Accupro, 40 mg 30 pcs.

Excipients:

magnesium carbonate,

gelatin,
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Lactose,

Crosspovidone,

Magnesium stearate.

Pharmgroup:

Angiotensin-converting enzyme (ACE) inhibitor

Pharmic action:

The ACE is an enzyme that catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictor effect and increases vascular tone, including by stimulating aldosterone secretion by the adrenal cortex. Quinapril competitively inhibits ACE and causes reduction of vasopressor activity and aldosterone secretion. Elimination of the negative effect of angiotensin II on renin secretion by a feedback mechanism leads to an increase in plasma renin activity. At the same time, a decrease in blood pressure (BP) is accompanied by a decrease in total peripheral vascular resistance (TPR) and renal vascular resistance, while changes in heart rate (HR), cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are negligible or absent.

Hinapril increases exercise tolerance. With long-term use, it promotes inverse development of myocardial hypertrophy in patients with arterial hypertension; it improves blood supply to the ischemic myocardium. Enhances coronary and renal blood flow. Reduces platelet aggregation. Onset of action after a single dose – 1 hour, maximum – 2-4 hours, the duration of action depends on the size of the dose taken (up to 24 hours). A clinically pronounced effect occurs several weeks after the start of therapy.

Pharmacokinetics: The concentration of quinapril in blood plasma after oral administration reaches a maximum within 1 hour, quinaprilat – 2 hours. Food intake does not affect the degree of absorption, but may increase the time to reach maximum concentration (TCmax) (fatty foods may reduce absorption). Taking into account the excretion of quinapril and its metabolites by the kidneys, the degree of absorption is about 60%. Under the action of hepatic enzymes quinapril is rapidly metabolized to quinaprilate by chipping off the ester group (the main metabolite is quinapril bivalent acid), which is a potent ACE inhibitor.

About 38% of the oral dose of quinapril circulates in blood plasma as quinaprilate. The elimination half-life (T1/2) of quinapril from blood plasma is about 1 hour, of quinaprilat 3 hours. Renal excretion is 61% (56% as quinapril and quinaprilat) and intestinal excretion is 37%. T1/2 of quinapril is 1-2 hours, of quinaprilat 3 hours. Approximately 97% of quinapril and quinaprilat circulate in blood plasma in protein-bound form. Quinapril and its metabolites do not penetrate the blood-brain barrier.

In patients with renal insufficiency, the T1/2 of quinaprilat increases as creatinine clearance (CK) decreases. Quinaprilat excretion is also decreased in elderly patients (over 65 years) and closely correlates with impaired renal function, but in general there are no differences in efficacy and safety in elderly and younger patients.
In patients with alcoholic liver cirrhosis quinaprilat concentration is reduced due to impaired deetherification of quinapril.

Indications

Arterial hypertension, chronic heart failure.

Pharmacological effect

Excipients:

magnesium carbonate,

gelatin,

lactose,

crospovidone,

magnesium stearate.

Pharmaceutical group:

Angiotensin converting enzyme (ACE) inhibitor

Pharmaceutical action:

ACE is an enzyme that catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictor effect and increases vascular tone, including by stimulating the secretion of aldosterone by the adrenal cortex. Quinapril competitively inhibits ACE and causes a decrease in vasopressor activity and aldosterone secretion. Elimination of the negative effect of angiotensin II on renin secretion via a feedback mechanism leads to an increase in plasma renin activity. In this case, a decrease in blood pressure (BP) is accompanied by a decrease in total peripheral vascular resistance (TPVR) and renal vascular resistance, while changes in heart rate (HR), cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are insignificant or absent.

Quinapril increases exercise tolerance. With long-term use, it promotes the reverse development of myocardial hypertrophy in patients with arterial hypertension; improves blood supply to ischemic myocardium. Strengthens coronary and renal blood flow. Reduces platelet aggregation. The onset of action after taking a single dose is after 1 hour, maximum after 2-4 hours, the duration of action depends on the size of the dose taken (up to 24 hours). A clinically pronounced effect develops several weeks after the start of therapy.

