Accupro® [Quinapril]

Pharmacological properties

Quinapril is hydrolyzed in the liver to form quinaprilat, which is an APF inhibitor. apf is a peptidyldipeptidase that converts angiotensin i into a vasoconstrictor substance angiotensin ii.

Inhibition of ACE leads to a decrease in the formation of angiotensin II, which has a vasoconstrictive effect in tissues and blood plasma, and this leads to a decrease in the secretion of aldosterone and, as a result, an increase in the concentration of potassium in the blood serum. Increased plasma renin activity is a consequence of the cessation of negative feedback between angiotensin II and renin secretion.

Since ACE also metabolizes the bradykinin molecule (a vasodilator peptide), inhibition of ACE leads to increased activity of circulating and local kallikrein-kinin systems (and, as a result, activation of the prostaglandins of the system). Perhaps this mechanism plays a role in the implementation of the hypotensive effect of ACE inhibitors and the development of certain adverse reactions.

In addition, clinical studies have shown that quinapril reduces acetylcholine-induced vasoconstriction, indicating an improvement in endothelial function.

Another effect, the mechanism of which is still unclear, is an increase in insulin sensitivity.

Pharmacodynamics In patients with hypertension, quinapril reduces blood pressure while lying and standing without a compensatory increase in heart rate.

During hemodynamic studies, quinapril caused a significant decrease in peripheral arterial resistance. Typically, clinically significant changes in renal plasma flow and glomerular filtration rate are absent.

The onset of antihypertensive action is noted within 1 hour, and the maximum effect is usually achieved approximately 2-4 hours after taking the drug.

The maximum hypotensive effect of a certain dose of quinapril is mainly achieved after 3-4 weeks. In the case of a daily dose, the antihypertensive effect persists even with prolonged therapy.

The sudden cessation of quinapril does not lead to a rapid excessive increase in blood pressure (recoil phenomenon).

A study of hemodynamics in patients with heart failure showed that quinapril causes a decrease in peripheral systemic resistance and an increase in venous capacity. This leads to a decrease in pre- and afterload on the heart (decrease in ventricular filling pressure). In addition, with treatment with quinapril, an increase in cardiac output, stroke index, and exercise tolerance was observed.

The concurrent use of an ACE inhibitor with an angiotensin II receptor blocker was evaluated in two large randomized controlled trials (ONTARGET [ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial] and monotherapy and in combination with ramipril] and VA NEPHRON-D [The Veterans Affairs Nephropathy in Diabetes / Veterans Study with Nephropathy and Diabetes]).

The ONTARGET study was performed in patients with a history of cardiovascular or cerebrovascular disease or type II diabetes mellitus with signs of target organ damage. The VA NEPHRON D study was performed in patients with type II diabetes mellitus and diabetic nephropathy.

These studies did not demonstrate a significant beneficial effect on renal and / or cardiovascular outcomes and mortality, while at the same time, there was an increased risk of hyperkalemia, acute kidney damage and / or arterial hypotension compared with monotherapy. Given the similar pharmacodynamic properties, these results also apply to other ACE inhibitors and angiotensin II receptor blockers.

Therefore, in patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor blockers should not be used simultaneously.

An ALTITUDE study (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was conducted to evaluate the benefits of adding aliskiren to standard ACE inhibitor therapy or an angiotensin II receptor blocker in patients with type II diabetes mellitus and chronic kidney disease, heart disease, or two diseases simultaneously. This study was terminated prematurely due to an increased risk of unwanted effects. Both mortality from cardiovascular diseases and stroke were recorded more often in the aliskiren group compared with the placebo group, and adverse reactions and some severe adverse reactions (hyperkalemia, arterial hypotension and impaired renal function) occurred more often in the aliskiren group compared to with a placebo group.

Children. In a randomized trial using quinapril at target doses of 2.5; 5; 10 and 20 mg, which was carried out with the participation of 112 children and adults with hypertension or a maximum increase in blood pressure for 8 weeks (2 weeks of using the drug in double-blind mode and 6 weeks of an extended study), failed to achieve the main goal - reducing diastolic blood pressure after 2 weeks of treatment. As for systolic blood pressure (a secondary goal in assessing effectiveness), at week 2, only a statistically significant linear dependence of the reaction on the dose of the drug was observed in all treatment groups, and the rates in patients receiving quinapril at a dose of 20 mg once a day differed significantly from indicators in patients receiving placebo.

