AKKUPRO

Active material: Quinapril
When ATH: C09AA06
CCF: ACE inhibitor
ICD-10 codes (testimony): I10, I50.0
Manufacturer: GOEDECKE GmbH (Germany

Pharmaceutical form, composition and packaging

Pills, covered shell white, Oval, lenticular, mark and digit “5” on both sides.

Excipients: magnesium carbonate, gelatin, lactose, krospovydon, magnesium stearate.

The composition of the shell: Opadry OY-white S-7331 (gipromelloza, hydroksypropyltsellyuloza, Titanium dioxide, macrogol 400), wax kandelila.

10 PC. – blisters (3) – packs cardboard.

Pills, coated white, Triangular, lenticular, scored on both sides and the numeral “10” on one side.

Excipients: magnesium carbonate, gelatin, lactose, krospovydon, magnesium stearate.

The composition of the shell: Opadry OY-white S-7331 (gipromelloza, hydroksypropyltsellyuloza, Titanium dioxide, macrogol 400), wax kandelila.

10 PC. – blisters (3) – packs cardboard.

Pills, coated white, round, lenticular, with Figure “20” on one side and scored on both sides of the tablets.

Excipients: magnesium carbonate, gelatin, lactose, krospovydon, magnesium stearate.

The composition of the shell: Opadry OY-white S-7331 (gipromelloza, hydroksypropyltsellyuloza, Titanium dioxide, macrogol 400), wax kandelila.

10 PC. – blisters (3) – packs cardboard.

Pills, coated red-brown, Oval, lenticular, with Figure “40” on one side and “PD 535” – another.

Excipients: magnesium carbonate, gelatin, lactose, krospovydon, magnesium stearate.

The composition of the shell: Opadry Brown Y-5-9020G (gipromelloza, hydroksypropyltsellyuloza, Titanium dioxide, macrogol 400, iron oxide red), wax kandelila.

10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Antihypertensive drugs, ACE inhibitor.

Hinaprila hydrochloride is a salt of hinaprila-ethyl ester ENZYME inhibitor hinaprilata, not containing sulfgidrilnuyu group.

Hinapril fast deesterificiruetsa hinaprilata education (hinapril diacid is the main metabolite of), that is a potent enzyme inhibitor. ACE is a peptidildipeptidaza, catalyzing transformation angiotenzina I angiotenzin II, which has vasoconstrictive effect and is involved in the control of tone and vascular function through various mechanisms, including the stimulation of production of aldosterone napochechnikov crust. Hinapril inhibits the activity of circulating and tissue ENZYME and thus reduces vazopressornuyu activity and aldosterone secretion. Reducing the level of angiotensin II on the feedback leads to an increase in Renin secretion and its activity in plasma.

The main mechanism of antigipertenzivnogo action hinaprila believe suppression of Renin-angiotensin-aldosterone system activity, However, the drug has shown the effect even in patients with nizkoreninovoj hypertension. ACE structure is identical to the kininaze II-enzyme, that causes the destruction of bradykinin is a peptide, with powerful sosudorasshiratmi properties. Remain unknown, does the increased levels of bradykinin to the therapeutic effect of hinaprila. Antigipertenzivnogo duration validity of hinaprila was higher than the duration of its inhibitory effect on circulating ACE. Revealed more correlations between the Suppression of tissue ACE and duration of action of the preparation antigipertenzivnogo.

ACE inhibitors, including hinapril, can improve insulin sensitivity.

Application of hinaprila in dose 10-40 mg in patients with arterial hypertension of mild to moderate severity leads to lower hell as in sitting position, and standing, and has minimal effect on HEART RATE. The antihypertensive effect is manifested within 1 h and usually reaches its peak during 2-4 h after dosing. In some patients the maximum antihypertensive effect is a 2 weeks after initiation of treatment.

Antihypertensive effects of the drug when used in recommended doses in most patients continues 24 h persisted amid prolonged therapy.

Hemodynamic study in patients with arterial hypertension revealed, that decline ad under the influence of hinaprila accompanied by a decrease in renal vascular resistance and outlines, While HR, cardiac index, renal blood flow, speed clubockova filtering and filtration fraction change slightly or remain unchanged.

Therapeutic effect of drug in identical daily doses is comparable in elderly people (senior 65 years) and younger patients; in the elderly, the frequency of adverse events is not increasing.

Application of hinaprila in patients with chronic heart failure leads to a decrease in the ROUND, the average AD, systolic and diastolic HELL, pressure jamming pulmonary capillaries and increase cardiac output.

