Hydrochlorothiazide, Captopril

Pharmacological properties

capotiazide is a combined antihypertensive drug. captopril, an inhibitor of apf, which is part of the drug, inhibits the formation of angiotensin ii, prevents its vasoconstrictor effect and stimulates the effect on the secretion of aldosterone in the adrenal glands. reduces opss, hell, pre- and afterload on the myocardium, pressure in the right atrium and in the pulmonary circulation.

Hydrochlorothiazide causes a moderately pronounced diuretic effect, increasing the excretion of water, sodium ions, chlorine, and potassium 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 After oral administration, captopril is rapidly absorbed. C_max in the blood is reached after about 1 hour. The minimum absorption is about 75%. C_max in blood plasma is reached within 60–90 min. The presence of food in the digestive tract reduces absorption by about 30–40%. 25-30% of the circulating drug binds to plasma proteins. T_½ unchanged captopril from blood plasma is about 2 hours.

More than 95% of the dose taken is excreted in the urine within 24 hours; 40-50% of the drug is unchanged, the remainder is unchanged metabolites.

Impaired renal function can lead to the accumulation of the drug in the body.

Animal studies indicate that captopril does not cross the BBB.

The absorption of hydrochlorothiazide when taken orally occurs quickly. The average half-life in plasma when taking the drug on an empty stomach is from 5 to 15 hours. Hydrochlorothiazide is rapidly excreted by the kidneys and 95% is excreted unchanged in the urine.

Indications

Treatment with ag.

Application

Capotiazide should be taken 1 hour before a meal, because if there is food, the absorption of the drug decreases.

The dose should be selected individually, in accordance with the clinical picture of the disease.

The initial dose is ½ tablet (25 mg of captopril and 6.25 mg of hydrochlorothiazide) once a day. If it is necessary to enhance the hypotensive effect, the dose of Capotiazide can be increased to 1 tablet (50 mg captopril and 12.5 mg hydrochlorothiazide) per day. The expected therapeutic effect occurs completely in 6-8 weeks after the start of treatment. Dose adjustment should be carried out at 6-week intervals, if clinical manifestations do not require a more rapid change in dosage. With an insufficient decrease in blood pressure, captopril and hydrochlorothiazide in the form of separate drugs can be included in the treatment regimen. In this case, the daily dose of captopril should not exceed 150 mg, hydrochlorothiazide - 50 mg.

Since captopril and hydrochlorothiazide are excreted primarily by the kidneys, if their function is impaired, the level of drugs may increase, therefore it is recommended to reduce the dose or increase the interval between doses. With creatinine clearance 30–80 ml / min: the initial dose is 25 mg / 6.25 mg once a day, in the morning.

The combination of captopril / hydrochlorothiazide is contraindicated in patients with severe renal failure (creatinine clearance of 30 ml / min).

For patients with impaired water-salt metabolism, elderly patients, with diabetes mellitus, the initial dose is 25 mg / 6.25 mg once a day.

After achieving the desired therapeutic effect, the dose of the drug is reduced to the minimum effective.

Contraindications

• Hypersensitivity to the active substances or to the auxiliary components of the drug, as well as to any other inhibitors of apf or sulfonamide derivatives; history of angioedema during treatment with APF inhibitors; hereditary / idiopathic angioedema; severe renal impairment (creatinine clearance 30 ml / min); severe liver dysfunction; pregnant women and women planning a pregnancy (see use during pregnancy and lactation; bilateral renal artery stenosis, affecting hemodynamics, or arterial stenosis of a single kidney, which is essential for hemodynamics; porphyria; anuria treatment-resistant hypo- or hypercalcemia; refractory hyponatremia; symptomatic hyperuricemia (gout); the simultaneous use of aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate of 60 ml / min / 1.73 m2).

Side effects

The following classification is used to determine the incidence of adverse reactions: often (1/100, 1/10), infrequently (1/1000, 1/100), rarely (1/10 000, 1/1000) and very rarely (1/10 000).

Captopril

On the part of the blood system and lymphatic system: very rarely - neutropenia / agranulocytosis, pancytopenia, especially in patients with impaired renal function, anemia (including aplastic and hemolytic anemia), thrombocytopenia, lymphadenopathy, eosinophilia, autoimmune diseases and / or positive ANA titers, leukopenia.

