Accupro® (Accupro®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceHinaprilHinapril
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  • Accupro®
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    Pfizer Manufakchuring Deutschland GmbH     Germany
  • Hinapril-C3®
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    NORTH STAR, CJSC     Russia
    • Dosage form: & nbsp

    film coated tablets.

    Composition:1 tablet coated with film Sheath, dosage of 5 mg contains:
    Active substances: quinapril hydrochloride 5.416 mg (equivalent to 5 mg of quinapril).
    Excipients: magnesium carbonate 46.584 mg, gelatin 5,000 mg, lactose monohydrate 38,000 mg, crospovidone 4,000 mg, magnesium stearate 1,000 mg, film sheath: Opadry white OY-S-7331 *, wax herbal 0.050 mg.
    * Drop off white OY-S-7331 contains: hypromellose 1,200 mg, giprolose 0.900 mg, titanium dioxide 0.600 mg, Macrogol-400 0.3300 mg.
    1 tablet coated with film shell, a dosage of 10 mg contains:
    Active substances: quinapril hydrochloride 10.832 mg (equivalent to 10 mg of quinapril).

    Excipients: Magnesium carbonate 93,168 mg, gelatin 10,000 mg, lactose monohydrate 76,000 mg, crospovidone 8,000 mg, magnesium stearate 2.0 mg, film coat: Opaprai white OY-S-7331 *, herbal wax 0,100 mg.

    * Drop off white OY-S-7331 contains: hypromellose 2,400 mg, giprolose 1,800 mg, titanium dioxide 1,200 mg, macrogol-400 0,600 mg.

    1 tablet, film-coated, 20 mg dosage contains:

    Active substances: quinapril hydrochloride 21.664 mg (equivalent to 20 mg of quinapril).

    Excipients: magnesium carbonate 125,000 mg, gelatin 10,000 mg, lactose monohydrate 33,336 mg, crospovidone 8,000 mg, magnesium stearate 2.0 mg, film sheath: opadame white OY-S-7331 *, herbal wax 0,100 mg.

    * Drop off white OY-S-7331 contains: hypromellose 2,400 mg, 1,800 mg, titanium dioxide 1,200 mg, macrogol-400 0,600 mg.

    1 tablet, film-coated, 40 mg dosage contains:

    Active substances: quinapril hydrochloride 43,328 mg (equivalent to 40 mg of quinapril).

    Excipients: magnesium carbonate 250,000 mg, gelatin 20,000 mg, lactose monohydrate 66.672 mg, crospovidone 16,000 mg, magnesium stearate 4.0 mg, film sheath: Fold brown Y-5-9020G *, herbal wax 0,200 mg.

    * Rape brown Y-5-9020G contains hypromellose 4,800 mg, giprolose 3,600 mg, titanium dioxide 1,368 mg, macrogol-400 1,200 mg, iron oxide dye red 1,032 mg.

    Description:

    Dosage of 5 mg: white, oval, biconvex tablets, film-coated, with a risk and number "5" on both sides.

    Dosage of 10 mg: white, triangular, biconvex tablets, film-coated, with a risk on both sides and the number "10" on one side.

    Dosage of 20 mg: white, round, biconvex tablets, film-coated, with a risk on both sides and the number "20" on one side.

    Dosage of 40 mg: red-brown, oval, biconvex tablets, film-coated, with the number "40" on one side and "PD 535 "on the other.

    Pharmacotherapeutic group:Angiotensin-converting enzyme (ACE) inhibitor
    ATX: & nbsp

    C.09.A.A.06   Hinapril

    Pharmacodynamics:

    The ACE is an enzyme that catalyzes conversion angiotensin I in angiotensin II, which has a vasoconstrictive effect and increases the tone of the vessels, including by stimulating the secretion of aldosterone with the adrenal cortex. Hinapril competitively inhibits 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 renin plasma activity. At the same time, lowering blood pressure (BP) is accompanied by a decrease in the total peripheral vascular resistance (OPSS) and resistance of renal vessels, while changes in the heart rate (HR), cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are minor or absent .