Pharmacokinetics: The concentration of quinapril in the blood plasma after oral administration reaches a maximum within 1 hour, quinapril – 2 hours. Food intake does not affect the degree of absorption, but may increase the time to reach maximum concentration (TCmax) (fatty foods may reduce absorption). Taking into account the excretion of quinapril and its metabolites by the kidneys, the degree of absorption is approximately 60%. Under the influence of liver enzymes, quinapril is quickly metabolized to quinapril by eliminating the ester group (the main metabolite is quinapril dibasic acid), which is a potent ACE inhibitor.

About 38% of an oral dose of quinapril circulates in the blood plasma in the form of quinapril. The half-life (T1/2) of quinapril from blood plasma is about 1 hour, quinapril – 3 hours. Excreted by the kidneys – 61% (56% in the form of quinapril and quinapril) and through the intestines – 37%. T1/2 of quinapril – 1-2 hours, quinapril – 3 hours. Approximately 97% of quinapril and quinapril circulate in the blood plasma in protein-bound form. Quinapril and its metabolites do not penetrate the blood-brain barrier.

In patients with renal failure, T1/2 of quinaprilat increases as creatinine clearance (CC) decreases. The elimination of quinaprilate is also reduced in elderly patients (over 65 years of age) and is closely correlated with renal dysfunction, however, in general, no differences in the effectiveness and safety of treatment were identified in elderly and younger patients.
In patients with alcoholic cirrhosis of the liver, the concentration of quinapril is reduced due to impaired deesterification of quinapril.

Special instructions

Caution must be exercised when prescribing to patients with reduced blood volume (including as a result of diuretic therapy, limiting NaCl intake, hemodialysis, diarrhea and vomiting) due to the increased risk of developing a sudden decrease in blood pressure after using even the initial dose of ACE.

Transient hypotension is not a contraindication for continuing treatment with the drug after stabilization of blood pressure (the dose should be reduced). In case of an excessive decrease in blood pressure, the patient is transferred to a horizontal position with a low head, and, if necessary, saline solution is infused (to increase the volume of the bcc).

Before starting treatment, 2-3 days before starting treatment, it is necessary to cancel previous diuretic therapy, except for patients with malignant or difficult-to-treat hypertension. In these patients, the use of quinapril can be started immediately, at a reduced dose, under close medical supervision (within 2 hours after administration and an additional 1 hour until blood pressure stabilizes) and a careful increase in dose. Patients with malignant arterial hypertension or concomitant severe heart failure should begin treatment in a hospital setting.

Before starting therapy with ACE inhibitors, it is necessary to count the total number of leukocytes, as well as monitor the leukocyte count once a month in the first 3-6 months of treatment, and at periodic intervals up to 1 year in patients with an increased risk of neutropenia (with impaired renal function, systemic connective tissue diseases, in those receiving high doses, at the first signs of infection).

Before and during treatment, monitoring of blood pressure, kidney function, K+ content in plasma, control of Hb content in peripheral blood, creatinine, urea, control of the concentration of electrolytes and liver enzymes in the blood is necessary. The use of AN69 dialysis membranes in combination with ACE inhibitors is not recommended (due to the possibility of developing anaphylactoid reactions in patients).

It is recommended that neonates exposed in utero to ACE inhibitors be closely monitored for hypotension, oliguria, and hyperkalemia.

In oliguria, it is necessary to maintain blood pressure and renal perfusion by administering appropriate fluids and vasoconstrictors. In newborns and infants, the risk of developing oliguria and neurological disorders is associated with a decrease in renal and cerebral blood flow due to the decrease in blood pressure caused by ACE inhibitors; in this case, lower initial doses and careful monitoring are recommended.

Care must be taken when driving vehicles or performing other work that requires increased attention, because Dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretics.

