Hydrochlorothiazide+Captopril, tablets 25 mg+50 mg 30 pcs

Pharmacotherapeutic group

Hypertensive combined (diuretic + ACE inhibitor)

ATX code

C09BA01

Pharmacodynamics:

Hydrochlorothiazide + Captopril is a combination drug with antihypertensive and diuretic effects.

Captopril is an angiotensin-converting enzyme (ACE) inhibitor reduces the formation of angiotensin II from angiotensin I reduces the release of aldosterone reduces total peripheral vascular resistance (TPR) blood pressure (BP) post- and preload. Dilates arteries more than veins. Enhances coronary and renal blood flow. Long-term use reduces myocardial and arterial wall resistance hypertrophy. Captopril improves blood supply to ischemic myocardium; reduces platelet aggregation.

Hydrochlorothiazide is a medium strength thiazide diuretic that reduces sodium ion reabsorption at the level of the cortical segment of the Genle loop. It does not affect the acid-base state. Lowers BP by changing the reactivity of the vascular wall, reducing the pressor effect of endogenous vasoconstrictors (adrenaline noradrenaline) and increasing the depressor effect on the autonomic ganglia (to a lesser extent by reducing the circulating blood volume (CBV)). It enhances the antihypertensive effect of captopril. Diuretic effect is noted after 2 hours and reaches a maximum of 4 hours after oral administration. The action lasts for 6-12 hours.

The efficacy and safety of captopril in children have not been established. Limited experience with captopril in children has been described in the literature. Children especially newborns may be more susceptible to the development of hemodynamic side effects. Cases of excessive prolonged and unpredictable increases in blood pressure and associated complications, including oliguria and seizures, have been reported.

Pharmacokinetics:

Captopril

Absorption is rapid at about 60-70% of the dose taken. Food intake reduces bioavailability by 30-40%. Maximum plasma concentration is noted 1 h after ingestion.

Binding to plasma proteins is 25-30%, mainly to albumin. Less than 0002% of the taken dose of captopril is secreted with breast milk does not penetrate the blood-brain barrier.

It is metabolized in the liver to form captopril disulfide dimer and captopril-cysteine sulfide. Metabolites are pharmacologically inactive.

The half-life (T1/2) of captopril is about 2-3 h. About 95% is excreted by the kidneys during the first day of use with 40-50% of it unchanged and the rest as metabolites. After 4 hours after a single oral administration, about 38% of unchanged captopril is in the urine and 28% as metabolites after 6 hours, only as metabolites; in daily urine – 38% of unchanged captopril and 62% as metabolites.

The accumulation of captopril and its metabolites in the kidneys may result in renal dysfunction. The half-life in renal failure is 35-32 hours. It accumulates in chronic renal failure. Therefore, patients with impaired renal function should reduce the dose of the drug and/or increase the interval between doses.

Hydrochlorothiazide

After oral administration, the absorption and bioavailability of hydrochlorothiazide is about 70%. The binding to blood plasma proteins is 60-80%.

In intake of 125 mg of hydrochlorothiazide maximum plasma concentration is reached after 15-4 hours and is 70 ng/ml, and in intake of 25 mg of hydrochlorothiazide maximum plasma concentration is reached after 2-5 hours and is 142 ng/ml.

In the therapeutic dose range, the mean area under the “concentration-time” curve (AUC) increases in direct proportion to increasing the dose when administered once daily, there is little cumulation. Penetrates through the blood-placental barrier and into breast milk. T1/2- 5-15 hours.

Hydrochlorothiazide is slightly metabolized in the liver. Hydrochlorothiazide is excreted almost completely (more than 95%) by the kidneys unchanged. 50-70% of the ingested dose is excreted within 24 hours.

Indications

Arterial hypertension.

Pharmacological effect

Pharmacotherapeutic group

Combination antihypertensive drug (diuretic + ACE inhibitor)

ATX code

C09BA01

Pharmacodynamics:

Hydrochlorothiazide + Captopril is a combined drug that has antihypertensive and diuretic effects.

Captopril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the formation of angiotensin II from angiotensin I, reduces the release of aldosterone, reduces total peripheral vascular resistance (TPVR), blood pressure (BP), 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. Captopril improves blood supply to ischemic myocardium; reduces platelet aggregation.

