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

Active ingredient

Composition

Per 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.

How to take, the dosage

To be taken by mouth, regardless of the time of meals, 1 tablet once a day.

The tablets should be swallowed whole without chewing, followed by a small amount of liquid.

Interaction

Captopril

Simultaneous use is contraindicated (see “Contraindications.

Aliskiren

In patients with diabetes mellitus or impaired renal function (GFR less than 60 mL/min/173 m2), there is an increased risk of hyperkalemia, impaired renal function, and increased incidence of cardiovascular morbidity and mortality.

The concomitant use is not recommended (see “Cautionary Note”)

Aliskiren

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

Double blockade of the RAAS

. In patients with established atherosclerotic heart disease or diabetes mellitus with target organ damage, simultaneous therapy with an ACE inhibitor and angiotensin II receptor antagonists (ARAII) has been reported in the literature to be associated with a higher incidence of arterial hypotension, syncope hyperkalaemia and impaired renal function (including acute renal failure) compared to the use of a single antagonist alone. Dual blockade (e.g., when ACE inhibitor is combined with APAII) should be limited to individual cases with close monitoring of renal function, potassium, and BP.

In patients taking diuretics, captopril may potentiate antihypertensive effects. Strict restriction of ingestion of table salt (salt-free diet) hemodialysis also has this effect. Usually excessive BP reduction occurs within 1 hour after the first dose of captopril.

Vasodilators (e.g., nitroglycerin) in combination with captopril should be used at the lowest effective dose because of the risk of excessive BP reduction.

It decreases the excretion of quinidine norepinephrine epinephrine and antipodagrel drugs.

Cautions should be taken when prescribing captopril concomitantly (without or with a diuretic) and drugs that affect the sympathetic nervous system (e.g., ganglioblocators alpha-adrenoblockers).

Concomitant use of captopril and nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease antihypertensive effects especially in hypertension accompanied by low renin levels. In patients with risk factors (elderly patients with hypovolemia receiving diuretics with impaired renal function), concomitant use of NSAIDs (including cyclooxygenase-2 inhibitors (COX-2)) and ACE inhibitors including captopril may lead to worsening of renal function up to acute renal failure. Usually renal function impairment in such cases is reversible. Renal function should be periodically monitored in patients taking captopril and NSAIDs.

In therapy with captopril, potassium-saving diuretics (e.g., triamterene amiloride spironolactone and its derivative, eplerenone) potassium supplements salt substitutes (containing large amounts of potassium) should only be prescribed when hypokalemia is proven, as their concomitant use increases the risk of hyperkalemia.

The simultaneous use of ACE inhibitors (especially in combination with diuretics) and lithium salts may increase the lithium concentration in plasma and thus the toxicity of lithium preparations. Plasma lithium concentrations should be periodically determined.

When prescribing captopril with allopurinol or procainamide increases the risk of neutropenia and/or Stevens-Johnson syndrome.

The use of captopril in patients taking immunosuppressants (e.g., cyclophosphacin or azathioprine) increases the risk of hematological disorders.

The ACE inhibitors including captopril may potentiate the hypoglycemic effects of insulin and oral hypoglycemic agents such as sulfonylurea derivatives, which may require reduction of the dose of hypoglycemic agents when combined with captopril.

Sympathomimetics may decrease the antihypertensive effect of captopril.

Enhances the plasma concentration of digoxin by 15-20%.

Lengthens the bioavailability of propranololol.

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

Concomitant use with thiazide diuretics vasodilators (minoxidil) verapamil beta-adrenoblockers tricyclic antidepressants or ethanolomuimulates the antihypertensive effect.

Estramustine

Concomitant use may increase the risk of side effects such as angioedema.

Baclofen

Accelerates the antihypertensive effect of ACE inhibitors. BP should be monitored carefully and the dosage of hypotensive drugs should be monitored if necessary.

Glyptins (linagliptin saxagliptin sitagliptin vildagliptin)

The combined use with ACE inhibitors may increase the risk of angioedema due to inhibition of dipeptidyl peptidase IV (DPP-IV) activity by glyptins.

Gold preparations

In the use of ACE inhibitors including captopril in patients receiving intravenous gold (sodium aurothiomalate), a symptom complex has been described including facial hyperemia nausea vomiting arterial hypotension.

Tricyclic antidepressants antipsychotics (neuroleptics) and agents for general anesthesia

Simultaneous use with ACE inhibitors may increase the antihypertensive effect (see section “Special Precautions”).

Hydrochlorothiazide

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

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

Other hypotensive agents – additive effect.