In 149 patients, which conducted Aortocoronary bypass surgery, hinaprilom treatment dose 40 mg/day versus placebo resulted in a decrease in the frequency of postoperative ischaemic complications within a year after surgery.

In patients with proven coronary atherosclerosis, which do not have hypertension or heart failure, hinapril improves disturbed function of endothelium in the coronary arteries and shoulder.

Effect of hinaprila on endothelial function is associated with an increase in nitric oxide production. Dysfunction of the endothelium deem important mechanism for the development of coronary atherosclerosis. Clinical value of improved endothelial function is not set.

Pharmacokinetics

Absorption, distribution, metabolism

After oral administration, C_max hinaprila in plasma achieved within 1 no. Absorption of the drug is about 60%. Eating does not affect the degree of suction, but the speed and extent of absorption of several hinaprila are reduced while receiving fatty foods.

Hinapril metabolised to hinaprilata (about 38% an oral dose) and a small number of other active metabolites. T_1/2 hinaprila of blood plasma is approximately 1 no. C_max hinaprilata in plasma is approximately 2 hours after the intake of hinaprila. About 97% hinaprila or hinaprilata circulates in the blood plasma proteins associated with the form. Hinapril and its metabolites do not penetrate the Geb.

Deduction

Hinapril and hinaprilat are excreted mainly with urine (61%), as well as feces (37%); T_1/2 is about 3 no.

Pharmacokinetics in special clinical situations

In patients with renal insufficiency, c T_1/2 hinaprilata increases with decreasing QC. Pharmacokinetic studies in patients with end stage renal failure (c), receiving treatment programme haemodialysis or continuous ambulatory dialysis peritonealnym, indicates, that dialysis exerts a small effect on the excretion of hinaprila and hinaprilata. Revealed a linear correlation between the ground of hinaprilata plasma and QC. Hinaprilata also decreases excretion in the elderly (senior 65 years) and correlated with their kidney function.

Testimony

- Arterial hypertension (in the form alone or in combination with tiazidnami dioretikami and beta-adrenoblokatorami);

- Congestive heart failure (in combination with dioretikami and/or cardiac glycosides).

Dosage regimen

When performing alone hypertension the recommended initial dose Akkupro^® patients, not receiving diuretics, is 10 mg or 20 mg 1 time / day. Depending on the clinical effect dose can be increased (increasing twice) until maintenance dose 20 mg or 40 mg / day, which is usually prescribed in 1 or divided into 2 parts. Usually, change the dose at intervals of 4 of the week. In most patients achieved adequate control HELL in long-term care cannot, by use of the drug 1 time / day. The maximum daily dose – 80 mg.

Patients, continue receiving diuretics, the recommended initial dose Akkupro^® is 5 mg; Thereafter it increases (as stated above) until, until you reach the optimal effect.

At chronic heart failure application of shows as an adjunct to therapy dioretikami and/or cardiac glycosides. The recommended initial dose in patients with chronic heart failure is 5 mg 1 or 2 times / day; After taking the drug the patient should be observed in order to identify symptomatic arterial hypotension. If portability is the initial dose Akkupro^® good, You can raise up to effective dose, which is usually 10-40 mg / day 2 equal reception in conjunction with concomitant therapy.

At impaired renal function the recommended initial dose Akkupro^® is 5 mg patients QC more 30 ml / min and 2.5 mg patients with KK less 30 ml / min. If portability is a good initial dose, then the next day Akkupro^® You can assign 2 times / day. In the absence of arterial expressed hypotension or significant deterioration of renal function dose can be increased to weekly intervals, taking into account the clinical and hemodynamic effects.

In accordance with clinical and pharmacokinetic data have patients with impaired renal function initial dose is recommended to pick up as follows.

*- at present, insufficient data, to give clearer guidance on dose Akkupro^® for such patients.

The recommended initial dose Akkupro^® in elderly patients is 10 mg 1 time / day; Subsequently, it increases until the, until you reach the optimal therapeutic effect.

Side effect

Adverse effects when applying Akkupro^® are usually transitory, and transient. Often highlights headache (7.2%), dizziness (5.5%), cough (3.9%), fatigue (3.5%), rhinitis (3.2%), nausea and / or vomiting (2.8%), myalgia (2.2%). It should be noted, that in a typical case of cough is unproductive, persistent and takes place after the end of treatment.

Adverse events, observed at 0.5-1% patients, receiving Akkupro^® (in combination with a diuretic or without it) listed below.

