Active substanceFosinoprilFosinopril
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  • Dosage form: & nbsppills
    Composition:
    1 tablet contains:
    active substance: fosinopril sodium - 0.01 g or 0.02 g;
    auxiliary substances: lactose monohydrate 0.1834 g or 0.3668 g, croscarmellose sodium (impellose) 0.0006 g or 0.0012 g, silicon dioxide colloid (aerosil) 0.004 g or 0.008 g, magnesium stearate 0.002 g or 0.004 g.

    Description:
    Tablets are white or white with a yellow shade of color, round, biconvex.

    Pharmacotherapeutic group:inhibitor of angiotensin-converting enzyme (ACE).
    ATX: & nbsp

    C.09.A.A   ACE Inhibitors

    C.09.A.A.09   Fosinopril

    Pharmacodynamics:
    The ACE inhibitor has antihypertensive, vasodilating, diuretic and potassium-sparing effects. Reduces the formation of angiotensin II from angiotensin I, which leads to a reduction in total peripheral vascular resistance (OPSS) and systemic blood pressure (BP). Suppresses the synthesis of aldosterone, inhibits
    tissue ACE.The hypotensive effect is also due to the suppression of the metabolism of bradykinin, which has a pronounced vasodilating effect. Decrease in blood pressure is not accompanied by a change in the volume of circulating blood (BCC), cerebral and renal blood flow, blood supply of internal organs, skeletal muscles, skin, reflex activity of the myocardium. With arterial hypertension and left ventricular (left ventricular) hypertrophy, treatment results in a decrease in its mass and the thickness of the wall of the septum. Long-term treatment does not lead to metabolic disorders. After oral administration, the hypotensive effect develops within 1 hour, reaches a maximum after 3-6 hours and persists for 24 hours. In heart failure, the positive effects of fosinopril are mainly achieved by inhibition of the renin-angiotensin-aldosterone system (RAAS). Suppression of ACE leads to a decrease in both preload and postload on the myocardium. The drug helps to increase tolerance to physical activity, reduce the severity of heart failure.

    Pharmacokinetics:
    After oral administration, the absorption is approximately 30-40%.The degree of absorption is not dependent on food intake, but its speed can be slowed down. The hydrolytic conversion of fosinopril under the action of enzymes to fosinoprilat occurs predominantly in the liver and mucosa of the gastrointestinal tract. If the liver function is impaired, the rate of hydrolysis can be slowed down, and the degree of transformation does not change noticeably. The maximum concentration (Сmах) in blood plasma is reached approximately in 3 hours and does not depend on the accepted dose. Fosinoprilat binds to blood proteins by 95%, has a relatively small volume of distribution and is slightly associated with cellular components of the blood. Do not penetrate the blood-brain barrier (GEB), the placenta, is secreted into breast milk (the detectable level of fosinoprilat is reached after applying 20 mg / day for 3 days). Metabolised to fosinoprilat (75%), fosinoprilate glucuronides (20-30%) and hydroxyl forms (1-5%), which can inhibit ACE in rats.
    Fosinopril is excreted from the body equally through the intestines with bile and kidneys. In patients with arterial hypertension with normal renal and hepatic function, the half-life (T1 / 2) of fosinoprilata is approximately 11.5 hours.In patients with heart failure, the T1 / 2 value is 14 hours. The clearance of fosinoprilat in hemodialysis and peritoneal dialysis is on average 2 and 7%, respectively, relative to the values ​​of urea clearance. In patients with impaired renal function (creatinine clearance less than 80 ml / min / 1.73 m2), the total clearance of fosinoprilat from the body is approximately twice lower than in patients with normal renal function, while absorption, bioavailability and binding to proteins are not noticeably are changing. Reduced excretion through the kidneys is compensated by increased excretion through the intestine with bile. A moderate increase in plasma concentration-time (AUC) in the blood plasma (less than twice the norm) is observed in patients with renal insufficiency of various degrees, including renal failure in the terminal stage (creatinine clearance less than 10 ml / min / 1 , 73 m2). In patients with impaired liver function (with alcoholic or biliary cirrhosis), the rate of hydrolysis of fosinopril may be reduced, but the degree of hydrolysis does not change noticeably. The total clearance of fosinoprilata from the body of such patients is approximately half that of patients with normal liver function
    Indications:
    Arterial hypertension (in monotherapy or as part of combination therapy);
    Chronic heart failure (as part of combination therapy).

    Contraindications:
    • Hypersensitivity to fosinopril or other components of the drug;
    • Pregnancy;
    • Lactation period (breastfeeding);
    • Lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome;
    • Hereditary or idiopathic angioedema;
    • Angioneuroticeski edema on the background of therapy with ACE inhibitors (in the anamnesis);
    • Age under 18 years of age (safety and efficacy not studied);
    • Simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus and / or moderate and severe impairment of kidney function (KK less than 60 ml / min).