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

The corticosteroids ACTH (adrenocorticotropic hormone) or glycyrrhizic acid (found in licorice root) – pronounced reduction of electrolytes in particular risk of hypokalemia.

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

Myorelaxants of the non-depolarizing type of action (e.g., tubocurarin) – increase the effect of myorelaxants.

Lithium – Diuretics decrease renal clearance of lithium and increase the risk of lithium toxicity; concomitant use is not recommended.

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

In some patients with impaired renal function (e.g., 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 impairment of renal function including development of acute renal failure. These effects are reversible. Concomitant use of these drugs should be used with caution in patients with impaired renal function.

The administration of these drugs may interfere with parathyroid function tests due to their effect on calcium metabolism.

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

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

Cytostatic drugs such as cyclophosphamide methotrexate: increases myeloprotective effects by slowing elimination from the body.

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

Methyldopa: there have been described individual cases of hemolytic anemia with concomitant use of hydrochlorothiazide and methyldopa.

The concomitant use of cyclosporine increases the risk of hyperuricemia and aggravation of gout.

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

Calcium salts – Thiazide diuretics may increase serum calcium content due to decreased calcium excretion. If it is necessary to use calcium preparations, the dose should be adjusted under control of serum calcium content.

Vitamin D – increases the risk of hypercalcemia.

Impacts on laboratory results – through effects on calcium excretion, thiazides can distort the results of parathyroid function tests.

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

Iodine-containing contrast agents – if dehydration is caused by taking diuretics, there is an increased risk of acute renal failure, especially when high doses of iodine-containing drugs are administered. The patient should be rehydrated prior to administering such agents.

Amphotericin B (intravenous) stimulant laxatives – hydrochlorothiazide may increase electrolyte-water balance disorders, especially hypokalemia.

Protein-binding drugs intensify diuretic effect. It may be necessary to adjust the dose of anticoagulants for oral administration of probenecid and sulfinpyrazone because hydrochlorothiazide may inhibit their effect.

Special Instructions

An excessive decrease in blood pressure may be observed at the beginning of treatment especially in patients with chronic heart failure of severe arterial hypertension (including renal genesis) and/or renal insufficiency. Before the start of treatment it is necessary to compensate the deficiency of sodium ions and BOD (decrease the dose of previously prescribed diuretics or in some cases discontinue them completely) and determine the renal function parameters.

Phase and plasma levels of potassium and calcium ions should be monitored regularly (especially in patients treated with foxglutinators who frequently use laxatives and in elderly patients) glucose uric acid lipids (cholesterol and triglycerides) urea and creatinine “liver” enzyme activity.

Particular close monitoring of BP and laboratory values is necessary in the following cases: patients with renal insufficiency; patients with severe arterial hypertension (including of renal genesis); elderly patients (>65 years); patients with electrolyte-water balance disorders and decompensated CHF; as well as patients simultaneously receiving allopurinol, lithium salt procainamide and immunosuppressant drugs.

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

In some patients with renal disease, especially with severe renal artery stenosis, there is an increase in serum urea nitrogen and creatinine concentrations after reduction of BP. This phenomenon is usually reversible and a decrease in serum urea nitrogen and creatinine concentrations is observed when the drug is withdrawn. It may be necessary to reduce the dose of the drug Hydrochlorothiazide + Captopril and/or cancel the diuretic.

In some cases, during the use of ACE inhibitors, an increase in serum potassium is observed. The risk of hyperkalemia when using ACE inhibitors is increased in patients with impaired renal function and diabetes as well as those taking potassium-saving diuretics and or other drugs that cause increase in blood potassium content (e.g. heparin). Concomitant use of potassium-saving diuretics and potassium preparations should be avoided.

In addition, when ACE inhibitors are used concomitantly with thiazide diuretics, there is a risk of hypokalemia, so regular monitoring of blood potassium levels should be performed during therapy.

Patients with mitral/aortic stenosis/hypertrophic obstructive cardiomyopathy should use ACE inhibitors with cardiogenic shock and hemodynamically significant obstruction with caution – admission is not recommended.

The use of dual RAAS blockade caused by concomitant use of ACE inhibitors and ARAII or aliskiren and aliskiren-containing drugs is not recommended because it has been associated with an increased incidence of side effects such as arterial hypotension hyperkalemia decreased renal function (including acute renal failure). If simultaneous use of ACE inhibitors and ARAII (dual RAAS blockade) is indicated, therapy should be performed under medical monitoring with continuous monitoring of renal function, blood electrolyte levels, and blood pressure.