The long-term effects of quinapril on growth, puberty, and overall development have not been investigated.

Pharmacokinetics After oral administration C_max Acupro in blood plasma is reached within 1 hour. Absorption is approximately 60% and does not depend on food intake. After absorption, Akkupro deesterifies to the main active metabolite - quinaprilat and minor inactive metabolites. Obvious t_½ Accupro is approximately 1 hour. C_max quinaprilat in blood plasma is detected approximately 2-3 hours after ingestion of quinapril. The binding of quinapril and quinaprilat to blood proteins is approximately 97%. About 60% of the administered dose of quinapril is excreted by the kidneys, and 40% with feces. Quinaprilat is removed mainly by renal excretion, the half-life of effective accumulation is about 3 hours, the half-life of ACE dissociation is about 26 hours.

Normal dynamics of plasma levels of quinapril and quinaprilat were recorded in patients with renal failure, creatinine clearance of up to 60 ml / min. In patients with creatinine clearance of 60 ml / min, quinaprilat levels are higher, time to reach C_max in plasma increases and also increases T_½.

Pharmacokinetic studies in patients with end-stage renal disease who underwent continuous hemodialysis or ambulatory peritoneal dialysis showed that dialysis only slightly affects the excretion of quinapril and quinaprilat.

The excretion of quinaprilat is also reduced in elderly patients (65 years) and in patients with severe heart failure. Slow excretion correlates with impaired renal function, often seen in the elderly. Therefore, in patients with impaired renal function of moderate (creatinine clearance of 30-60 ml / min) or severe (10-30 ml / min) and in elderly patients, it may be necessary to reduce the dose of quinapril.

In patients with alcoholic cirrhosis of the liver, the concentration of quinaprilat is reduced due to violation of the deacidification of Acupro. Studies in rats showed that Akkupro and its metabolites do not penetrate the BBB.

Bioavailability. Based on the results of determining the presence of a drug in the urine, the absorption rate of quinapril after oral administration is about 60%.

The period of breastfeeding. After a single dose of quinapril at a dose of 20 mg in 6 breast-feeding women, the ratio of the concentration of quinapril in milk and blood plasma was 0.12. Quinapril is not detected in breast milk 4 hours after administration. The levels of quinaprilat in milk were below the limit of determination (5 μg / L) at each time of the study. It is believed that together with breast milk, the baby can receive about 1.6% of the maternal dose of quinapril, adjusted for body weight.

Children. The pharmacokinetics of quinapril were studied in a study with a single administration of the drug (0.2 mg / kg) to 24 children aged 2.5 months to 6.8 years and a study with repeated administration of the drug (0.016-0.468 mg / kg) to 38 children aged 5-16 years old with an average body weight of 66 kg (primary school children) or 98 kg (adolescents).

As in adults, quinapril quickly turned into quinaprilat. C_max quinaprilat, as a rule, is achieved 1–2 hours after drug administration, after which it decreases, and the average T_½ is 2.3 hours. In infants and young children, exposure after a single administration of 0.2 mg / kg is comparable to that in adults after a single administration of 10 mg. In a study with repeated administration of the drug to schoolchildren and adolescents, AUC and C indicators_max quinaprilat increased linearly with increasing dose of quinapril in mg / kg.

Indications

Essential hypertension. heart failure - as an adjuvant in combination with diuretics, especially in severe heart failure - in combination with digitalis preparations.

Application

Mode of application. Accupro can be used regardless of food intake; the daily dose can be used 1 time or divided into 2 doses.

The duration of use is determined by the doctor.

Doses Notes. At the beginning of Acupro treatment, an excessive decrease in blood pressure may be noted, in particular in patients with a deficiency of salts and / or liquid (for example, in case of vomiting, diarrhea, treatment with diuretics), heart failure, acute myocardial infarction, unstable angina or severe hypertension.

If possible, before starting treatment with Acupro, you should make up for the deficiency of salts and / or liquid, or reduce the dose accordingly or stop using the diuretic. Such patients should begin treatment with a low single dose of 2.5 mg of quinapril in the morning and closely monitor blood pressure.

After applying the first dose, as well as in the case of increasing the dose of quinapril and / or loop diuretics, medical supervision should be performed for at least 6 hours in order to avoid the development of an uncontrolled hypotensive reaction.

Patients with malignant hypertension or severe heart failure should be treated in a clinic setting with Accupro therapy.

In other cases, the following dosage recommendations should be followed unless otherwise indicated.

