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

Composition

For 1 tablet:

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

Auxiliary substances:  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

Pharmacological action

Pharmacotherapy group

Combined antihypertensive agent (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 (OPSS) blood pressure (BP) post-and preload. Dilates the arteries to a greater extent than the veins. Increases coronary and renal blood flow. With prolonged use, hypertrophy of the myocardium and arterial walls of the resistive type decreases. Captopril improves blood supply to the ischemic myocardium; reduces platelet aggregation.

A medium-strength hydrochlorothiazide-thiazide diuretic reduces the reabsorption of sodium ions at the level of the cortical segment of the Henle loop. It 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 (epinephrine norepinephrine) and increasing the depressive effect on the autonomic ganglia (to a lesser extent by reducing the volume of circulating blood (BCC)). Enhances the antihypertensive effect of captopril. The diuretic effect is noted in 2 hours and reaches a maximum in 4 hours after ingestion. The action lasts for 6-12 hours.

The efficacy 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 likely to develop hemodynamic side effects. There have been cases of excessive prolonged and unpredictable increases in blood pressure and associated complications including oliguria and seizures.

Pharmacokinetics:

Captopril

Absorption-fast is about 60-70% of the dose taken. Food intake reduces bioavailability by 30-40%. The maximum concentration in the blood plasma is noted 1 hour after ingestion.

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

It is metabolized in the liver to form a disulfide dimer of captopril and captopril-cysteine sulfide. The metabolites are pharmacologically inactive.

The half-life (T 1/2) 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 elimination half-life in renal failure is 35-32 hours. Accumulates 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 use, the absorption and bioavailability of hydrochlorothiazide is about 70%. The relationship with plasma proteins is 60-80%.

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

In the therapeutic dose range, the average area under the concentration – time curve (AUC) increases directly in proportion to the dose increase when administered once a day, the accumulation is insignificant. Penetrates through the blood-placental barrier and into breast milk. T 1/2 – 5-15 hours.

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

Indications

Arterial hypertension.

Use during pregnancy and lactation

Application of the drug Hydrochlorothiazide+Captopril is contraindicated during pregnancy.

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

It is known that prolonged exposure to ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to impaired development (decreased renal function, oligohydramnios, slowing of 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, an ultrasound examination of the fetus is recommended 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 water-electrolyte imbalance and possibly other adverse reactions observed in adults.

The use of ACE inhibitors during pregnancy can cause developmental disorders (including hypotension, neonatal cranial hypoplasia, anuria, reversible or irreversible renal failure) and fetal death. When diagnosing pregnancy, the use of the drug Hydrochlorothiazide+Captopril should be discontinued as soon as possible.

Captogtril and hydrochlorothiazide are found in breast milk after oral use by a nursing woman. Due to the risk of serious adverse reactions in the child caused by both active substances breastfeeding should be discontinued or therapy with Hydrochlorothiazide should be discontinued+Captopril in the mother during breastfeeding.

Contraindications

Hypersensitivity to captopril or other ACE inhibitors thiazide diuretics and other sulfonamide derivatives (possible cross-allergic reactions) to any component of the drug; hereditary or idiopathic angioedema, including in the anamnesis, while taking ACE inhibitors; aortic stenosis mitral stenosis; hypertrophic obstructive cardiomyopathy; bilateral renal artery stenosis renal artery stenosis of a single kidney condition after transplantation heart failure; cardiogenic shock hypotension tachycardia; severe hepatic insufficiency (precoma or coma); severe renal insufficiency (serum creatinine greater than 18 mg/100 ml or creatinine clearance less than 20-30 ml/min anuria); primary hyperaldosteronism; pregnancy breast-feeding age up to 18 years (efficacy and safety have not been established) concomitant use with the following medications: 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 insufficiency (creatinine clearance 30-60 ml/min) proteinuria (more than 1 g/day) liver function disorders progressive liver diseases hypokalemia (not corrected by drugs); hyponatremia hypovolemia hypercalcemia gout hyperuricemia systemic connective tissue diseases and other immune diseases (including systemic lupus erythematosus scleroderma nodular periarteritis); elderly (over 65 years) concomitant use of drugs that suppress protective functions body reactions (glucocorticosteroids (corticosteroids) cytostatics immunosuppressants) allopurinol procainamide surgical intervention/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 salt substitutes lithium preparations acute myopia and secondary angle-closure glaucoma.