    Hinapril increases exercise tolerance. With prolonged use contributes to the reverse development of myocardial hypertrophy in patients with arterial hypertension; improves blood circulation ischemic myocardium. Strengthens coronary and renal blood flow. Reduces the aggregation of platelets. The onset of action after taking a single dose - after 1 hour, maximum - after 2-4 hours, the duration of action depends on the amount of the dose taken (up to 24 hours). Clinically pronounced effect develops a few weeks after the initiation of therapy.

    Pharmacokinetics:

    The concentration of quinapril in the blood plasma after ingestion reaches a maximum within 1 h, quinaprilat -2 hours. Eating does not affect the degree of absorption, but can increase the time to reach maximum concentration (TCmax) (fatty foods can 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 hepatic enzymes quinapril is rapidly metabolized to quinaprilate by cleavage of the ester group (the main metabolite is dibasic acid of quinapril), which is a potent inhibitor of ACE.

    About 38% of the ingested dose of quinapril circulates in the blood plasma in the form of quinaprilate. Half-life (T 1/2) quinapril from the blood plasma is about 1 hour, quinaprilat - 3 hours. It is excreted by the kidneys - 61% (56% in the form of quinapril and quinaprylate) and through the intestine - 37%. T1/2 quinapril - 1 -2 h, quinaprylate - 3 h. About 97% of quinapril and quinaprilate circulate in blood plasma in protein-related form. Hinapril and its metabolites do not penetrate across blood-brain barrier.

    In patients with renal insufficiency T ½ Hinaprilat increases with decreasing creatinine clearance (CK). The excretion of quinaprilat is also reduced in elderly patients (over 65 years) and closely correlates with impaired renal function, however, in general, there is no difference in the efficacy and safety of treatment in elderly and younger patients.

    In patients with alcoholic cirrhosis of the liver, the concentration of quinaprilat is reduced by the violation of the de-esterification of quinapril.

    Indications:

    Arterial hypertension (in monotherapy or in combination with thiazide diuretics and beta-blockers).

    Chronic heart failure (in combination with diuretics and / or cardiac glycosides).

    Contraindications:

    - Hypersensitivity to any component of the drug.

    - Angioedema in history as a result of previous therapy with ACE inhibitors, hereditary and / or idiopathic angioedema.

    - Age to 18 years.

    - Pregnancy and lactation.

    - Text field: ADeficiency of lactase, lactose intolerance and glucose-gapaktotic malabsorption syndrome.

    Carefully:

    Symptomatic arterial hypotension in patients who had previously taken diuretics and followed a diet with restricted intake of table salt; severe heart failure in patients with a high risk of hypotension; conditions, accompanied by a decrease in the volume of circulating blood (bcc) (including vomiting and diarrhea); hyperkalemia; oppression of bone marrow hematopoiesis; aortic stenosis; cerebral circulatory insufficiency, ischemic heart disease, coronary insufficiency - a sharp decrease in blood pressure on the background of therapy with ACE inhibitors, can worsen the course of these diseases; bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, condition after kidney transplantation; impaired renal function; in patients on hemodialysis (CC less than 10 ml / min) (data on the use of Accupro® in such patients is not enough); autoimmune systemic diseases of connective tissue (including,systemic lupus erythematosus, scleroderma); violations of the liver (especially with simultaneous use with diuretics); with simultaneous use with potassium-sparing diuretics; diabetes; extensive surgical interventions and general anesthesia.

    Pregnancy and lactation:

    The use of the drug Akkupro is contraindicated during pregnancy, in women planning pregnancy, as well as in women of reproductive age who do not use reliable methods of contraception.

    Women of reproductive age who take Acquupro® should use reliable contraceptive methods.

    When diagnosing pregnancy, the drug Accupro® should be discontinued as soon as possible.