Essential hypertension. Typically, the initial dose is 10 mg of quinapril per day. If this dose does not contribute to the normalization of blood pressure, it can be increased by 20 mg / day. This dose can be taken once or divided into 2 doses (morning and evening). Raising the dose for 3 weeks is undesirable. Typically, the maintenance dose is 10 mg of quinapril per day, the maximum dose should not exceed 20 mg of quinapril 2 times a day (40 mg).

Heart failure.Accupro is used as an adjunct to diuretic and / or cardiac glycoside therapy. The recommended starting dose of Accupro is 2.5 mg in the morning and evening. Dosage can only be increased gradually depending on the individual patient response to treatment. Usually, the maintenance dose is 10–20 mg of quinapril per day, the maximum dose should not exceed 20 mg of quinapril 2 times a day. (see INTERACTIONS).

Moderate impaired renal function (creatinine clearance 30-60 ml / min) and patients over the age of 65 years. The initial dose is 5 mg of quinapril, the maintenance dose is usually 5–10 mg of quinapril per day. The maximum dose should not exceed 20 mg of quinapril per day.

Severe impaired renal function (creatinine clearance 10-30 ml / min). The initial dose is 2.5 mg of quinapril (respectively ½ tablet film-coated, Akkupro 5 mg), the maintenance dose is usually also 2.5 mg of quinapril per day (respectively ½ tablet film-coated, Akkupro 5 mg). The maximum dose is 5 mg of quinapril per day (respectively 1 film-coated tablet, Accupro 5 mg). The interval between two doses should be at least 24 hours due to the long half-life.

Children. Currently available data on the use of quinapril in children are given in the sections “Pharmacokinetics” and “Pharmacodynamics”; however, dosing recommendations are not available.

Contraindications

Hypersensitivity to the components of the drug.

The presence of a history of angioedema, including that associated with previous therapy with ACE inhibitors.

Accupro is contraindicated in patients with hereditary / idiopathic angioedema.

Patients with bilateral renal artery stenosis or single kidney artery stenosis.

Patients with hemodynamically significant stenosis of the aortic or mitral valve.

Patients after kidney transplantation.

Hypertrophic cardiomyopathy.

Primary hyperaldosteronism.

Pregnancy (see. Use during pregnancy and lactation).

Breastfeeding (see. Use during pregnancy and lactation).

Do not use preparations containing aliskiren together with quinapril in patients with diabetes mellitus or renal failure (glomerular filtration rate of 60 ml / min / 1.73 m²) (see INTERACTIONS and Pharmacodynamics).

Dialysis or hemofiltration using poly (acrylonitrile, sodium-2-methylalyl sulfonate) -high-flow membranes (e.g. AN69) is contraindicated during therapy with Accupro, since there is a risk of hypersensitivity reactions (anaphylactic reactions), including a life-threatening shock during dialysis or hemofiltration.

If emergency dialysis or hemofiltration is necessary, the drug should first be replaced with a drug that is not an ACE inhibitor, or alternative dialysis membranes should be used (see SPECIAL INSTRUCTIONS).

During apheresis of LDL (in the case of severe hypercholesterolemia) with the use of dextransulfate and the concomitant use of an ACE inhibitor, life-threatening hypersensitivity reactions occurred.

Sometimes life-threatening hypersensitivity reactions (for example, decreased blood pressure, shortness of breath, vomiting, allergic skin reactions) can occur during treatment aimed at reducing or eliminating the tendency to develop allergic reactions (desensitizing therapy) to insect toxins (such as bee venom or wasp), and concomitant use of an ACE inhibitor.

If it is necessary to carry out LDL apheresis or desensitization with respect to insect toxins, the drug should be temporarily replaced with other drugs intended for the treatment of hypertension or heart failure.

Side effects

Very often (≥1 / 10), often (from ≥1 / 100 to 1/10), infrequently (from ≥1 / 1000 to 1/100), rarely (from ≥1 / 10,000 to 1/1000), very rarely (≤1 / 10,000), unknown (impossible to establish based on available data).

The following adverse reactions occurred during treatment with Accupro or other ACE inhibitors.

General disorders and changes at the injection site: often - chest pain, fatigue, asthenia; rarely - fever, generalized edema, peripheral edema.

From the immune system: the frequency is unknown - anaphylactoid reactions.

From the side of the heart: infrequently - angina pectoris, palpitations, tachycardia, edema, myocardial infarction; very rarely - arrhythmia, cerebral stroke.