The concomitant use of ACE inhibitors and ARASII is not recommended in patients with diabetic nephropathy.

When performing hemodialysis in patients treated with ACE inhibitors, the use of dialysis membranes with high permeability (e.g., AN®69) should be avoided because this increases the risk of anaphylactoid reactions. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein removal (apheresis) by absorption with dextran sulfate. The use of either a different class of hypotensive drugs or a different type of dialysis membrane should be considered.

If angioedema develops, the drug should be withdrawn and closely monitored until symptoms have completely resolved. Angioedema of the larynx may be fatal. Subcutaneous administration of epinephrine (adrenaline) (03-05 ml diluted 1:1000) is usually unnecessary if the swelling is localized to the face (antihistamines may be used to relieve symptoms), but if it spreads to the tongue, pharynx or larynx and there is danger of airway obstruction. In rare cases, patients have experienced angioedema of the intestine accompanied by abdominal pain (with or without nausea and vomiting) after ACE inhibitors administration. Sometimes, with normal values of C-1 esterase activity and without preceding facial edema. Intestinal edema should be included in the spectrum of differential diagnosis of patients with complaints of abdominal pain while taking ACE inhibitors.

The incidence of angioneurotic edema was higher in the Negro race than in the Caucasian race.

Two patients undergoing Hymenoptera venom desensitization on captopril experienced life-threatening anaphylactoid reactions. Temporary withdrawal of the ACE inhibitor prevented anaphylactoid reactions. Caution should be exercised when performing desensitization therapy in patients taking ACE inhibitors.

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

In major surgical procedures or when using general anesthesia drugs with antihypertensive effect, patients receiving ACE inhibitors may experience an excessive decrease in BP. In these cases, it is possible to increase the OBC.

In rare cases when taking ACE inhibitors a syndrome has been observed that begins with the appearance of cholestatic jaundice followed by fulminant hepatonecrosis sometimes with a lethal outcome. The mechanism of this syndrome is unknown. If a patient on ACE inhibitor therapy develops jaundice or transient increase in liver transaminase activity, discontinue ACE inhibitor therapy and establish patient monitoring.

In patients taking ACE inhibitors neutropenia/agranulocytosis thrombocytopenia and anemia have been reported. In patients with normal renal function and in the absence of other disorders neutropenia is rare.

Hydrochlorothiazide + captopril should be used with caution in patients with autoimmune connective tissue diseases in patients taking immunosuppressors allopurinol and procainamide especially if there is a history of renal impairment. Because most fatal cases of neutropenia with ACE inhibitors have occurred in these patients, their white blood cell count should be monitored every two weeks for the first three months and then every two months thereafter.

All patients should have their blood leukocyte counts monitored monthly for the first 3 months of therapy and then every 2 months thereafter. If leukocyte count is below 4000/μL, a repeat of general blood test below 1000/μL is indicated – the drug should be discontinued and the patient should be monitored further. Usually restoration of neutrophil number occurs within 2 weeks after captopril withdrawal. In 13% of cases of neutropenia, a lethal outcome has been observed.

In almost all cases, death has been seen in patients with connective tissue disease of renal or cardiac insufficiency while taking immunosuppressors or a combination of both.

When using ACE inhibitors, proteinuria may occur primarily in patients with impaired renal function and when using high doses of the drugs. In most cases, proteinuria with captopril has disappeared or reduced within 6 months irrespective of whether or not the drug was discontinued. Renal function parameters (urea nitrogen and creatinine concentrations) in patients with proteinuria were almost always within normal limits. In patients with kidney disease the urine protein content should be determined before the start of treatment and periodically during the course of therapy.

In cases of agranulocytosis and inhibition of bone marrow function have been reported while taking thiazide diuretics.

Hydrochlorothiazide may cause an idiosyncratic reaction leading to the development of acute myopia and an acute attack of secondary closed angle glaucoma. Symptoms include a sudden decrease in visual acuity or eye pain that usually occurs within hours or weeks of starting hydrochlorothiazide therapy. Untreated acute angle-closure glaucoma can lead to permanent loss of vision. Treatment: Discontinue hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medication or surgery may be required. Risk factors for acute angle-closure glaucoma include a history of allergic reaction to sulfonamides or penicillin.