From the side of metabolism and nutrition: rarely - anorexia; very rarely - hyperkalemia, hypoglycemia.

Mental disorders: often - sleep disturbances; very rarely - confusion, depression.

From the nervous system: often - taste disturbance, dizziness; rarely - drowsiness, headache, paresthesia; very rarely - cerebrovascular disorders, including stroke or syncope.

From the side of the organ of vision: very rarely - blurred vision.

From the cardiovascular system: infrequently - tachycardia or tachyarrhythmia, angina pectoris, palpitation, arterial hypotension, Raynauds syndrome, swim, pallor; very rarely - cardiac arrest, cardiogenic shock.

On the part of the respiratory system, chest and mediastinum: often - dry, irritating (unproductive) cough and dyspnea; very rarely - bronchospasm, rhinitis, allergic alveolitis / eosinophilic pneumonia.

From the digestive system: often - nausea, vomiting, stomach irritation, abdominal pain, diarrhea, constipation, dry mouth; rarely - stomatitis / aphthous ulcers, interstitial angioedema; very rarely - glossitis, peptic ulcer, pancreatitis.

Hepatobiliary disorders: very rarely - impaired liver function and cholestasis (including jaundice), hepatitis (including necrosis), increased levels of liver enzymes and bilirubin.

On the part of the skin and subcutaneous tissue: often - itching with a rash or without a rash, alopecia; infrequently - angioedema; very rarely - urticaria, Stevens-Johnson syndrome, erythema multiforme, photosensitivity, erythroderma, pemphigoid reactions and exfoliative dermatitis.

From the muscles and connective tissue: very rarely - myalgia, arthralgia.

From the side of the kidneys and urinary tract: rarely - impaired renal function (including renal failure), polyuria, oliguria, increased frequency of urination; very rarely - nephrotic syndrome.

From the reproductive organs and mammary glands: very rarely - impotence, gynecomastia.

General disorders: infrequently - chest pain, fatigue, malaise; very rarely - fever, weakness.

Laboratory indicators: very rarely - proteinuria, eosinophilia, an increase in serum potassium concentration, a decrease in serum sodium concentration, an increase in urea nitrogen, serum creatinine and bilirubin, a decrease in hemoglobin, hematocrit, white blood cells, platelets, positive ANA titers, an increase ESR, false-positive urine test for acetone.

Hydrochlorothiazide

Infections and infestations: sialadenitis.

On the part of the blood and lymphatic system: leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, inhibition of bone marrow function.

Metabolic and nutritional disorders: anorexia, hyperglycemia, glucosuria, hyperuricemia, electrolyte imbalance (including hyponatremia and hypokalemia), increased cholesterol and triglycerides, hypomagnesemia, hyperglycemia, hypochloremic alkalosis, which can induce hepatic encephalopathy, which can cause liver disease seizures in patients with an asymptomatic course of the disease, a decrease in glucose tolerance, which can lead to the manifestation of latent diabetes mellitus.

Mental disorders: anxiety, depression, sleep disturbance, nervousness, confusion, disorientation, mood changes.

From the nervous system: loss of appetite, paresthesia, dizziness, headache, cramps, drowsiness.

From the side of the organ of vision: xanthopsia, passing blurred vision, acute myopia and secondary acute angle-closure glaucoma.

From the side of the organ of hearing and the labyrinth: vertigo.

From the cardiovascular system: orthostatic hypotension, cardiac arrhythmia; necrotic angiitis (vasculitis, skin vasculitis).

On the part of the respiratory system, chest and mediastinal organs: respiratory distress (including pneumonitis and pulmonary edema).

From the digestive system: stomach irritation, diarrhea, constipation, pancreatitis, dry mouth, thirst, nausea, vomiting.

Hepatobiliary disorders: jaundice (intrahepatic cholestatic jaundice), cholecystitis.

On the part of the skin and subcutaneous tissue: photosensitivity reactions, rash, skin manifestations of lupus-like syndrome, reactivation of lupus erythematosus, urticaria, anaphylactic reactions, toxic epidermal necrolysis, shock, purple, Stevens-Johnson syndrome.

From the muscles and connective tissue: muscle spasm, muscle pain.

From the kidneys and urinary tract: impaired renal function, interstitial nephritis.