On the part of the vessels: often - especially at the beginning of Acupro treatment and in patients with deficiency of salts and / or liquid (for example, due to vomiting, diarrhea, previous treatment with diuretics), heart failure or severe hypertension, but also with an increase in the dose of Accupro and / or diuretics there may be an excessive decrease in blood pressure (arterial hypotension, orthostatic hypotension) with symptoms such as dizziness, a feeling of weakness, visual impairment, which in rare cases is accompanied by loss of consciousness (syncope); rarely - vasodilation, transient ischemic disturbance of cerebral circulation; frequency unknown - orthostatic hypotension.

From the digestive system: often - nausea, vomiting, diarrhea, dyspepsia, abdominal pain (in the upper sections), pharyngitis, indigestion; infrequently - dry mouth or throat, flatulence, pancreatitis (sometimes fatal), constipation, anorexia; rarely - taste change, glossitis; very rarely - ileus, intestinal angioedema.

From the blood system and lymphatic system: rarely - thrombocytopenia; the frequency is unknown - neutropenia, agranulocytosis, hemolytic anemia.

From the side of the psyche / nervous system: often - headache, lethargy, loss of strength, insomnia, paresthesia, increased fatigue, dizziness; infrequently - depression, nervousness, drowsiness, sleep disturbance, tingling sensation, imbalance, confusion, transient loss of taste; rarely - fainting.

On the part of the skin and subcutaneous tissue: often - allergic skin reactions, such as exanthema; infrequently - alopecia, increased sweating, pemphigus, itching, rash, angioedema of the lips, face and / or limbs (in rare cases with damage to the larynx, tongue / pharynx (see emergency measures)), urticaria and photosensitivity; rarely - erythema multiforme; very rarely - skin reactions, such as psoriasis-like changes in the skin, hot flashes, hyperhidrosis, onycholysis, increased severity of symptoms of Raynauds syndrome; frequency unknown - Stevens-Johnson syndrome, exfoliative dermatitis, epidermal necrolysis.

In case of suspicion of the development of severe skin reactions, you should immediately consult a doctor and, if necessary, stop treatment with Accupro.

Note: patients of the Negroid race have an increased risk of developing angioedema.

Changes in the skin can be accompanied by fever, pain in the muscles and joints (myalgia, arthralgia, arthritis), vascular inflammation (vasculitis), inflammation of the serous tissues and certain changes in laboratory parameters (eosinophilia, leukocytosis and / or increased titers of antinuclear antibodies, increased ESR) .

On the part of the kidneys and urinary tract: often - impaired renal function; infrequently - urinary tract infections, proteinuria (sometimes with concomitant deterioration of kidney function); very rarely - acute renal failure.

From the reproductive system and mammary glands: infrequently - impotence; rarely - erectile dysfunction.

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

From the side of the organ of hearing and balance: infrequently - ringing in the ears, vertigo.

From the musculoskeletal system and connective tissue: often - back pain, myalgia.

From the respiratory system, chest and mediastinal organs: often - cough, irritating cough, shortness of breath, rhinitis; infrequently - sinusitis, upper respiratory tract infection, bronchitis, eosinophilic pneumonitis; rarely thirst; frequency unknown - bronchospasm.

In some cases, angioedema with damage to the upper respiratory tract caused fatal airway obstruction.

From the hepatobiliary system: rarely - hepatitis; very rarely - cholestatic jaundice or impaired liver function (in case of jaundice or a marked increase in the level of hepatic enzymes, ACE inhibitor therapy should be discontinued).

Hereditary, familial and genetic disorders: see the CONTRAINDICATIONS sections and Use during pregnancy and lactation.

Laboratory and instrumental studies: often - a decrease in the concentration of hemoglobin, hematocrit, a decrease in the number of leukocytes or platelets, and also, especially in patients with impaired renal function, an increase in the concentration of urea or creatinine in the blood plasma (more likely in patients receiving concomitant treatment with diuretics than in patients receiving quinapril monotherapy, it often has a reversible character if treatment is continued), increased potassium concentration, decreased plasma concentration of sodium; infrequently - anemia, eosinophilia can develop, in rare cases even pancytopenia, especially in patients with impaired renal function, collagenosis or concomitant therapy with allopurinol, procainamide or certain drugs that suppress the bodys defenses; very rarely - hemolysis, increased concentrations of bilirubin and liver enzymes; the frequency is unknown - in patients with congenital glucose-6-phosphate dehydrogenase deficiency, isolated cases of hemolytic anemia have been reported.