From the hematopoietic system: hemolytic anemia *, thrombocytopenia. *

Allergic reactions: anaphylacticskie reaction. *

From the central and peripheral nervous system: depression, hypererethism, drowsiness, vertigo.

On the part of the organ of vision: caligation.

Cardio-vascular system: angina, heartbeat, tachycardia, postural hypotension *, fainting *, vasodilation.

From the digestive system: dry mouth or throat, flatulence, pancreatitis *.

Dermatological reactions: alopecia *, exfoliativei Dermatitis *, increased sweating, Pemphigus *, photosensitivity *, itch, rash.

On the part of the musculoskeletal system: arthralgia.

From the urinary system: urinary tract infection.

Increase (more than 1.25 fold compared with CAH) the level of creatinine in the serum and blood urea nitrogen was observed respectively 2% and 2% patients, treated with aciclovir Akkupro^®. The likelihood of an increase in these indices in patients with, at the same time receiving dioretiki, higher, than against the backdrop of the admission of one Akkupro^®. With continued therapy both indicators often return to normal.

On the part of the reproductive system: reduced potency.

Other: peripheral edema and generalized, hyperkalemia; rarely – agranulocytosis and neutropenia, Although their relationship with the admission Akkupro^® remains unclear.

Rarely: patients, receiving hinapril, cases of angioneuroticeski pain (0.1%). Other ACE inhibitors were observed cases of Eosinophilic pnevmonita and hepatitis, who in the treatment hinaprilom were rare.

* – less frequent adverse events.

Contraindications

- A history of angioedema, associated with treatment with ACE inhibitors;

- Childhood and adolescence up 18 years;

- Hypersensitivity to any component of the drug.

Cross-sensitivity to other ACE inhibitors have not studied.

FROM caution should designate product with a history of angioneuroticeski pain, not associated with the use of ACE inhibitors, patients with symptomatic hypotension, previously took diuretics and observe a diet with restriction of salt intake or in gemodialise, with severe cardiac insufficiency in patients with high risk expressed hypotension, by reducing the amount of BCC (incl. If vomiting or diarrhea), when hyperkalemia, suppression of bone marrow hematopoiesis, aortic stenosis, cerebrovascular diseases, condition after kidney transplantation, When bilateral stenosis of renal artery or artery only kidneys, If the kidney function, severe autoimmune systemic diseases of connective tissue, abnormal liver function (especially if you are applying with a diuretic), in combination therapy with kalijsberegajushhim diuretic, for patients with diabetes, extensive surgical interventions and conduct of general anesthesia.

Pregnancy and lactation

In appointing pregnant hinaprila should take into account the possibility of adverse effects on the fetus. If a woman becomes pregnant during treatment Akkupro^®, the drug should be discontinued.

When using ACE inhibitors in groups II and III trimestrah pregnancy cases of arterial hypotension, renal failure, hypoplasia of the skull bones and/or neonatal death. It also describes cases of oligogidroamniona, presumably associated with decreased kidney function in fetuses; against this background, the State registered contractures of the limbs, deformation of the front part of the skull, gipoplaziu light and delay of intrauterine growth retardation. In the treatment of ACE inhibitors in the first trimester of pregnancy only these unwanted effects did not develop, Nevertheless, women, the group receiving the drug in the first trimester, should be informed of adverse events.

Women, who need therapy, ACE inhibitors in groups II and III trimestrah pregnancy, You must evaluate the potential risk of fetal development; with a view to identifying oligogidroamniona (which may develop after the irreversible damage to the foetus) should regularly conduct ULTRASOUND. When signs of oligogidroamniona hinapril should be abolished except, when its use is vital for mother.

Other possible complications in fetus/newborn include intrauterine growth delay, prematurity and nezareatmene arteriosus; Describes the death of the fetus. It remains unclear, do these unwanted phenomena with therapy, ACE inhibitors or with the disease of the mother. It is also not known, whether the use of ACE inhibitors in the first trimester of pregnancy only to exert adverse effects on the fetus.

Newborn, exposed in-utero exposure to ACE inhibitors, It should be observed with the aim of identifying arterial hypotension, oliguria and hyperkalemia. If oligurii appears should support hell and perfusion of the kidneys.

ACE inhibitors, including hinapril, to a limited extent made with breast milk. Therefore, you should exercise caution when using hinaprila in women during lactation (breast-feeding).