Hydrochlorothiazide is a moderate-strength thiazide diuretic that reduces the reabsorption of sodium ions at the level of the cortical segment of the loop of Henle. Does not affect the acid-base state. Reduces blood pressure by changing the reactivity of the vascular wall, reducing the pressor effect of endogenous vasoconstrictors (adrenaline norepinephrine) and enhancing the depressor effect on the autonomic ganglia (to a lesser extent due to a decrease in circulating blood volume (CBV)). Enhances the antihypertensive effect of captopril. The diuretic effect is observed after 2 hours and reaches a maximum 4 hours after oral administration. The effect lasts for 6-12 hours.

The effectiveness and safety of captopril in children have not been established. The literature describes limited experience with the use of captopril in children. Children, especially newborns, may be more susceptible to developing hemodynamic side effects. There have been cases of excessive, prolonged and unpredictable increases in blood pressure, as well as associated complications including oliguria and convulsions.

Pharmacokinetics:

Captopril

Absorption – rapid is about 60-70% of the dose taken. Eating reduces bioavailability by 30-40%. The maximum concentration in blood plasma is observed 1 hour after oral administration.

Binds to plasma proteins – 25-30% mainly with albumin. Less than 0002% of the taken dose of captopril is secreted into breast milk and does not penetrate the blood-brain barrier.

Metabolized in the liver to form the disulfide dimer of captopril and captopril-cysteine ​​sulfide. Metabolites are pharmacologically inactive.

The half-life (T1/2) of captopril is about 2-3 hours. About 95% is excreted by the kidneys during the first day, of which 40-50% is unchanged, the rest is in the form of metabolites. 4 hours after a single oral dose, the urine contains about 38% unchanged captopril and 28% in the form of metabolites after 6 hours – only in the form of metabolites; in daily urine – 38% unchanged captopril and 62% in the form of metabolites.

As a result of the accumulation of captopril and its metabolites in the kidneys, their function may be impaired. The half-life for renal failure is 35-32 hours. Cumulates in chronic renal failure. Therefore, in patients with impaired renal function, the dose of the drug should be reduced and/or the interval between doses should be increased.

Hydrochlorothiazide

After oral administration, the absorption and bioavailability of hydrochlorothiazide is about 70%. Communication with blood plasma proteins – 60-80%.

When 125 mg of hydrochlorothiazide is taken orally, the maximum plasma concentration is reached after 15-4 hours and is 70 ng/ml, and when 25 mg of hydrochlorothiazide is taken orally, the maximum plasma concentration is achieved after 2-5 hours and is 142 ng/ml.

In the therapeutic dose range, the average area under the concentration-time curve (AUC) increases in direct proportion to the increase in dose when administered once a day, the accumulation is insignificant. Penetrates through the hematoplacental barrier and into breast milk. T1/2- 5-15 hours.

Hydrochlorothiazide is slightly metabolized in the liver. Hydrochlorothiazide is excreted almost completely (more than 95%) by the kidneys unchanged. 50-70% of the dose taken orally is eliminated within 24 hours.

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 bcc (reduce the dose of previously prescribed diuretics or, in some cases, completely cancel them) and also determine indicators of kidney function.

It is necessary to regularly monitor the content of potassium and calcium ions in the blood plasma (especially in patients receiving treatment with digitalis glucocorticosteroids, who often use laxatives, as well as in elderly patients), glucose, uric acid, lipids (cholesterol and triglycerides), urea and creatinine, and the activity of “liver” enzymes.

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 old); in patients with water-electrolyte imbalance and decompensated CHF; as well as those receiving simultaneously allopurinol, lithium salts, procainamide and drugs that reduce immunity.

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

Some patients with kidney disease, especially those with severe renal artery stenosis, experience an increase in serum urea nitrogen and creatinine concentrations after lowering blood pressure. This phenomenon is usually reversible and a decrease in serum urea nitrogen and creatinine concentrations is observed if the drug is discontinued. It may be necessary to reduce the dose of Hydrochlorothiazide + Captopril and/or discontinue the diuretic.