In patients with diabetes mellitus, an increase in the level of potassium in the blood plasma was noted. Perhaps increased proteinuria.

From the side of metabolism and nutrition: often - hyperkalemia.

Notes. Monitoring of the above laboratory parameters should be carried out before treatment and at regular intervals during the course of treatment with Acupro. Careful monitoring of the level of electrolytes and creatinine in blood plasma and the number of blood cells should be carried out, especially at the beginning of treatment and in patients at risk (patients with impaired renal function, collagenoses, patients receiving treatment with immunosuppressive drugs, cytostatics, allopurinol, procainamide, digitalis glycosides , Corticosteroids, laxatives, elderly patients).

If symptoms such as fever, swelling of the lymph nodes, and / or sore throat occur, you should immediately determine the number of white blood cells in the blood.

With the use of other ACE inhibitors, cases of vasculitis and gynecomastia have been reported; it is possible that these adverse reactions develop in special groups of patients.

special instructions

Warning. acupro should not be used simultaneously with membranes with high hydraulic permeability, made from poly (acrylonitrile, sodium-2-methylalyl sulfonate) (for example an69), during LDL apheresis with dextransulfate or during desensitizing therapy for insect toxins (see contraindications )

Special security measures

Since the experience of using Accupro for the treatment of the following patients is not enough, this drug should not be prescribed:

• with very severe impaired renal function (creatinine clearance 10 ml / min);
• hemodialysis patients;
• with primary diseases and liver failure.

Accupro can be used only after a very thorough assessment of the ratio of benefit and risk and under constant monitoring of the characteristic clinical and laboratory chemical parameters with:

• serious impaired renal function (creatinine clearance of 10-30 ml / min);
• clinically significant proteinuria (1 g / day);
• clinically significant electrolyte imbalance;
• impaired immune reactivity or the presence of collagen diseases (systemic lupus erythematosus, scleroderma);
• the simultaneous use of drugs that suppress the protective functions of the body (corticosteroids, cytostatics, antimetabolites), allopurinol, procainamide, lithium.

It is necessary to monitor kidney function before using the drug Akkupro.

In particular, at the beginning of therapy, Akkupro should be used only in conditions of intensive monitoring of blood pressure and / or relevant laboratory parameters:

• patients with a deficiency of salts and / or liquid;
• patients with reduced renal function;
• patients with hypertension;
• patients over the age of 65;
• patients with heart failure (cardiogenic shock).

Double blockade of the renin-angiotensin-aldosterone system (RAAS). There is evidence that the simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and impaired renal function (including acute renal failure). Therefore, the use of double blockade of RAAS by the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see INTERACTIONS and Pharmacodynamics).

If the use of double blockade is considered essential, it can only be carried out under the supervision of a specialist and subject to careful monitoring of kidney function, electrolyte balance and blood pressure.

Patients with diabetic nephropathy should not use ACE inhibitors and angiotensin II receptor blockers at the same time.

Symptomatic hypotension. Isolated cases of symptomatic hypotension in patients with uncomplicated hypertension were noted. In patients with hypertension receiving quinapril, hypotension is more likely to develop with fluid loss due to diuretic therapy, salt diet, dialysis, diarrhea, vomiting, or severe renin-dependent hypertension. In case of development of symptomatic hypotension, the patient should be placed on his back and, if necessary, injected with a physiological solution in the form of an iv infusion. A short-term hypotensive reaction is not a contraindication to further treatment; however, if such a reaction occurs, consideration should be given to using lower doses of Accupro or a concomitant diuretic.

In patients with congestive heart failure, for whom there is a risk of excessive hypotension, the use of quinapril should be started under close monitoring; these patients should be closely monitored during the first 2 weeks of treatment and with an increase in the dose of quinapril.

Similarly, the drug should be used to treat patients with coronary heart disease or cerebrovascular accident, in which an excessive decrease in blood pressure can lead to myocardial infarction or cerebral hemorrhage.

Impaired renal function. In susceptible patients, changes in renal function may be expected due to inhibition of RAAS. In patients with severe heart failure, in whom renal function depends on the activity of RAAS, quinapril therapy can lead to oliguria and / or progressive azotemia and, in rare cases, to acute renal failure and / or death.

