Accupro, 20 mg 30 pcs

Accupro is an antihypertensive drug, an ACE inhibitor.

ACE catalyzes conversion of angiotensin I into angiotensin II, which has a vasoconstrictor effect and increases vascular tone, including through stimulation of aldosterone production by adrenal cortex. Quinapril competitively inhibits ACE activity and reduces vasopressor activity and aldosterone production. 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 BP is accompanied by a decrease in RPS and renal vascular resistance, while changes in HR, cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are insignificant 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.

After a single dose the antihypertensive effect develops in 1 hour, reaches a maximum in 2-4 hours. The duration of action depends on the dose taken (up to 24 hours). A clinically pronounced effect occurs several weeks after the start of therapy.

Pharmacokinetics

Absorption, distribution, metabolism

After oral administration Cmax of quinapril in blood plasma is reached within 1 h, quinaprilat – within 2 h. Food intake has no effect on the degree of absorption, but it may increase the time to reach maximum concentration (fatty foods may decrease absorption of the drug). Taking into account excretion of quinapril and its metabolites by kidneys the degree of absorption of the drug is about 60%.

Under the action of hepatic enzymes quinapril is rapidly metabolized by splitting the ester group to quinaprilate (the main metabolite is quinapril double-base acid), which is a potent ACE inhibitor. About 38% of the oral dose of quinapril circulates in plasma as quinaprilate.

Approximately 97% of quinapril or quinaprilate circulates in plasma in protein-bound form. Quinapril and its metabolites do not penetrate the BBB.

Extracted mainly in the urine – 61% (56% in the form of quinapril and quinaprilate), and through the intestine – 37%. T1/2 of quinapril from blood plasma is about 1-2 hours, of quinaprilat – 3 hours.

Pharmacokinetics in special clinical cases

In patients with renal insufficiency, the T1/2 of quinaprilat increases as the CK decreases.

The excretion of quinaprilat is also decreased in elderly patients (older than 65 years) and closely correlates with impaired renal function, but in general no differences in efficacy and safety have been found in elderly and younger patients.

In patients with alcoholic cirrhosis, quinaprilat concentrations are decreased due to impaired deetherification of quinapril.

Indications

Arterial hypertension (as monotherapy or in combination with thiazide diuretics and beta-blockers); various forms of hypertension; chronic heart failure (in combination with diuretics and/or cardiac glycosides).

Pharmacological effect

Accupro is an antihypertensive drug, an ACE inhibitor.

ACE catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictor effect and increases vascular tone, incl. due to stimulation of aldosterone production by the adrenal cortex. Quinapril competitively inhibits ACE activity and reduces vasopressor activity and aldosterone production. 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 is accompanied by a decrease in peripheral vascular resistance and renal vascular resistance, while changes in heart rate, cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are insignificant or absent.

Quinapril increases exercise tolerance. With long-term use, it helps reverse the development of myocardial hypertrophy in patients with arterial hypertension; improves blood supply to ischemic myocardium. Strengthens coronary and renal blood flow. Reduces platelet aggregation.

After taking a single dose, the antihypertensive effect develops after 1 hour and reaches a 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

Absorption, distribution, metabolism

After oral administration, Cmax of quinapril in the blood plasma is achieved within 1 hour, quinapril – within 2 hours. Food intake does not affect the degree of absorption, but may increase the time to reach maximum concentration (fatty foods can reduce absorption of the drug). Taking into account the excretion of quinapril and its metabolites by the kidneys, the degree of absorption of the drug is about 60%.

Under the influence of liver enzymes, quinapril is rapidly metabolized by cleavage of the ester group to quinapril (the main metabolite is quinapril dibasic acid), which is a powerful ACE inhibitor. About 38% of an oral dose of quinapril circulates in the blood plasma in the form of quinapril.

Approximately 97% of quinapril or quinaprylate circulates in the blood plasma in protein-bound form. Quinapril and its metabolites do not penetrate the BBB.

Removal

It is excreted mainly in the urine – 61% (56% in the form of quinapril and quinaprylat), and also through the intestines – 37%. T1/2 of quinapril from blood plasma is about 1-2 hours, quinapril – 3 hours.

Pharmacokinetics in special clinical situations

In patients with renal failure, T1/2 of quinaprilat increases as CC decreases.

The elimination of quinaprilat 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 found 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

Active ingredient:

10 mg quinapril hydrochloride;

Excipients:

magnesium carbonate,

magnesium stearate,

lactose,

gelatin,

crospovidone,

hydroxypropyl methylcellulose,

hydroxypropylcellulose,

titanium dioxide,

macrogol 400,

candelilla wax,

Opadry White OY-S-7331.

Pregnancy

Accupro is contraindicated during pregnancy and breastfeeding

Contraindications

history of angioedema associated with treatment with ACE inhibitors, hereditary and/or idiopathic angioedema;
children and adolescents up to 18 years of age;
pregnancy;
lactation period (breastfeeding);
lactase deficiency, lactose intolerance and glucose-galactose malabsorption syndrome;
simultaneous use with aliskiren and aliskiren-containing drugs, with angiotensin II receptor antagonists or with other drugs that inhibit the RAAS (dual blockade of the RAAS), in patients with diabetes mellitus or in patients with diabetes mellitus with target organ damage (diabetic nephropathy), with impaired renal function (GFR less than 60 ml/min/1.73 m2), with hyperkalemia (more than 5 mmol/l), with chronic heart failure and arterial hypertension;
hypersensitivity to any component of the drug.

The drug should be prescribed with caution to patients with symptomatic arterial hypotension, who have previously taken diuretics and are on a diet with limited salt intake; for severe heart failure in patients at high risk of severe arterial hypotension; with a decrease in the volume of bcc (including with vomiting or diarrhea); with hyperkalemia; inhibition of bone marrow hematopoiesis; with aortic stenosis, hypertrophic obstructive cardiomyopathy, mitral stenosis; with cerebrovascular insufficiency, coronary artery disease, coronary insufficiency (a sharp decrease in blood pressure during therapy with ACE inhibitors can worsen the course of these diseases); condition after kidney transplantation, with bilateral renal artery stenosis or stenosis of the artery of a single kidney; with impaired renal function; in patients on hemodialysis (creatinine clearance less than 10 ml/min), because there is insufficient data on the use of Accupro in such patients; for severe autoimmune systemic connective tissue diseases (including SLE, scleroderma); in case of liver dysfunction (especially when used simultaneously with a diuretic); in combination therapy with a potassium-sparing diuretic; for diabetes mellitus; extensive surgical interventions and general anesthesia; while taking other antihypertensive drugs, as well as mTOR and DPP-4 enzyme inhibitors.

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 impairment of renal function.

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: – 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

Pfizer Manufacturing Deutschland GmbH, Germany