Accusid, 12.5 mg+20 mg, film-coated tablets, 30 pcs.: instructions for use, reviews and analogues, prices in pharmacies. Buy and deliver to the nearest pharmacy or home in Moscow. Produce

Pharmacological properties of the drug Accusid

A combination drug consisting of the ACE inhibitor quinapril (INN - Quinaprilum) and the diuretic hydrochlorothiazide. The simultaneous use of quinapril and hydrochlorothiazide lowers blood pressure more than either drug alone and does not have a negative effect on their pharmacokinetics. Due to diuretic activity, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, reduces serum potassium concentrations and increases urinary potassium excretion. Quinapril inhibits the renin-angiotensin-aldosterone system and reduces potassium loss caused by hydrochlorothiazide. Quinapril rapidly de-esterifies to quinapril (the diacid of quinapril, the main metabolite), which is an effective ACE inhibitor. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor angiotensin II, which is involved in the regulation of vascular tone, and exerts its influence in various ways, including through stimulation of aldosterone secretion by the adrenal cortex. The mechanism of action of quinapril is to inhibit the activity of circulating and tissue ACE, and therefore vasopressor activity and aldosterone secretion are reduced. A decrease in the level of angiotensin II through a feedback mechanism leads to an increase in the secretion of renin and its activity in the blood plasma. Although it is generally accepted that the main mechanism of antihypertensive action is realized through the renin-angiotensin-aldosterone system, quinapril exhibits an antihypertensive effect even in patients with low renin hypertension (arterial hypertension). Studies have shown that quinapril monotherapy was effective in patients of different races, although the effect was somewhat less pronounced in black patients (a group with predominantly low renin levels). ACE, like enzyme kinase II, is involved in the breakdown of bradykinin, a powerful vasodilator peptide. By increasing bradykinin levels, ACE and kinase II play a role in the therapeutic effect of quinapril, but this mechanism requires further study. The use of 10–80 mg of quinapril in patients with mild to severe hypertension (arterial hypertension) causes a moderate decrease in blood pressure when measured in both sitting and standing positions and has a minimal effect on heart rate. The antihypertensive effect of the drug begins within 1 hour, and its maximum severity occurs 2–4 hours after administration. When used in recommended doses, the antihypertensive effect of the drug lasts for 24 hours and persists with long-term treatment. Studies in patients with hypertension (arterial hypertension) showed that a decrease in blood pressure due to the use of quinapril was accompanied by a decrease in peripheral vascular resistance and renal vascular resistance without a significant change in heart rate, cardiac index, renal blood flow, glomerular filtration rate or filtration fraction. Hydrochlorothiazide is a diuretic that has a direct effect on the kidney, increasing the excretion of sodium and chlorine, and with them the corresponding volume of water. Hydrochlorothiazide also increases the excretion of potassium and bicarbonates and reduces the excretion of calcium. Long-term use of hydrochlorothiazide increases plasma renin activity by 2–6 times. After oral administration of hydrochlorothiazide, its stimulating effect on diuresis begins after approximately 2 hours, reaches a maximum after 4 hours and lasts 6–12 hours. After oral administration of the drug, the maximum concentration of quinapril in the blood plasma is achieved within 1 hour. Hydrochlorothiazide is excreted unchanged by the kidneys. The half-life from blood plasma is 4–15 hours. About 61% of an oral dose is excreted unchanged within 24 hours. Hydrochlorothiazide penetrates the placental barrier and does not penetrate the BBB. Based on the detection of quinapril and its metabolites in urine, the extent of absorption is approximately 60%. Absorption of hydrochlorothiazide occurs more slowly (from 1 to 2.5 hours) and more completely (50–80%). About 38% of orally administered quinapril is metabolized to quinapril. The half-life of quinapril from blood plasma is about 1 hour. The maximum concentration of quinapril in blood plasma is observed approximately 2 hours after oral administration of the drug. Quinaprilat is eliminated primarily through renal excretion with a half-life of approximately 3 hours. Approximately 97% of quinapril or quinaprilat circulating in plasma is protein bound. In patients with renal impairment, the significant elimination half-life of quinaprilat increases with a decrease in creatinine clearance. Pharmacokinetic studies in patients with severe renal impairment on chronic hemodialysis or continuous ambulatory peritoneal dialysis indicate negligible removal of quinapril and quinaprylat by these methods. Quinaprilat elimination is also reduced in elderly patients (≥65 years) and correlates well with their renal function (see USAGE section for further information). In elderly patients, the AUC and maximum plasma concentration of quinaprilat are higher than in other patients, which is associated more with a decrease in renal function than with age-related changes. 15% of the total number of patients who took part in clinical trials of the quinapril/hydrochlorothiazide combination were patients over 65 years of age, of which 1.5% were over 75 years of age. No differences were found in the effectiveness and safety of the drug in elderly and other patients. However, greater sensitivity to the drug in some older people cannot be ruled out.

Accuzide®

Angioedema

During treatment with ACE inhibitors, cases of angioedema of the face and neck have been described, including in 0.1% of patients receiving quinapril. If a guttural whistle or angioedema of the face, eyes, tongue or vocal folds, or difficulty swallowing food or breathing occurs, Accusid® should be discontinued immediately. The patient must be given adequate treatment and observed until the symptoms of edema disappear. Antihistamines may be used to reduce symptoms.

Angioedema involving the larynx can be fatal. If swelling of the tongue, vocal folds or larynx threatens the development of airway obstruction, adequate emergency therapy is necessary, including subcutaneous administration of a solution of adrenaline 1: 1000 (0.3-0.5 ml).

Patients receiving concomitant therapy with mTOR enzyme inhibitors (eg, temsirolimus) or DPP-4 (eg, vildagliptin) or neutral endopeptidase inhibitors (NEP) may be at greater risk of developing angioedema. Caution should be exercised when using these drugs simultaneously with Accusid®. Cases of intestinal angioedema have also been described during treatment with ACE inhibitors. Patients reported abdominal pain (with/without nausea and vomiting); in some cases without previous angioedema of the face and normal C1-esterase activity. The diagnosis was made using computed tomography of the abdominal region, ultrasound examination, or at the time of surgery. Symptoms disappeared after stopping the ACE inhibitors.