Side effects

The frequency of side effects is described according to the World Health Organization classification: common – ≥ 1/100 – < 1/10 uncommon – ≥ 1/1000 – < 1/100 rare – ≥ 1/10000 – < 1/1000 very rare –

From the cardiovascular system:

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

Respiratory system disorders:

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

Allergic reactions:

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

Central and peripheral nervous system disorders:

often – drowsiness dizziness insomnia; rarely-headache ataxia paresthesia; very rarely-confusion depression circulatory disorders 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 against the background of 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-passing sense of taste nausea vomiting constipation or diarrhea, discomfort in the stomach dyspepsia abdominal pain, dryness of the mucous membrane of the mouth; rarely – stomatitis aphthous stomatitis anorexia; very rarely – glossitis gastric ulcer pancreatitis, gingival hyperplasia violation of 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:

infrequently-impaired renal function (including renal failure) polyuria oliguria frequent urination nephrotic syndrome.

From the side of the reproductive system:

very often – impotence gynecomastia.

Other:

infrequently-chest pain increased fatigue poor health.

Laboratory parameters:

often – eosinophilia;

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

From the side of metabolism:

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

Treatment with thiazides may impair glucose tolerance and latent diabetes mellitus may manifest. When using high doses, the concentration of lipids in the blood serum may increase.

Impaired water and electrolyte balance: hypokalemia hypomagnesemia hypercalcemia and hypochloremic alkalosis: dry oral mucosa feeling thirsty irregular heart rate changes in mood or psyche muscle cramps and 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 preparation (sodium aurothiomalate) a symptom complex was described that includes facial skin hyperemia nausea vomiting and 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) have an increased risk of hyperkalemia, deterioration of renal function, and increased incidence of cardiovascular morbidity and mortality.

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

Aliskiren

Patients who do not have diabetes mellitus or impaired renal function may have an increased risk of hyperkalemia, deterioration of renal function, and increased incidence of cardiovascular morbidity and mortality.

Double blockade of the RAAS

In the literature, it has been reported that in patients with established atherosclerotic disease, heart failure, or diabetes mellitus with target organ damage, concomitant therapy with an ACE inhibitor and angiotensin II (ARAII) receptor antagonists is associated with a higher incidence of hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared to using only one drug that affects the RAAS. Double blockade (for example, when an ACE inhibitor is combined with ARAII) should be limited to individual cases with careful monitoring of renal function, potassium content and blood pressure.

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

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

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

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

Concomitant use of captopril and nonsteroidal anti-inflammatory drugs (NSAIDs) there may be a decrease in the antihypertensive effect, especially in arterial hypertension accompanied by a low renin content. Concomitant use of NSAIDs (including cyclooxygenase-2 (COX-2) inhibitors) and ACE inhibitors, including captopril, may lead to deterioration of renal function up to acute renal failure in patients with risk factors (elderly patients, hypovolemic patients, taking diuretics with impaired renal function). Usually, kidney function disorders in such cases are reversible. Renal function should be monitored periodically in patients taking captopril and NSAIDs.

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

Concomitant use of ACE inhibitors (especially in combination with diuretics) and lithium salts may increase the concentration of lithium in blood plasma and, consequently, the toxicity of lithium preparations. It is necessary to periodically determine the concentration of lithium in the blood plasma.

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

Use of captopril in patients taking immunosuppressants (e. g. cyclophosphacin or azathioprine) increases the risk of developing hematological disorders.

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

Sympathomimetics can reduce the antihypertensive effect of captopril.

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

Increases the bioavailability of propranolol.

Cimetidine slows down the metabolism in the liver and increases the concentration of captopril in the blood plasma.

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

Estramustin

Concomitant use may lead to an increased risk of side effects such as angioedema.

Baclofen

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

Gliptins (linagliptin saxagliptin sitagliptin vildagliptin)

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

Gold preparations

When using ACE inhibitors, including captopril, in patients receiving intravenous gold preparation (sodium aurothiomalate) a symptom complex was described that includes facial skin hyperemia nausea vomiting and hypotension.