In some patients with hypertension or heart failure who do not have a clear pre-existing kidney disease, an increase (more than 1.25 times higher than the upper limit of the norm) in the blood plasma levels of urea and creatinine was noted.Usually this increase was insignificant and temporary, in particular with the simultaneous use of quinapril and diuretic. Plasma urea and creatinine nitrogen levels were increased by 2% in patients with hypertension who received quinapril as monotherapy, and by 4 and 3%, respectively, in patients with hypertension who received quinapril / hydrochlorothiazide. Such an increase is recorded more often in patients with pre-existing renal failure. Dose reduction and / or withdrawal of a diuretic and / or quinapril may be required.

Cough. Patients taking ACE inhibitors, including quinapril, reported coughing. Characteristically, the cough was unproductive, persistent, and disappeared after cessation of therapy. The occurrence of cough induced by the use of ACE inhibitors should also be taken into account in the differential diagnosis of cough.

Hypersensitivity reactions. Hypersensitivity reactions can occur in patients with or without a history of allergies or AD, such as purpura, photosensitivity, urticaria, necrotizing angiitis, shortness of breath, including pneumonitis and pulmonary edema, and anaphylactic reactions.

Angioneurotic edema. Angioneurotic edema of the head and neck. Cases of angioedema have been reported in patients treated with ACE inhibitors. For quinapril, the incidence of angioedema is 0.1%. If there is a laryngeal stridor or angioedema of the face, tongue or glottis, the use of the drug should be stopped immediately. The patient should receive appropriate therapy in accordance with generally accepted rules of medical care, careful monitoring of the patient should be carried out until the edema disappears. In cases where edema is limited to the face and lips, specific treatment in most cases is not required; antihistamines can be used to eliminate symptoms. Angioneurotic edema, accompanied by damage to the larynx, can be fatal. In cases of damage to the tongue, glottis or larynx, which is likely to cause obstruction of the airways, it is immediately necessary to prescribe the appropriate emergency treatment, which includes, among other things, sc administration of r-r adrenaline (epinephrine) 1: 1000 (from 0.3 to 0.5 ml).

Patients taking concurrent treatment with an MTOP inhibitor (mammalian rapamycin target) (e.g. temsirolimus) or a DPP-IV inhibitor (dipeptidyl peptidase-IV) (e.g. vildagliptin) may be at increased risk for angioedema. Use of an MTOR inhibitor or DPP-IV inhibitor should be started with caution in patients who have already taken ACE inhibitors.

Intestinal angioedema. In patients taking ACE inhibitors, cases of intestinal angioedema have been reported. In these patients, abdominal pain (accompanied or not accompanied by nausea or vomiting) occurred, in some patients there was no history of angioedema of the face, and the level of C1 esterase was normal. The diagnosis of angioedema was established using computed tomography or ultrasound of the abdominal cavity or during surgery, while the symptoms disappeared after the withdrawal of the ACE inhibitor. It should be borne in mind the likelihood of intestinal angioedema in the differential diagnosis of abdominal pain in patients who use ACE inhibitors.

Patients with a history of angioedema not associated with ACE inhibitor therapy may have an increased risk of developing angioedema with an ACE inhibitor (see CONTRAINDICATIONS).

Ethnic features.In patients of the Negroid race who took ACE inhibitors, cases of the development of angioedema were recorded more often than in patients of other races. It should also be noted that in controlled clinical trials in patients of the Negroid race, a slightly lesser effect of ACE inhibitors on blood pressure was noted than in other patients.

Neutropenia / agranulocytosis. In rare cases, the use of ACE inhibitors was accompanied by agranulocytosis and bone marrow suppression in patients with hypertension, but more often these diseases were noted in patients with renal failure, especially with concomitant collagenosis.

In rare cases, the development of agranulocytosis in the treatment of quinapril has been reported. Therefore, in patients with collagenosis and / or kidney disease, the possibility of monitoring the number of leukocytes in the blood should be considered.

Hyperkalemia In patients receiving quinapril as monotherapy, serum potassium levels may increase. Due to the risk of further potentiating an increase in the level of potassium in the blood plasma, it is recommended that caution be taken to start combination therapy with potassium-sparing diuretics or other drugs that increase the potassium content in the blood serum and carefully monitor the level of potassium in the patients blood plasma (see INTERACTIONS). With the simultaneous use of quinapril can reduce the degree of hypokalemia caused by thiazide diuretics.

Impaired liver function. In rare cases, the use of ACE inhibitors is associated with a syndrome that began to develop as cholestatic jaundice, and then progressed to fulminant liver necrosis (in some cases