Instructions for Normopres tablets No. 20
Composition
active ingredients: captopril, hydrochlorothiazide;
1 tablet contains captopril 50 mg, hydrochlorothiazide 25 mg;
Excipients: lactose monohydrate; potato starch; microcrystalline cellulose; povidone; talc; stearic acid; calcium stearate.
Dosage form
Pills.
Main physicochemical properties: round tablets with a flat surface, with beveled edges and a score, white or pale yellow in color.
Pharmacotherapeutic group: ACE inhibitor combinations. Captopril and diuretics. ATC code: C09B A01.
Pharmacological properties
Pharmacodynamics.
Normopres is a combined antihypertensive drug containing a dosed combination of captopril and hydrochlorothiazide.
Captopril is an angiotensin-converting enzyme (ACE) inhibitor. It inhibits the formation of angiotensin II, preventing its vasoconstrictor action and stimulating effect on the secretion of aldosterone in the adrenal glands. It reduces total peripheral vascular resistance, blood pressure, reduces preload on the myocardium, and reduces pressure in the right atrium and the pulmonary circulation.
Hydrochlorothiazide exhibits a moderately pronounced diuretic effect, increasing the excretion of sodium, chlorine, potassium and water ions from the body. Reduces the content of sodium ions in the vascular wall, reducing its sensitivity to vasoconstrictor effects and thereby enhancing the antihypertensive effect of captopril.
Pharmacokinetics.
Captopril is actively absorbed in the digestive tract when administered orally. The time to reach maximum plasma concentration is approximately 1 hour. 25-30% of captopril is bound to plasma proteins. Metabolized in the liver. The main metabolites are captopril-cysteine, a disulfide dimer of captopril. The half-life (T½) is approximately 2-3 hours. 95% of captopril is excreted by the kidneys: 50% as metabolites, up to 50% unchanged.
Hydrochlorothiazide is absorbed from the gastrointestinal tract by 68-78% when administered orally. The elimination half-life (T½) is approximately 3-4 hours. 20-75% of hydrochlorothiazide is excreted unchanged by the kidneys.
In patients with renal insufficiency, the elimination of the drug is slowed down.
Indication
Arterial hypertension.
Contraindication
Hypersensitivity to captopril, to other ACE inhibitors, to hydrochlorothiazide, to other sulfonamide-derived drugs, or to any of the other ingredients of the drug.
History of angioedema during treatment with other ACE inhibitors.
Congenital (idiopathic) angioedema.
Bilateral renal artery stenosis or stenosis of the artery to a solitary kidney with progressive azotemia.
Condition after kidney transplantation.
Anury.
Narrowing of the aortic orifice or mitral stenosis, the presence of other obstacles to the outflow of blood from the left ventricle of the heart.
Hypertrophic cardiomyopathy with low cardiac output.
Hyperkalemia.
Treatment-resistant hypokalemia or hypercalcemia.
Refractory hyponatremia.
Symptomatic hyperuricemia (gout).
Primary hyperaldosteronism.
Porphyria.
Severe renal impairment (creatinine clearance < 30 ml/min).
Severe liver dysfunction (precomatose state, hepatic coma, liver failure).
Pregnant women or women planning to become pregnant (see section “Use during pregnancy or breastfeeding”).
Breastfeeding (see section "Use during pregnancy or breastfeeding").
Concomitant use of aliskiren-containing drugs in patients with diabetes mellitus or renal impairment (glomerular filtration rate < 60 ml/min/1.73 m2).