Patients who have experienced angioedema not associated with taking ACE inhibitors may be at risk of developing it when treated with drugs of this group.

Patients receiving concomitant therapy with mTOR enzyme inhibitors (eg, temsirolimus) and DPP-4 (eg, vildagliptin) may be at greater risk of developing angioedema.

Ethnic differences

ACE inhibitors are more likely to cause angioedema in black patients than in Caucasian patients. As with other ACE inhibitors, quinapril may be less effective in lowering blood pressure in black patients.

Carrying out desensitizing therapy

Patients receiving ACE inhibitors during desensitizing therapy with hymenoptera (wasp, bee) venom may develop persistent life-threatening anaphylactoid reactions. Temporary cessation of ACE inhibitor therapy promotes regression of symptoms, but they may recur when ACE inhibitor therapy is resumed.

Hemodialysis

Anaphylactoid reactions may also occur with the use of ACE inhibitors in patients undergoing low-density lipoprotein apheresis using dextran sulfate or in patients undergoing hemodialysis using high-flux membranes such as polyacrylonitrile membranes. It is necessary to use alternative lipid-lowering therapy or use other membranes for hemodialysis.

Arterial hypotension

The drug Accusid® can cause transient arterial hypotension, but not more often than in monotherapy with the components included in the drug. Symptomatic arterial hypotension rarely occurs during treatment with quinapril in patients with uncomplicated arterial hypertension, but it can develop as a result of therapy with ACE inhibitors in patients with reduced blood volume, for example, after previous therapy with diuretics, while following a diet with limited salt, or during hemodialysis. If symptomatic arterial hypotension occurs, the patient should take a supine position with legs elevated and receive an intravenous infusion of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication to further use of the drug Accusid®, however, in such cases it is advisable to reduce its dose.

Chronic heart failure

In patients with chronic heart failure with renal failure, and/or chronic heart failure without renal failure, ACE inhibitor therapy for hypertension may lead to an excessive decrease in blood pressure, which may be accompanied by oliguria, azotemia and, in rare cases, acute renal failure and even death. Treatment of such patients with Accusid® should be initiated under close medical supervision and monitoring during the first 2 weeks of therapy and as the dose of the drug is increased.

Agranulocytosis

In rare cases, therapy with ACE inhibitors may be accompanied by the development of agranulocytosis and suppression of bone marrow function in patients with uncomplicated arterial hypertension, but more often in patients with impaired renal function, especially with connective tissue diseases. In these cases, the number of leukocytes in the blood should be monitored.

If any symptoms of infection (eg, sore throat, fever) occur, patients should consult a doctor immediately, as they may be a manifestation of neutropenia.

Non-melanoma skin cancer

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of nonmelanoma skin cancer (NMSC) basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide.

Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.

Any suspicious skin changes should be reported to your doctor immediately. Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment.

In patients with a history of non-melanoma skin cancer, it is recommended to reconsider the use of hydrochlorothiazide.

Systemic lupus erythematosus

Thiazide diuretics can sometimes cause exacerbation of systemic lupus erythematosus.

Kidney function

The drug Accusid® is not recommended for use in patients with severely impaired renal function (creatinine clearance less than 30 ml/min), because Thiazide diuretics contribute to the progression of azotemia and have a cumulative effect with long-term use in such patients. The drugs of choice in this group of patients receiving quinapril therapy are loop diuretics. For this reason, the fixed combination hydrochlorothiazide/quinapril should not be used in patients with severe renal impairment (see section "Contraindications").

T1/2 of quinaprilat increases with a decrease in CC. In patients with CC less than 60 ml/min, but more than 30 ml/min, quinapril should be prescribed at a lower initial dose. In such patients, the dose of Accusid® should be increased taking into account the patient's clinical condition, with regular monitoring of renal function, although in clinical studies no further deterioration of renal function was observed during treatment with Accusid®.

In patients with arterial hypertension without obvious signs of initial renal impairment, when using quinapril, especially in combination with a diuretic, an increase in the concentration of urea nitrogen in the blood and creatinine in the serum was noted, which is usually mild and usually transient. Such changes are most likely in patients with underlying renal impairment. In such cases, it may be necessary to reduce the dose of Accusid®. Renal function should be monitored in all patients with hypertension.

Accusid® should not be used as initial therapy in patients with CC less than 60 ml/min.

Effect of the renin-angiotensin-aldosterone system (RAAS)

In some patients, suppression of RAAS activity can lead to renal dysfunction. In patients with severe chronic heart failure, renal function is dependent on the activity of the RAAS, therefore treatment with ACE inhibitors, including quinapril, can lead to oliguria and/or progressive azotemia, and in rare cases, acute renal failure and/or death.

Double blockade of RAAS activity

The simultaneous use of RAAS-active agents and quinapril should be avoided. The use of this combination should be limited to individual cases with careful monitoring of renal function and plasma potassium levels.

Renal artery stenosis

In clinical studies in hypertensive patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney, increases in serum urea nitrogen and creatinine concentrations were observed in some cases during treatment with ACE inhibitors. These changes are almost always reversible and resolved after discontinuation of the ACE inhibitor and/or diuretic. In such cases, monitoring of renal function is necessary during the first few weeks of treatment with Accusid®.

Liver dysfunction

The drug Accusid® should be used with caution in patients with impaired liver function or progressive liver disease, since even minor disturbances in water and electrolyte balance can cause the development of hepatic coma.

Water and electrolyte balance

In order to identify possible disturbances in water-electrolyte balance, it is necessary to regularly monitor the content of electrolytes in the blood serum. In patients receiving monotherapy with quinapril, as with other ACE inhibitors, potassium levels may increase.