In some cases, during the use of ACE inhibitors, an increase in potassium levels in the blood serum is observed. The risk of developing hyperkalemia when using ACE inhibitors is increased in patients with impaired renal function and diabetes mellitus, as well as those taking potassium-sparing diuretics, potassium preparations and or other drugs that cause an increase in potassium levels 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 levels in the blood during therapy should be carried out.

Caution should be exercised when taking ACE inhibitors in patients with mitral/aortic stenosis/hypertrophic obstructive cardiomyopathy in the case of cardiogenic shock and hemodynamically significant obstruction – use is not recommended.

The use of dual blockade of the RAAS caused by the simultaneous use of ACE inhibitors and ARAII or aliskiren and aliskiren-containing drugs is not recommended since it has been associated with an increased incidence of side effects such as arterial hypotension, hyperkalemia, decreased renal function (including acute renal failure). If the simultaneous use of ACE inhibitors and ARA II (double blockade of the RAAS) is necessary, then treatment should be carried out under the supervision of a physician and with constant monitoring of renal function, the content of electrolytes in the blood and blood pressure.

The simultaneous use of ACE inhibitors and ARA II in patients with diabetic nephropathy is not recommended.

When performing hemodialysis in patients receiving ACE inhibitors, the use of high-permeability dialysis membranes (for example AN®69) should be avoided as in such cases the risk of developing anaphylactoid reactions increases. Anaphylactoid reactions have also been observed in patients undergoing low-density lipoprotein removal (apheresis) by absorption 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 used 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 (03-05 ml in a dilution of 1:1000). In rare cases, patients after taking ACE inhibitors have experienced angioedema of the intestine, which was accompanied by abdominal pain (with or without nausea and vomiting). Sometimes – with normal values ​​of C-1-esterase activity and without previous facial swelling. Intestinal edema should be included in the differential diagnosis of patients complaining of abdominal pain while taking ACE inhibitors.

In representatives of the Negroid race, cases of the development of angioedema were noted with greater frequency compared to representatives of the Caucasian race.

In two patients undergoing desensitization procedure with hymenoptera venom while taking captopril, life-threatening anaphylactoid reactions were noted. By temporarily discontinuing the ACE inhibitor, anaphylactoid reactions were avoided. Caution should be exercised when conducting desensitizing therapy in patients taking ACE inhibitors.

In patients with diabetes mellitus receiving oral hypoglycemic agents and insulin, glycemic levels should be carefully monitored, especially during the first month of therapy with ACE inhibitors.

When undergoing major surgical interventions or when using general anesthesia agents that have an antihypertensive effect, patients taking ACE inhibitors may experience an excessive decrease in blood pressure. In these cases, it is possible 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 therapy with ACE inhibitors develops jaundice or there is a temporary increase in the activity of liver transaminases, treatment with ACE inhibitors should be discontinued and the patient should be monitored.

In patients taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia were observed. Neutropenia is rare in patients with normal renal function and no other abnormalities.

The drug Hydrochlorothiazide + Captopril should be used with caution 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 due to ACE inhibitors developed in such patients, their blood 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 below 1000/μl is indicated, the drug should be stopped while monitoring the patient. Typically, restoration of the number of neutrophils occurs within 2 weeks after discontinuation of captopril. In 13% of cases of neutropenia, death was noted.

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.

When using ACE inhibitors, proteinuria may occur, mainly in patients with impaired renal function and also when using high doses of drugs. In most cases, proteinuria when taking the drug captopril disappeared or its severity decreased within 6 months, regardless of whether the drug was stopped or not. Renal function tests (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.

When taking thiazide diuretics, cases of agranulocytosis and suppression of bone marrow function have been reported.

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 decrease in 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 permanent vision loss. Treatment: Stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medication 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.

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

Hypokalemia can provoke or enhance the cardiotoxic effect of cardiac glycosides. 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, table salt is prescribed. During therapy with thiazide diuretics, hyperuricemia or exacerbation of gout may occur; Latent diabetes mellitus may also manifest itself.

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

When 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 testing the function of the parathyroid glands, you should stop taking thiazide diuretics. While taking thiazide diuretics, there was an increase in magnesium excretion, which can lead to hypomagnesemia.