Caution should be exercised during exercise or hot weather due to the risk of dehydration and hypotension due to decreased fluid volume. Before surgery (including dentistry), the surgeon/anesthesiologist must be warned about the use of ACE inhibitors.

Active ingredient

Quinapril

Composition

1 film-coated tablet contains 40 mg of quinapril hydrochloride.

excipients:

magnesium carbonate,

magnesium stearate,

lactose,

gelatin,

crospovidone,

hydroxypropyl methylcellulose,

hydroxypropylcellulose,

titanium dioxide,

macrogol 400,

candelilla wax,

Opadry White OY-S-7331.

Contraindications

– Hypersensitivity to any component of the drug.
– History of angioedema as a result of previous therapy with ACE inhibitors, hereditary and/or idiopathic angioedema.
– Age up to 18 years.
– Pregnancy and lactation.
– Lactase deficiency, lactose intolerance and glucose-galactose malabsorption syndrome.

With caution.

Symptomatic arterial hypotension in patients who have previously taken diuretics and are on a diet with limited salt intake; severe heart failure in patients at high risk of arterial hypotension; conditions accompanied by a decrease in circulating blood volume (CBV) (including vomiting and diarrhea); hyperkalemia; inhibition of bone marrow hematopoiesis; aortic stenosis; cerebrovascular insufficiency, coronary heart disease, coronary insufficiency – a sharp decrease in blood pressure during therapy with ACE inhibitors can worsen the course of these diseases; bilateral renal artery stenosis or stenosis of the artery of a single kidney, a condition after kidney transplantation; renal dysfunction; in patients on hemodialysis (creatinine clearance less than 10 ml/min) (there is insufficient data on the use of Accupro® in such patients); autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma); liver dysfunction (especially when used simultaneously with diuretics); when used simultaneously with potassium-sparing diuretics; diabetes mellitus; extensive surgical interventions and general anesthesia.

Side Effects

From the central nervous system and peripheral nervous system: possible dizziness, weakness, headache; rarely – paresthesia, mood and sleep disturbances.

From the cardiovascular system: possible arterial hypotension; rarely – tachycardia.

From the digestive system: possible dyspeptic symptoms (including dry mouth, loss of appetite); rarely – stomatitis, abdominal pain, pancreatitis, cholestatic jaundice.

Metabolism: possible hyperkalemia, hyponatremia; rarely – proteinuria, increased levels of urea and creatinine in the blood (mainly in patients with impaired renal function).

From the respiratory system: dry cough, bronchitis, rhinitis are possible.

From the hematopoietic system: rarely – neutropenia, agranulocytosis, thrombocytopenia, anemia.

From the urinary system: possible renal dysfunction.

From the reproductive system: rarely – impotence.

Allergic reactions: skin rash, angioedema, and other hypersensitivity reactions are possible.

Dermatological reactions: rarely – alopecia.

Other: rarely – muscle spasms.

Interaction

Antihypertensive, diuretic, opioid analgesics, and general anesthesia agents enhance the hypotensive effect. NSAIDs, table salt – weaken the effect.

Potassium supplements, potassium-sparing diuretics (amiloride, spironolactone, triamterene) increase the risk of developing hyperkalemia. Enhances the effect of ethanol, slows down the excretion of Li+.

Enhances the hypoglycemic effect of sulfonylurea derivatives and insulin.

Increases the risk of developing leukopenia when used simultaneously with allopurinol, cytostatic agents, immunosuppressants, procainamide.

Estrogens weaken the hypotensive effect due to fluid retention.

Drugs that cause bone marrow suppression increase the risk of neutropenia and/or agranulocytosis, including death.

Overdose

Symptoms: marked decrease in blood pressure, dizziness, weakness, visual impairment.

Treatment is symptomatic.

The patient should take a horizontal position; it is advisable to carry out an intravenous infusion using 0.9% sodium chloride solution (in order to increase the blood volume).

Hemodialysis and peritoneal dialysis are not effective.

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Manufacturer

USA