Common disorders: fever, weakness, sexual disorders.

special instructions

A fixed-dose combination drug is indicated for patients in whom hell cannot be adequately controlled only by captopril or hydrochlorothiazide alone.

Captopril

Arterial hypotension: rarely hypotension occurs in patients with uncomplicated hypertension.

Symptoms of arterial hypotension are most often noted in patients with hypertension, in which the water-electrolyte balance is reduced due to diuretic therapy, diets low in sodium, diarrhea, vomiting, or hemodialysis. Before the appointment of ACE inhibitors, you should disaggregate the water-electrolyte balance, and also decide on the appointment of the minimum effective dose of the drug.

As with any other antihypertensive drug, an intense decrease in blood pressure in patients with ischemic cardiovascular or cerebrovascular diseases can increase the risk of myocardial infarction or stroke. If arterial hypotension occurs, the patient needs to be given a horizontal position (lying on his back) with raised legs. An increase in bcc may be required by iv administration of 0.9% sodium chloride solution.

AH. Patients with heart failure are also at risk for symptomatic hypotension with ACE inhibitors. Therefore, it is recommended that these patients be prescribed captopril with a low initial dose. An increase in the dose of ACE inhibitors and diuretics should be carried out under the supervision of a doctor.

Renovascular hypertension: There is an increased risk of developing arterial hypotension or renal failure in patients with bilateral renal artery stenosis or arterial stenosis of the only functioning kidney who take ACE inhibitors. In these patients, therapy should be started at low doses, under close medical supervision and careful titration and monitoring of renal function.

Angioedema: Angioedema of the face, limbs, lips, tongue, pharynx and / or larynx has been reported in patients taking ACE inhibitors, including captopril.Angioneurotic edema can occur at any time during drug therapy. In the event of edema, stop using captopril immediately and begin appropriate treatment. The patient must be hospitalized and monitored for at least 12-24 hours until the symptoms disappear completely. Patients of the Negroid race are characterized by an increased risk of developing angioedema. Patients with angioedema not associated with a history of ACE inhibitors may have an increased risk of developing angioedema while taking ACE inhibitors. Intestinal angioedema has rarely been reported in patients taking ACE inhibitors. These patients showed abdominal pain (with or without nausea and vomiting); in some cases, without prior angioedema of the face and with a normal level of C-1 esterase. Angioedema was diagnosed using procedures that included an abdominal CT scan or ultrasound, or during surgery. Symptoms disappeared after stopping ACE inhibitors. Intestinal angioedema should be included in the differential diagnosis of patients taking ACE inhibitors who complain of abdominal pain.

Cough: During therapy with ACE inhibitors, patients may experience persistent non-productive cough that disappears after treatment is discontinued.

Hepatic failure: in rare cases, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and quickly progresses to liver necrosis and (sometimes) leads to death. The mechanism of this syndrome is unknown. Patients receiving ACE inhibitors who develop jaundice or a marked increase in liver enzymes should stop using ACE inhibitors and consult a doctor.

Hyperkalemia: in some patients taking ACE inhibitors, including captopril, there is an increase in the level of potassium in the blood plasma. The risk group for hyperkalemia includes patients with kidney failure, diabetes mellitus, people taking potassium-sparing diuretics, potassium supplements, and people taking other drugs that increase serum potassium (such as heparin). If taking the above drugs during treatment with ACE inhibitors is necessary, regular monitoring of the level of potassium in the blood plasma should be carried out.

Lithium: A combination of lithium and captopril is not recommended (see INTERACTIONS).

Aortic and mitral valve stenosis / obstructive hypertrophic cardiomyopathy / cardiogenic shock: ACE inhibitors should be used with caution in patients with valve obstruction and left ventricular outlet obstruction, they should be avoided in case of cardiogenic shock and significant hemodynamic disturbances.