Cautions

In the treatment of ACE inhibitors described cases of angioneuroticeski pain in the head and neck; When treating hinaprilom he met u 0.1% patients. When you see the faces of angioneuroticeski pain or laringospazma, language or the epiglottis should immediately discontinue treatment hinaprilom; the patient should designate the proper treatment and watch it before cupping edema. Swelling of the face and lips usually goes away without treatment; to reduce symptoms can be used antihistamines. Angioedema, exciting larynx, can lead to death. If the impact of language, the epiglottis or larynx probably development of airway obstruction, need emergency treatment, includes s/to the introduction of a solution of epinephrine (adrenaline) 1:1000 (0.3-0.5 ml) and other measures.

In the treatment of ACE inhibitors also described instances of angioneuroticeski pain bowel. Patients noted stomach pain (with or without nausea and vomiting); in some cases, without prior angioneuroticeski pain face and normal levels of c-1 esterase. The diagnosis is installed using abdominal CT scan, ultrasound or surgery.

Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, in patients with pain in the abdominal area, taking ACE inhibitors, When performing a differential diagnosis must take into account the possibility of angioneuroticeski pain bowel.

Patients, have a history of angioedema are observed, not associated with the enzyme inhibitor, can be increased risk for its development in the treatment of drug in this group.

Patients, receiving ACE inhibitors during desensibilizirujushhej therapy Hymenoptera venom (Hymenoptera: this, Bees, Ants), can develop anaphylactoidnye reaction, life threatening. Such patients avoided these reactions by suspending ACE inhibitors, However, they evolved once again after accidentally taking medication.

Anaphylactoidnye reaction in the treatment of ACE inhibitors have been reported in patients, which was held at the same time low density lipoprotein Apheresis with dextran sulphate absorption-help.

Patients, receiving haemodialysis treatment using specific vysokoprotochnyh membranes (eg, from poliakrilnitrila), increased risk of anaphylactoidnykh reactions while treatment of enzyme inhibitor. To avoid them, You should use other antihypertensives or other membranes for hemodialysis.

Symptomatic hypotension has rarely met in patients with uncomplicated hypertension, receiving Akkupro^®, However, it is a possible complication of therapy in patients with ACE Inhibitors lower content of salts in the body or gipovolemiei, eg, After treatment dioretikami, limiting salt consumption or on the background of dialysis.

When symptoms of arterial hypotension should stow the patient, and, if necessary, start the in/in infusion of isotonic saline solution. Transient hypotension is not a contraindication to further treatment; but in such cases it is advisable to discuss the possibility of lowering the dose or to assess the feasibility of simultaneous therapy with diuretics.

Patients, receiving diuretics, appointment of Akkupro^® could lead to the development of symptomatic arterial hypotension. If a patient requires dioretical therapy, It is advisable to temporarily stop for 2-3 days before the start of treatment hinaprilom. If monotherapy hinaprilom does not provide sufficient antigipertenzivnogo effect, the treatment diuretic should resume. If you cancel the diuretic you cannot, the Akkupro^® assign a low initial dose.

Patients with chronic heart failure, have increased risk of arterial expressed hypotension, treatment Akkupro^® You should start with the recommended dose, under the close supervision of a physician; patients must be observed during the first 2 weeks of treatment, and in all cases, When dose increases Akkupro^®.

Treatment of ACE inhibitors in patients with uncomplicated hypertension in rare cases was accompanied by agranoulozitozom and oppression bone marrow; these unwanted phenomena often met in patients with the human kidney, especially suffering from connective tissue diseases. When treating Akkupro^® agranulocytosis rarely developed. When using this medication (as well as other ACE inhibitors) in patients with connective tissue disease and/or kidney disease should monitor the number of leukocytes in the blood.

In susceptible patients the Suppression of Renin-angiotensin-aldosterone system activity can lead to changes in kidney function. In patients with severe heart failure, whose kidney function may depend on the Renin-angiotensin-aldosterone system activity, treatment with ACE inhibitors, including hinapril, may be accompanied by oliguria and/or increasing azotemia and, rarely, acute renal failure and/or, rarely, death.

T_1/2 hinaprila increases with decreasing QC. Patients with CC <60 mL/min hinapril should be appointed in lower initial dose. In these patients, the dose should be gradually increased, taking into account the therapeutic effect under the control of the kidney, Although clinical trials have been reported further deterioration in kidney function in the treatment of drug.

Some patients with arterial hypertension or heart failure without clear signs of the original renal vascular lesions in treatment of Akkupro^®, especially in combination with a diuretic, There was an increase in levels of urea nitrogen and creatinine serum, which was usually slight and reversible. The risk of such changes is higher in patients with baseline kidney function. In such cases, you might need to reduce the dose and/or cancellation of diuretic effectively delivered and/or hinaprila.