Tricyclic antidepressants antipsychotics (neuroleptics) and general anaesthetics

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

Hydrochlorothiazide

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

Hypoglycemic agents (for oral use and insulin) – it may be necessary to adjust the dose of hypoglycemic agents.

Other antihypertensive agents have an additive effect.

Colestyramine and colestipol – in the presence of anion exchange resins, the absorption of hydrochlorothiazide is disrupted. Colestyramine 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) – a pronounced decrease in the content of electrolytes, in particular the risk of hypokalemia.

Pressor amines (e. g. epinephrine porepinephrine) – reduced response to pressor amines.

Non-depolarizing muscle relaxants (for example, tubocurarin) – enhance the effect of muscle relaxants.

Lithium diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity; concomitant 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. Concomitant use of these drugs should be carried out with caution in patients with impaired renal function.

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

Medications used for the treatment of gout (probenecid sulfinpyrazone and allopurinol): it may be necessary to adjust the dose of uricosuric drugs as hydrochlorothiazide can cause an increase in the concentration of uric acid in the blood serum. Thiazide diuretics may increase the frequency of hypersensitivity reactions to allopurinol.

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

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

Salicylates-when taking high doses of salicylates, hydrochlorothiazide can increase their toxic effect on the central nervous system.

Methyldopa: Isolated cases of hemolytic anemia have been reported with concomitant use of hydrochlorothiazide and methyldopa.

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

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

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

Vitamin D-increases the risk of hypercalcemia.

Effects on laboratory results-due to their effect on calcium excretion, thiazides can distort the results of studies of parathyroid function.

Carbamazepine-increases the risk of symptomatic hyponatremia. It is necessary to monitor the sodium content in the blood serum.

Iodine-containing contrast agents-dehydration caused by diuretics increases the risk of acute renal failure, especially when high doses of iodine-containing drugs are administered. Before the introduction of such drugs, the patient should be rehydrated.

Amphotericin B (for intravenous use) laxatives of stimulating action-hydrochlorothiazide may increase water-electrolyte balance disorders, especially hypokalemia.

Drugs that intensively bind to proteins enhance the diuretic effect. Oral anticoagulants probenecid and sulfinpyrazone may need to be adjusted as hydrochlorothiazide may inhibit their action.

How to take, course of use and dosage

Inside, regardless of the time of food intake,1 tablet 1 time a day.

Tablets should be swallowed whole without chewing and washed down with a small amount of liquid.

Overdose

Symptoms: marked decrease in blood pressure shock stupor bradycardia water-electrolyte balance disorders renal failure lethargy (which can progress to a coma within a few hours) not accompanied by a violation of water-electrolyte balance and causing only a slight suppression of respiratory and heart function. Irritation of the gastric mucosa and increased contractile activity of the gastrointestinal tract may occur.

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

For bradycardia or severe vagal reactions-use of atropine.

The use of an artificial pacemaker may be considered.

Peritoneal dialysis is ineffective in removing captopril from the body.

Description

Round, flat-cylindrical tablets with a risk on one side and chamfers on both sides, white or white with a beige tint, with a characteristic smell, slight marbling is allowed.

Special instructions

At the beginning of treatment, an excessive decrease in blood pressure may occur, especially in patients with chronic heart failure, severe arterial hypertension (including renal genesis) and/or renal insufficiency. 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), as well as determine the indicators of renal 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 preparations, glucocorticosteroids, often using 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 insufficiency; patients with severe arterial hypertension (including renal genesis); in elderly patients (older than 65 years); in patients with impaired water-electrolyte balance and decompensated CHF; as well as receiving simultaneously allopurinol lithium salts procainamide and drugs that reduce immunity.

When taking ACE inhibitors, there is a characteristic unproductive cough that stops after discontinuation of ACE inhibitor therapy.

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

In some cases, against the background of the use of ACE inhibitors, an increase in the content of potassium in the blood serum is observed. The risk of developing hyperkalemia with ACE inhibitors is increased in patients with impaired renal function and diabetes mellitus, as well as taking potassium-sparing diuretics, potassium preparations and or other drugs that cause an increase in blood potassium (for example, heparin). Concomitant 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 is not excluded, so in such cases, regular monitoring of blood potassium levels during therapy should be carried out.