Neutropenia / agranulocytosis: Cases of neutropenia, agranulocytosis, thrombocytopenia, and anemia have been reported in patients using ACE inhibitors. In patients with normal renal function, in the absence of other factors, neutropenia is rare. Extremely carefully, the drug should be prescribed to patients with collagenosis, patients who are undergoing treatment with immunosuppressants, take allopurinol or procainamide, as well as with a combination of these conditions, especially against the background of existing renal dysfunction. Some of these patients develop severe infections that are not always amenable to intensive antibiotic therapy. When using the drug in these patients, it is necessary to periodically monitor the number of leukocytes in the blood and their differential count (before treatment, every 2 weeks during the first 3 months of therapy and periodically in the future) and warn the patient about the need to report any signs of infection (for example, fever body, sore throat). When neutropenia occurs (neutrophil count 1000 / mm³) the use of the drug should be discontinued. After stopping captopril therapy in most patients, the number of neutrophils quickly normalizes.

Proteinuria: in patients with impaired renal function or in those using captopril in relatively high doses (150 mg / day), proteinuria may develop. Urine protein content of 1 g / day has been reported in approximately 0.7% of patients receiving captopril. Nephrotic syndrome is 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, have rarely changed. In patients with impaired renal function, the urine protein content should be determined before treatment and periodically monitored during drug therapy.

Anaphylactoid reactions: in patients using ACE inhibitors during desensitization with hymenoptera venom allergen, persistent life-threatening anaphylactoid reactions may develop. Therefore, treatment with ACE inhibitors should be used with caution in patients undergoing similar desensitization procedures.

Anaphylactoid reactions during high-flow dialysis / LDL apheresis: in patients using ACE inhibitors during hemodialysis using high-flow membranes, the development of persistent anaphylactoid reactions is possible. The development of these reactions can be avoided by replacing dialysis membranes with membranes of a different type or by taking antihypertensive agents of a different class.

In patients using ACE inhibitors, persistent anaphylactoid reactions may occur during LDL apheresis. The development of these reactions can be avoided by temporarily stopping the use of ACE inhibitors before each apheresis.

Surgery / Anesthesia: Patients who undergo major surgery or anesthesia with blood pressure lowering drugs may develop arterial hypotension. Arterial hypotension that occurred in this case should be corrected by increasing the bcc by introducing an additional volume of fluid.

Patients with diabetes mellitus: ACE inhibitors should be used with caution in patients with diabetes using oral antidiabetic drugs or insulin, and also regularly monitor blood glucose levels, especially during the 1st month of treatment.

The use of ACE inhibitors, including captopril, in patients of the Negroid race is less effective in lowering blood pressure than in patients of another race, due to the predominance of low renin fractions.

Hydrochlorothiazide

Renal failure: the drug should be used with caution in case of impaired renal function, since thiazide diuretics can lead to azotemia. Cumulation of the drug is also possible. With the progression of kidney diseases, which are characterized by an increase in the level of residual nitrogen in the blood, the appropriateness of continuing therapy should be carefully assessed and, if necessary, discontinuing treatment.

Hepatic insufficiency: it is necessary to use the drug with caution in case of impaired liver function or with progressive liver diseases, since thiazide diuretics can cause a violation of the water-electrolyte balance, which, in turn, can lead to the rapid development of hepatic coma.

Metabolic and endocrine disorders: in the treatment of thiazides, a decrease in glucose tolerance is possible. It may be necessary to modify the doses of antidiabetic agents, including insulin. During therapy with thiazides, latent diabetes mellitus can manifest.

With the use of thiazide diuretics, an increase in the level of cholesterol and TG was associated.

Some patients taking thiazides may experience hyperuricemia or exacerbation of gout.

Violation of electrolyte balance: in the case of diuretic therapy, periodic monitoring of the level of electrolytes in blood serum should be carried out.

Thiazides, including hydrochlorothiazide, can cause water-electrolyte imbalance (hypokalemia, hyponatremia and hypochloremic alkalosis). Warning symptoms suggesting water-electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscle weakness, arterial hypotension, oliguria, tachycardia, as well as gastrointestinal disturbances, such like nausea and vomiting.

Although concurrent 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 loss, as well as those receiving GCS or ACTH therapy are at increased risk of hypokalemia.

In hot weather, patients prone to edema may experience hyponatremia, usually mild and not requiring treatment.

Thiazides can reduce renal excretion of calcium and thus cause fluctuation or slight increase in calcium concentration. Therefore, before determining the functional state of the parathyroid glands, the use of the drug should be discontinued.

Anti-Doping Test: The hydrochlorothiazide that is contained in this preparation can give a positive result when conducting an anti-doping test.

