Expiration date: 11/2024

The composition and form of issue:

Tablets, film-coated. 1 tablet contains:

quinapril hydrochloride 10, 832 mg

corresponds to 10 mg of quinapril 

hydrochlorothiazide 12, 5 mg

excipients: lactose monohydrate magnesium carbonate povidone K25 crospovidone magnesium stearate 

film shell: Opadry pink OY-S-6937 (hypromellose, hyprolose, titanium dioxide, macrogol 400, dye iron oxide yellow, pigment iron oxide red) wax herbal 

blistere in 10 PCs. in cardboard pack 3 blisters.

Tablets, film-coated. 1 tablet contains:

quinapril hydrochloride 21, 664 mg

corresponds to 20 mg of quinapril 

hydrochlorothiazide 12, 5 mg

excipients: lactose monohydrate magnesium carbonate povidone K25 crospovidone magnesium stearate 

film shell: Opadry pink OY-S-6937 (hypromellose, hyprolose, titanium dioxide, macrogol 400, dye iron oxide yellow, pigment iron oxide red) wax herbal 

blistere in 10 PCs. in cardboard pack 3 blisters.

Tablets, film-coated. 1 tablet contains:

quinapril hydrochloride 21, 664 mg

corresponds to 20 mg of quinapril 

hydrochlorothiazide 25 mg

excipients: lactose monohydrate magnesium carbonate povidone K25 crospovidone magnesium stearate 

film shell: Opadry pink OY-S-6937 (hypromellose, hyprolose, titanium dioxide, macrogol 400, dye iron oxide yellow, pigment iron oxide red) wax herbal 

blistere in 10 PCs. in cardboard pack 3 blisters.

Description of dosage form:

Tablets, film-coated, 10 mg + 12, 5 mg: pink, oval, lenticular, scored on both sides and marked "PD 222" on one side.

Tablets, film-coated, 20 mg + 12, 5 mg: pink, triangular, biconvex, scored and coded "PD 220" on one side.

Tablets, film-coated, 20 mg + 25 mg: pink, round, biconvex, marked with "PD 223" on one side.

Characteristic:

Accuzide combined drug, which includes ACE inhibitor Quinapril and thiazide diuretic hydrochlorothiazide.

Pharmacokinetics:

Quinapril and hydrochlorothiazide do not affect the pharmacokinetics of each other.

Quinapril. Cmax quinapril in plasma when administered is achieved within 1 h. Quinapril is rapidly metabolized to quinaprilat by cleavage of the ester group (the main metabolite — dibasic acid quinapril), which is a powerful ACE inhibitor.

Taking into account the excretion of quinapril and its metabolites by the kidneys, the degree of absorption is approximately 60%. About 38% of the oral dose of quinapril circulates in the blood plasma in the form of quinaprilate. T1/2 Quinapril of blood plasma is approximately 1 h. C max Quinapril in plasma is approximately 2 h after the intake of Quinapril. The Quinapril write mainly kidneys, T1/2 about 3 h. About 97% Quinapril circulate in plasma is associated with the protein form. Quinapril and its metabolites do not penetrate the BBB.

In patients with renal insufficiency T1/2 quinaprilat increases with decreasing creatinine clearance. Excretion of quinaprilate is also reduced in elderly patients (over 65 years) and is closely correlated with impaired renal function, but in General, differences in the effectiveness and safety of treatment of elderly and younger patients have not been identified.

Hydrochlorothiazide. Absorbed more slowly (1-2. 5 hours) and fuller (50-80%). Hydrochlorothiazide is not metabolized in the liver and excreted unchanged by the kidneys. T1/2 ranges from 4 to 15 h. About 61% of an oral dose is excreted unchanged within 24 h. Hydrochlorothiazide crosses the placenta and in breast milk, but it passes through GEB.

Description of pharmacological action:

Quinapril is an enzyme that catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictive effect and controls vascular tone, including by stimulating the secretion of aldosterone by the adrenal cortex. Quinapril inhibits circulating and tissue ACE and causes a decrease in vasopressor activity and aldosterone secretion. Elimination of the negative effect of angiotensin II on renin secretion by the feedback mechanism leads to an increase in plasma renin activity. At the same time, the decrease in blood PRESSURE is accompanied by a decrease in OPSS and resistance of renal vessels, while changes in heart rate, cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are insignificant or absent. In addition, quinapril slightly reduces potassium excretion caused by hydrochlorothiazide, which due to its diuretic action also increases plasma renin activity, aldosterone secretion, reduces serum potassium and increases its excretion by the kidneys.