The drug may cause a false-positive reaction in a urine test for acetone and distort the results of a test with bentiromide.

If fever, enlarged lymph nodes and/or signs of laryngitis and/or pharyngitis occur, the white blood cell count should be immediately determined.

Athletes should be informed that the drug contains hydrochlorothiazide, which may give false positive results during doping control.

Impact on the ability to drive vehicles. Wed and fur.:

While taking the drug, care should be taken when driving vehicles, operating machinery and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Hydrochlorothiazide, Captopril

Composition

For 1 tablet:

Active ingredients: hydrochlorothiazide – 25 mg, captopril – 50.0 mg;

Excipients: lactose monohydrate (milk sugar) – 169.0 mg, microcrystalline cellulose – 100.0 mg, corn starch – 40.0 mg, croscarmellose sodium – 12.0 mg, magnesium stearate – 4.0 mg.

Pregnancy

The use of the drug Hydrochlorothiazide + Captopril during pregnancy is contraindicated.

Epidemiological data indicating a risk of teratogenicity after exposure to ACE inhibitors in the first trimester of pregnancy have not been convincing; however, some increase in risk cannot be excluded. If the use of an ACE inhibitor is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive therapy with a proven safety profile for use during pregnancy.

It is known that long-term exposure to ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to disruption of its development (decreased renal function, oligohydramnios, slow ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If the patient received the drug Hydrochlorothiazide + Captopril during the second or third trimester of pregnancy, it is recommended to conduct an ultrasound examination of the fetus to assess the condition of the skull bones and kidney function.

The use of hydrochlorothiazide during pregnancy is not recommended as it may impair placental perfusion and cause fetal/newborn 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 (including arterial hypotension, neonatal hypoplasia of the skull bones, anuria, reversible or irreversible renal failure) and fetal death. If pregnancy is diagnosed, the use of the drug Hydrochlorothiazide + Captopril should be discontinued as soon as possible.

Captogtril 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 Hydrochlorothiazide + Captopril should be discontinued in the mother during the period of breastfeeding.

Contraindications

Hypersensitivity to captopril or other ACE inhibitors, thiazide diuretics and other sulfonamide derivatives (cross-allergic reactions are possible) to any component of the drug; hereditary or idiopathic angioedema, including a history of taking ACE inhibitors; aortic stenosis mitral stenosis; hypertrophic obstructive cardiomyopathy; bilateral renal artery stenosis, renal artery stenosis of a single kidney, condition after kidney transplantation (history); chronic heart failure; cardiogenic shock arterial hypotension tachycardia; severe liver failure (precoma or coma); severe renal failure (serum creatinine more than 18 mg/100 ml or creatinine clearance (CC) less than 20-30 ml/min anuria); primary hyperaldosteronism; pregnancy period of breastfeeding age up to 18 years (efficacy and safety have not been established) simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) less than 60 ml/min/173 m2) lactose intolerance lactase deficiency and glucose-galactose malabsorption syndrome.

With caution:

Moderate renal failure (creatinine clearance 30-60 ml/min), proteinuria (more than 1 g/day), liver dysfunction, progressive liver disease, hypokalemia (not corrected by drugs); hyponatremia, hypovolemia, hypercalcemia, gout, hyperuricemia, systemic connective tissue diseases and other immune diseases (including systemic lupus erythematosus, scleroderma nodosa); old age (over 65 years old) simultaneous use of drugs that suppress the body’s defense reactions (glucocorticosteroids (GCS), cytostatics, immunosuppressants) allopurinol procainamide surgery/general anesthesia use in black patients hemodialysis using high-flow membranes (for example AN69®) desensitizing therapy simultaneous use of potassium-sparing diuretics potassium preparations and potassium-containing substitutes for table salt, lithium preparations, acute myopia and secondary angle-closure glaucoma.

Side Effects

The frequency of side effects is presented in accordance with the World Health Organization classification: often – ≥ 1/100 – < 1/10 uncommon - ≥ 1/1000 - < 1/100 rare - ≥ 1/10000 - < 1/1000 very rare - < 1/10000.