Serum potassium

Hyperkalemia

(≥5.8 mmol/l) was observed in approximately 2% of patients taking quinapril, but in most cases this deviation was isolated and resolved with further therapy. Risk factors for the development of hyperkalemia are: impaired renal function, diabetes mellitus and concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that increase the content of potassium in the blood serum.

Concomitant use of potassium-sparing diuretics with Accusid®, which contains a thiazide diuretic, is not recommended. Treatment with thiazide diuretics, on the contrary, is accompanied by hypokalemia, hyponatremia and hypochloremic alkalosis. These disorders are sometimes manifested by the following symptoms: dryness of the oral mucosa, thirst, weakness, lethargy, drowsiness, restlessness, muscle weakness, muscle pain or spasm, decreased blood pressure, oliguria, tachycardia, nausea, confusion, convulsions and vomiting.

Hypokalemia

may also enhance the toxic effect of cardiac glycosides. The risk of hypokalemia is increased with liver cirrhosis, forced diuresis, inadequate use of drugs that improve myocardial metabolism, concomitant therapy with glucocorticosteroids or adrenocorticotropic hormone (ACTH), and concomitant use with drugs that increase the risk of hypokalemia while taking thiazide diuretics. In most patients, the opposing effects of quinapril and hydrochlorothiazide on serum potassium should be expected to balance.

In some cases, the effect of one component of the drug Accusid® may prevail over the other. Before and during treatment with Accusid®, electrolyte levels should be periodically monitored in order to identify possible disturbances in water and electrolyte balance. Chloride deficiency associated with thiazide diuretic therapy is usually mild and only in exceptional cases requires appropriate treatment (for example, in cases of liver and/or kidney disease).

Hyponatremia

In hot weather, patients with peripheral edema may develop hyponatremia. For hyponatremia, adequate replacement therapy is necessary.

Hypocalcemia

Thiazide diuretics reduce the excretion of calcium by the kidneys.

Parathyroid glands

In rare cases, patients receiving long-term therapy with thiazide diuretics have developed changes in the parathyroid glands, accompanied by hypercalcemia and hypophosphatemia. More serious complications of hyperparathyroidism (nephrolithiasis, bone resorption and peptic ulcer) have not been described. Before testing the function of the parathyroid glands, thiazide diuretics must be discontinued.

Magnesium

Thiazide diuretics increase renal excretion of magnesium and may cause hypomagnesemia.

Other metabolic disorders

Thiazide diuretics increase serum concentrations of cholesterol, triglycerides and uric acid. These effects are usually minor, but the development of overt gout or diabetes mellitus can be triggered in patients with a predisposition to these diseases.

Diabetes

Hyperglycemia induced by high doses of thiazide diuretics (including hydrochlorothiazide ≥ 100 mg/day) may impair control of plasma glucose concentrations. A decrease in potassium content in the blood plasma leads to an increase in glucose tolerance. The concentration of glucose in the blood plasma should be monitored and, if necessary, potassium supplements should be prescribed in order to maintain the potassium content in the blood plasma and adjust hypoglycemic therapy.

Therapy with ACE inhibitors may be accompanied by the development of hypoglycemia in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents. When treating patients with diabetes mellitus, more careful monitoring and dosage adjustment of hypoglycemic agents may be required.

Cough

When treated with ACE inhibitors, including quinapril, the development of cough was noted. Typically, it is nonproductive, persistent, and resolves upon cessation of therapy. In the differential diagnosis of cough, its possible connection with the use of ACE inhibitors should be taken into account.

Surgical intervention

In patients undergoing surgery or general anesthesia, ACE inhibitors should be used with caution because they block the formation of angiotensin II caused by compensatory renin secretion. This can lead to arterial hypotension, which is eliminated by increasing blood volume. In case of surgery, the patient must warn the anesthesiologist that he is taking an ACE inhibitor.

BCC

Patients should be warned that insufficient fluid intake and increased sweating can lead to an excessive decrease in blood pressure due to a decrease in blood volume. Other causes of decreased blood volume, such as vomiting or diarrhea, can also lead to a sharp drop in blood pressure.

Choroidal effusion, acute myopia and angle-closure glaucoma

Hydrochlorothiazide (a sulfonamide derivative) can lead to the development of choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma. Symptoms include an acute attack of decreased visual function or eye pain and usually occur within the first hours to weeks after starting therapy. Without proper treatment, angle-closure glaucoma can lead to permanent vision loss. The main treatment for this condition is to discontinue hydrochlorothiazide therapy as soon as possible. Prompt medical or surgical intervention may be needed if intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of allergic reactions to sulfonamides and penicillin.

Doping control results

Hydrochlorothiazide may give a positive result during doping control.

Left ventricular outflow tract obstruction

The use of Accusid® is contraindicated in patients with obstruction of the left ventricular outflow tract (aortic or mitral stenosis; hypertrophic obstructive cardiomyopathy).

Hypersensitivity reactions

When using thiazide diuretics, a hypersensitivity reaction and severe skin complications may develop.

Use of the drug Accusid

For patients who have not previously used a diuretic and who were prescribed quinapril monotherapy, the recommended initial dose of Accusid is 10/12.5 mg. According to the clinical effect, the dose can be increased to 20/12.5 mg. Effective blood pressure control in most cases is achieved when taking from 10/12.5 mg to 20/12.5 mg of the drug. The dosage range of the drug allows you to flexibly select the ratio of components depending on clinical needs. In patients who have previously used a diuretic, to prevent an excessive decrease in blood pressure, the recommended initial dose of quinapril is 5 mg. In the future, the dose of the drug is selected individually. If the selected ratio of quinapril and hydrochlorothiazide corresponds to that in the tablet, you can switch to Accuside 10 or Accuside 20. Accuside should not be used as a starting drug in patients with impaired renal function (creatinine clearance less than 60 ml/min). In patients with moderate renal failure (creatinine clearance within 30–60 ml/min), therapy begins with the appointment of 5 mg of quinapril with further dose titration. If additional prescription of diuretics is necessary, their dose can be titrated using Accusid. The starting dose is 10/12.5 mg. When it becomes necessary to use diuretics in combination with quinapril in patients with severe kidney damage (creatinine clearance less than 30 ml/min), loop diuretics should be preferred over thiazide diuretics. The therapeutic effect of the drug when using the same doses was similar in both elderly and mature patients. There was no increase in the incidence of side effects in elderly patients. The safety and effectiveness of Accusid in the treatment of children has not been established.