In patients with arterial hypertension, with unilateral or bilateral renal artery stenosis, in the treatment of ACE inhibitors in some cases observed increased level of blood urea nitrogen and serum creatinine. These changes were almost always reversible and disappear after the abolition of ENZYME inhibitor and/or diuretic effectively delivered. In such cases, within the first few weeks of treatment should monitor kidney function.

Hinapril in combination with a diuretic should be used with caution in patients with impaired or progressive liver disease, tk. small changes vodno-elektrolitnogo balance may cause the development of hepatic coma.

Metabolism of hinaprila to hinaprilata OK occurs under the influence of liver esterase. Hinaprilata concentration is reduced in patients with alcoholic cirrhosis of the liver at the expense of dejeterifikacii hinaprila.

Patients, receiving hinapril, like other ACE inhibitors, may increase potassium levels in blood serum. If you are applying to hinapril can reduce gipokaliemia, called tiazidnami dioretikami. Combined use of hinaprila with kalisberegatmi dioretikami was not investigated. Given the risk of further increases in the level of potassium in the blood serum, combination therapy with kalisberegatmi dioretikami should be carefully controlled by the level of potassium in the blood serum.

ACE inhibitors therapy is sometimes accompanied by the development of hypoglycemia in patients with diabetes mellitus, receiving insulin or oral gipoglikemicakie means; patients with diabetes mellitus may require more careful observation and correction doses of hypoglycemic drugs.

When treatment with ACE inhibitors, including hinapril, noted development of cough. In a typical case, it is unproductive, persistent and goes after cessation of therapy. In the differential diagnosis of cough should take into account its possible link with ACE inhibitors.

Patients, the surgical interventions or general anesthesia, ACE inhibitors should be used with caution, because they block education angiotenzina II, caused by compensatory Renin secretion. This can cause arterial hypotension, that eliminates by introducing plazmozamenitelei.

Patients should be warned that, that inadequate fluid intake, excessive sweating or dehydration can lead to excessive reduction of HELL due to reduction of BCC. Other causes of dehydration, such as vomiting or diarrhea, can also lead to reduced expressed HELL. In such cases, patients should see a doctor.

When you see any symptoms of infection (eg, sore throat, fever) the patient should seek medical advice immediately, because they can be a manifestation of neutropenia.

Use in Pediatrics

The safety and efficacy of hinaprila u children and adolescents under the age of 18 years not set.

Effects on ability to drive vehicles and management mechanisms

Caution must be exercised, especially at the beginning of treatment, in potentially hazardous activities, require increased attention and psychomotor speed reactions.

Overdose

Symptoms characteristic expressed AD decline.

Treatment: appropriate in/in a liquid; symptomatic therapy. Hemodialysis and peritoneal dialysis have a small effect on the excretion of hinaprila and hinaprilata.

Drug Interactions

Tetracycline and other drugs, interact with magnesium

Application of tetracycline with hinaprilom was accompanied by a decrease in suction tetracycline approximately 28-37% due to the presence of magnesium carbonate as an auxiliary substances form hinaprila reception inside. Together with the appointment of hinaprila and tetracycline should take into account the possibility of such interactions.

Preparations lithium

Patients, treated with drugs lithium and ACE inhibitors, observed increase in the level of lithium in the blood serum and signs of intoxication lithium through increased excretion of sodium. Assign these drugs simultaneously should be carefully; When treating shows regular determination of the level of lithium in the blood serum. Simultaneous reception dioretika can increase the risk of lithium intoxication.

Diuretki

As with other ACE inhibitors, patients, receiving diuretics, especially if dioretical therapy was initiated recently, the appointment of hinaprila sometimes leads to excessive reduction of HELL. Arterial hypotension first dose when using hinaprila can be minimized by the suspension of diuretic effectively delivered a few days before the start of treatment. If you cancel the diuretic is impossible, the hinapril should be appointed in lower initial dose. If the patient continues to welcome dioretika, It should be observed for up to 2 hours after the first dose hinaprila.

If the patient, receiving hinapril, showing kalisberegate dioretiki (eg, spironolactone, triamterene or amiloride), drugs and potassium salt substitutes, containing potassium, the use should be carefully controlled by the level of potassium in the blood serum, tk. increased risk of hyperkalemia.

Other drugs

Signs of clinically significant pharmacokinetic interaction hinaprila with propranolol, hydrochlorothiazide, digoxin or zimetidine not detected. Use hinaprila 2 times/day did not significantly affect antikoaguljantnom effect of warfarin in a single application (assessed on the basis of protrombinovogo time).

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.