    Carefully:
    Aortic stenosis, cerebrovascular and cardiovascular diseases (including cerebrovascular insufficiency, ischemic heart disease, coronary insufficiency), severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), oppression of bone marrow hematopoiesis,diabetes, hyperkalemia, bilateral renal artery stenosis, stenosis of the artery only kidney condition after kidney transplantation, renal failure, during the desensitization treatments, liver failure, chronic heart failure III - IV NYHA functional class classification, hypotension, restricted diet cookbook salts, conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), advanced age, hemodialysis with the use of it vysokoprotochnyh membranes (e.g., AN69®), apheresis low density lipoprotein (LDL).

    Pregnancy and lactation:
    Fosinopril is contraindicated in pregnancy. The use of ACE inhibitors during the II and III trimesters of pregnancy causes damage or death of the developing fetus. Fosinopril teratogenic, foetotoxic action - violation of fetal kidneys, reduced blood pressure of the fetus and newborn, renal dysfunction, hyperkalemia, hypoplasia of bones of the skull, oligohydramnios, contracture limbs, lung hypoplasia.
    In newborns and infants, there is a risk of oliguria and neurological disorders, possibly due to a reduction in renal and cerebral blood flow due to a reduction in blood pressure caused by ACE inhibitors; lower initial doses and careful monitoring are recommended.
    Fosinopril is excreted in breast milk, so taking the drug during lactation is not recommended. If the drug is used during this period, breastfeeding should be discontinued.

    Dosing and Administration:
    Inside. The dosage of the drug should be selected individually.
    Arterial hypertension. The recommended initial dose of the drug is 10 mg once a day. The dose should be selected depending on the dynamics of blood pressure lowering. The usual dose is 10 to 40 mg once a day. In the absence of sufficient hypotensive effect, additional prescription of diuretics is possible.
    If treatment with fosinopril is initiated against a background of diuretic therapy, then its initial dose should not exceed 10 mg with careful medical monitoring of the patient's condition.
    Chronic heart failure.The recommended initial dose is 5 mg 1 or 2 times a day (fosinopril may be given in tablets of 10 mg with a risk or in tablets of 5 mg each). Depending on the therapeutic effectiveness, the dose can be increased at a weekly interval up to a maximum of -40 mg once a day. Arterial hypertension and heart failure with impaired renal function or liver. Since the removal of the drug from the body occurs in two ways (through the intestines with bile and kidneys), the reduction in doses to patients with impaired renal or hepatic function is usually not required.
    Elderly patients. Differences in efficacy and safety of treatment with the drug of patients aged 65 years and older and young patients are not observed. However, it is impossible to exclude a greater susceptibility in some elderly patients to the drug, due to possible overdose phenomena due to delayed excretion.
    The maximum daily intake for oral administration is 40 mg.

    Side effects:
    Side effect
    From the cardiovascular system: a feeling of heartbeat, arrhythmia, chest pain, angina, rhythm disturbances,myocardial infarction, fainting, "tides" of blood to the face; Orthostatic hypotension, sudden death, cardiopulmonary failure, cardiogenic shock, or bradi- tachycardia (heart failure), marked reduction in blood pressure, cardiac arrest.
    From the genitourinary system: proteinuria, oliguria, development or strengthening of chronic renal failure, anuria, disorders of the prostate gland.
    From the nervous system and sensory organs: peripheral edema, angioneurotic intestinal edema, stroke, cerebral ischemia, impaired memory, fatigue, weakness, headache, dizziness, syncope, hearing and visual impairment, tinnitus, when used in high doses - insomnia, anxiety, depression, confusion, violations of the vestibular apparatus, drowsiness, paresthesia.
    From the digestive system: dryness of the oral mucosa, taste disturbance, decreased appetite, stomatitis, glossitis, dysphagia, dyspepsia, flatulence, nausea, vomiting, diarrhea / constipation, ileus, pancreatitis, liver dysfunction, impaired activity of "liver" transaminases , hepatitis, cholestatic jaundice, abdominal pain, anorexia, weight change.
    On the part of the skin: photosensitization, urticaria, skin rash, itching, exfoliative dermatitis, bulez pemphigus and other hypersensitivity reactions.
    On the part of the respiratory system: dry cough, rhinorrhea, sinusitis, pulmonary infiltrates, dyspnea, dysphonia, laryngitis, pharyngitis, tracheobronchitis, bronchospasm, nosebleeds.
    On the part of the organs of hematopoiesis: inflammation of the lymph nodes.
    From the side of metabolism: exacerbation of gout.
    From the musculoskeletal system: myalgia, arthralgia, arthritis, convulsions. Laboratory indicators: hypercreatininaemia, increased urea concentration, hyperbilirubinemia, hyperkalemia, hyponatremia; reduction of hemoglobin and hematocrit, neutropenia, leukopenia, eosinophilia, increased erythrocyte sedimentation rate (ESR). There have been reports of cases of hypoglycemia in patients with diabetes who took insulin and hypoglycemic medications for oral administration.
    Teratogenic, fetotoxic effects - impaired fetal kidney development, fetal and newborn fetus, renal dysfunction, hyperkalemia, hypoplasia of the skull bones, oligohydramnion, limb contracture, lung hypoplasia.
    With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate) describes a symptom complex, which includes facial flushing, nausea, vomiting and lowering blood pressure.