Interaction with other medicinal products and other types of interactions
When using the drug simultaneously with such drugs, it is possible:
with diuretics (thiazide or loop) - risk of developing arterial hypotension due to dehydration caused by taking high doses of diuretics; the hypotensive effect can be reduced by stopping diuretics, increasing fluid and salt intake, and reducing the initial doses of captopril;
with potassium-sparing diuretics or potassium supplements. ACE inhibitors reduce potassium loss caused by diuretics. Potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), potassium supplements or salt substitutes containing potassium may lead to hyperkalaemia. When co-administered because of pre-existing hypokalaemia, they should be used with great caution and with frequent monitoring of serum potassium.
with α- and β-adrenergic blockers, long-acting calcium channel blockers and other antihypertensive agents, organic nitrates, MAO inhibitors, hypnotics (nitrazepam), tranquilizers (alprazolam) - increased hypotensive effect of the drug; use the combination of these drugs with caution;
with sympathomimetics, estrogens, methanamine - weakening of the hypotensive effect of the drug, therefore the patient's blood pressure should be carefully monitored;
with nonsteroidal anti-inflammatory drugs (NSAIDs) – weakening of the hypotensive effect of the drug and decreased renal function with an increase in the concentration of potassium in the blood plasma; rarely, the development of acute renal failure is possible, especially in patients with impaired renal function.
The combination of these drugs should be used with caution. Before starting treatment, water-salt metabolism should be normalized, and during treatment, periodic monitoring of renal function should be carried out. When using large doses of salicylates, hydrochlorothiazide may enhance their toxic effect on the central nervous system;
with drugs that increase the concentration of potassium in the blood serum (heparin, cyclosporine, potassium-sparing diuretics - amiloride, spironolactone, triamterene), drugs and supplements containing potassium - a noticeable increase in the concentration of potassium in the blood plasma; it is not recommended to use the combination of these drugs simultaneously; when prescribed simultaneously due to existing hypokalemia, they should be used with great caution and with frequent monitoring of the concentration of potassium in the blood serum;
with allopurinol, procainamide, immunosuppressive (azathioprine) and cytostatic agents - concomitant use with ACE inhibitors may lead to an increased risk of leukopenia, especially if the latter are used in doses higher than recommended;
with diazoxide - increased hyperglycemic, hyperuricemic, hypotensive effects; periodic monitoring of blood glucose levels and uric acid concentration may be necessary;
with anesthetics, non-depolarizing muscle relaxants, drugs for initiating anesthesia (tubocurarine chloride, gallamine triethiodide) - increased action of the above drugs; it may be necessary to adjust the dose and water-salt metabolism before surgery;
with lithium preparations - simultaneous use of ACE inhibitors and lithium may cause a temporary increase in serum lithium levels and lithium intoxication. Concomitant use of ACE inhibitors and thiazide diuretics may further increase serum lithium levels and increase the risk of lithium intoxication. Therefore, simultaneous use of captopril with lithium is not recommended. If such a combination of drugs is necessary, careful monitoring of serum lithium levels should be carried out;
with cardiac glycosides – increased toxicity of digitalis drugs (arrhythmias) against the background of hypokalemia caused by hydrochlorothiazide;
with carbamazepine - increased risk of hyponatremia; periodic monitoring of electrolyte levels may be necessary;
with amphotericin B, carbenoxolone, glucocorticosteroids, corticotropin, stimulant laxatives - increased electrolyte imbalance, in particular the occurrence of hypokalemia;
with metformin – metabolic acidosis in patients with impaired renal function;
with methyldopa – in some cases – hemolytic anemia;
with antidiabetic drugs, oral anticoagulants, drugs for the treatment of gout - weakening of the effect of the above drugs; dose adjustment of the drugs may be necessary;
with drugs whose effects are affected by changes in blood plasma potassium levels, including:
antiarrhythmic drugs of class IA (quinidine, hydroquinidine, disopyramide), class III (amiodarone, sotalol, dofetilide, ibutilide);
neuroleptics (thioridazine, chlorpromazine, levomepromazine, trifluoroperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);
other agents: bepridil, cisapride, diphemanil, erythromycin intravenously, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine intravenously – there is a risk of developing torsades de pointes against the background of possible hypokalemia and hypomagnesemia; periodic monitoring of potassium levels in blood plasma and electrocardiogram (ECG) is necessary;
with pressor amines (noradrenaline) – treatment with the drug should be discontinued one week before the start of surgery;
with antacids, food, colestipol, cholestyramine – reduced absorption and reduced bioavailability of the drug;
with probenecid – decreased excretion of captopril;
with iodinated contrast media - increased risk of acute renal failure, especially with high doses, due to dehydration caused by hydrochlorothiazide. Before the administration of iodine, it is necessary to normalize the fluid level in the body.