From the cardiovascular system:

infrequently – chest pain angina pectoris “flushes” of blood to the skin of the face tachycardia or tachyarrhythmia palpitations peripheral edema marked decrease in blood pressure (including orthostatic) with symptoms of dizziness feeling of weakness Raynaud’s syndrome myocardial infarction fainting; very rarely – cardiac arrest, cardiogenic shock.

From the respiratory system:

often – “dry” non-productive cough, shortness of breath; very rarely – bronchospasm, eosinophilic pneumonitis, sinusitis, rhinitis, laryngitis, pulmonary edema.

Allergic reactions:

often – skin itching with or without rashes, sometimes accompanied by fever and arthralgia; skin rashes; alopecia; infrequently – vascular edema of the skin and subcutaneous tissue; rarely – angioedema – intestines; very rarely – urticaria Stevens-Johnson syndrome erythema multiforme photosensitivity erythroderma reversible pemphigoid reactions exfoliative dermatitis as well as toxic epidermal necrolysis (Lyell’s syndrome) allergic alveolitis eosinophilic pneumonia angioedema of the larynx pharynx tongue face lips mucous membranes (including fatal outcomes) respiratory distress syndrome (including pneumonitis and non-cardiogenic pulmonary edema).

From the central and peripheral nervous system:

often – drowsiness, dizziness, insomnia; rarely – headache, ataxia, paresthesia; very rarely – confusion, depression, cerebrovascular accidents including stroke and syncope, blurred vision.

From the hematopoietic system:

very rarely – anemia, including aplastic and hemolytic forms, decreased hematocrit, thrombocytopenia, leukopenia, neutropenia (up to the development of pancytopenia and agranulocytosis – especially during the simultaneous use of allopurinol procainamide and immunosuppressants) eosinophilia, lymphadenopathy, increased titer of antinuclear antibodies, autoimmune diseases.

From the digestive system:

often – reversible and usually self-limiting disturbance of the sense of taste nausea, vomiting, constipation or diarrhea, discomfort in the stomach, dyspepsia, abdominal pain, dry oral mucosa; rarely – stomatitis, aphthous stomatitis, anorexia; very rarely – glossitis, gastric ulcer, pancreatitis, gingival hyperplasia, impaired liver function and cholestasis (including jaundice), increased activity of liver transaminases, hepatitis (including necrosis), hyperbilirubinemia.

From the musculoskeletal system:

very rarely – myalgia, arthralgia, myasthenia gravis.

From the urinary system:

uncommon – impaired renal function (including renal failure), polyuria oliguria, frequent urination, nephrotic syndrome.

From the reproductive system:

very often – impotence gynecomastia.

Other:

infrequently – chest pain, increased fatigue, poor health.

Laboratory indicators:

often – eosinophilia;

very rarely – proteinuria, hyperkalemia, hyponatremia (including symptomatic) increased concentration of urea nitrogen, bilirubin and creatinine in the blood, decreased hematocrit of hemoglobin of platelet leukocytes.

From the side of metabolism:

very rarely – hyperglycemia; hyperuricemia (up to exacerbation of gout).

Treatment with thiazides may impair glucose tolerance and latent diabetes mellitus may manifest itself. When using high doses, serum lipid concentrations may increase.

Fluid and electrolyte imbalance: hypokalemia hypomagnesemia hypercalcemia and hypochloremic alkalosis: dry oral mucosa feeling thirst irregular heart rhythm changes in mood or psyche cramps and muscle pain nausea vomiting unusual fatigue or weakness. Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma.

Hyponatremia: confusion, convulsions, lethargy, slow thinking, increased fatigue, excitability, muscle cramps.

When using ACE inhibitors, including captopril, in patients receiving intravenous gold (sodium aurothiomalate), a symptom complex was described, including facial flushing, nausea, vomiting, arterial hypotension.

Interaction

Captopril

Concomitant use is contraindicated (see section “Contraindications”)

Aliskiren

Patients with diabetes mellitus or impaired renal function (GFR less than 60 ml/min/173 m2) are at increased risk of hyperkalemia, deterioration of renal function and increased incidence of cardiovascular morbidity and mortality.