Akkuzid

Use during pregnancy and breastfeeding

The use of Accusid® is contraindicated during pregnancy, women planning pregnancy, as well as women of reproductive age who do not use reliable methods of contraception.
Women of reproductive age taking Accusid® should use reliable methods of contraception.

If pregnancy occurs during treatment with Accusid, the drug should be discontinued as soon as possible.

The prescription of ACE inhibitors during pregnancy is accompanied by an increased risk of developing abnormalities of the cardiovascular and nervous system of the fetus. In addition, with the use of ACE inhibitors during pregnancy, cases of oligohydramnios, premature birth, birth of children with arterial hypotension, impaired renal function, including acute renal failure, hypoplasia of the skull bones, contractures of the limbs, craniofacial anomalies, pulmonary hypoplasia, intrauterine growth retardation have been described. , patent ductus arteriosus, as well as cases of intrauterine fetal death and neonatal death. Often, oligohydramnios is diagnosed after the fetus has been irreversibly damaged.

Neonates exposed in utero to ACE inhibitors should be monitored for hypotension, oliguria, and hyperkalemia. If oliguria occurs, blood pressure and renal perfusion should be maintained.

Thiazides penetrate the placental barrier and are found in the umbilical cord blood. Non-teratogenic effects of thiazides include jaundice and thrombocytopenia in the fetus and/or newborn, and there may be other adverse effects observed in adults.

ACE inhibitors, including quinapril, pass into breast milk to a limited extent. Thiazide diuretics are excreted in breast milk. Given the possibility of serious adverse reactions in newborns, Accusid® should not be used during lactation, and if its use is necessary, breastfeeding should be stopped.

Use for liver dysfunction

Use is contraindicated in severe liver failure.

Use with caution in cases of impaired liver function or progressive liver disease.

Use for renal impairment

The use of the drug is contraindicated in severe renal failure (creatinine clearance less than 30 ml/min).

In patients with mild renal impairment (creatinine clearance >60 ml/min), the initial dose of Accusid® is 10 mg + 12.5 mg.

Accusid® should not be prescribed as initial therapy in patients with impaired renal function with CC <60 ml/min. In patients with moderate renal impairment (creatinine clearance 60-30 ml/min), quinapril should be used at an initial dose of 5 mg with further dose titration.

The drug is prescribed with caution in conditions after kidney transplantation, bilateral renal artery stenosis or stenosis of the artery of a single kidney.

Use in children

The use of the drug is contraindicated in children and adolescents under 18 years of age (the effectiveness and safety of the drug have not been established).

special instructions

Angioedema

During treatment with ACE inhibitors, cases of angioedema of the face and neck have been described, incl. in 0.1% of patients receiving quinapril. If a guttural whistle or angioedema of the face, tongue or glottis, or difficulty swallowing food or breathing occurs, Accusid® should be discontinued immediately. The patient must be given adequate treatment and observed until the swelling disappears. Antihistamines may be used to reduce symptoms. Angioedema affecting the larynx can be fatal. If swelling of the tongue, glottis or larynx threatens the development of airway obstruction, adequate emergency therapy is necessary, including subcutaneous administration of a solution of epinephrine (adrenaline) 1:1000 (0.3-0.5 ml). Cases of intestinal angioedema have also been described during treatment with ACE inhibitors. Patients reported abdominal pain (with/without nausea and vomiting); in some cases without previous angioedema of the face and normal C1-esterase activity. The diagnosis was made using abdominal computed tomography, ultrasound, or at the time of surgery. Symptoms disappeared after stopping the ACE inhibitors.

In patients who have experienced angioedema not associated with an ACE inhibitor, the risk of its development may be increased when treated with drugs of this group.

Patients receiving concomitant therapy with mTOR enzyme inhibitors (eg, temsirolimus) and DPP-4 (eg, vildagliptin) may be at greater risk of developing angioedema.

Patients receiving ACE inhibitors during desensitization therapy with hymenoptera (wasp, bee) venom may develop persistent, life-threatening anaphylactoid reactions. Temporary cessation of ACE inhibitor therapy promotes regression of symptoms, but they may recur when ACE inhibitor therapy is resumed.

Anaphylactoid reactions may also occur when ACE inhibitors are administered to patients undergoing LDL apheresis using dextran sulfate or to patients undergoing hemodialysis using high-flux membranes such as polyacrylonitrile membranes. It is necessary to use alternative lipid-lowering therapy or use other membranes for hemodialysis.

Arterial hypotension

Accusid® may cause transient arterial hypotension, but not more often than with monotherapy with both components of the drug. Symptomatic hypotension is rare during treatment with quinapril in patients with uncomplicated arterial hypertension, but it can develop as a result of therapy with ACE inhibitors in patients with reduced blood volume, for example, after treatment with diuretics, while following a diet with limited sodium intake, or during hemodialysis. If symptomatic hypotension occurs, the patient should be placed in a horizontal position and, if necessary, given an intravenous infusion using 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication to further use of the drug, however, in such cases it is advisable to reduce its dose.

Chronic heart failure

In patients with chronic heart failure with or without renal failure, ACE inhibitor therapy for hypertension can lead to an excessive decrease in blood pressure, which may be accompanied by oliguria, azotemia and, in rare cases, acute renal failure and even death. Treatment of such patients with Accusid® should be started under close medical supervision and supervision during the first 2 weeks and with an increase in the dose of the drug.

Agranulocytosis

In rare cases, therapy with ACE inhibitors may be accompanied by the development of agranulocytosis and suppression of bone marrow hematopoiesis in patients with uncomplicated arterial hypertension, but more often in patients with impaired renal function, especially with connective tissue diseases. In these cases, the number of leukocytes in the blood should be monitored.

