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-adrenoblockers); various forms of hypertension; chronic heart failure (in combination with diuretics and/or cardiac glycosides).

Active ingredient

Composition

Active ingredient:

10 mg quinapril hydrochloride;

Associates:

magnesium carbonate,

magnesium stearate,

lactose,

gelatin,

crospovidone,

hydroxypropyl methylcellulose,

hydroxypropylcellulose,

titanium dioxide,

macrogol 400,

candelilla wax,

Opadry White OY-S-7331.

How to take, the dosage

In arterial hypertension monotherapy, the recommended starting dose of quinapril in patients not receiving diuretics is 10 mg or 20 mg once daily.

Depending on clinical effect, the dose may be increased to a maintenance dose of 20 mg or 40 mg/day, which is usually administered in 1 dose or divided into 2 parts. As a rule, the dose should be changed at 4-week intervals.

In most patients, it is possible to achieve adequate BP control with long term treatment by using the drug once daily. In some patients the dose of quinapril has reached 80 mg/day.

Interaction

Hypotensive drugs, diuretics, opioid analgesics, drugs for general anesthesia increase the hypotensive effect. NSAIDs, table salt – weaken the effect.

Potassium preparations, potassium-saving diuretics (amiloride, spironolactone, triamterene) – increase the risk of hyperkalemia. It enhances the effect of ethanol and slows the excretion of Li+.

It enhances hypoglycemic effect of sulfonylurea derivatives and insulin. Increases the risk of leukopenia when concomitant use 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 up to death.

Special Instructions

Caution should be exercised when prescribing in patients with decreased blood pressure (including as a result of diuretic therapy, restriction of NaCl intake, hemodialysis, diarrhea and vomiting) due to increased risk of sudden BP decrease after administration of even the initial dose of ACE.

Transient hypotension is not a contraindication to continue treatment with the drug after BP stabilization (the dose should be reduced). In case of excessive BP decrease the patient should be placed in horizontal position with low head rest, if necessary, the physiological solution should be infused (for increase of the circulatory blood volume).

Before starting treatment it is necessary to cancel 2-3 days prior therapy with diuretics, except for patients with malignant or difficult to treat hypertension. In these patients, quinapril may be started immediately, at a reduced dose, under close medical supervision (for 2 h after administration and an additional 1 h before BP stabilizes) and cautious dose escalation.

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 and to monitor the leukocyte formula once a month during the first 3-6 months of treatment, and at periodic intervals up to 1 year in patients with increased risk of neutropenia (with renal dysfunction, systemic connective tissue diseases, in those receiving high doses, at first signs of infection).

Before and during the treatment it is necessary to monitor BP, renal function, K+ in plasma, control of Hb in peripheral blood, creatinine, urea, control of electrolyte and “liver” enzymes concentration in blood. It is not recommended to use dialysis membranes AN69 in combination with ACE inhibitors (because of the possibility of anaphylactoid reactions in patients). Careful monitoring is recommended for newborns who have had intrauterine exposure to ACE inhibitors to detect hypotension, oliguria and hyperkalemia.

In oliguria, BP and renal perfusion should be maintained by administration of appropriate fluids and vasoconstrictors. In newborns and infants, the risk of oliguria and neurological disorders is associated with decreased renal and cerebral blood flow due to the decrease in BP caused by ACE inhibitors; in this case, use at lower initial doses and close monitoring is recommended.

Caution should be exercised when driving vehicles or performing other work requiring increased attention because dizziness is possible, especially after the initial dose of ACE inhibitor in patients taking diuretics.

Perhaps caution should be exercising or in hot weather because of the risk of dehydration and hypotension due to decreased fluid volume. A surgeon/anesthesiologist should be advised of the use of ACE inhibitors before surgical procedures (including dentistry).

Contraindications

Patients with symptomatic arterial hypotension who have previously taken diuretics and are on a salt restricted diet; with severe cardiac insufficiency in patients with high risk of severe arterial hypotension; with decreased oncotic blood circulation (including angina pectoris).ч. in case of vomiting or diarrhea; in hyperkalemia; inhibition of medullary hematopoiesis; in aortic stenosis, hypertrophic obstructive cardiomyopathy, mitral stenosis; in case of cerebral insufficiency, CHD, coronary artery disease (sharp decrease of BP during ACE inhibitor therapy can worsen the course of these diseases); in patients after renal transplantation, with bilateral stenosis of the renal arteries or stenosis of the artery of the only kidney, with renal dysfunction, in patients on hemodialysis (CK value less than 10 ml/min).as there is insufficient data on the use of Accupro in such patients; in severe autoimmune systemic connective tissue diseases (incl. SLE, scleroderma); in liver dysfunction (especially concomitant use with diuretics); combined therapy with potassium-saving diuretics; diabetes mellitus; major surgical interventions and general anesthesia; concomitant use of other hypotensive agents as well as mTOR and DPP-4 enzyme inhibitors.

Side effects

CNS and peripheral nervous system: dizziness, weakness, headache are possible; rarely – paresthesias, mood and sleep disorders.

Cardiovascular system: arterial hypotension possible; rarely – tachycardia.

Digestive system: dyspeptic symptoms (including dry mouth) possible.

Dyspeptic symptoms (including dry mouth, poor appetite); rarely – stomatitis, abdominal pain, pancreatitis, cholestatic jaundice.

Metabolism: hyperkalemia, hyponatremia are possible; rarely – proteinuria, increased urea and creatinine in blood (especially in patients with renal dysfunction).

Respiratory system: dry cough, bronchitis, rhinitis are possible.

Blood system: rare – neutropenia, agranulocytosis, thrombocytopenia, anemia.

Urinary system disorders: possibly impaired renal function.

Reproductive system disorders: rarely – impotence.

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

Dermatological reactions: rare – alopecia.

Other: rare – muscle cramps.

Overdose

Symptoms: marked BP decrease, dizziness, weakness, visual disturbances.

Treatment: – Symptomatic. The patient should take a horizontal position, it is advisable to carry out intravenous infusion with 0.9% sodium chloride solution (in order to increase the blood circulation).

Hemodialysis and peritoneal dialysis are not effective.

Pregnancy use

Accupro is contraindicated in pregnancy and lactation