Other: hypersensitivity reactions may occur in patients with a history of history of allergy or AD. A possible development or exacerbation of systemic lupus erythematosus has been reported.

Acute myopia and secondary acute angle-closure glaucoma: drugs containing sulfanilamide or its derivatives can cause idiosyncrasy, which leads to transient myopia and acute angle-closure glaucoma. Hydrochlorothiazide is a sulfanilamide derivative, however, until that time, only isolated cases of acute angle-closure glaucoma were reported with the use of hydrochlorothiazide. Symptoms of this disease include a sharp decrease in visual acuity or eye pain. As a rule, these symptoms develop within a few hours or several weeks after the start of therapy with this drug. If acute angle-closure glaucoma is left untreated, this can lead to irreversible loss of vision in the patient. If such a symptom is detected, first of all, it is necessary to cancel therapy with this drug as soon as possible. If after this intraocular pressure remains uncontrolled, the feasibility of drug or surgical treatment may be considered. Risk factors for developing acute angle-closure glaucoma may include a history of allergies to sulfonamide or penicillin.

The drug may affect the results of the following laboratory tests:

• reduce plasma protein-bound iodine;
• increase the concentration of free bilirubin in blood plasma;
• treatment should be discontinued before conducting a laboratory examination to assess the function of the parathyroid glands.

The combination of captopril and hydrochlorothiazide

Pregnancy. The drug should not be used by pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with this agent, its use should be stopped immediately and replaced with another drug approved for use in pregnant women.

The risk of hypokalemia: a combination of ACE inhibitors and thiazides does not exclude the possibility of hypokalemia. You should regularly monitor the concentration of potassium in the blood.

Combination with lithium: the simultaneous use of captopril with lithium is not recommended due to the increased toxicity of the latter (see INTERACTIONS).

Lactose: due to the presence of lactose in the composition of the drug Kapothiazide, patients with rare hereditary galactose tolerance disorders, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Patients receiving concurrent therapy with ACE inhibitors and MRI (mammalian rapamycin target) inhibitors (e.g. temsirolimus, sirolimus, everolimus) may have an increased risk of developing angioedema.

If therapy, including double blockade, is considered absolutely necessary, then this should happen only under the supervision of a doctor and careful monitoring of kidney function, electrolytes and blood pressure.

Use during pregnancy and lactation. The drug is contraindicated in pregnant women or women planning a pregnancy. If pregnancy is confirmed during treatment with the drug, its use should be stopped immediately and replaced with another drug approved for use in pregnant women.

During breastfeeding, the drug is not prescribed.

Children. There are no data on the use of the drug in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. As with other antihypertensive drugs, the ability to drive vehicles or work with other mechanisms may be impaired, especially at the beginning of treatment or in the case of a change in dosage, as well as in combination with alcohol. These effects depend on the individual sensitivity of the patient.

Interactions

Captopril

Potassium-sparing diuretics or potassium supplements. ACE inhibitors reduce the loss of potassium caused by the use of diuretics. Potassium-sparing diuretics (e.g. spironolactone, triamteren, or amiloride), potassium supplements, or salt substitutes containing potassium can lead to hyperkalemia. With simultaneous use against the background of existing hypokalemia, they should be used with great care and with frequent monitoring of the concentration of potassium in the blood plasma.

Diuretics (thiazide or loop diuretics): There is a risk of developing arterial hypotension due to dehydration caused by taking high-dose diuretics when taking captopril. The severity of the hypotensive effect can be reduced by canceling diuretics, increasing fluid and salt intake, lowering the initial doses of captopril. However, no clinically significant interactions were detected in specific studies with hydrochlorothiazide and furosemide.

Other antihypertensive drugs: captopril is safe to combine with other commonly used antihypertensive drugs (for example, β-adrenergic blockers and calcium channel blockers of prolonged action). The combined use with these drugs can increase the hypotensive effect of captopril. Concomitant use with nitroglycerin, other nitrates, or other vasodilators should be prescribed with caution.

Α-adrenergic blockers: combined use with α-adrenergic blockers can enhance the hypotensive effect of captopril and increase the risk of orthostatic hypotension.

Treatment for acute myocardial infarction: captopril can be used in combination with acetylsalicylic acid (in cardiac dosage), with thrombolytics, β-adrenergic blockers and / or nitrates in patients with myocardial infarction.

