarction. Water-electrolyte imbalance: dry mouth, thirst, feeling tired, depressed, drowsiness, weakness. In rare cases, a decrease in the formation of tear fluid. Bronchospasm, dry cough, in rare cases - respiratory failure, sinusitis, rhinitlaryngitis. Angioedema of the larynx, pharynx and/or tongue, Quincke's edema, allergic reactions (up to the development of pulmonary edema), skin rash (exanthema, in rare cases, urticaria). Exfoliative dermatitis, erythema multiforme, malignant exudative erythema (Stevens-Johnson syndrome), and toxic epidermal necrolysis (Lyell's syndrome). These skin changes may be accompanied by a rise in temperature, pain in muscles and joints, and the development of vasculitis. In some cases, skin changes resembling psoriasis, photosensitivity, hair loss, nail disorders (onycholysis). Nausea, vomiting, constipation or diarrhea, discomfort in the stomach, abdominal pain, anorexia, acute cholecystitis (with cholelithiasis), hemorrhagic pancreatitis, hepatitis, cholestatic jaundice. With long-term use: gum hyperplasia, asthenic syndrome, change in taste, impaired renal function, nephritis. Headache, feeling tired, in rare cases - depression, depression, sleep disturbances, decreased potency, convulsions, impaired sense of balance, dizziness, tinnitus, visual impairment, progression of myopia, tremor, paresthesia, taste disturbances. Anemia, decreased hematocrit, thrombocytopenia, leukopenia, neutropenia (up to the development of pancytopenia and agranulocytosis - especially against the background of simultaneous administration of allopurinol, procainamide, as well as immunosuppressants), eosinophilia, increased titer of antinuclear antibodies, proteinuria, increased activity of “liver” transaminases, hyperlipidemia, hyperbilirubinemia; hyperglycemia; hyperuricemia (up to exacerbation of gout). In rare cases, especially in patients with renal failure, increased serum concentrations of urea, creatinine and K+ may be observed (the risk of hyperkalemia is also increased in patients with diabetes), as well as hyponatremia.

Special instructions Capozide

At the beginning of treatment, an excessive decrease in blood pressure may be observed, especially in patients with heart failure, severe arterial hypertension (including of renal origin) and/or renal failure. Before starting treatment, it is necessary to compensate for the deficiency of Na+ and bcc (reduce the dose of previously prescribed diuretics or, in some cases, completely cancel them), and also determine indicators of kidney function. Regular monitoring of plasma levels of K+ and Ca2+ is necessary (especially in patients receiving treatment with digitalis, corticosteroids, often using laxatives, as well as in elderly patients), glucose, uric acid, lipids (cholesterol and TG), urea and creatinine, activity " liver" transaminases. Particularly careful monitoring of blood pressure levels and laboratory parameters is necessary in the following cases: in patients with renal failure, patients with severe arterial hypertension (including renal origin), in elderly patients (over 65 years), in patients with fluid disorders -electrolyte balance and severe heart failure, as well as those simultaneously receiving allopurinol, Li+ salts, procainamide and drugs that reduce immunity. During treatment, you should refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions. If fever, swollen lymph nodes and/or signs of laryngitis and/or pharyngitis occur, the white blood cell count must be immediately determined.

Drug interactions Capozide

Increases the concentration of digoxin in plasma by 15-20%, increases the bioavailability of propranolol. Cimetidine, slowing down the metabolism of captopril in the liver, increases its concentration in plasma. Combination with nitrates, thiazide diuretics, verapamil, beta-blockers and other antihypertensive drugs, as well as tricyclic antidepressants, hypnotics and ethanol enhances the severity of the hypotensive effect. The risk of developing immunosuppressive effects increases when combined with procainamide, as well as drugs that block tubular secretion (reducing the number of leukocytes and granulocytes). When prescribed simultaneously with Li+ drugs, a slowdown in the excretion of Li+ may occur (increased damaging effects on the heart and central nervous system). Drugs that bind intensively to proteins enhance the diuretic effect. Increases the neurotoxicity of salicylates, the effect of curare-like muscle relaxants, ethanol. Reduces the excretion of quinidine, the effect of oral hypoglycemic drugs, norepinephrine, epinephrine and anti-gout drugs. Increases the side effects of cardiac glycosides, especially when administered simultaneously with drugs that increase the release of K+ and Mg2+ and/or retain Ca2+ (for example, diuretics, adrenal hormones, laxatives, amphotericin B, carbenoxolone, penicillin G, salicylates). When taking methyldopa simultaneously, hemolysis of red blood cells may develop. Cholestyramine reduces absorption. Table salt and NSAIDs reduce the severity of the hypotensive effect. K+ salts, potassium-sparing diuretics and heparin contribute to the development of hyperkalemia. Prescription during hemodialysis using certain high-permeability dialysis membranes (for example, polyacrylonitrile-methalylsulfonate membranes) increases the risk of developing hypersensitivity reactions (anaphylactoid reactions).

Analogs

Level 4 ATX code matches:
Akkuzid

Enap-N

Iruzid

Co-Diroton

Enalozide

Enap NL

Enapril-N

Tritace Plus

Enzix

Liprazid

Co-Renitec

Hartil N

Hartil D

Noliprel

Ko-Perineva

Kaptopres

Analogues of the drug:

• Normopres;
• Kaptopres-Darnitsa;
• Capothiazide.

Capozide price, where to buy

The price of Capozide in Russia is on average 280 rubles (30 tablets), in Ukraine - on average 400 hryvnia (28 tablets).

• Online pharmacies in RussiaRussia

ZdravCity

• Capozide tab.
  50+25 mg No. 28 UNDEFINED 517 rub. order