The use of the drug may lead to a positive result in a urine test for acetone.
Cytotoxic agents (e.g. cyclophosphamide, methotrexate): Thiazides may reduce the renal excretion of cytotoxic drugs and potentiate their myelosuppressive effect.
Anticholinergics (e.g. atropine, biperiden): Bioavailability of thiazide-type diuretics increases due to decreased gastrointestinal motility and decreased gastric emptying rate.
Cyclosporine: Concomitant use of cyclosporine may exacerbate hyperuricemia and increase the risk of complications such as gout.
NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid >3 g/day and non-selective NSAIDs. When taken concomitantly, NSAIDs may reduce the antihypertensive effect of hydrochlorothiazide and increase the effect of hydrochlorothiazide on serum potassium levels.
Medicinal products affected by changes in serum potassium: Periodic monitoring of serum potassium and ECG is recommended when hydrochlorothiazide is administered concomitantly with medicinal products affected by changes in serum potassium (e.g. digitalis glycosides and antiarrhythmic medicinal products) and medicinal products known to induce torsades de pointes (ventricular tachycardia) (including some antiarrhythmic medicinal products), as hypokalaemia is a predisposing factor to torsades de pointes.
The drug can be used for the treatment of acute myocardial infarction in combination with acetylsalicylic acid (cardiological doses), thrombolytic agents, β-adrenoblockers and/or nitrates.
Other antihypertensive drugs. The simultaneous use of captopril with other antihypertensive drugs (e.g., β-blockers and long-acting calcium channel blockers) is safe, but concomitant use of such drugs may increase the hypotensive effect of captopril. Caution should be exercised when nitroglycerin, other nitrates, or other drugs are used concomitantly.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is associated with a higher incidence of adverse reactions such as hypotension, hyperkalemia, and decreased renal function (including acute renal failure) compared with the use of RAAS-acting agents alone.
Application features
Before starting the drug, diuretics should be reduced or completely discontinued. Before prescribing ACE inhibitors, the circulating blood volume (CVV) should be corrected, and the issue of prescribing the lowest effective optimal dose of the drug should be resolved.
During the use of the drug, the level of electrolytes (in particular potassium), the content of urea and creatinine in blood plasma, and the peripheral blood picture should be periodically determined.
A low-sodium diet is recommended while using the drug.
It is not recommended to drink alcoholic beverages while using the medicine.
The drug should be used with caution in patients with impaired water and electrolyte balance (due to intensive diuretic therapy, diarrhea, vomiting, low-sodium diet) and in patients on hemodialysis, as the development of arterial hypotension is possible. Before using the drug, correction of water and electrolyte balance should be performed.
The drug should be used with caution in patients with severe cardiac disorders, elderly patients (aged 65 and over). The drug should be prescribed to this category of patients only under careful monitoring of blood pressure, kidney function, and water and electrolyte metabolism.
In case of hypotension, the patient should be placed in a horizontal position (on his back), and if necessary, increase the BCC by administering 0.9% sodium chloride solution.
Features of use related to the presence of captopril in the composition of the medicinal product
The drug should be used with caution in patients with impaired renal function (creatinine clearance less than 40 ml/min). Initial doses of captopril should be prescribed in accordance with creatinine clearance, and subsequently - depending on the patient's response to treatment. Regular monitoring of renal function indicators should be carried out (at the beginning and periodically during treatment): determine the level of potassium and creatinine in the blood plasma.