In all patients receiving thiazide diuretics, clinical signs of water-electrolyte imbalance (hyponatremia hypochloremic alkalosis hypokalemia) should be identified. It is especially important to determine the content of electrolytes in the serum and urine in case of severe vomiting or infusion of infusion solutions. Signs of disorders of water-electrolyte balance may be dryness of the mucous membrane of the mouth thirst weakness lethargy confusion restlessness pain or muscle cramps muscle weakness excessive decrease in BP oliguria tachycardia nausea vomiting.

Hypokalemia may provoke or exacerbate the cardiotoxic effects of cardiac glycosides. In patients with edema in hot weather there may be hyponatremia caused by increase in CIC. Fluid intake should be restricted. In cases of life-threatening hyponatremia, administration of table salt is prescribed. During therapy with thiazide diuretics hyperuricemia or aggravation of gout course may be noted; latent diabetes mellitus may also manifest.

Thiazide diuretics may decrease serum concentrations of bound iodine without evidence of thyroid dysfunction.

The administration of thiazide diuretics decreases calcium excretion; cases of parathyroid gland pathological changes accompanied by hypercalcemia and hypophosphatemia have been reported. Before examining the parathyroid gland function, thiazide diuretics should be discontinued. Increased magnesium excretion has been noted with thiazide diuretics, which may lead to hypomagnesemia.

The drug may cause false-positive urinalysis for acetone and distort the results of the benthiromide test.

In case of fever, lymph node enlargement and/or signs of laryngitis and/or pharyngitis, the leukocyte count should be determined immediately.

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

When taking this medicine, caution should be exercised while driving vehicles, operating machinery, and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Synopsis

Contraindications

Hypersensitivity to captopril or other ACE inhibitors thiazide diuretics and other sulfonamide derivatives (cross-allergic reactions possible) to any component of the drug; hereditary or idiopathic angioedema including history of ACE inhibitors; aortic stenosis mitral stenosis; hypertrophic obstructive cardiomyopathy; bilateral renal artery stenosis renal artery stenosis of a single kidney condition after renal transplantation (in anamnesis); chronic heart failure; cardiogenic shock arterial hypotension tachycardia severe hepatic insufficiency (precoma or coma); severe renal insufficiency (serum creatinine greater than 18 mg/100 ml or creatinine clearance (CK) less than 20-30 ml/min anuria); primary hyperaldosteronism; pregnancy breastfeeding age less than 18 years (efficacy and safety not established) concomitant 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.

Moderate renal insufficiency (CK 30-60 ml/min) proteinuria (more than 1 g/day) hepatic function disorders progressive liver disease hypokalemia (not corrected by medication); hyponatremia hypovolemia hypercalcemia gout hyperuricemia systemic connective tissue diseases and other immune diseases (including.ч. systemic lupus erythematosus scleroderma nodular periarteritis); elderly (>65 years) concomitant use of drugs that suppress immune responses (glucocorticosteroids (GCS) cytostatics immunosuppressants) allopurinol procainamide surgery/general anesthesia use in patients of non-high non-human race patients hemodialysis using high-flow membranes (e.g., AN69®) desensitization therapy concomitant use of potassium-saving diuretics potassium preparations and potassium-containing salt substitutes lithium preparations acute myopia and secondary closed-angle glaucoma.

Side effects

The frequency of side effects is stated according to the World Health Organization classification: frequently – ≥ 1/100 – < 1/10 infrequently – ≥ 1/1000 – < 1/100 rarely – ≥ 1/10000 – < 1/1000 very rarely – < 1/10000.

Cardiovascular system disorders:

infrequent – chest pain angina pectoris “rushes” of blood to the skin of the face tachycardia or tachyarrhythmia feeling of palpitations peripheral edema pronounced BP decrease (including orthostatic) with symptoms of dizziness feeling of weakness Raynaud’s syndrome myocardial infarction fainting; very rare – cardiogenic shock.

Respiratory system disorders:

often – “dry” non-productive cough dyspnea; very rare – bronchospasm eosinophilic pneumonitis sinusitis rhinitis laryngitis pulmonary edema.

Allergic reactions:

often- skin itching with or without rashes sometimes accompanied by fever and arthralgia skin rash alopecia; infrequent- vascular edema of the skin and subcutaneous tissue; rare- angioedema- bowel; very rare – urticaria Stevens-Johnson syndrome erythema multiforme erythema photosensitivity erythroderma reversible pemphigoid reactions exfoliative dermatitis and toxic epidermal necrolysis (Lyell syndrome) allergic alveolitis eosinophilic pneumonia angioedema pharynx pharynx tongue face mucous membranes (including fatal) respiratory distresssyndrome (including pneumonitis and noncardiogenic pulmonary edema).

