Instructions for Kaptopres-Darnitsa tablets No. 20
Composition
active ingredients: captopril, hydrochlorothiazide;
1 tablet contains: captopril 50 mg; hydrochlorothiazide 25 mg;
Excipients: potato starch, lactose monohydrate, colloidal anhydrous silicon dioxide, povidone, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white tablets, flat-cylindrical in shape with a bevel and a score, with a specific odor.
Pharmacotherapeutic group
Combined ACE inhibitor preparations. Captopril and diuretics. ATC code C09B A01.
Pharmacological properties
Pharmacodynamics.
Kaptopres-Darnitsa 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 causes 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 about 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 is approximately 2-3 hours. 95% of captopril is excreted by the kidneys: 50% in the form of metabolites and 50% in an unchanged state.
Hydrochlorothiazide is absorbed from the gastrointestinal tract by 68-78% when administered orally. The elimination half-life 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, other ACE inhibitors, hydrochlorothiazide, other drugs, sulfonamide derivatives, or to other components of the drug.
History of angioedema during treatment with other ACE inhibitors.
Congenital (idiopathic) angioedema.
Severe renal dysfunction (plasma creatinine concentration more than 1.8 mg/100 ml or creatinine clearance less than 30 ml/min), severe renal failure.
Bilateral renal artery stenosis or stenosis of the artery to a solitary kidney with progressive azotemia.
Condition after kidney transplantation.
Anury.
Aortic stenosis and other obstructive disorders that complicate the ejection of blood from the left ventricle.
Hypertrophic cardiomyopathy with low cardiac output.
Severe liver dysfunction (precomatose state, hepatic coma, liver failure).
Primary hyperaldosteronism.
Porphyria.
Hypokalemia, hyperkalemia, hyponatremia in hypovolemia, hypercalcemia, gout.
Pregnant women or women planning to become pregnant (see Use during pregnancy or breastfeeding).
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 the use of diuretics, increasing fluid and salt intake, reducing the initial doses of captopril;
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 ethanol-containing drugs and drinks, barbiturates, narcotics, neuroleptics, tricyclic antidepressants - increased hypotensive effect of the drug and orthostatic hypotension;
with sympathomimetics, estrogens, methanamine - weakening of the hypotensive effect of the drug, therefore the patient's blood pressure should be carefully monitored;
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 a combination of these drugs simultaneously. When administered simultaneously due to existing hypokalemia, they should be used with caution and with frequent monitoring of the concentration of potassium in the blood serum;
with allopurinol, procainamide, immunosuppressive (azathioprine) and cytostatic agents – inhibition of hematopoiesis;
with diazoxide - increased hyperglycemic, hyperuricemic, hypotensive effects; periodic monitoring of blood glucose levels and uric acid concentration may be necessary;
with non-depolarizing anesthetics, muscle relaxants, drugs for initiating anesthesia (tubocurarine chloride, gallamine triethiodide) - increased action of the above drugs; dose adjustment and water-salt metabolism may be required before surgery;
with lithium preparations, calcium salts - increased action of the above drugs; simultaneous use of these drugs is not recommended. Simultaneous use of ACE inhibitors and lithium may lead to 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 required;
with amphotericin, 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 rare cases – hemolytic anemia;
with antidiabetic drugs, oral anticoagulants, drugs for the treatment of gout - weakening of the above-mentioned drugs; dose adjustment of drugs may be required;
with drugs whose effects are affected by changes in plasma potassium levels, including:
- Antiarrhythmic drugs of class I A (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 arrhythmia against the background of possible hypokalemia and hypomagnesemia; periodic monitoring of potassium levels in blood plasma and electrocardiogram is necessary;
with pressor amines (noradrenaline) – treatment should be discontinued one week before 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 when administered in large doses, due to dehydration caused by hydrochlorothiazide. Before the administration of iodine, it is necessary to normalize the water level in the body.
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): Due to decreased gastrointestinal motility and decreased gastric emptying rate, the bioavailability of thiazide-type diuretics is increased.
Cyclosporine: Concomitant use of cyclosporine may increase hyperuricemia and increase the risk of gout-like complications.
Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of side effects caused by amantadine.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid >3 g/day and non-selective NSAIDs. NSAIDs may reduce the antihypertensive effect of hydrochlorothiazide and increase the effect of hydrochlorothiazide on serum potassium when administered concomitantly.
Clinical trial data have shown that 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 arterial hypotension. including acute renal failure), compared with the separate use of drugs acting on the RAAS.
The use of the drug may cause a positive result in a urine test for acetone.
The drug can be used for the treatment of acute myocardial infarction in combination with acetylsalicylic acid (cardiological doses), thrombolytic agents, β-blockers and/or nitrates.
Application features
Diuretics should be reduced or completely discontinued before starting treatment.
Before prescribing ACE inhibitors, the circulating blood volume (CVV) should be corrected, and the issue of prescribing a low effective optimal dose of the drug should be addressed.
When using the drug, the level of electrolytes (in particular potassium), the content of urea and creatinine in blood plasma, and the picture of peripheral blood should be periodically determined.
A low-sodium diet is recommended when using the drug.