If any symptoms of infection appear (for example, sore throat, fever), patients should immediately consult a doctor, because similar symptoms may be a manifestation of neutropenia.

Systemic lupus erythematosus

Thiazide diuretics can sometimes cause exacerbation of SLE.

Renal dysfunction

Accusid® should not be used in patients with severely impaired renal function (creatinine clearance less than 30 ml/min), because Thiazide diuretics contribute to the progression of azotemia and have a cumulative effect with long-term use in such patients. The drugs of choice in this group of patients receiving quinapril therapy are loop diuretics. For this reason, the fixed combination hydrochlorothiazide/quinapril should not be used in patients with severe renal impairment.

In patients with arterial hypertension without obvious signs of initial renal dysfunction, when using quinapril, especially in combination with a diuretic, an increase in the concentration of urea nitrogen in the blood and creatinine in the blood serum was noted, which is usually mild and, as a rule, transient. Such changes are most likely in patients with underlying renal impairment. In such cases, it may be necessary to reduce the dose of Accusid®. In all patients with arterial hypertension, renal function should be monitored. Accusid® should not be used as initial therapy in patients with CC less than 60 ml/min.

Impact of the RAAS

In some patients, suppression of RAAS activity can lead to renal dysfunction. In patients with severe heart failure, renal function may be affected by the activity of the RAAS, so treatment with ACE inhibitors, including quinapril, may lead to oliguria and/or progressive azotemia, and in rare cases, acute renal failure and/or death.

Double blockade of RAAS activity

The use of angiotensin II receptor antagonists, ACE inhibitors or aliskiren can lead to double blockade of RAAS activity. This effect may be manifested by a decrease in blood pressure, hyperkalemia and changes in renal function (including acute renal failure) compared with monotherapy. Blood pressure, renal function and plasma electrolytes should be carefully monitored in patients taking Accusid® and other drugs that affect the RAAS. The simultaneous use of RAAS-active agents and quinapril should be avoided. The use of this combination should be limited to individual cases with careful monitoring of renal function and plasma potassium levels.

Renal artery stenosis

In clinical studies in hypertensive patients with bilateral renal artery stenosis or solitary kidney artery stenosis, increases in blood urea nitrogen and serum creatinine were observed in some cases when treated with ACE inhibitors. These changes were almost always reversible and disappeared after discontinuation of the ACE inhibitor and/or diuretic. In such cases, renal function should be monitored during the first few weeks of treatment with Accusid®.

Liver dysfunction

Accusid® should be used with caution in patients with impaired liver function or progressive liver disease, because slight changes in water and electrolyte balance can cause the development of hepatic coma.

Water and electrolyte balance

Serum electrolyte levels should be monitored regularly to identify possible electrolyte imbalances. In patients receiving monotherapy with quinapril, as with other ACE inhibitors, serum potassium levels may increase.

Hyperkalemia (>5.8 mmol/l) was noted in approximately 2% of patients taking quinapril, but in most cases this deviation was isolated and resolved during treatment. Risk factors for the development of hyperkalemia include impaired renal function, diabetes mellitus and concomitant use of potassium-sparing diuretics, potassium supplements and/or salt substitutes containing potassium. Concomitant use of a potassium-sparing diuretic with Accusid, which contains a thiazide diuretic, is not recommended. Treatment with thiazide diuretics, on the contrary, is accompanied by hypokalemia, hyponatremia and hypochloremic alkalosis. These disorders are sometimes manifested by symptoms such as dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle weakness, muscle pain or cramps, decreased blood pressure, oliguria, tachycardia, nausea, confusion, convulsions and vomiting.

Hypokalemia may also enhance the toxic effect of cardiac glycosides. The risk of hypokalemia is especially high with liver cirrhosis, forced diuresis, inadequate consumption of drugs that improve myocardial metabolism, concomitant therapy with GCS or ACTH, and concomitant use with drugs that increase the risk of developing hypokalemia while taking thiazide diuretics. The opposing effects of Accusid's components on serum potassium levels result in serum potassium levels remaining unchanged in many patients.

In some cases, the effect of one component of the drug Accusid® may prevail over the other. Before and during treatment, serum electrolyte levels should be periodically determined to identify possible disturbances in electrolyte metabolism.

Chloride deficiency associated with thiazide diuretic therapy is usually mild and only in exceptional cases requires special treatment (for example, in cases of liver or kidney disease).

In hot weather, patients with peripheral edema may develop hyponatremia. In this case, adequate replacement therapy is necessary.

Thiazide diuretics reduce calcium excretion.

In rare cases, patients receiving long-term therapy with thiazides have developed pathological changes in the parathyroid glands, accompanied by hypercalcemia and hypophosphatemia. More serious complications of hyperparathyroidism (nephrolithiasis, bone resorption and peptic ulcer) have not been described. Before testing the function of the parathyroid glands, thiazide diuretics should be discontinued.

Thiazide diuretics increase urinary excretion of magnesium and may cause hypomagnesemia.

Thiazide diuretics may increase serum levels of cholesterol, triglycerides, and uric acid. These effects are usually mild, but thiazide diuretics may precipitate the development of gout or diabetes mellitus in susceptible patients.

Diabetes

Hyperglycemia induced by high doses of thiazide diuretics (including hydrochlorothiazide at a dose of >100 mg/day) may impair control of plasma glucose concentrations. A decrease in potassium content in the blood plasma leads to an increase in glucose tolerance. The concentration of glucose in the blood plasma should be monitored and, if necessary, potassium supplements should be prescribed to maintain the potassium content in the blood plasma and the hypoglycemic therapy should be adjusted. Therapy with ACE inhibitors may be accompanied by the development of hypoglycemia in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents. When treating patients with diabetes mellitus, more careful monitoring and dosage adjustment of hypoglycemic agents may be required. Therapy with ACE inhibitors may be accompanied by the development of hypoglycemia in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents. More careful monitoring may be required when treating patients with diabetes.