The central and peripheral nervous system:

often drowsiness dizziness insomnia; rarely headache ataxia paresthesia; very rarely confusion depression cerebral circulatory disorders including stroke and syncope blurred vision.

The hematopoietic system:

very rare – anemia including aplastic and hemolytic forms decrease in hematocrit thrombocytopenia leukopenia neutropenia (up to development of pancytopenia and agranulocytosis – especially with simultaneous administration of allopurinol procainamide and also immunosuppressants) eosinophilia lymphadenopathy increased antinuclear antibody titer autoimmune diseases.

Digestive system disorders:

Frequent – reversible and usually self-cure impairment of sense of taste nausea vomiting constipation or diarrhea feeling of discomfort in the stomach area dyspepsia abdominal pain dry oral mucosa; anorexia – stomatitis aphthous stomatitis; very rare – glossitis pancreatitis gastric ulcer hyperplasia gum disorders and cholestasis (including jaundice) increased “liver” transaminases activity hepatitis (including necrosis) hyperbilirubinemia.

Musculoskeletal system disorders:

very rarely – myalgia arthralgia myasthenia.

Anxiety of the urinary system:

infrequent – impaired renal function (including renal failure) polyuria oliguria rapid urination nephrotic syndrome.

Reproductive system disorders:

very common – impotence gynecomastia.

Others:

infrequent – breast pain increased fatigue malaise.

Laboratory findings:

often – eosinophilia;

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

Mechanical side:

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

Tiazide treatment may impair glucose tolerance and latent diabetes mellitus may manifest. Serum lipid concentrations may increase with high doses.

Disorders of water-electrolyte balance: hypokalemia hypomagnesemia hypercalcemia and hypochloremic alkalosis: dry oral mucosa thirst feeling irregular heart rhythm changes in mood or psyche cramps and muscle pain nausea vomiting unusual tiredness or weakness. Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma.

Hyponatremia: confusion convulsions lethargy slowed thought process increased fatigue excitability muscle cramps.

In the use of ACE inhibitors, including captopril in patients receiving intravenous gold (sodium aurothiomalate), a symptom complex has been described including facial hyperemia, nausea, vomiting, arterial hypotension.

Overdose

Symptoms: marked BP decrease shock stupor bradycardia impairment of water-electrolyte balance renal failure lethargy (which may progress to coma within hours) without impairment of water-electrolyte balance and causing only slight suppression of respiratory and cardiac function. Irritation of the gastric mucosa and increased gastrointestinal contractility may be noted.

Treatment: gastric lavage administration of adsorbents and sodium sulfate for 30 minutes after administration of 09% sodium chloride solution or other plasma substitute solutions hemodialysis.

In case of bradycardia or marked vagus reactions, atropine administration.

The use of an artificial pacemaker may be considered.

Peritoneal dialysis is ineffective in eliminating captopril from the body.

Pregnancy use

The use of hydrochlorothiazide + captopril during pregnancy is contraindicated.

Epidemiologic data suggesting a risk of teratogenicity after exposure to ACE inhibitors in the first trimester of pregnancy have not been conclusive; however, some increased risk cannot be excluded. If ACE inhibitor use is deemed necessary, patients planning pregnancy should be switched to an alternative hypotensive therapy with a proven safety profile during pregnancy.

It is known that long-term exposure of the fetus to ACE inhibitors in the second and third trimesters of pregnancy may lead to impaired fetal development (decreased renal function, oligohydramnios delayed ossification of the cranial bones) and development of complications in the newborn (renal failure, hypotension, hyperkalemia).

If the patient received hydrochlorothiazide + captopril during the second or third trimester of pregnancy, an ultrasound examination of the fetus is recommended to evaluate cranial bones and renal function.

The use of hydrochlorothiazide in pregnancy is not recommended because it may impair placental perfusion and cause fetal/neonatal thrombocytopenia thrombocytopenia impaired water-electrolyte balance and possibly other adverse reactions observed in adults.

The use of ACE inhibitors during pregnancy may cause developmental abnormalities (including arterial hypotension neonatal skull bone hypoplasia anuria reversible or irreversible renal failure) and fetal death. If pregnancy is diagnosed, hydrochlorothiazide + captopril should be discontinued as soon as possible.

Captopril and hydrochlorothiazide are detected in breast milk after oral administration by a nursing woman. Because of the risk of serious adverse reactions in the baby caused by both active substances, breastfeeding should be stopped or therapy with hydrochlorothiazide + captopril with the mother should be discontinued while breastfeeding.

Similarities