The drug should be used with caution in patients with uncomplicated arterial hypertension, since in some cases symptomatic arterial hypotension may develop. The likelihood of its development increases in patients with impaired water and electrolyte balance (due to intensive diuretic therapy, diarrhea, vomiting, low-sodium diet) and in patients on hemodialysis. Symptomatic hypotension has also been observed in patients with heart failure. Treatment of such patients should be started under medical supervision, with low doses, and the doses should be carefully selected. This also applies to patients with ischemic heart disease or cerebrovascular diseases, in whom a significant decrease in blood pressure can lead to myocardial infarction or cerebrovascular accident (stroke).
It is necessary to avoid taking captopril in the event of the development of cardiogenic shock and significant hemodynamic disturbances.
It is clear that the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended.
If dual blockade therapy is necessary, it should be carried out under medical supervision with frequent monitoring of renal function, electrolytes and blood pressure.
ACE inhibitors and angiotensin II receptor blockers should not be used simultaneously in patients with diabetic nephropathy.
The drug should be used with caution in diabetic patients taking oral antidiabetic agents or insulin, and blood glucose levels should be monitored regularly, especially during the first month of treatment.
Very rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses rapidly to hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not known. Patients receiving ACE inhibitors who develop jaundice or marked elevations of liver enzymes should discontinue ACE inhibitors and consult a physician.
In patients with impaired renal function or those taking relatively high doses of captopril (more than 150 mg/day), proteinuria may develop. Proteinuria of more than 1 g/day has been reported in approximately 0.7% of patients treated with captopril. Nephrotic syndrome has been diagnosed in 20% of patients with proteinuria. In most cases, proteinuria resolved within 6 months of drug withdrawal. Renal function parameters such as blood urea nitrogen and creatinine levels were rarely altered. In patients with impaired renal function, proteinuria should be determined before treatment and periodically monitored during drug therapy.
Cases of neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients taking ACE inhibitors. Neutropenia is rare in patients with normal renal function in the absence of other factors. The drug should be administered with extreme caution to patients with collagen diseases, patients receiving immunosuppressants, taking allopurinol or procainamide, and in combination with these conditions, especially against the background of existing renal dysfunction. Some such patients develop severe infections that do not always respond to intensive antibiotic therapy. When using the drug in such patients, periodic monitoring of the number of leukocytes in the blood and their differential count should be carried out (before treatment, every 2 weeks during the first three months of therapy and periodically thereafter) and the patient should be warned about the need to report any signs of infection (fever, enlarged lymph nodes, sore throat). If neutropenia (neutrophil count < 1000/mm3) occurs, the drug should be discontinued. After discontinuation of therapy, the neutrophil count rapidly returns to normal in most patients.
Some patients taking ACE inhibitors, including captopril, have experienced increases in serum potassium. Patients at risk for hyperkalemia include patients with renal insufficiency, diabetes mellitus, those taking potassium-sparing diuretics, potassium supplements, and those taking other medicinal products that increase serum potassium. If the use of these medicinal products during treatment with ACE inhibitors is necessary, serum potassium levels should be monitored regularly.
Angioedema of the face, extremities, lips, tongue, glottis and larynx has been reported in some patients receiving ACE inhibitors, especially during the first weeks of treatment. In some cases, angioedema may develop even after prolonged treatment with ACE inhibitors. Isolated fatalities have been reported due to angioedema of the larynx or tongue. If edema develops, captopril should be discontinued immediately and appropriate treatment should be initiated. The patient should be hospitalized and observed for at least 12-24 hours until symptoms have resolved. Black patients are at increased risk of developing angioedema.
In patients undergoing surgery or anesthesia with drugs that lower blood pressure, captopril may block the increase in angiotensin II formation under the influence of compensatory renin release. Hypotension resulting from this mechanism should be corrected by the introduction of additional fluid volume.