Tricyclic antidepressants / antipsychotics: ACE inhibitors may enhance the hypotensive effect of certain tricyclic antidepressants and antipsychotics, which can lead to orthostatic hypotension.

Allopurinol, procainamide, cytostatic or immunosuppressive drugs: combined use with ACE inhibitors can lead to an increased risk of developing leukopenia, especially if the latter are used at doses higher than recommended.

Lithium: The combined use of ACE inhibitors and lithium can cause a temporary increase in plasma lithium levels and lithium intoxication. The simultaneous use of ACE inhibitors and thiazide diuretics can further increase plasma lithium levels and the risk of lithium intoxication. Captopril with lithium is not recommended. If such a combination is necessary for the patient, careful monitoring of serum lithium levels should be carried out (see SPECIAL INSTRUCTIONS).

Sympathomimetics: can reduce the antihypertensive effect of ACE inhibitors, so patients should carefully monitor the level of blood pressure.

NSAIDs: it is described that ACE inhibitors and NSAIDs have an additional effect on increasing serum potassium levels, which can lead to impaired renal function. Usually this effect is reversible. ARF is rarely possible, especially in patients with impaired renal function, such as the elderly or patients with dehydration. Administration of NSAIDs may reduce the antihypertensive effect of an ACE inhibitor.

Hypoglycemic drugs: pharmacological studies suggest that ACE inhibitors, including captopril, can potentiate the hypoglycemic effect of insulin and oral hypoglycemic drugs, such as sulfonylureas, in patients with diabetes. In the event of such an interaction, a reduction in the dose of hypoglycemic drugs may be required.

Hydrochlorothiazide

Amphotericin B (parenteral dosage forms), carbenoxolone, corticosteroids, corticotropin (ACTH) or stimulant laxatives: hydrochlorothiazide can increase electrolyte imbalance, in particular hypokalemia.

Calcium salts: an increase in serum calcium concentration may occur due to a decrease in its excretion when administered simultaneously with thiazide diuretics.

Cardiac glycosides: There is an increased risk of cardiac glycosides toxicity associated with hypokalemia caused by thiazide diuretics.

Colestyramine and colestipol: may impair or decrease the absorption of hydrochlorothiazide. Sulfonamide diuretics should be taken at least 1 hour before or 4-6 hours after taking these drugs.

Non-depolarizing muscle relaxants (e.g. tubocurarine chloride): the effect of these drugs can be potentiated by hydrochlorothiazide.

Medicines whose action is associated with ventricular tachycardia of the pirouette type: due to the risk of developing hypoglycemia, hydrochlorothiazide should be used with caution when combined with drugs whose effect is associated with ventricular tachycardia of the pirouette type, for example, some antiarrhythmic drugs, some antipsychotics.

Carbamazepine: The combined use of carbamazepine with hydrochlorothiazide has been associated with the development of symptomatic hyponatremia. During such treatment, it is necessary to control the level of electrolytes. If possible, a different class of diuretics should be prescribed.

The combination of captopril and hydrochlorothiazide

Lithium: a reversible increase in serum lithium concentration and its toxicity were noted during combined use with ACE inhibitors. The simultaneous use of thiazide diuretics can increase the risk of lithium toxicity and increase the already existing risk of lithium toxicity associated with ACE inhibitors.Therefore, the combined use of a combination of captopril with hydrochlorothiazide and lithium is not recommended, and in case of proven need for such use, careful monitoring of the concentration of lithium in blood serum should be carried out.

NSAIDs: in combination with ACE inhibitors can have an additive effect on increasing serum potassium levels and therefore impair renal function. Usually these effects are reversible. Rarely, acute renal failure may occur in patients with impaired renal function, in particular in elderly patients or those with dehydration. Prolonged use of NSAIDs can reduce the antihypertensive effect of ACE inhibitors, as well as reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics.

Alcohol, barbiturates, drugs or antidepressants. May enhance orthostatic hypertension.

Antidiabetic drugs (oral hypoglycemic drugs and insulin): against the background of thiazide treatment, glucose tolerance may decrease. It may be necessary to change the dosage. Use metformin with caution, given the risk of lactic acidosis due to possible functional renal failure due to hydrochlorothiazide.

Pressor amines (e.g. epinephrine): weakening effect of pressor amines is possible, but not