It is not recommended to drink alcoholic beverages when 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 arterial hypotension may develop. 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, in elderly patients (65 years). The drug should be prescribed to this category of patients only under careful monitoring of blood pressure, kidney function, and the state of 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.
The specifics of use are related to the presence of hydrochlorothiazide in the composition of the drug.
As with other antihypertensive drugs, some patients may experience symptomatic hypotension.
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 without previous history of 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 conducting a laboratory examination to assess the function of the parathyroid glands;
− the drug is capable of increasing the concentration of free bilirubin in 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 the state of 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.
Hydrochlorothiazide can cause water and electrolyte imbalance (hypokalemia, hyponatremia and hypochloremic alkalosis). Symptoms: dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscle weakness, 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 glucocorticoid therapy are at high risk of developing hypokalemia. In hot weather, hyponatremia may occur in patients prone to edema, which is usually mild and does not require treatment.
Hydrochlorothiazide may cause hypercalcemia. Therefore, the drug should be discontinued before determining parathyroid function.
Hydrochlorothiazide may increase cholesterol and triglyceride levels, and decrease magnesium and iodine-binding thyroglobulins (without signs of thyroid dysfunction).
Hydrochlorothiazide may cause a positive doping test.
Hydrochlorothiazide can cause acute respiratory toxicity, including acute respiratory distress syndrome (ARDS). Very rare cases of severe acute respiratory toxicity, including ARDS, have been reported following the administration of hydrochlorothiazide. Pulmonary edema usually develops within minutes to hours of hydrochlorothiazide administration. Early symptoms include dyspnea, fever, worsening pulmonary function, and hypotension. If ARDS is suspected, hydrochlorothiazide should be discontinued and appropriate treatment initiated. Hydrochlorothiazide should not be given to patients who have previously experienced ARDS after taking hydrochlorothiazide.
The specifics of use are related to the presence of captopril in the composition of the drug.
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 according to creatinine clearance, and then, 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 patients on hemodialysis. Symptomatic hypotension has also been observed in patients with heart failure. Treatment of such patients should be started under the supervision of a physician with low doses, carefully selecting the dose. 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).
Captopril should be avoided in the development of cardiogenic shock and in cases of significant hemodynamic disturbances.
The drug should be used with caution in patients with renovascular hypertension, since concomitant use with ACE inhibitors increases the risk of severe hypotension and renal failure. Treatment of such patients should be initiated under medical supervision with low doses, with careful titration of the dose.
The combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is clearly associated with an increased risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the renin-angiotensin-aldosterone system (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 concurrently 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.
In patients taking relatively high doses of captopril (more than 150 mg per day) or with impaired renal function, proteinuria may develop. Proteinuria in the urine of more than 1 g per day was recorded in approximately 0.7% of patients receiving captopril. Nephrotic syndrome was diagnosed in 20% of patients with proteinuria. In most cases, proteinuria disappeared within 6 months after discontinuation of the drug. Renal function parameters, such as urea nitrogen and creatinine levels, rarely changed. In patients with impaired renal function, proteinuria should be determined before treatment and periodically monitored during drug therapy.
Neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. Neutropenia is rare in patients with normal renal function in the absence of other confounding factors. The drug should be used with extreme caution in patients with collagen diseases, patients receiving immunosuppressants, allopurinol or procainamide, and in the presence of these conditions, especially in the presence of impaired renal function. Some patients develop severe infections that always require 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 performed (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). In case of neutropenia (neutrophil count < 1000/mm3), the drug should be discontinued. After discontinuation of therapy, the neutrophil count quickly 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 the above-mentioned medicinal products during treatment with ACE inhibitors is necessary, serum potassium 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 an ACE inhibitor. 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 given. The patient should be hospitalized and observed for at least 12-24 hours until symptoms resolve. Black patients are at increased risk of 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 additional fluid volume.
When using ACE inhibitors, patients may develop a persistent non-productive cough that disappears after discontinuation of treatment.
Patients taking ACE inhibitors during desensitization with hymenoptera venom allergen may develop persistent anaphylactoid reactions. These reactions can be avoided by temporarily stopping ACE inhibitors.
Patients receiving ACE inhibitors on hemodialysis using high-flux membranes may develop persistent anaphylactoid reactions. These reactions can be avoided by replacing the dialysis membranes with another type of membrane or by using a different class of antihypertensive agent.
Patients taking ACE inhibitors may develop persistent anaphylactoid reactions during LDL apheresis. These reactions can be avoided by
temporary discontinuation of ACE inhibitors before each apheresis
Cross-hypersensitivity is possible for medicinal products containing ACE inhibitors.
The use of ACE inhibitors, in particular 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.
The medicine contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not take the medicine.
Use during pregnancy or breastfeeding
The medicine should not be used during breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
When using the drug, you should refrain from driving vehicles or working with other mechanisms, 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 the absorption of the drug is reduced if food is present in the stomach.
The dose of the drug is set by the doctor individually, depending on the clinical picture of the disease.
The initial dose is 1/2 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 faster 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 dosage of captopril should not exceed 150 mg, hydrochlorothiazide - 50 mg.