    The use of ACE inhibitors during pregnancy is accompanied by an increased risk of anomalies from the cardiovascular and nervous systems of the fetus. In addition, against the background of taking ACE inhibitors during pregnancy, cases of low blood pressure, premature birth, birth of children with arterial hypotension, renal pathology (including acute kidney failure), hypoplasia of the skull bones, contractures of the limbs, craniofacial deformities,lung hypoplasia, intrauterine growth retardation, open arterial duct, as well as cases of intrauterine fetal death and newborn death. Often, anhydration is diagnosed after the fetus has been irreversibly damaged. Newborns who have been exposed to ACE inhibitors in utero should be monitored for the purpose of identifying arterial hypotension, oliguria, and hyperkalemia. When oliguria occurs, blood pressure and renal perfusion should be maintained.

    The drug Akkupro® should not be given during breastfeeding.

    Dosing and Administration:

    Take inside, without chewing, regardless of the time of eating, squeezed with water.

    Arterial hypertension

    Monotherapy: the recommended initial dose of the drug Akkupro® in patients not receiving diuretics is 10 mg once a day. Depending on the clinical effect, the dose can be increased (doubling) to a maintenance dose of 20 or 40 mg / day, which is usually prescribed in 1 or 2 doses. As a rule, the dose should be changed at intervals of 4 weeks. In most patients, the use of the drug Akkupro once a day allows to achieve a stable therapeutic response.The maximum daily dose is 80 mg / day.

    Combination with diuretics: the recommended initial dose of the drug Akkupro® in patients who continue to take diuretics is 5 mg 1 time per day; in the subsequent it is increased (as indicated above) until the optimal therapeutic effect is achieved (see the section "Interaction with other medicinal products").

    Chronic heart failure

    The recommended initial dose of the drug Accupro® is 5 mg 1 or 2 times a day.

    After taking the drug, the patient must be under medical supervision to detect symptomatic arterial hypotension. In case of good tolerability of the initial dose of the drug Akkupro, it can be increased to 10-40 mg / day in 2 equal doses.

    Use in patients with impaired renal function: Given the clinical and pharmacokinetic data in patients with impaired renal function, the initial dose should be selected as follows:

    QC Recommended initial dose

    (ml / min) (mg)

    more than 60 10

    30-60 5

    10-30 2,5 (1/2 pills 5 mg)

    If tolerability of the initial dose is good, then the drug Akkupro can be used 2 times a day.The dose of the drug Akkupro can be gradually, not more often than once a week, to increase taking into account clinical, hemodynamic effects, as well as kidney function.

    Application the elderly patients: The recommended initial dose of the drug Akkupro in elderly patients is 10 mg once a day; in the subsequent it is increased until the optimal therapeutic effect is achieved.

    Side effects:

    Undesirable effects with the use of the drug Akkupro usually are mild and transitory. The most common symptoms are headache (7.2%), dizziness (5.5%), coughing (3.9%), fatigue (3.5%), rhinitis (3.2%), nausea and / or vomiting (2.8%) and myalgia (2.2%). It should be noted that in a typical case, cough is unproductive, persistent and occurs after discontinuation of treatment.

    Cancellation of the drug Akkupro as a result of side effects was observed in 5.3% of cases.

    Below is a list of undesirable reactions, distributed according to organ systems and frequency of occurrence (classification of the World Health Organization):

    very often - more than 1/10,

    often from more than 1/100 to less than 1/10,

    infrequently - from more than 1/1000 to less than 1/100,

    rarely from more than 1/10000 to less than 1/1000,

    very rarely - from less than 1/10000, including individual messages.

    From the nervous system

    Often: headache, dizziness, insomnia, paresthesia, increased fatigue.

    Infrequently: depression, increased excitability, drowsiness, vertigo.

    From the side of the digestive tract

    Often: nausea and / or vomiting, diarrhea, dyspepsia, abdominal pain.

    Infrequently: dryness of the mucous membrane of the mouth or throat, flatulence, pancreatitis *, angioedema, intestinal edema, gastrointestinal bleeding.

    Rarely: hepatitis.