    Overdose:
    Symptoms: marked decrease in blood pressure, bradycardia, shock, violation of water
    electrolyte balance, acute renal failure, stupor.
    Treatment: the patient should be placed in the "lying" position with raised legs. In mild cases of overdose - gastric lavage, the introduction of adsorbents and sodium sulfate for 30 minutes after ingestion. With a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution; with bradycardia - the use of pacemaker. The use of hemodialysis is ineffective.

    Interaction:
    Fosinopril enhances the hypoglycemic effect of derivatives of sulfonylurea, insulin, with simultaneous application with allopurinol, cytostatic drugs, immunosuppressants, procainamide, there is a risk of developing leukopenia.
    With simultaneous administration with lithium preparations, it is possible to increase its concentration in the blood plasma and the risk of lithium intoxication (it is necessary to monitor the concentration of lithium in the blood plasma).
    The simultaneous use of antacids (for example, aluminum or magnesium hydroxide, simicon) can reduce the absorption of the drug. Therefore, it is necessary to apply these means with an interval of at least 2 hours.
    Diuretics, hypotensive, narcotic analgesics, medicines for general anesthesia increase the antihypertensive effect of fosinopril.
    Non-steroidal anti-inflammatory drugs (NSAIDs), table salt can reduce the antihypertensive effect of ACE inhibitors, especially in patients with hypertension and low renin activity in blood plasma.
    When combined with fosinopril with potassium preparations, potassium-sparing diuretics (including amiloride, spironolactone, triamterene, eplerenone), with additives to food containing potassium, the risk of hyperkalemia increases. In patients with chronic heart failure, diabetes mellitus, concurrently taking potassium-sparing diuretics, potassium-containing salt substitutes, or other agents that cause hyperkalemia (eg, heparin), ACE inhibitors increase the risk of hyperkalemia in the serum.
    Estrogens weaken the hypotensive effect of fosinopril because of its ability to retain water.
    Insulin and hypoglycemic drugs for oral administration increase the risk of hypokalemia.
    Bioavailability of the drug with simultaneous application with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propanthelin bromide, digoxin, acetylsalicylic acid as antiplatelet agent and warfarin does not change.
    In the literature, it has been reported that in patients with diagnosed atherosclerotic disease, heart failure or diabetes with target organ damage, a double blockade of RAAS using angiotensin II receptor antagonists (APA II), ACE inhibitors or aliskiren (direct renin inhibitor) is associated with an increased incidence the occurrence of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure), when compared with the use of a single drug, influence on the RAAS. Double blockade (for example, the appointment of an ACE inhibitor with ARA II or aliskiren) should be performed only in certain specific cases, regularly monitoring the kidney function.