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

The use of double 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 frequency of side effects such as hypotension hyperkalemia and decreased renal function (including acute renal failure). If the simultaneous use of ACE inhibitors and ARAII (double blockade of RAAS) is necessary, then treatment should be carried out under the supervision of a doctor and with constant monitoring of renal function, blood electrolyte content and blood pressure.

Concomitant use of ACE inhibitors and ARAII is not recommended in patients with diabetic nephropathy.

When performing hemodialysis in patients receiving ACE inhibitors, the use of dialysis membranes with high permeability (for example, AN®69) should be avoided, since in such cases the risk of anaphylactoid reactions increases. Anaphylactoid reactions were also observed in patients who underwent low-density lipoprotein removal (apheresis) by absorption with dextran sulfate. Consideration should be given to using either a different class of antihypertensive drugs or a different type of dialysis membrane.

If angioedema develops, the drug is discontinued and careful medical supervision is carried out until the symptoms completely disappear. Angioedema of the larynx can be fatal.If the edema is localized on the face, special treatment is usually not required (antihistamines can be used to reduce the severity of symptoms). If the edema spreads to the tongue, pharynx or larynx and there is a threat of airway obstruction, epinephrine (epinephrine) should be immediately administered subcutaneously (03-05 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 – at normal values of C-1-esterase activity and without previous facial edema. Intestinal edema should be included in the differential diagnosis of patients with complaints of abdominal pain when taking ACE inhibitors.

In representatives of the black race, cases of angioedema development were noted with a higher frequency compared to representatives of the Caucasian race.

Life-threatening anaphylactoid reactions were observed in two patients undergoing hymenopteran venom desensitization while taking captopril. When the ACE inhibitor was temporarily discontinued, anaphylactoid reactions were avoided. Caution should be exercised when conducting desensitizing therapy in patients taking ACE inhibitors.

In patients with diabetes mellitus receiving hypoglycemic drugs for oral use and insulin, the level of glycemia should be carefully monitored, especially during the first month of therapy with ACE inhibitors.

When performing extensive 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, you can increase the BCC.

In rare cases, when taking ACE inhibitors, a syndrome is noted that begins with the appearance of cholestatic jaundice, which turns into 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 there is a temporary increase in the activity of” hepatic ” transaminases, 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 in the absence of other disorders.

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 most fatal cases of neutropenia on the background of 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 number of white blood cells in the blood should be monitored monthly for the first 3 months after the start of therapy, then every 2 months. If the number of white blood cells is below 4000 / mcl, a second general blood test below 1000/mcl is indicated – the drug is stopped while continuing to monitor the patient. Neutrophil count usually recovers within 2 weeks after captopril is discontinued. In 13% of cases of neutropenia, a fatal outcome was noted.

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

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

Cases of agranulocytosis and bone marrow suppression have been reported with thiazide diuretics.

Hydrochlorothiazide can cause an idiosyncratic reaction leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include: a sudden decrease in visual acuity or pain in the eyes that usually occurs within a few hours or 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, urgent medical treatment or surgery may be required. Risk factors for acute angle-closure glaucoma include: a history of allergic reaction to sulfonamides or penicillin.

All patients taking thiazide diuretics should show clinical signs of impaired water-electrolyte balance (hyponatremia hypochloremic alkalosis hypokalemia). It is especially important to determine the content of electrolytes in the blood serum and urine with severe vomiting or with the introduction of infusion solutions. Signs of impaired water and electrolyte balance may include dryness of the oral mucosa thirst weakness lethargy confusion anxiety pain or cramps in the muscles muscle weakness excessive decrease in blood pressure oliguria tachycardia nausea vomiting.

Hypokalemia can trigger or increase the cardiotoxic effect of cardiac glycosides. Patients with edema in hot weather may experience hyponatremia caused by an increase in BCC. Limit your fluid intake. 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 occur.

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

Against the background of 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 studying the function of the parathyroid glands, you should stop taking thiazide diuretics. While taking thiazide diuretics, an increase in magnesium excretion was noted, which can lead to hypomagnesemia.

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

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

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

Influence on the ability to drive vehicles and mechanisms:

Against the background of taking the drug, caution should be exercised when driving vehicles, working with mechanisms and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Hydrochlorothiazide, Captopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets