Fosinopril - instructions for use, doses, side effects, contraindications

auxiliary substances: glyceryl distearate - 1.50 mg; silicon dioxide colloidal - I 50 mg; sodium carboxymethyl starch - 3.00 mg; sodium stearyl fumarate - 3.00 mg; trehalose dihydrate 7.50 mg; cellulose microcrystalline - 123,50 mg.

1 tablet of 20 mg contains:

Active substance: fosinopril sodium - 20,00 mg.

auxiliary substances: glyceryl distearate - 3.00 mg; silicon dioxide colloid - 3.00 mg; sodium carboxymethyl starch - 6.00 mg; sodium cgearyl fumarate - 6.00 mg; trehalose dihydrate - 15.00 mg; cellulose microcrystalline - 247.00 mg.

Description:

Tablets 10 mg

Tablets are round, biconvex, white or almost white, with a risk on one side.

Tablets 20 mg

Tablets are round, biconvex, white or almost white in color, with a risk on one side and embossed in the form of the symbol "f" on the other side.

Pharmacotherapeutic group:inhibitor of angiotensin-converting enzyme (AIF)

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.09 Fosinopril

Pharmacodynamics:

Inhibitor of AIF. Fosinopril - an ester from which the active compound fospronylate is formed into the body of hydrolysis under the action of enzymes. Fosinopril, due to the specific bond of the phosphate group to the AIF. prevents the conversion of angiotensin I into a vasoconstrictor substance, angiotensin II, as a result of which the vasopressor activity and secretion of aldosterone are reduced. The latter effect can lead to an insignificant increase in the content of potassium ions in the blood serum (an average of 0.1 meq / L) with the simultaneous loss of sodium and liquid ions by the body.

Fosinopril inhibits the metabolic degradation of bradykinin, which has a powerful vasopressor effect, due to this antihypertensive effect of the drug can be enhanced.

Reduction of blood pressure (BP) is not accompanied by a change in the volume of circulating blood (BCC), cerebral and renal blood flow, blood supply to internal organs, skeletal muscles, skin,reflex activity of the myocardium. After oral administration, the anti-hypertensive effect develops within 1 hour reaches a maximum after 3-6 hours and lasts for 24 hours.

In heart failure, the positive effects of fosinopril are achieved mainly by suppressing the renin-angiotensin-aldosterone (RAAS) system. 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:

Suction

After ingestion, absorption from the gastrointestinal tract (GIT) is about 30-40%. The degree of absorption does not depend on the time of reception of the feed, but the rate of absorption can be slowed down. The maximum concentration (Cmax) of fosinoprilat in blood plasma is reached after 3 hours and does not depend on the dose taken.

Distribution

Binding to plasma proteins is more than 95%. Fosprenylat has a relatively small volume of distribution (Vd) and is slightly associated with the cellular components of the blood.

Metabolism

Fosinopril hydrolysis under the action of enzymes occurs mainly in the liver and mucous membrane of the gastrointestinal tract

Excretion

Fosinopril is excreted from the body in equal parts by the kidneys and through the liver. In arterial hypertension in patients with normal renal and hepatic function, the elimination period (T1 / 2) of fosinoprilat is about 11.5 hours. In heart failure, T1 / 2 is 14 hours.

Pharmacokinetics in special clinical cases

In patients with impaired renal function (glomerular filtration rate (GFR) 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. At the same time, absorption, bioavailability and binding to proteins are not significantly altered. Reduced excretion by the kidneys is compensated by increased excretion of the liver. A moderate increase in the area under the concentration-time curve (AUC) in blood plasma (less than half the battle with the norm) was observed in patients with renal insufficiency of various severity, including renal failure in the terminal stage (GFR less than 10 ml / min / 1 , 73 m2). The clearance of fosinoprilat in hemodialysis and peritoneal dialysis is on average 2% and 7% (in relation to the values of urea clearance), respectively.In patients with impaired liver function (with alcoholic or biliary cirrhosis), a decrease in the rate of hydrolysis of fosinopril is possible without significant changes in its degree. The total clearance of fosinoprilata from the body of such patients is approximately twice lower than in patients with normal liver function.

Indications:

Arterial hypertension - in monotherapy or in combination with other antihypertensive drugs (in particular, with thiazide diuretics).

Chronic heart failure - as part of combination therapy.