Simultaneous use is not recommended (see section “Special instructions”)

Aliskiren

In patients without diabetes mellitus or impaired renal function, there may be an increased risk of hyperkalemia, deterioration of renal function and increased incidence of cardiovascular morbidity and mortality.

Double blockade of the RAAS

The literature has reported that in patients with established atherosclerotic heart failure or diabetes mellitus with end-organ damage, concomitant therapy with an ACE inhibitor and angiotensin II receptor antagonists (ARAs) is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared with the use of only one drug affecting the RAAS. Double blockade (for example, when combining an ACE inhibitor with an ARA II) should be limited to individual cases with careful monitoring of renal function, potassium levels and blood pressure.

In patients taking diuretics, captopril may potentiate the antihypertensive effect. A similar effect is also exerted by strictly limiting the intake of table salt into the body (salt-free diets) and hemodialysis. Typically, an excessive decrease in blood pressure occurs within 1 hour after taking the first dose of captopril.

Vasodilators (eg nitroglycerin) in combination with captopril should be used in the lowest effective doses due to the risk of excessive reduction in blood pressure.

Reduces the excretion of quinidine norepinephrine, epinephrine and anti-gout drugs.

Caution should be exercised when prescribing captopril (without or with a diuretic) and drugs that affect the sympathetic nervous system (for example, ganglion blockers, alpha-blockers).

With the simultaneous use of captopril and nonsteroidal anti-inflammatory drugs (NSAIDs), a decrease in the antihypertensive effect may be observed, especially in arterial hypertension accompanied by low renin levels. In patients with risk factors (elderly patients, hypovolemic patients taking diuretics with impaired renal function), the simultaneous use of NSAIDs (including cyclooxygenase-2 (COX-2) inhibitors) and ACE inhibitors including captopril can lead to a deterioration in renal function, including acute renal failure. Usually, renal dysfunction in such cases is reversible. Renal function should be periodically monitored in patients taking captopril and NSAIDs.

When treating with captopril, potassium-sparing diuretics (for example, triamterene amiloride spironolactone and its derivative eplerenone), potassium supplements, potassium supplements, salt substitutes (contain large amounts of potassium) should be prescribed only for proven hypokalemia because their simultaneous use increases the risk of developing hyperkalemia.

With the simultaneous use of ACE inhibitors (especially in combination with diuretics) and lithium salts, it is possible to increase the concentration of lithium in the blood plasma and, consequently, the toxicity of lithium preparations. The concentration of lithium in the blood plasma should be periodically determined.

When prescribing captopril while taking allopurinol or procainamide, the risk of developing neutropenia and/or Stevens-Johnson syndrome increases.

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

ACE inhibitors, including captopril, may potentiate the hypoglycemic effect of insulin and oral hypoglycemic agents such as sulfonylureas, which may require a reduction in the dose of hypoglycemic drugs when used concomitantly with captopril.

Sympathomimetics may reduce the antihypertensive effect of captopril.

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

Increases the bioavailability of propranolol.

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

When used simultaneously with thiazide diuretics, vasodilators (minoxidil), verapamil, beta-blockers, tricyclic antidepressants or ethanol, the antihypertensive effect is enhanced.

Estramustine

Concomitant use may result in an increased risk of side effects such as angioedema.

Baclofen

Enhances the antihypertensive effect of ACE inhibitors. Blood pressure and, if necessary, dosage of antihypertensive drugs should be carefully monitored.

Gliptins (linagliptin saxagliptin sitagliptin vildagliptin)

Concomitant use with ACE inhibitors may increase the risk of developing angioedema due to the inhibition of dipeptidyl peptidase IV (DPP-IV) activity by gliptins.

Gold preparations

When using ACE inhibitors, including captopril, in patients receiving intravenous gold (sodium aurothiomalate), a symptom complex was described, including facial flushing, nausea, vomiting, arterial hypotension.

Tricyclic antidepressants, antipsychotics (neuroleptics) and general anesthesia

Concomitant use with ACE inhibitors may lead to increased antihypertensive effects (see section “Special Instructions”).

Hydrochlorothiazide

With thiazide diuretics, drugs such as ethanol barbiturates and narcotics may potentiate the risk of orthostatic hypotension.

Hypoglycemic agents (oral and insulin) – dosage adjustment of hypoglycemic agents may be required.