Hydrochlorothiazide is a diuretic that has a direct effect on the kidneys, increasing the excretion of sodium, chloride, liquid, as well as potassium and bicarbonate and reducing calcium excretion. With long-term use, there is a decrease in OPSS. Thus, the use of a combination of quinapril and hydrochlorothiazide leads to a more pronounced decrease in blood PRESSURE than therapy with each drug separately.

The antihypertensive effect of Quinapril develops within 1 h after ingestion, reaches its maximum after 2-4 h and persisted for 24 h after prolonged treatment. In some cases, to achieve the maximum antihypertensive effect requires at least 2 weeks of therapy.

The diuretic effect of hydrochlorothiazide develops within 2 hours, reaches a maximum after about 4 hours and persists for about 6-12 hours.

Indications:

  • Arterial hypertension.

Contraindications:

  • increased sensitivity to active substances, other auxiliary components of the drug, sulfonamide derivatives
  • angioedema in history as a result of previous therapy with ACE inhibitors
  • idiopathic and hereditary angioedema
  • anuria
  • severe liver failure
  • addison
  • refractory hypokalemia, hypercalcemia and hyponatremia
  • diabetes mellitus (difficult to control)
  • children up to age 18 years (effectiveness and safety have not been established)
  • severe renal failure (CL creatinine - <30 p="">)

With caution:

  • in patients previously taking diuretics and follow a diet with restriction of salt or in gemodialise
  • severe chronic heart failure in patients with or without concomitant renal failure
  • conditions with reduced BCC (including vomiting and diarrhea)
  • oppression kostnomozgovy blood
  • aortic stenosis
  • cerebrovascular diseases (a sharp decrease in blood PRESSURE during therapy with ACE inhibitors can worsen the course of these diseases)
  • condition after kidney transplantation
  • bilateral renal artery stenosis or stenosis of the artery to a solitary kidney
  • severe autoimmune systemic diseases of connective tissue (including systemic lupus erythematosus, scleroderma)
  • hepatic impairment or progressive liver disease
  • diabetes
  • extensive surgery and General anesthesia
  • simultaneous administration of other antihypertensive drugs
  • violation of water-electrolyte balance, hyperkalemia.

Use during pregnancy and breast-feeding:

The use of the drug Accused contraindicated during pregnancy, women planning pregnancy and women of childbearing age not using reliable methods of contraception.

Women of childbearing age taking the drug Accused should use reliable methods of contraception.

When the diagnosis of pregnancy drug Accused should be abolished as quickly as possible.

Appointment of ACE inhibitors during pregnancy is accompanied by an increase in the risk of abnormalities of the cardiovascular and nervous system of the fetus. In addition, the use of ACE inhibitors during pregnancy described cases of malnutrition, premature birth, birth of children with arterial hypotension, impaired renal function, including acute renal failure, hypoplasia of the skull bones, limb contractures, craniofacial abnormalities, pulmonary hypoplasia, intrauterine growth retardation, open arterial duct, as well as cases of fetal death and neonatal death. Often, lack of water is diagnosed after the fetus has been irreversibly damaged.

Infants who have been exposed to intrauterine ACE inhibitors should be monitored for hypotension, oliguria and hyperkalemia. If oligurii should support AD and perfusion of the kidneys.

Thiazides penetrate the placenta and are found in the umbilical cord blood. Non-teratogenic effects of thiazides include jaundice and thrombocytopenia of the fetus and/or newborn, and the possibility of other adverse events observed in the mother.

ACE inhibitors, including quinapril, to a limited extent penetrate into breast milk. Thiazides penetrate into breast milk. Given the possibility of serious adverse effects in the newborn, drug Accused need to cancel during lactation or to stop breast-feeding.

Side effect:

More than 1% of patients, receiving quinapril in combination with hydrochlorothiazide, met the following adverse events: headache (6, 7%), dizziness (4, 8%), cough (3, 2%), unproductive, persistent cough, which took place after discontinuation of therapy increased fatigue (2, 9%).

In General, adverse events were mild and transient, independent of age, sex, race and duration of therapy.

Laboratory parameters: an increase (more than 1, 25 times compared with IOP) in the concentration of creatinine and urea nitrogen in the blood, respectively, in 3 and 4% of patients receiving quinapril and hydrochlorothiazide.

In 0, 5-1% of patients treated with quinapril in combination with hydrochlorothiazide, the following adverse events occurred:

From the hematopoietic system: hemolytic anemia, thrombocytopenia, leukopenia, agranulocytosis.

CNS: increased excitability, asthenia, paresthesia, depression, dizziness, drowsiness.

CCC: palpitations, tachycardia, marked decrease in blood PRESSURE, orthostatic hypotension, fainting, cardiac arrhythmia, myocardial infarction, ischemic stroke, peripheral edema (including generalized).

Respiratory system: shortness of breath, sinusitis, syncope.

From the digestive system: dryness of the mucous membrane of the mouth and throat, nausea, constipation or diarrhea, flatulence, pancreatitis, hepatitis, angioedema intestinally.

Allergic reactions: skin rash, itching, angioedema, photosensitization, multiform exudative erythema, exfoliative dermatitis, pemphigus, Stevens-Johnson syndrome, anaphylactic reactions, increased sweating.

From the musculoskeletal system and connective tissue: joint pain.

From the genitourinary system: urinary tract infections, impaired renal function, decreased potency.

On the part of the organ of vision: visual impairment.

Other: alopecia.

Drug interaction:

Tetracycline and other drugs that interact with magnesium. While the use of the drug Accused and tetracycline the absorption of the latter is reduced by approximately 28 to 37% due to the presence in the composition of the drug Accused magnesium carbonate as filler. You should take into account this interaction while the use of the drug Accused and tetracycline or other drugs that can interact with magnesium.

Lithium. Usually lithium should not be used in combination with diuretics, as the latter reduce renal clearance of lithium and increase the risk of adverse effects. In patients taking lithium preparations and ACE inhibitors, there is an increase in serum lithium concentrations and symptoms of lithium intoxication. These changes are associated with the loss of sodium under the influence of ACE inhibitors. In applying the drug Accused the risk of lithium toxicity may be increased. At the same time, these drugs should be used with caution.

With the use of propranolol, digoxin and cimetidine evidence of clinically significant pharmacokinetic interactions have been identified.

Anticoagulant effect of one dose of warfarin (evaluated by PV) did not change significantly while the use of quinapril 2 times a day.

Ethanol, barbiturates and narcotic analgesics. At simultaneous application with the drug Accused may increase risk of orthostatic hypotension (part of the drug is thiazide diuretic — hydrochlorothiazide).

Hypoglycemic agents (hypoglycemic agents for oral administration and insulin). You may need to adjust the dose of hypoglycemic agents.

Other antihypertensive agents. Thiazide diuretic that is part of the drug Accused, may enhance the action of other antihypertensive drugs, especially ganglionic or beta-blockers. Due to the content of hydrochlorothiazide hypotensive effect of the drug Accused may increase after sympathectomy.

Corticosteroids, corticotropin (ACTH). Increased loss of electrolytes, especially potassium.

Pressor amines (for example norepinephrine). It is possible to reduce the therapeutic effect of Pressor amines (clinical significance is insignificant).

Non-depolarizing muscle relaxants (e.g. tubocurarine chloride). Possible strengthening of muscle relaxants action.

NSAIDs. In some patients, NSAIDs can cause a weakening of the diuretic, natriuretic and hypotensive effect of loop, potassium-sparing and thiazide diuretics. In this regard, while the use of these drugs with the drug Accused patients should be monitored to assess the effectiveness of therapy.

Drugs that can cause hyperkalemia. Quinapril-ACE inhibitor, which reduces the concentration of aldosterone, which in turn can lead to hyperkalemia. In this regard, in the treatment of drugs Accuzide potassium and salt substitutes containing potassium should be used with caution, controlling the potassium content in the blood serum. Given that part of the drug Accused included a diuretic, the addition of kalisberegauschee diuretic is not recommended.

Ion exchange resin. Absorption of hydrochlorothiazide is reduced in the presence colestyramine and colestipol. With a single application, these drugs bind hydrochlorothiazide and reduce its absorption in the gastrointestinal tract by 85 and 43%, respectively.

Method of application and doses:

Inside 1 time per day, regardless of the meal.

For patients who do not receive diuretics (regardless of whether previously conducted monotherapy with quinapril or not), the recommended initial dose is 1 table. drug Accused (10 mg +12, 5 mg) 1 times a day. Subsequently, if necessary, the dose can be increased to 2 tables. drug Accused (10 mg + 12, 5 mg) 1 times a day or up to the maximum recommended daily dose of the drug Accused — (20 mg + 25 mg) 1 times a day.

Patients with impaired renal function. The initial dose of the drug is Accused 1 table. (10 mg +12, 5 mg).

Elderly patient. Correction doses of the drug Accused in elderly patients is not required. The initial dose of the drug Accused — 1 table. (10 mg +12, 5 mg).

Overdose:

Information about overdose of the drug Accused and special measures for its therapy is available.

Symptoms: marked decrease in blood PRESSURE, violation of water-electrolyte balance-hyponatremia, hypochloremia, hypokalemia (while the use of cardiac glycosides increases the risk of arrhythmia), decrease in BCC on the background of forced diuresis.

Treatment: discontinuation of the drug, gastric lavage, the appointment of activated carbon,/in the introduction of 0, 9% sodium chloride solution, restoration of water-electrolyte balance of blood, symptomatic and supportive therapy.

Special instruction:

Angioneurotic edema. In the treatment of ACE inhibitors described cases of angioedema of the face and neck, including 0, 1% of patients receiving quinapril. The appearance of laryngeal whistling or angioedema of the face, tongue or glottis Accused the drug should be discontinued immediately. The patient should be given adequate treatment and observe it until the symptoms of edema disappear. Swelling of the face and lips usually goes away without treatment. Antihistamines may be used to reduce symptoms. Angioedema involving the larynx can lead to death. If swelling of the tongue, glottis or larynx threatens the development of airway obstruction, adequate emergency therapy, including the p / C administration of epinephrine (adrenaline) 1:1000 (0, 3-0, 5 ml).

In the treatment of ACE inhibitors also described cases of angioedema of the intestine. Patients had abdominal pain (with / without nausea and vomiting) in some cases without prior angioedema of the face and with normal activity of C1-esterase. The diagnosis was established by ultrasound, computed tomography of the abdominal area or at the time of surgery. The symptoms disappeared after discontinuation of ACE inhibitors. Therefore, in patients with abdominal pain, taking ACE inhibitors, when establishing a differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

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

Conducting desensitizing therapy. Patients receiving ACE inhibitors during desensitizing therapy with the venom of Hymenoptera (wasps, bees) may develop persistent anaphylactoid reactions that threaten life. Temporary discontinuation of ACE inhibitor contributes to regression of symptoms, but they may occur again with the resumption of therapy with ACE inhibitors.

Hemodialysis. Anaphylactoid reactions may also develop with the use of ACE inhibitors in patients who underwent LDL apheresis using dextran sulfate or in patients undergoing hemodialysis using a high-flow membranes, such as polyacrylonitrile.

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

Arterial hypotension. Drug Accused can cause transient hypotension, but not more frequently than in the monotherapy components that are part of the drug. Symptomatic hypotension is rare in the treatment of quinapril in patients with uncomplicated hypertension, but it can develop as a result of therapy with ACE inhibitors in patients with reduced BCC, for example, after previous diuretic therapy, in compliance with a diet with salt restriction or hemodialysis. In the case of symptomatic hypotension, the patient should be given a horizontal position and hold it in/infusion using 0, 9% sodium chloride solution. Transient hypotension is not a contraindication to further use of the drug Accused, however, in such cases it is advisable to reduce the dose.

Chronic heart failure. In patients with chronic heart failure with and/or without renal insufficiency, therapy with ACE inhibitor on arterial hypertension may lead to excessive decrease in blood pressure, which may be accompanied by oliguria, azotemia and, in rare cases, acute renal failure, and even death. The treatment of these patients with drug Accused should start under close medical supervision and monitoring during the first 2 weeks of therapy and when increasing doses of the drug.

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

When any symptoms of infection (eg sore throat, fever) patients should immediately consult a doctor, because they can be a manifestation of neutropenia.

Systemic lupus erythematosus. Thiazide diuretics can sometimes cause exacerbation of systemic lupus erythematosus.

Kidney function. Drug Accused is not recommended 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 prolonged use in such patients. Loop diuretics are the drugs of choice for this group of patients receiving quinapril therapy. For this reason, a fixed combination of hydrochlorothiazide/quinapril should not be used in patients with severe renal failure (see section "Contraindications").

T1 / 2 quinaprilate increases with a decrease in creatinine clearance. Patients with Cl creatinine less than 60 ml / min, but more than 30 ml/min Quinapril should be administered in a lower initial dose. In these patients, the dose of the drug Accused should be increased taking into account the clinical condition of the patient, with regular monitoring of renal function, although clinical studies have not noted further deterioration of renal function in the treatment of drug Accused.

In hypertensive patients with no apparent signs of the source of violation of the blood vessels of the kidneys when using Quinapril, especially in combination with a diuretic, a marked increase in the concentration of urea nitrogen in blood and creatinine in the serum, which was usually weakly expressed and transient. Such changes are most likely in patients with initial renal impairment. In such cases, you may need a lower dose of the drug Accused. In all patients with hypertension should monitor renal function.

Influence of the renin-angiotensin-aldosterone system (RAAS). In some patients, suppression of RAAS activity can lead to impaired renal function. In patients with severe chronic heart failure, renal function depends on the activity of RAAS, so treatment with ACE inhibitors, including quinapril, can lead to oliguria and/or progressive nitrogen, and in rare cases — to acute renal failure and/or death.

Renal artery stenosis. In clinical studies in patients with hypertension with bilateral renal artery stenosis or single kidney artery stenosis in the treatment of ACE inhibitors in some cases, there was an increase in the concentration of urea nitrogen and creatinine in the blood serum. These changes are almost always reversible and took place after the abolition of ACE inhibitor and/or diuretic. In such cases, during the first few weeks of drug treatment, Accused requires monitoring of kidney function.

Hepatic impairment. Drug Accused should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor violations vodno-elektrolitnogo balance may cause hepatic coma.

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

The 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 took place during further therapy. Risk factors for hyperkalemia are: impaired renal function, diabetes and simultaneous administration of potassium-sparing diuretics, potassium preparations and / or salt substitutes containing potassium. Concomitant use of potassium-sparing diuretics with drug Accused, which includes 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, anxiety, muscle weakness, muscle pain or spasm, decreased blood PRESSURE, oliguria, tachycardia, nausea, confusion, convulsions and vomiting.

Hypokalemia can also increase the toxic effect of cardiac glycosides. The risk of hypokalemia is increased in liver cirrhosis, forced diuresis, inadequate use of drugs that improve myocardial metabolism, concomitant therapy with corticosteroids or ACTH. Most patients should expect a balancing of opposite effects of Quinapril and hydrochlorothiazide with respect to the content of potassium in the blood serum.

In some cases, the effect of one component of the drug Accused can dominate others. Before and during treatment with the drug Accused should periodically monitor the content of electrolytes to detect possible disorders of water and electrolyte balance.

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

Hyponatremia. In hot weather, patients with peripheral edema may develop hyponatremia. Such patients rather shows the limitation of the use of liquid, rather than increasing the use of table salt except when hyponatremia is life threatening. With hyponatremia, adequate replacement therapy is needed.

Hypocalcemia. Thiazide diuretics reduce calcium excretion by the kidneys.

Parathyroid. 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 (renal lithiasis, bone resorption, and peptic ulcer) has not been described. Before the study of the function of the parathyroid glands thiazide diuretics should be abolished.

Magnesium. Thiazide diuretics increase the excretion of magnesium by the kidneys and can cause hypomagnesemia.

Glucose. Thiazide diuretics may reduce glucose tolerance and to raise serum concentrations of cholesterol, triglycerides and uric acid. These changes are usually mild, but in patients at risk of thiazide diuretics can provoke an exacerbation of gout or diabetes.

Therapy with ACE inhibitors may be accompanied by the development of hypoglycemia in diabetic patients receiving insulin or hypoglycemic agents for oral administration. In the treatment of patients with diabetes may require more careful monitoring and correction of the dose of hypoglycemic agents.

Cough. In the treatment of ACE inhibitors, including quinapril, noted the development of cough. In a typical case, it is unproductive, persistent and passes after discontinuation of therapy. In the differential diagnosis of cough should take into account its possible relationship with the use of ACE inhibitors.

Surgery. In patients who are 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 hypotension, which is eliminated by increasing the BCC. In the case of surgery, the patient should warn the anesthesiologist that he is taking an ACE inhibitor.

BCC. Patients should be warned that insufficient fluid intake, increased sweating can lead to excessive blood PRESSURE reduction by reducing BCC. Other causes of BCC decline, such as vomiting or diarrhea, can also lead to a sharp drop in blood PRESSURE.

Influence on the ability to drive vehicles and other mechanisms. Use caution when driving or performing other work, requiring greater attention, especially at the beginning of treatment Accused.

Accuzide
(Hydrochlorothiazide
+
Quinapril)