Contraindications:

increased sensitivity to fosinopril and other components of the drug;
angioedema in the anamnesis (including against the background of the use of other inhibitors of AMP);
pregnancy;
lactation period (breastfeeding);
age under 18 years (effectiveness and safety not established);
hereditary / idiopathic angioedema;
simultaneous use with aliskiren and aliskirene-containing drugs in patients with diabetes mellitus and / or moderate or severe renal dysfunction (GFR less than 60 ml / min / 1.73 m2) (see "Interactions with other drugs" and "Special instructions" ),

Carefully:

Applied with kidney failure; hyponatremia (risk of dehydration, arterial hypotension, chronic renal failure); bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; aortic stenosis; mitral stenosis; hypertrophic obstructive cardiomyopathy; condition after kidney transplantation; when carrying out desensitization; systemic diseases of connective tissue (including systemic lupus erythematosus, scleroderma) due to increased risk of developing neutropenia or agranulocytosis; hemodialysis; when cerebrovascular diseases (including cerebral circulatory insufficiency); ischemic heart disease; chronic heart failure III-IV functional class but the classification of NYHA; diabetes mellitus; oppression of bone marrow hematopoiesis; hyperkalemia; in elderly patients; at a gout, against a diet with restriction of table salt; at conditions accompanied by a decrease in BCC (including diarrhea, vomiting, previous treatment with diuretics); use in patients of the Negroid race (see section "Special instructions").

Pregnancy and lactation:

Fosinopril is contraindicated in pregnancy. For newborns whose mothers have been taking AMP inhibitors during pregnancy, careful monitoring is recommended for the timely detection of arterial hypotension, oliguria and hyperkalemia.

The use of the drug in the II and III trimesters of pregnancy causes damage or death of the developing fetus. Fosinonilate, which penetrates the placenta, is removed from the neonatal circulation by peritoneal dialysis with some positive clinical result and, theoretically, can be removed by exchange blood transfusion.

If pregnancy is established against ACE inhibitors, treatment should be stopped immediately and, if necessary, an alternative therapy should be prescribed that has an established safety profile during pregnancy. Patients undergoing therapy with ACE inhibitors and planning a pregnancy should also be prescribed alternative therapy.

Since fosinoprilat is excreted in breast milk, if necessary, the drug Fosinopril during lactation breastfeeding is discontinued.

Dosing and Administration:

Inside. The dosage of the drug should be selected individually.

Arterial hypertension

The recommended initial dose of the drug Fosinopril is 10 mg once a day. The dose should be selected depending on the dynamics of blood pressure lowering. The usual dose is from 10 mg to 40 mg once a day. In the absence of sufficient antihypertensive effect, additional prescription of diuretics is possible.

If the drug treatment Fosinopril begin against the background of ongoing therapy with a diuretic, 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 (1/2 tablet of 10 mg) 1 or 2 times a day. Depending on the therapeutic effectiveness, the dose can be increased with a weekly interval up to a maximum dose of 40 mg once a day.

Arterial hypertension and heart failure with impaired renal or hepatic function

Since the removal of the drug from the body occurs in two ways, lowering the doses to patients with impaired renal or hepatic function usually requires ns.

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, in connection with possible overdose phenomena.

Side effects:

The following classification of the World Health Organization is used to estimate the incidence of adverse events:

Very often (> 1/10)

Often (> 1/100 and <1/10)

Infrequently (> 1/1000 and <1/100)

Rarely (> 1/10 000 and <1/1000)

Very rarely (> 1/10 000)

The frequency is unknown (can not be calculated based on available data). From the cardiovascular system:

often - tachycardia, marked decrease in blood pressure, orthostatic collapse

infrequently - angina, myocardial infarction, palpitation, cardiac arrest, arrhythmia, cardiac conduction abnormalities, increased blood pressure, shock, sudden death;

rarely - "tides" of blood to the face skin, hemorrhage, peripheral vascular disease.

From the urinary system:

infrequently - renal failure, proteinuria;

Rarely - the pathology of the prostate (hyperpalasia, adenoma), polyuria, oliguria;

very rarely acute renal failure.

From the genitals and dairy glands:

infrequently, sexual dysfunction.

From the central and peripheral nervous system:

often - dizziness, headache;

infrequently, cerebral infarction, paresthesia, drowsiness, stroke, syncope, transient ischemic attack, tremor, sleep disturbance. depression, confusion;

rarely - memory impairment, dysphasia, disturbance of orientation, anxiety.

From the sense organs:

infrequently - hearing and visual impairment, noise in the ears, pain in the ears, a violation of taste.

From the digestive system:

often - nausea, vomiting, diarrhea;

infrequent - constipation, dry mouth. flatulence;

rarely - damage to the oral mucosa, pancreatitis, glossitis, bloating, dysphagia, hepatitis, cholestatic jaundice, abdominal pain, anorexia;

Seldom is an angioedema, (partial) intestinal obstruction, hepatic insufficiency.