Cough

Surgical intervention

In patients undergoing surgery or general anesthesia, ACE inhibitors should be used with caution, because they block the formation of angiotensin II caused by compensatory secretion of renin. This can lead to arterial hypotension, which is eliminated by increasing blood volume. Before surgery, the patient must warn the anesthesiologist that he is taking an ACE inhibitor.

BCC

Patients should be warned that insufficient fluid intake and increased sweating can lead to an excessive decrease in blood pressure due to a decrease in blood volume. Other causes of dehydration, such as vomiting or diarrhea, can also lead to a drop in blood pressure.

Acute myopia and angle-closure glaucoma

Hydrochlorothiazide (a sulfonamide derivative) can lead to the development of acute transient myopia and acute angle-closure glaucoma. Symptoms include sudden loss of vision or eye pain and usually occur within the first hours to weeks after starting therapy. Without proper treatment, angle-closure glaucoma can lead to permanent vision loss. The main treatment for this condition is immediate discontinuation of hydrochlorothiazide. Emergency medical or surgical intervention may be needed if intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of allergic reactions to sulfonamides and penicillin.

Impact on the ability to drive vehicles and operate machinery

Caution should be exercised when driving or performing other work that requires increased attention, especially at the beginning of treatment.

Side effects of the drug Accusid

When using quinapril and hydrochlorothiazide, the following adverse reactions were observed with a frequency of over 1%: headache, dizziness, cough, fatigue. It should be noted that the cough is usually dry, persistent and disappears after cessation of therapy. Adverse reactions were usually minor, short-lived, and were not related to age, gender, race, or duration of use (see SPECIAL INSTRUCTIONS section for more information). Discontinuation of the drug due to side effects was observed in 2% of patients. The most common reason for discontinuation of the drug was headache, accompanied by cough and nausea and/or vomiting. Headache, dizziness, cough, fatigue, myalgia, viral infection, rhinitis, nausea and/or vomiting, abdominal pain, back pain, diarrhea, upper respiratory tract infection, insomnia, drowsiness have been observed in controlled studies with quinapril/hydrochlorothiazide. , bronchitis, dyspepsia, asthenia, pharyngitis, vasodilation, vertigo, chest pain.

Special instructions for the use of the drug Accusid

To stabilize blood pressure, 2 weeks of treatment may sometimes be needed. If laryngeal stridor or angioedema of the face, tongue or glottis occurs, the use of the quinapril/hydrochlorothiazide combination should be stopped immediately and the necessary treatment measures should be taken, carefully monitoring the patient's condition until the edema disappears. Quinapril/hydrochlorothiazide should be used with caution in the treatment of patients with severe renal impairment. In some patients, thiazides can cause azotemia, and with repeated administration this effect becomes more pronounced. Patients with creatinine clearance ≤60 mL/min require a lower dose of quinapril (see USAGE section for further information). The dose for such patients should be titrated from the lowest to the necessary, focusing on the therapeutic effect; Renal function should also be closely monitored, even if initial studies do not reveal deterioration in renal function. When using quinapril in some patients without manifestations of renal vascular disease, the level of urea nitrogen and creatinine in the blood serum may increase. Typically, such manifestations are minor and transient; they occur more often when quinapril is used in combination with diuretics. Such cases are more often observed in patients with already impaired renal function. In such patients the dose should be reduced. The examination of patients with hypertension (arterial hypertension) should always include a study of renal function (additional information is provided in the APPLICATION section). Discontinuation of quinapril therapy due to hyperkalemia was necessary in 0.1% of cases. Risk factors for the development of hyperkalemia are renal failure, diabetes mellitus, concomitant therapy with potassium-sparing diuretics, and the use of drugs containing potassium and its salts. The use of potassium-sparing diuretics simultaneously with Accusid is not recommended. Conversely, hypokalemia, hyponatremia and hypochloremic alkalosis may occur with the use of thiazide diuretics. Hypokalemia increases the sensitivity of the myocardium to digitalis drugs and increases their toxicity. The risk of hypokalemia is higher in patients with liver cirrhosis, polakiuria, in case of insufficient oral replacement of electrolyte loss, and simultaneous use of corticosteroids and adrenocorticotropic hormone. Thiazides reduce calcium excretion. Thiazides increase urinary excretion of magnesium, which may lead to hypomagnesemia (see INTERACTIONS section for more information). The use of ACE inhibitors may be accompanied by hypoglycemia in patients with diabetes mellitus taking insulin or oral hypoglycemic agents. Therefore, the condition of such patients should be carefully monitored. Cough has sometimes occurred in patients taking ACE inhibitors, including quinapril. Usually the cough was dry, persistent and disappeared after cessation of therapy. Cough induced by the use of ACE inhibitors should be considered in the differential diagnosis of cough. If major surgery is necessary, it should be taken into account that an ACE inhibitor may block the secondary formation of angiotensin II during compensatory renin release. This can cause hypotension, which is corrected by intravenous administration of solutions in sufficient volume.

Accusid, 12.5 mg+20 mg, film-coated tablets, 30 pcs.

Angioedema.

During treatment with ACE inhibitors, cases of angioedema of the face and neck have been described, incl. in 0.1% of patients receiving quinapril. If a guttural whistle or angioedema of the face, tongue or glottis appears, Accusid® should be discontinued immediately. The patient must be given adequate treatment and observed until the symptoms of edema disappear. Antihistamines may be used to reduce symptoms. Angioedema involving the larynx can be fatal. If swelling of the tongue, glottis or larynx threatens the development of airway obstruction, adequate emergency therapy is necessary, including subcutaneous administration of a solution of adrenaline 1:1000 (0.3–0.5 ml).

Cases of intestinal angioedema have also been described during treatment with ACE inhibitors. Patients reported abdominal pain (with/without nausea and vomiting); in some cases without previous angioedema of the face and with normal C1-esterase activity. The diagnosis was made using ultrasound, computed tomography of the abdominal region, or at the time of surgery. Symptoms disappeared after stopping the ACE inhibitors.