    General disorders and disorders at the site of administration

    Infrequently: edema (peripheral or generalized), malaise, viral infections.

    From the side of the circulatory and lymphatic systems

    Infrequently: hemolytic anemia *, thrombocytopenia *.

    From the side of the cardiovascular system Often: marked decrease in blood pressure.

    Infrequently: angina, palpitations, tachycardia, heart failure, myocardial infarction, stroke, increased blood pressure, cardiogenic shock, postural hypotension *, fainting *, symptoms of vasodilation.

    On the part of the respiratory system, the organs of the thorax and the mediastinum Often: cough, dyspnea, pharyngitis, chest pain.

    From the skin and subcutaneous tissues

    Infrequently: alopecia *, exfoliative dermatitis *, increased sweating, pemphigus *, photosensitivity reactions *, skin itching, rash.

    From the musculoskeletal and connective tissue Often: backache.

    Infrequently: arthralgia.

    From the side of the kidneys and urinary tract

    Infrequently: urinary tract infection, acute renal failure.

    From the genitals and breast Infrequently: decreased potency.

    From the side of the organ of vision:

    Infrequently: weakening of vision.

    From the immune system:

    Infrequently: anaphylactic reactions.

    Rarely: angioedema.

    Other:

    Rarely: eosinophilic pneumonitis.

    Laboratory indicators:

    very rarely noted agranulocytosis and neutropenia, although the cause-and-effect relationship with the use of the drug Akkupro has not yet been established.

    Hyperkalemia: (see "Special instructions")

    Creatinine and blood urea nitrogen: an increase (more than 1.25 times in comparison with the upper limit of the norm) of serum creatinine and blood urea nitrogen was observed in 2% and 2% of patients receiving Akkupro ® monotherapy, respectively.The likelihood of an increase in these indicators in patients receiving diuretics simultaneously is higher than against the background of the use of one drug Akkupro. With further therapy, the indicators often return to normal.

    * - less frequent adverse events or those noted during post-marketing research.

    With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate, intravenously), a symptom complex is described, including facial flushing, nausea, vomiting, and lowering blood pressure.

    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 intravenous infusion with a 0.9% solution of sodium chloride (to increase the BCC).

    Hemodialysis and peritoneal dialysis are not effective.

    Interaction:Tetracycline and other drugs, interacting with magnesium:

    simultaneous use of tetracycline with quinapril reduces the absorption of tetracycline by approximately 28-37% due to the presence of magnesium carbonate as an auxiliary component of the drug.At simultaneous application it is necessary to consider the possibility of such interaction.

    Lithium: patients who simultaneously received lithium preparations and ACE inhibitors, observed an increase in the concentration of lithium in the blood serum and signs of lithium intoxication due to increased sodium excretion. Use these drugs simultaneously with caution; the treatment shows a regular determination of the concentration of lithium in the blood serum. The simultaneous use of diuretics can increase the risk of lithium intoxication.
    Diuretics: with simultaneous The use of quinapril with diuretics is marked by an increase in antihypertensive action

    (see section "Special instructions").
    Preparations, increasing serum potassium concentration

    blood: if the patient receiving quinapril, potassium-sparing diuretics are shown (for example, spironolactone, triamterene or amiloride), potassium preparations and salt substitutes containing potassium, then they should be used carefully under the control of potassium in the blood serum.

    Ethanol (drinks. containing alcohol): ethanol intensifies the action of quinapril. Hypoglycemic agents for ingestion and insulin: therapy with ACE inhibitors is sometimes accompanied by the development of hypoglycemia in diabetic patients receiving insulin or hypoglycemic agents for oral ingestion. Hinapril enhances the effect of hypoglycemic agents for ingestion and insulin.

    Other drugs: indications clinically significant pharmacokinetic interaction of quinapril with propranolol, hydrochlorothiazide, digoxin or cimetidine was not revealed. The use of quinapril 2 times a day did not significantly affect the anticoagulant effect of warfarin when it was applied once (evaluated on the basis of prothrombin time).

    With simultaneous repeated use of atorvastatin in a dose of 10 mg with quinapril at a dose of 80 mg did not lead to significant changes in the equilibrium pharmacokinetic parameters of atorvastatin.

    Hinapril increases the risk of developing leukopenia with concomitant use with allopurinol, cytostatic agents, immunosuppressants, procaine home.

    Hypotensive drugs, narcotic analgesics, drugs for general anesthesia increase the antihypertensive effect of quinapril.

    Estrogens, non-steroidal anti-inflammatory drugs (including selective inhibitors of cyclooxygenase-2) weaken the antihypertensive effect of quinapril due to fluid retention.

    Drugs that cause depression of bone marrow function increase the risk of developing neutropenia and / or agranulocytosis.

    With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate, intravenously), a symptom complex is described, including facial flushing, nausea, vomiting, and lowering blood pressure.

    Special instructions:In the treatment of ACE inhibitors, cases of angioedema in the head and neck, including 0.1 % patients who received Accupro®. If a laryngeal whistle or angionevrotic edema of the face, tongue, or vocal folds occurs, the drug Accupro® should be immediately withdrawn. Patient it is necessary to prescribe adequate treatment and to observe before the regression of the symptoms of edema. To reduce the symptoms can be used antihistamines.

    Angioedema with involvement of the larynx can lead to death. If swelling of the tongue, vocal cords or larynx threatens with the development of airway obstruction, a adequate emergency therapy, including subcutaneous injection of a solution of epinephrine (adrenaline) 1: 1000 (0.3-0.5 ml).

    In the treatment of ACE inhibitors, cases angioedema of the intestine. Patients noted abdominal pain (with / without nausea or vomiting); in some cases without a previous angioedema and a normal activity of C1-esterase. The diagnosis was established using computed tomography of the abdominal region, ultrasound examination or at the time of surgery.

    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 angioedema development of the intestine.

    Patients who have a history of angioedema, not associated with an ACE inhibitor, may be at increased risk of developing it when treated with drugs of this group.

    In patients receiving ACE inhibitors during desensitizing therapy with Hepaticoptera venom, anaphylactoid reactions may develop, life-threatening.By temporarily stopping the use of ACE inhibitors, these reactions could be avoided, but they arose again with the occasional administration of these drugs. Anaphylactoid reactions can also develop with the use of ACE inhibitors in patients who undergo low-density lipoprotein apheresis by absorption dextran sulfate or in patients on hemodialysis using high-flow membranes, such as polyacrylonitrile. Therefore, similar combinations should be avoided, using either other antihypertensive drugs, or alternative membranes for hemodialysis.

    Symptomatic arterial hypotension is rarely seen with Accupro® in patients with uncomplicated hypertension, but it can develop as a result of therapy with ACE inhibitors in patients with reduced BCC, for example, when a diet with limited consumption salt, hemodialysis. In case of symptomatic arterial hypotension, symptomatic therapy should be performed (the patient should take a horizontal position and, if necessary, administer an intravenous infusion with a 0.9% solution of sodium chloride).Transient arterial hypertension is not a contraindication to the further use of the drug, however in such cases it is necessary to reduce its dose or assess the advisability of simultaneous therapy with diuretics.

    Other causes of BCC reduction, such as vomiting or diarrhea, can also lead to a marked decrease in blood pressure. In such cases, patients should consult a doctor.

    In patients receiving diuretics, the use of the drug Accupro® can also lead to the development of symptomatic arterial hypotension. It is advisable for such patients to temporarily stop taking a diuretic 2-3 days before the start of treatment with Accupro®, except for patients with malignant or difficult to treat hypertension. If monotherapy with Accupro® does not provide the necessary therapeutic effect, diuretic therapy should be resumed. If it is not possible to cancel the diuretic, then the drug Akkupro ® is used in a low initial dose. In patients with chronic heart failure, who are at increased risk of severe arterial hypotension, treatment with Accupro® should be started with the recommended dose under close medical supervision; patientsIt is necessary to observe during the first two weeks of treatment, as well as in all cases when the dose of the drug Accupro® increases. In the treatment of ACE inhibitors in patients with uncomplicated arterial hypertension, in rare cases agranulocytosis developed, which was more frequent in patients with impaired renal function and connective tissue diseases. When treating with the drug Accupro® agranulocytosis developed rarely. When using this drug (as well as other ACE inhibitors) in patients with connective tissue diseases and / or kidney disease, the number of leukocytes in the blood should be monitored.