From the respiratory system:

often - cough;

infrequently - shortness of breath, rhinitis, sinusitis, tracheobronchitis;

rare - bronchospasm, nasal bleeding, laryngitis / dysphonia, pneumonia, pulmonary infiltrates.

From the hematopoiesis:

infrequently - a temporary decrease in the concentration of hemoglobin, a decrease in hematocrit;

rarely - anemia, eosinophilia, leukopenia, lymphadenitis, her throes. thrombocytopenia;

very rarely - agranulocytosis.

From the musculoskeletal system:

infrequently - myalgia; rarely arthritis.

From the side of metabolism:

infrequently - decreased appetite, exacerbation of gout, hypercalism;

Allergic reactions:

often - skin rash, angioedema, dermatitis;

infrequently - a hyperhidrosis, a skin itch, a urticaria;

rarely - ecchymosis.

General disorders and disorders at the site of administration:

often - chest pain (non-cardiological), weakness;

infrequently - fever, peripheral edema;

rarely - weakness in one limb, viral infections.

From the laboratory indicators:

often - increased alkaline phosphatase activity, gynerbilirubinemia, increased lactate dehydrogenase activity, increased activity of "liver" transaminases; infrequently - an increase in body weight, increased urea concentration in the blood, hyperkreatiinemia, hyperkalismia; rarely - hyponatremia.

Influence on the fetus: impaired fetal kidney development, decreased fetal and newborn blood pressure,renal dysfunction, hyperkalemia, hypoplasia of the skull bones, oligohydramnion, limb contractures, lung hypoplasia.

There have been reports of various symptom complexes that manifest themselves or in combination of the following symptoms: fever, myalgia, arthralgia / arthritis, increased titer for antinuclear antibodies, increased erythrocyte sedimentation rate, eosinophilia and leukocytosis, skin rash, photosensitivity, or other dermatological reactions.

With simultaneous use of ACE inhibitors. in t.ch. fosinopril, patients receiving the drug gold (sodium aurotomy malate) in / in. describes a symptom complex that includes flushing of the facial skin, nausea, vomiting and a decrease in blood pressure.

Overdose:

Symptoms: marked decrease in blood pressure, bradycardia, shock, disturbance of water-electrolyte balance, acute renal failure, stupor.

Treatment: the drug should be discontinued, gastric lavage, intake of sorbents (eg activated carbon), vasopressor agents, infusion of 0.9% sodium chloride solution and further symptomatic and supportive treatment.

The use of hemodialysis is ineffective.

Interaction:

Simultaneous use of antacids (including aluminum hydroxide, magnesium hydroxide, simethicone) can reduce the absorption of fosinopril (fosinopril and these preparations should be taken with an interval of less than 2 h).

In patients receiving fosinopril simultaneously with lithium salts, it is possible to increase the concentration of lithium in blood plasma and the risk of lithium intoxication (simultaneously apply with caution).

When prescribing fosinopril, it should be borne in mind that ipmedometacin and other non-heroin anti-inflammatory drugs (incl. acetylsalicylic acid (more than 3 g / day)) can reduce the antihypertensive effect of ACE inhibitors, especially in patients with low-grade hypertension.

When the joint application of fosinopril with diuretics or in combination with a strict diet, limiting salt intake, dialysis or may develop severe arterial hypotension, particularly in the first hour after taking the initial dose of fosinopril.

When the joint application of fosinopril with potassium preparations, diuretics kaliysbsregayuschimi (including with amiloride, spironolactone, eplerenone (a derivative of spironolactone), triamterene), with food supplements containing potassium, increases the risk of hyperkalemia.In patients with heart failure, diabetes mellitus, concomitantly taking potassium-sparing diuretics, potassium, calgary substitutes for edible salt, or other agents that cause gyerculochemia (eg, heparin), ACE inhibitors increase the risk of an increase in serum potassium.

Fosinopril enhances the hypoglycemic effect of derivatives of sulfonylmachine, insulin.

With simultaneous use with allopurinol, cytostatic agents, immunosuppressants, procainamide, there is a risk of developing leukopenia.

Estrogens weaken the antihypertensive effect of fosinopril because of its ability to retain fluid.

Hypotensive drugs, oioid analgesics, medicines for general anesthesia increase the antihypertensive effect of fosinopril.

Bioavailability of fosinopril with simultaneous application with chlorthalidone, nifediline, 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 that affects 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:

Before the beginning of treatment it is required to conduct an analysis of previous antihypertensive therapy, the degree of increase in blood pressure, restriction of ration for salt and / or fluid and other clinical circumstances.

If possible, discontinue previous antihypertensive treatment several days before the start of treatment with Fosinopril.

To reduce the likelihood of developing arterial hypotension, diuretics should be discontinued 2-3 days before the start of treatment with Fosinopril. Before and during treatment, it is necessary to monitor blood pressure.the function of the kidneys, the content of potassium ions, creatinine, urea, the content of electrolytes and the activity of "hepatic" enzymes in the blood.

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. In case of development of such reactions, patients should stop taking the drug and take emergency measures, including. subcutaneous injection of epinephrine (adrenaline) solution (1: 1000).

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, the edema of the intestinal mucosa appeared without a face stack, the level of Cl-esterases was normal. Symptoms disappeared after the cessation of the use of ACE inhibitors. Intestinal edema of the intestine should be taken into account in the diphtheria diagnosis in patients with complaints of abdominal pain while treating with ACE inhibitors.

Against the background of therapy with ACE inhibitors, anaphylactic reactions may develop during hemodialysis through highly permeable membranes, as well as during apheresis of low density lipoproteins with adsorption to dextran should consider the possibility of using dialysis membranes of a different type or drug treatment.

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 (si: dark red 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).

Patients with uncomplicated form of arterial hypertension may develop arterial hypotension due to the use of the drug Fosinopril. Symptomatic arterial hypotension with ACE inhibitors most often develops in patients after intensive treatment with diuretics, diets with restriction of table 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 chronic heart failure, treatment with ACE inhibitors may cause an excessive antihypertensive effect, which can lead to oliguria or azotemia with a legal outcome. Therefore, in the treatment of chronic heart failure, fosinopril should carefully monitor patients, especially during the first 2 weeks of treatment, as well as with any increase in the dose of fosinoyril or diuretic.

It may be necessary to reduce the dose of diuretic in patients with hyponatremia and patients previously intensively treated with diuretics. Transient arterial hypotension is not a contraindication for the further administration of the drug Fosinopril. 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.

If there is a noticeable icterus and a marked increase in the activity of enzymes penes, the treatment with fosinopril should be discontinued and appropriate treatment should be prescribed.

In patients with arterial gingertenzie with bilateral 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 can increase. These effects are usually reversible and pass after discontinuation of treatment. May require a reduction in the dose of a diuretic and / or fosinopril.

In patients with severe chronic heart failure, with altered activity of RAAS, treatment with ACE inhibitors can lead to oliguria, progressive azotemia, and in rare cases to acute renal failure and a possible fatal outcome.

Like other preparations of the ACE inhibitor group, Fosinopril should be used with caution in patients with mitral and aortic stenosis, as well as with hypertrophic obstructive cardiomyopathy.

ACE inhibitors can increase the anti-hypersensitivity effect of the agents used for general anesthesia. Before surgery (including dentistry), a doctor should be warned about the use of ACE inhibitors.Care should be taken when doing physical exercises or in hot weather because of the risk of dehydration and arterial hypotension due to the bovine plaque.

Based on 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 blood glucose concentrations, especially during the first month of therapy with an ACE inhibitor.

There is evidence that simultaneous use of ACE inhibitors, ARA II or aliskiren increases the risk of hypotension, hyperkalemia and reduces kidney function (including causing acute kidney failure). In this regard, the double blockade of RAAS by the simultaneous use of ACE inhibitors. ARA II or aliskiren is not recommended. If therapy with double blockade of RAAS is considered necessary, treatment should be performed under the supervision of a specialist with regular monitoring of kidney function,the content of electrolytes and AD - The use of ACE inhibitors and ARAP in patients with diabetic nephropathy is not recommended.

Fosinopril (like other ACE inhibitors) has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races.

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

Care must be taken when driving a vehicle or doing other work that requires increased attention, because possibly the development of dizziness, especially after taking the initial dose of an ACE inhibitor in patients taking diuretics.

Form release / dosage:

Tablets 10 mg, 20 mg.

Packaging:

For 10 or 15 tablets in a contour mesh box made of 11VX film and aluminum foil printed lacquered.

1. 2, 3, 5. 6 or 9 contiguous cell packs but 10 tablets or 2, 4 or 6 contiguous cell packs of 15 tablets together with instructions for use are placed 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 Goth.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003197

Date of registration:16.09.2015

The owner of the registration certificate:IZVARINO PHARMA, LLC IZVARINO PHARMA, LLC Russia

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Representation: & nbspIZVARIN PHARMA LLC IZVARIN PHARMA LLC Russia

Information update date: & nbsp25.10.2015

Illustrated instructions

Instructions

Fosinopril (Fosinopril)