During the use of ACE inhibitors, patients may develop a persistent non-productive cough that disappears after discontinuation of treatment.
Patients receiving ACE inhibitors during hemodialysis using high-flux membranes may develop persistent anaphylactoid reactions. These reactions can be avoided by changing the dialysis membrane to a different type of membrane or by using a different class of antihypertensive agent.
Patients receiving ACE inhibitors may develop persistent anaphylactoid reactions during low-density lipoprotein apheresis. These reactions can be avoided by changing the dialysis membrane to a different type of membrane or by using a different class of antihypertensive agent.
Cross-hypersensitivity is possible for drugs containing ACE inhibitors.
The use of ACE inhibitors, including captopril, in patients of the Negroid race is less effective in lowering blood pressure than in patients of other races, due to the predominance of low-renin fractions.
Concomitant use of the drug with lithium is not recommended due to increased toxicity of the latter.
Features of use related to the presence of hydrochlorothiazide in the composition of the medicinal product
As with other antihypertensive drugs, symptomatic hypotension may occur in some patients.
Thiazide therapy may reduce glucose tolerance. It may be necessary to modify the doses of antidiabetic agents, including insulin. Latent diabetes mellitus may manifest during thiazide therapy.
Thiazides may reduce renal calcium excretion and may also cause a small, transient increase in serum calcium. Significant hypercalcemia may be a manifestation of latent hyperparathyroidism.
Hypersensitivity reactions may occur in patients receiving thiazides, especially in patients with a history of allergy or bronchial asthma, and in patients who have not previously suffered from these diseases. There have been reports of exacerbation or activation of systemic lupus erythematosus while taking thiazides.
The medicine may affect the results of the following laboratory tests:
the drug may reduce the level of protein-bound iodine in blood plasma;
Treatment with the drug should be discontinued before laboratory testing to assess parathyroid function;
The drug is capable of increasing the concentration of free bilirubin in the blood serum.
The drug should be used with caution in cases of impaired liver function or progressive liver disease, since thiazide diuretics can cause disturbances in water and electrolyte balance, which can lead to the rapid development of hepatic coma. The drug should be prescribed to this category of patients only under careful monitoring of blood pressure, kidney function, and water and electrolyte metabolism.
The drug should be used with caution in cases of impaired renal function, since thiazide diuretics can cause azotemia. Cumulation of the drug is also possible. In the case of progression of kidney diseases characterized by an increase in the level of residual blood nitrogen, the feasibility of continuing therapy should be carefully assessed and, if necessary, treatment should be discontinued.
The hypotensive effect of hydrochlorothiazide may be enhanced after sympathectomy.
Patients taking hydrochlorothiazide may experience exacerbation of gout due to increased uric acid concentration, clinical detection of latent diabetes mellitus, and exacerbation of systemic lupus erythematosus.
Photosensitivity reactions have been reported during treatment with thiazide diuretics. If photosensitivity reactions occur during treatment with the drug, it is recommended to discontinue the drug. If the doctor considers it necessary to re-prescribe the diuretic, it is recommended to protect areas of the body exposed to sunlight or artificial UV radiation.
Hydrochlorothiazide can cause water and electrolyte imbalance (hypokalemia, hyponatremia and hypochloraemic alkalosis). Symptoms: dry mouth, thirst; weakness, lethargy, drowsiness, restlessness; muscle pain or cramps, muscle weakness; arterial hypotension; oliguria; tachycardia and gastrointestinal disorders such as nausea and vomiting. Although concomitant use with captopril reduces the risk of developing hypokalemia caused by hydrochlorothiazide, patients with cirrhosis of the liver, increased diuresis, insufficient oral replacement of electrolyte losses, as well as individuals receiving therapy with glucocorticosteroids or adrenocorticotropic hormone may develop hyponatremia in hot weather in patients prone to edema, usually mild and not requiring treatment.
Hydrochlorothiazide may cause hypercalcemia, therefore, the drug should be discontinued before determining parathyroid function.