For patients who have suffered angioedema not associated with taking ACE inhibitors, there is a risk of its development when treated with drugs of this group.

Patients receiving concomitant therapy with mTOR

(eg temsirolimus) and DPP-4 (eg vildagliptin) may be at greater risk of developing angioedema.

Ethnic differences.

Carrying out desensitizing therapy.

Patients receiving ACE inhibitors during desensitizing therapy with hymenoptera (wasp, bee) venom may develop persistent anaphylactoid reactions that are life-threatening. Temporary cessation of ACE inhibitor therapy promotes regression of symptoms, but they may recur when ACE inhibitor therapy is resumed.

Hemodialysis.

Anaphylactoid reactions may also occur with the use of ACE inhibitors in patients undergoing LDL apheresis using dextran sulfate, or in patients undergoing hemodialysis using high-flux membranes such as polyacrylonitrile membranes.

It is necessary to use alternative antihypertensive therapy or use other membranes for hemodialysis.

Arterial hypotension.

The drug Accusid® can cause transient arterial hypotension, but not more often than with monotherapy with the components included in the drug. Symptomatic arterial hypotension rarely occurs during treatment with quinapril in patients with uncomplicated arterial hypertension, but it can develop as a result of therapy with ACE inhibitors in patients with reduced blood volume, for example, after previous therapy with diuretics, when following a diet with limited salt or hemodialysis. If symptomatic arterial hypotension occurs, the patient should be placed in a supine position with legs elevated and given an intravenous infusion of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication to further use of the drug Accusid®, however, in such cases it is advisable to reduce its dose.

CHF.

In patients with CHF with and/or without renal failure, treatment with an ACE inhibitor for hypertension can lead to an excessive decrease in blood pressure, which may be accompanied by oliguria, azotemia and, in rare cases, acute renal failure and even death. Treatment of such patients with Accusid® should be started under close medical supervision and supervision during the first 2 weeks of therapy and with an increase in the dose of the drug.

Agranulocytosis.

If any symptoms of infection appear (for example, sore throat, fever), patients should immediately consult a doctor, because they may be a manifestation of neutropenia.

Systemic lupus erythematosus.

Thiazide diuretics can sometimes cause exacerbation of systemic lupus erythematosus.

Kidney function.

The drug Accusid® is not recommended for use in patients with severe renal impairment (Cl creatinine less than 30 ml/min), because Thiazide diuretics contribute to the progression of azotemia and have a cumulative effect with long-term use in such patients. The drugs of choice in this group of patients receiving quinapril therapy are loop diuretics. For this reason, the fixed combination hydrochlorothiazide + quinapril should not be used in patients with severe renal failure (see "Contraindications").

T1/2 of quinaprilat increases with a decrease in creatinine clearance. In patients with creatinine Cl less than 60 ml/min, but more than 30 ml/min, quinapril should be prescribed at a lower initial dose. In such patients, the dose of Accusid® should be increased taking into account the clinical condition of the patient, with regular monitoring of renal function, although in clinical studies no further deterioration of renal function was noted during treatment with Accusid®.

In patients with arterial hypertension without obvious signs of initial renal vascular impairment, when using quinapril, especially in combination with a diuretic, an increase in the concentration of urea nitrogen in the blood and creatinine in the blood serum was noted, which was usually mild and transient. Such changes are most likely in patients with underlying renal impairment. In such cases, it may be necessary to reduce the dose of Accusid®. In all patients with arterial hypertension, renal function should be monitored.

Accusid® should not be used as initial therapy in patients with creatinine Cl less than 60 ml/min.

The influence of the RAAS.

In some patients, suppression of RAAS activity can lead to renal dysfunction. In patients with severe CHF, renal function depends on the activity of the RAAS, therefore treatment with ACE inhibitors, including quinapril, can lead to oliguria and/or progressive azotemia, and in rare cases, to acute renal failure and/or death.

Double blockade of RAAS activity.

Renal artery stenosis.

In clinical studies in patients with arterial hypertension with bilateral renal artery stenosis or stenosis of the artery of a single kidney, when treated with ACE inhibitors, an increase in the concentration of urea nitrogen and creatinine in the blood serum was observed in some cases. These changes are almost always reversible and resolved after discontinuation of the ACE inhibitor and/or diuretic. In such cases, monitoring of renal function is necessary during the first few weeks of treatment with Accusid®.

Liver dysfunction.

Accusid® should be used with caution in patients with impaired liver function or progressive liver disease, because even minor disturbances in the water-electrolyte balance of the blood can cause the development of hepatic coma.

Water-electrolyte balance of blood.

In order to identify possible disturbances in the water-electrolyte balance of the blood, it is necessary to regularly monitor the content of electrolytes in the blood serum. In patients receiving monotherapy with quinapril, as with other ACE inhibitors, potassium levels may increase.

Serum potassium.

Hyperkalemia (≥5.8 mmol/l) was observed in approximately 2% of patients taking quinapril, but in most cases this deviation was isolated and resolved with further therapy. Risk factors for the development of hyperkalemia are: impaired renal function, diabetes mellitus and simultaneous use of potassium-sparing diuretics, potassium supplements and/or salt substitutes containing potassium. Concomitant use of potassium-sparing diuretics with Accusid®, which contains a thiazide diuretic, is not recommended. Treatment with thiazide diuretics, on the contrary, is accompanied by hypokalemia, hyponatremia and hypochloremic alkalosis. These disorders are sometimes manifested by the following symptoms: dryness of the oral mucosa, thirst, weakness, lethargy, drowsiness, restlessness, muscle weakness, muscle pain or spasm, decreased blood pressure, oliguria, tachycardia, nausea, confusion, convulsions and vomiting.

Hypokalemia may also enhance the toxic effect of cardiac glycosides. The risk of hypokalemia is increased with liver cirrhosis, forced diuresis, inadequate use of drugs that improve myocardial metabolism, concomitant therapy with GCS or ACTH, and concomitant use with drugs that increase the risk of hypokalemia while taking thiazide diuretics. In most patients, the opposing effects of quinapril and hydrochlorothiazide on serum potassium should be expected to counterbalance.