Other antihypertensive drugs have an additive effect.

Cholestyramine and colestipol – in the presence of anion exchange resins, the absorption of hydrochlorothiazide is impaired. Cholestyramine and colestipol in a single dose bind hydrochlorothiazide and reduce its absorption in the gastrointestinal tract by 85% and 43%, respectively.

Corticosteroids ACTH (adrenocorticotropic hormone) or glycyrrhizic acid (found in licorice root) – marked reduction in electrolytes, particularly the risk of hypokalemia.

Pressor amines (for example, epinephrine porepinephrine) – a decrease in the severity of the response to taking pressor amines.

Muscle relaxants of a non-depolarizing type of action (for example tubocurarine) – enhance the effect of muscle relaxants.

Lithium – diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity; simultaneous use is not recommended.

NSAIDs (including COX-2 inhibitors) – may reduce the diuretic natriuretic and antihypertensive effect of diuretics.

In some patients with impaired renal function (for example, elderly patients or patients with dehydration, including those taking diuretics) receiving NSAID therapy, including COX-2 inhibitors, treatment with ARAP or ACE inhibitors may cause further deterioration of renal function, including the development of acute renal failure. These effects are reversible. The simultaneous use of these drugs should be used with caution in patients with impaired renal function.

Due to their effect on calcium metabolism, their intake may distort the results of studies of parathyroid function.

Medicines used to treat gout (probenecid sulfinpyrazone and allopurinol): dose adjustment of uricosuric drugs may be required as hydrochlorothiazide may cause an increase in serum uric acid concentrations. Thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergic drugs (eg atropine biperiden): increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and the rate of gastric emptying.

Cytotoxic drugs such as cyclophosphamide methotrexate: increases myelosuppressive effect by slowing elimination from the body.

Salicylates – when taking high doses of salicylates, hydrochlorothiazide may enhance their toxic effect on the central nervous system.

Methyldopa: Isolated cases of hemolytic anemia have been described with the simultaneous use of hydrochlorothiazide and methyldopa.

Concomitant use of cyclosporine increases the risk of developing hyperuricemia and exacerbation of gout.

Cardiac glycosides: hypokalemia and hypomagnesemia caused by the use of thiazide diuretics increases the risk of developing arrhythmias when treated with cardiac glycosides.

Calcium salts – thiazide diuretics can increase the calcium content in the blood serum due to a decrease in its excretion. If it is necessary to use calcium supplements, the dose is selected under the control of calcium levels in the blood serum.

Vitamin D increases the risk of developing hypercalcemia.

Impact on laboratory results – Due to their effect on calcium excretion, thiazides may interfere with the results of tests of parathyroid function.

Carbamazepine increases the risk of symptomatic hyponatremia. Serum sodium levels must be monitored.

Iodine-containing contrast agents – with dehydration caused by taking diuretics, the risk of developing acute renal failure increases, especially when high doses of iodine-containing drugs are administered. Before administering such drugs, the patient must be rehydrated.

Amphotericin B (for intravenous administration) stimulant laxatives – hydrochlorothiazide may increase water and electrolyte imbalance, especially hypokalemia.

Drugs that intensively bind to proteins enhance the diuretic effect. It may be necessary to adjust the dose of anticoagulants for oral probenecid and sulfinpyrazone since hydrochlorothiazide may suppress their effect.

Overdose

Symptoms: marked decrease in blood pressure, shock stupor, bradycardia, water-electrolyte imbalance, renal failure, lethargy (which can progress to coma over several hours) not accompanied by water-electrolyte imbalance and causing only slight suppression of respiratory and cardiac function. There may be irritation of the gastric mucosa and increased contractile activity of the gastrointestinal tract.

Treatment: gastric lavage, administration of adsorbents and sodium sulfate within 30 minutes after taking 09% sodium chloride solution or other plasma-substituting hemodialysis solutions.

In case of bradycardia or pronounced vagal reactions, administration of atropine.

The use of an artificial pacemaker may be considered.

Peritoneal dialysis is not effective in removing captopril from the body.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life

3 years.

Do not use after expiration date.

Manufacturer

Ozon, Russia