Patients with impaired kidney 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 1/2 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: a sharp decrease in blood pressure, tachycardia, headache, lack 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 stop taking the drug and consult a doctor.
Treatment: 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.
Symptomatic therapy is aimed at normalizing blood pressure and eliminating other symptoms.
Hydrochlorothiazide.
Symptoms: weakness, nausea, vomiting, thirst, diarrhea. These phenomena quickly disappear when the dose is reduced or the drug is canceled. In some cases, when taking high doses of the drug, the following symptoms have been reported: tachycardia, hypotension, shock, dizziness, confusion, impaired consciousness, muscle spasms, paresthesias, exhaustion, polyuria, oliguria, anuria, hypokalemia, hypochloremia; 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 CNS.
Treatment. To remove the drug from the stomach, it is recommended to induce vomiting; gastric lavage; use of 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. There is no specific antidote.
Adverse reactions
Captopril.
From the organs of vision: blurred vision.
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.
Gastrointestinal: dry mouth, nausea, vomiting, epigastric discomfort, abdominal pain, diarrhea, constipation, stomatitis/aphthous ulcers, glossitis, peptic ulcer, pancreatitis.
Hepatobiliary disorders: hepatic dysfunction and cholestasis (including jaundice), hepatitis (including necrosis), increased liver enzymes, hyperbilirubinemia.
Renal and urinary disorders: renal dysfunction (including renal failure), proteinuria, polyuria, oliguria, increased urinary frequency, nephrotic syndrome.
Metabolism: anorexia, hypoglycemia, hyperkalemia, hyponatremia.
Nervous system: headache, drowsiness, taste disturbance, dizziness, asthenia, paresthesia, cerebrovascular accident (including stroke and syncope).
Cardiovascular system: arterial hypotension, orthostatic hypotension, Raynaud's syndrome, hot flashes, pallor, tachycardia or tachyarrhythmia, angina pectoris, palpitations, cardiogenic shock, cardiac arrest.
Blood and lymphatic system disorders: eosinophilia, pancytopenia (especially in patients with impaired renal function), thrombocytopenia, anemia (including aplastic and hemolytic), leukopenia, neutropenia, agranulocytosis.
On the part of the immune system: itching with or without rash, rash, alopecia, angioedema of the face, eyelids, tongue, interstitial angioedema, peripheral edema, urticaria, Stevens-Johnson syndrome, erythema multiforme, photosensitivity exfoliative, photosensitivity exfoliative.
Skin and subcutaneous tissue disorders: pruritus with or without rash, rash, alopecia, erythema multiforme, photosensitivity, erythroderma, pemphigoid reactions, exfoliative dermatitis.
Musculoskeletal and connective tissue disorders: myalgia, arthralgia.
From the reproductive system and mammary gland function: impotence, gynecomastia.
General disorders: weakness, fatigue, lymphadenopathy.
Laboratory indicators: increased BUN, serum creatinine, decreased hemoglobin, hematocrit, increased ESR, increased antinuclear antibodies may lead to a false-positive result of urine analysis for acetone.
Hydrochlorothiazide.
On the part of the organs of vision: xanthopsia, transient blurred vision, acute myopia, acute glaucoma.
Respiratory, thoracic and mediastinal disorders: respiratory disorders (including pneumonitis and pulmonary edema), very rarely - acute respiratory distress syndrome (ARDS) (see section "Special warnings and precautions for use").
Gastrointestinal: sialadenitis, loss of appetite, thirst, dry mouth, nausea, vomiting, stomach irritation, diarrhea, constipation, pancreatitis.
Liver and biliary tract disorders: jaundice (intrahepatic cholestatic jaundice), cholecystitis.
Renal and urinary disorders: renal dysfunction, renal failure, interstitial nephritis.
Metabolism: anorexia, hyperglycemia, glucosuria, decreased glucose tolerance, which can provoke the manifestation of diabetes mellitus; hyperuricemia, which can provoke gout attacks in patients with asymptomatic disease; electrolyte imbalance, in particular hypochloremic alkalosis, which can induce hepatic encephalopathy and coma; acidosis; hypokalemia; hyponatremia; hypomagnesemia; hypercalcemia; increased cholesterol and triglyceride levels.
From the nervous system: headache, drowsiness, seizures, paresthesia, vertigo, dizziness.
Mental: anxiety, nervousness, depression, mood swings, sleep disturbances, disorientation, confusion.
Cardiovascular system: postural hypotension, cardiac arrhythmia; necrotizing vasculitis (vasculitis, cutaneous vasculitis).
From the blood and lymphatic system: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, bone marrow dysfunction.
On the part of the immune system: photosensitivity reactions, rash, eczema, purpura, lupus-like syndrome, reactivation of systemic lupus erythematosus, urticaria, anaphylactic reactions, anaphylactic shock, toxic epidermal necrolysis, Stevens-Johnson syndrome.
Skin and subcutaneous tissue disorders: photosensitivity reactions, rash, eczema, purpura, lupus-like syndrome, reactivation of systemic lupus erythematosus, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome.
Musculoskeletal and connective tissue disorders: muscle pain, muscle spasm.
On the part of the reproductive system and mammary gland function