Hydrochlorothiazide may increase cholesterol and triglyceride levels, and decrease blood levels of magnesium and iodine-binding thyroglobulin (without signs of thyroid dysfunction).
Non-melanoma skin cancer. The results of two recent pharmacoepidemiological studies (based on Danish national data sources, including the Danish Cancer Registry and the National Register of Prescribed Medicines) have shown a cumulative dose-dependent association between the use of hydrochlorothiazide and the occurrence of basal cell carcinoma and squamous cell carcinoma. The photosensitizing effect of hydrochlorothiazide may be a cause of the development of these pathologies. Patients taking hydrochlorothiazide alone or in combination with other drugs should be informed of the risk of non-melanoma skin cancer and advised to regularly examine their skin for new lesions, as well as changes in existing ones, and to report any suspicious skin lesions.
Suspicious skin lesions should be histologically examined by biopsy. Patients should be advised to limit exposure to sunlight and UV rays and to use appropriate protection when exposed to sunlight and UV rays to minimize the risk of skin cancer.
The use of hydrochlorothiazide should also be carefully reconsidered in patients with a history of skin cancer (see section 4.8).
The medicinal product contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not take this medicine.
Use during pregnancy or breastfeeding
The drug is contraindicated for use in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with the drug, its use should be immediately discontinued and replaced with another drug approved for use in pregnant women.
The medicine should not be used during breastfeeding.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
When using the drug, you should refrain from driving vehicles or working with other mechanisms, as dizziness and drowsiness are possible, especially at the beginning of therapy.
Method of administration and doses
The drug should be taken orally 1 hour before meals, as its absorption is reduced if food is present in the stomach.
The dose of the drug should be set individually, depending on the clinical picture of the disease.
The initial dose is ½ tablet (25 mg captopril and 12.5 mg hydrochlorothiazide) once a day.
In the future, if necessary, the maintenance dose can be increased to 1 tablet (50 mg of captopril and 25 mg of hydrochlorothiazide) once a day.
The maximum therapeutic effect occurs 6-8 weeks after the start of treatment. Dose adjustment should be carried out at 6-week intervals, unless clinical manifestations require a more rapid change in dosage. If blood pressure is insufficiently reduced, captopril and hydrochlorothiazide can be additionally included in the treatment regimen as monodrugs. In this case, the daily dose of captopril should not exceed 150 mg, hydrochlorothiazide - 50 mg.
Patients with impaired renal function.
Since captopril and hydrochlorothiazide are excreted from the body mainly by the kidneys, the level of the drugs may increase if their function is impaired. It is recommended to reduce the dose of the drug: with creatinine clearance from 30 to 80 ml/min, the initial dose is ½ tablet (25 mg of captopril and 12.5 mg of hydrochlorothiazide) once a day, in the morning.
Children.
There is no data on the use of the drug in children.
Overdose
Captopril
Symptoms: sudden decrease in blood pressure, tachycardia, headache, loss of appetite, taste disturbances, skin allergic reactions, neutropenia. In severe cases, convulsions, paresis, shock, stupor, cardiac arrhythmia, bradycardia, renal failure, electrolyte imbalance are possible. If these symptoms appear, you should immediately stop taking the drug and consult a doctor.
The patient should be placed in a horizontal position and the stomach should be washed.
In case of severe symptoms of overdose, the patient should be urgently hospitalized for intensive detoxification methods, including hemodialysis, and measures aimed at increasing the volume of circulating blood, normalizing the functions of the cardiovascular, respiratory and nervous systems, and restoring kidney function. It is necessary to avoid hemodialysis through high-performance membranes made of polyacrylonitrile metallosulfate (AN69), hemofiltration due to the possibility of developing anaphylactoid reactions. Peritoneal dialysis is ineffective.
Treatment: Symptomatic therapy aimed at normalizing blood pressure and eliminating other symptoms.