    In susceptible patients, suppression of the activity of the renin-angiotensin-aldosterone system (RAAS) can lead to disruptionkidney function. In patients with severe chronic cardiac deficiency in which renal function may depend on RAAS activity, treatment with ACE inhibitors, including quinapril, may be accompanied by oliguria and / or progressive azotemia, and in rare cases, with acute renal failure and / or death.

    In patients with chronic heart failure or hypertension with unilateral or bilateral stenosis of the renal artery,in the treatment of ACE inhibitors, in some cases, an increase in the concentration of urea nitrogen in the blood and serum creatinine was observed. These changes were almost always reversible and disappeared after the withdrawal of the ACE inhibitor and / or diuretic. In such cases, during the first few weeks of treatment, monitor kidney function. The half-life of quinaprilate increases with decreasing CC. In patients with SC less than 60 ml / min, the drug Accupro® should be used at a lower initial dose. In such patients, the dose of the drug should be increased taking into account the therapeutic effect, with regular monitoring of kidney function, although in clinical studies there was no further deterioration in renal function in drug treatment.

    Accupro® in combination with diuretics should be used with caution in patients with impaired function or progressive liver disease, since small changes in water-electrolyte balance can cause the development of hepatic coma. ACE inhibitors, including quinapril, can increase the potassium content in the blood serum.

    Accupro® can reduce hypokalemia caused by thiazide diuretics with simultaneous application.

    The use of the drug Accupro® in combination therapy with potassium-sparing diuretics has not been studied. Given the risk further increase in serum potassium, combined therapy with potassium-sparing diuretics should be carried out with caution under the control of potassium in the serum.

    Patients with diabetes may need more careful observation and correction of a dose of hypoglycemic agents for oral and insulin intake, especially during the first month of therapy with an ACE inhibitor, including quinapril.

    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, its possible association with ACE inhibitors should be considered.

    Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.

    If any symptoms of infection (eg acute tonsillitis, fever) occur, the patient should immediately consult a doctor, as they may be manifestation of neutropenia.

    Effect on the ability to drive transp. cf. and fur:

    When using the drug Accupro®, care should be taken when driving vehicles or doing other work that requires increased attention, especially at the beginning of treatment.

    Form release / dosage:

    Tablets, film-coated, 5 mg, 10 mg, 20 mg, 40 mg.

    Packaging:

    Film-coated tablets. 5 mg: 10 tablets in a blister of aluminum - PA / aluminum / PVC foil, 3 blisters together with instructions for use in a cardboard pack.

    Tablets coated with a film coating, 10 mg: 10 tablets in a blister of aluminum - PA / aluminum / PVC foil, 3 blisters together with instructions for use in a cardboard pack.

    Film-coated tablets, 20 mg: 10 tablets in a blister of aluminum - PA / aluminum / PVC foil, 3 blisters together with instructions for use in a cardboard pack.

    Tablets, film-coated, 40 mg: 6 tablets in a blister of aluminum - PA / aluminum / PVC foil, 5 blisters together with instructions for use in a cardboard pack.

    Storage conditions:

    At a temperature of no higher than 25 ° C. Keep out of the reach of children.

    Shelf life:

    3 years. Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:014329/01
    Date of registration:01.04.2011
    The owner of the registration certificate:Pfizer Manufakchuring Deutschland GmbH Pfizer Manufakchuring Deutschland GmbH Germany
    Manufacturer: & nbsp
    Information update date: & nbsp25.09.2015
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