    Special instructions:
    Patients with malignant hypertension or concomitant decompensated chronic heart failure should begin treatment in a hospital setting.
    Before the beginning of therapy with ACE inhibitors and during treatment, the total number of leukocytes and the leukocyte count are calculated (once a month for the first 3-6 months of treatment and at periodic intervals up to year I in patients with an increased risk of neutropenia: in case of impaired renal function, systemic connective tissue diseases, in those receiving high doses), as well as at the first signs of infection. Before and during treatment, it is necessary to monitor blood pressure, kidney function, potassium (K +) content in blood plasma, hemoglobin and creatinine, urea, electrolyte content and activity of "liver" enzymes in the blood.
    Based on the results of epidemiological studies, it is assumed that simultaneous administration of ACE inhibitors and insulin, as well as hypoglycemic drugs for oral administration may lead to the development of hypoglycemia. The greatest risk of development is observed during the first weeks of combination therapy, as well as in patients with impaired renal function.Patients with diabetes require careful monitoring of glycemia, especially during the first month of therapy with an ACE inhibitor.
    Care should be taken when prescribing to patients on a low-salt or salt-free diet (an increased risk of developing hypotension).
    Safety and efficacy in pediatric practice: for newborns who have been exposed to intrauterine exposure to ACE inhibitors, careful monitoring is recommended to identify hypotension, oliguria, and hyperkalemia.
    Caution should be exercised when performing physical exercises or in hot weather due to the risk of dehydration and a decrease in blood pressure due to a decrease in fluid volume.
    Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.
    With the use of ACE inhibitors in the II-III trimesters of pregnancy, there may be oligohydroamnion, arterial hypotension of the fetus and newborn, oliguria and lethal outcomes.
    It was reported on the development of angioedema in patients with fosinopril.When swelling of the tongue, throat or larynx, airway obstruction may develop with possible fatal outcome. If such reactions develop, patients should stop taking the drug and subcutaneously inject epinephrine (epinephrine) (1: 1000), as well as taking other emergency measures.
    During the administration of ACE inhibitors, edema of the intestinal mucosa was rarely observed. In such cases, patients complained of abdominal pain (with nausea and vomiting may not be), in some cases, edema of the intestinal mucosa appeared without edema of the face, the level of C1-esterases was normal. Symptoms disappeared after the cessation of the use of ACE inhibitors. Swelling of the intestinal mucosa should be taken into account in differential diagnosis in patients with complaints of abdominal pain while treating with ACE inhibitors.
    Against the background of therapy with ACE inhibitors, it is possible to develop anaphylactic reactions during hemodialysis through highly permeable membranes, as well as during LDL apheresis with adsorption to dextran sulfate. In such cases, the use of dialysis membranes of a different type or other medication should be considered.
    Perhaps the development of agranulocytosis and suppression of bone marrow function during treatment with ACE inhibitors. These cases are more common in patients with impaired renal function, especially in the presence of systemic connective tissue diseases (systemic lupus erythematosus or scleroderma). Before the beginning of therapy with ACE inhibitors and during the treatment, the total number of leukocytes and the leukocyte formula are determined (once a month for the first 3-6 months of treatment and in the first year of use in patients with an increased risk of neutropenia).
    When there is noticeable icterus and a marked increase in the activity of liver enzymes, treatment with fosinopril should be discontinued and appropriate treatment prescribed.
    In patients with hypertension with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, and also with the simultaneous use of diuretics without signs of renal vascular disease during treatment with ACE inhibitors, the concentration of blood urea nitrogen and serum creatinine may increase. These effects are usually reversible and pass after discontinuation of treatment.You may need to reduce the dose of a diuretic and / or fosinopril.
    Patients with uncomplicated form of hypertension may develop arterial hypotension due to the use of the drug fosinopril.
    Symptomatic arterial hypotension with the use of ACE inhibitors is most often developed in patients after intensive treatment with diuretics, a diet limiting the intake of salt, or in the conduct of renal dialysis. Temporary arterial hypotension is not a contraindication for the use of the drug after carrying out measures for hydration of the body.
    In patients with severe chronic heart failure, with altered RAAS activity, treatment with ACE inhibitors can cause an excessive antihypertensive effect, which can lead to oliguria, progressive azotemia and, in rare cases, acute renal failure with possible fatal outcome. Therefore, in the treatment of chronic heart failure with fosinopril, patients should be closely monitored, especially during the first 2 weeks of treatment, as well as with any increase in the dose of fosinopril or diuretic.
    Some reduction in systemic BP is a common and desirable effect at the beginning of the drug in heart failure. The degree of this decrease is maximal at early stages of treatment and stabilizes within 1-2 weeks from the beginning of treatment. BP usually returns to the values ​​of the period before the start of treatment without decreasing the therapeutic effectiveness.
    ACE inhibitors can enhance the antihypertensive effect of agents used for general anesthesia. Before surgery (including dentistry), a doctor should be warned about the use of ACE inhibitors.

    Effect on the ability to drive transp. cf. and fur:
    Care must be taken when driving vehicles or performing any work that requires increased attention due to possible dizziness, especially after the initial dose of the drug in patients taking diuretic medicines.

    Form release / dosage:
    Tablets of 10 mg and 20 mg.


    Packaging:
    For 7 or 10 tablets in a contour mesh package.
    For 1, 2, 3 or 4 contour squares with instructions for use in a pack of cardboard.
    Storage conditions:
    In the dark place at a temperature of no higher than 25 ° C.
    Keep out of the reach of children.

    Shelf life:
    2 years. Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002622
    Date of registration:15.09.2014
    The owner of the registration certificate:BIOKOM, CJSC BIOKOM, CJSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp25.10.2015
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