Symptoms: weakness, nausea, vomiting, diarrhea. These phenomena quickly disappear when the dose is reduced or the drug is discontinued. In some cases, when taking high doses of the drug, the following symptoms have been reported: tachycardia, arterial hypotension, shock, dizziness, confusion, impaired consciousness, muscle spasms, paresthesias, exhaustion, polyuria, oliguria, anuria, hypokalemia, hyponatremia, hypochloremia, alkalosis, increased blood urea nitrogen (in patients with renal failure). Severe manifestations of overdose may be severe disturbances of water and electrolyte balance and the development of a comatose state as a result of the direct pathological effect of hydrochlorothiazide on the central nervous system, weakness, nausea, vomiting, thirst.
Treatment. To remove the drug from the stomach, it is recommended to induce vomiting, rinse the stomach, and use sorbents. In case of severe manifestations of overdose, the patient is subject to immediate hospitalization in a specialized medical institution for intensive detoxification measures (hemodialysis), as well as elimination of water and electrolyte disorders, normalization of the function of the cardiovascular, respiratory and central nervous systems, and restoration of kidney function. There is no specific antidote. In case of arterial hypotension and shock, administration of fluid and electrolytes (potassium, sodium, magnesium) is recommended. Until the patient's condition normalizes, control of fluid and electrolyte balance and kidney function is necessary.
Adverse reactions
Captopril
From the blood and lymphatic system: eosinophilia, pancytopenia (especially in patients with impaired renal function), thrombocytopenia, anemia (including aplastic and hemolytic), leukopenia, neutropenia, agranulocytosis.
Metabolism: anorexia, hypoglycemia, hyperkalemia, hyponatremia.
From the side of the central nervous system: headache, drowsiness, taste disturbance, dizziness, paresthesia, cerebrovascular accident (including stroke and syncope), asthenia.
Psychiatric: sleep disturbances, confusion, depression.
From the organs of vision: blurred vision.
Cardiovascular system: tachycardia or tachyarrhythmia, angina pectoris, palpitations, cardiogenic shock, cardiac arrest, hypotension, Raynaud's syndrome, hot flashes, pallor, orthostatic hypotension.
On the part of the respiratory system, thoracic organs and mediastinum: dry irritating (non-productive) cough, dyspnea, bronchospasm, rhinitis, laryngitis, allergic alveolitis/eosinophilic pneumonia, pain behind the sternum.
On the part of the digestive system: dry mouth, nausea, vomiting, epigastric discomfort, abdominal pain, diarrhea, constipation, stomatitis/aphthous ulcers, glossitis, peptic ulcer, pancreatitis, gastric irritation, decreased appetite, acidosis.
Hepatobiliary system: impaired liver function and cholestasis (including jaundice), hepatitis (including necrosis), increased liver enzymes, hyperbilirubinemia.
Immune system, skin and subcutaneous tissue disorders: pruritus with or without rash, rash, alopecia, angioedema of the face, eyelids, tongue; interstitial angioedema, peripheral edema, urticaria, Stevens-Johnson syndrome, erythema multiforme, photosensitivity, erythroderma, pemphigoid reactions, exfoliative dermatitis, autoimmune diseases, fever.
Musculoskeletal and connective tissue disorders: myalgia, arthralgia.
On the part of the urinary system and kidneys: impaired renal function (including renal failure), proteinuria, polyuria, oliguria, increased urinary frequency, nephrotic syndrome.
From the reproductive system and mammary glands: impotence, gynecomastia.
General disorders: fatigue, lymphadenopathy, weakness.
Laboratory indicators: increased BUN, serum creatinine, decreased hemoglobin, hematocrit, increased ESR, increased antinuclear antibodies, may cause a false-positive urine test result for acetone.
Hydrochlorothiazide
Infections and infestations: sialoadenitis.
From the blood and lymphatic system: leukopenia, neutropenia, agranulocytosis, thrombus