Chloride deficiency associated with thiazide diuretic therapy is usually mild and only in exceptional cases requires appropriate treatment (for example, in cases of liver and/or kidney disease).

Hyponatremia.

In hot weather, patients with peripheral edema may develop hyponatremia. For hyponatremia, adequate replacement therapy is necessary.

Hypocalcemia.

Thiazide diuretics reduce the excretion of calcium by the kidneys.

Parathyroid glands.

In rare cases, patients receiving long-term therapy with thiazide diuretics developed changes in the parathyroid glands, accompanied by hypercalcemia and hypophosphatemia. More serious complications of hyperparathyroidism (nephrolithiasis, bone resorption and peptic ulcer) have not been described. Before testing the function of the parathyroid glands, thiazide diuretics must be discontinued.

Magnesium.

Thiazide diuretics increase renal excretion of magnesium and may cause hypomagnesemia.

Glucose.

Thiazide diuretics increase serum levels of cholesterol, triglycerides, and uric acid. These effects are usually minor, but the development of overt gout or diabetes mellitus can be triggered in patients with a predisposition to these diseases.

Diabetes.

Hyperglycemia induced by high doses of thiazide diuretics (including hydrochlorothiazide at a dose of ≥100 mg/day) may impair control of plasma glucose concentrations. A decrease in potassium content in the blood plasma leads to an increase in glucose tolerance. The concentration of glucose in the blood plasma should be monitored, potassium supplements should be prescribed as necessary to maintain potassium levels in the blood plasma, and hypoglycemic therapy should be adjusted.

Cough.

Surgical intervention.

In patients undergoing surgery or general anesthesia, ACE inhibitors should be used with caution, because they block the formation of angiotensin II caused by compensatory secretion of renin. This can lead to arterial hypotension, which is eliminated by increasing blood volume. In case of surgery, the patient should warn the anesthesiologist that he is taking an ACE inhibitor.

OCC.

Patients must be warned that insufficient fluid intake and increased sweating can lead to an excessive decrease in blood pressure due to a decrease in blood volume. Other causes of decreased blood volume, such as vomiting or diarrhea, can also lead to a sharp drop in blood pressure.

Acute myopia and angle-closure glaucoma.

Hydrochlorothiazide (a sulfonamide derivative) can lead to the development of acute transient myopia and acute angle-closure glaucoma. Symptoms include an acute attack of decreased visual function or eye pain and usually occur within the first hours/weeks after starting therapy. Without proper treatment, angle-closure glaucoma can lead to permanent vision loss. The main treatment for this condition is to discontinue hydrochlorothiazide therapy as soon as possible. Prompt medical or surgical intervention may be needed if the IOP remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of allergic reactions to sulfonamides and penicillin.

Impact on the ability to drive vehicles and operate machinery.

Caution should be exercised when driving or performing other work that requires increased attention, especially when starting treatment with Accusid®.

Interactions of the drug Accusid

Use of tetracycline with quinapril reduces the absorption of tetracycline by approximately 28–37%. This is due to the presence of magnesium carbonate in the preparation as a filler. The possibility of such an interaction should be kept in mind when quinapril/hydrochlorothiazide is co-administered with tetracycline or other drugs that react with magnesium. Lithium is not usually prescribed with diuretics. Diuretics reduce its renal clearance and increase the risk of toxic effects. Increased serum lithium concentrations and symptoms of lithium poisoning as a consequence of sodium loss under the influence of quinapril/hydrochlorothiazide were detected in patients concomitantly taking lithium and ACE inhibitors. The risk of lithium toxicity may be increased when using quinapril/hydrochlorothiazide. The simultaneous use of these drugs should be done with caution; Frequent monitoring of serum lithium levels is recommended. Concomitant use of a diuretic may increase the risk of lithium toxicity. No clinically important pharmacokinetic interactions were observed when quinapril was used with propranolol, hydrochlorothiazide, digoxin or cimetidine. The anticoagulant effect of a single dose of warfarin (assessed by prothrombin time) did not change significantly with simultaneous administration of quinapril 2 times a day. Alcohol, barbiturates or drugs - orthostatic hypotension may occur; antidiabetic agents (oral hypoglycemic agents and insulin) - it may be necessary to increase the dose of antidiabetic agents; other antihypertensive drugs - additive effect or potentiation of effect; GCS, adrenocorticotropic hormone - increased loss of electrolytes, especially hypokalemia; pressor amines (for example, norepinephrine) - there may be a slight decrease in the response to the use of these drugs; non-depolarizing muscle relaxants (for example tubocurarine) - it is possible to increase the response to the use of muscle relaxants; NSAIDs - in some patients, the use of NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when quinapril/hydrochlorothiazide and NSAIDs are used concomitantly, patients need careful monitoring to obtain the desired effect from Accuside; drugs that increase serum potassium levels - quinapril can reduce aldosterone levels, which in turn can cause potassium retention. Therefore, the simultaneous use of quinapril and potassium preparations or preparations containing potassium salts should be cautious, with appropriate monitoring of serum potassium concentrations (additional information is provided in the SPECIAL INSTRUCTIONS section); anion exchange resins - absorption of hydrochlorothiazide is impaired by the influence of anion exchange resins such as cholestyramine and colestipol. The simultaneous use of an anion exchange resin binds hydrochlorothiazide and reduces its absorption from the digestive tract to 85 and 43%, respectively.

Accusid overdose, symptoms and treatment

There is no information about an overdose of Accusid during the treatment of people. The main clinical manifestations of hydrochlorothiazide motor therapy are symptoms associated with loss of electrolytes (hypokalemia, hypochloremia, hyponatremia) and dehydration due to stimulation of diuresis. With concomitant use of digitalis preparations, hypokalemia may increase cardiac arrhythmia. There is no information on specific treatment for quinapril/hydrochlorothiazide overdose. The effectiveness of hemodialysis and peritoneal dialysis is insignificant. Treatment is symptomatic.