Fosinopril, 30 pcs., 10 mg, tablets

Release form and composition

Dosage form of Fozinopril - tablets: flat-cylindrical, white or almost white, with chamfers on both sides and a score on one side - for dosages of 5 and 10 mg; with a cross-shaped mark on one side - for a dosage of 20 mg (10, 14, 25 or 50 pcs. in blister packs, in a cardboard box 1, 2, 3 or 10 packs; 10, 20, 30, 40, 50 or 100 tablets in a jar, 1 jar in a cardboard box).

Composition of 1 tablet:

• active substance: fosinopril sodium – 5/10/20 mg;
• auxiliary components: lactose, microcrystalline cellulose, croscarmellose sodium, povidone-K25, colloidal silicon dioxide, sodium stearyl fumarate.

Fosinopril

Active substance:

Fosinopril*

Pharmgroup:

ACE inhibitors

Average price in pharmacies

Pharmacological properties

Pharmacodynamics

Fosinopril is an ACE inhibitor with hypotensive, diuretic, vasodilating, and potassium-sparing properties. It prevents the transformation of angiotensin I into angiotensin II, and, as a result, reduces systemic blood pressure (BP) and total peripheral vascular resistance, inhibits aldosterone replication, and inhibits tissue ACE.

In addition, the drug inhibits the metabolism of bradykinin, which has a powerful vasodilator effect.

When taking Fosinopril, a decrease in blood pressure occurs without a decrease in circulating blood volume (CBV), renal, cerebral circulation, blood supply to skeletal muscles, internal organs, skin, as well as reflex contraction of the myocardium.

Treatment of hypertension in left ventricular dystrophy leads to a decrease in its mass, as well as a narrowing of the septal wall. Long-term treatment does not lead to metabolic disorders.

After taking Fosinopril, the hypotensive effect occurs after 1 hour, the maximum effectiveness of the drug is achieved after 3-6 hours. The duration of exposure to a single dose is 24 hours.

Pharmacokinetics

Absorption of fosinopril is 36% and does not depend on food intake. In the liver and mucous membrane of the gastrointestinal tract (GIT), hydrolysis of the drug occurs with the release of fosinoprilat. The time to reach the maximum concentration of the substance is 3 hours. Its half-life (T1/2) is 11 hours.

Communication with plasma proteins is 95%. Fosinopril penetrates the blood-brain barrier. Excreted from the body with urine and bile.

Pharmacokinetics

After oral administration, absorption of the drug is approximately 30-40%. The extent of absorption is independent of food intake, but the rate of absorption may be slow.

The hydrolytic conversion of fosinopril under the action of esterases into fosinoprilat occurs mainly in the liver. If liver function is impaired, the rate of hydrolysis may be slowed down, but the degree of conversion does not change noticeably. The maximum concentration in blood plasma is reached after approximately 3 hours and does not depend on the dose taken. Fosinoprilat is 95% bound to blood proteins, has a relatively small volume of distribution and is only slightly bound to cellular components of the blood.

Fosinopril is eliminated from the body equally through the liver and kidneys. In hypertensive patients with normal renal and hepatic function, the half-life of fosinoprilat is approximately 11.5 hours. In patients with heart failure, the half-life is 14 hours. The clearance of fosinoprilat during hemodialysis and peritoneal dialysis averages 2% and 7%, respectively, relative to the clearance values ​​of urea.

In patients with impaired renal function (creatinine clearance <80 ml/min/1.73 m2), the total clearance of fosinoprilat from the body is approximately half that of patients with normal renal function. While absorption, bioavailability and protein binding are not noticeably altered. Reduced excretion through the kidneys is compensated by increased excretion through the liver. A moderate increase in plasma AUC values ​​(the area under the plasma concentration-time curve after administration of a 1 mg dose) (less than twice the normal value) was observed in patients with varying degrees of renal failure, including end-stage renal failure (clearance creatinine < 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 fosinoprilat from the body of such patients is approximately half that of patients with normal liver function.

In men aged 65 to 74 years with clinically normal renal and liver function, there are no noticeable differences in the pharmacokinetic parameters of fosinoprilat compared to young patients (20-35 years old). Fosinopril is found in breast milk.

Contraindications

Absolute:

• angioedema – idiopathic, or hereditary (as well as having occurred in the past and associated with the use of ACE inhibitors);
• galactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• combined use with aliskiren and aliskiren-containing drugs in patients with impaired renal function (glomerular filtration rate less than 60 ml/min/1.73 m2) and diabetes mellitus;
• age under 18 years;
• pregnancy and lactation;
• increased sensitivity to the components of Fosinopril, as well as other ACE inhibitors.

Relative contraindications:

• aortic stenosis;
• cerebro- and cardiovascular pathologies (coronary heart disease, insufficiency of cerebral blood supply, coronary insufficiency);
• systemic autoimmune connective tissue diseases in a severe stage (including scleroderma, systemic lupus);
• inhibition of hematopoiesis;
• hyperkalemia;
• hyponatremia (due to the risk of arterial hypotension, dehydration, chronic renal failure);
• diabetes;
• bilateral renal artery stenosis or stenosis of the artery of a single kidney;
• condition after kidney transplantation;
• gout, low sodium diet;
• renal/liver failure;
• chronic heart failure (III-IV functional class according to the NYHA classification);
• conditions leading to a decrease in circulating blood volume (including vomiting, diarrhea);
• conducting desensitization programs;
• hemodialysis using high-flow membranes;
• low-density lipoprotein apheresis;
• elderly age.

Instructions for use of Fozinopril: method and dosage

Fosinopril tablets are intended for oral administration.

Recommended dosage according to indications:

• arterial hypertension: the initial dose is 10 mg/day for 1 dose. Next, the dose is adjusted depending on the dynamics of the decrease in blood pressure, and is usually 10–40 mg/day per dose. In case of insufficient antihypertensive effect, the combined use of diuretics is possible when fosinopril is started against the background of diuretic therapy, its initial dose should not exceed 10 mg/day with regular medical monitoring of the patient's condition. The maximum recommended dose of the drug is 40 mg;
• chronic heart failure (CHF): the initial dose is 5 mg 1 or 2 times a day; when the patient tolerates the drug well, the dose is gradually increased to 40 mg/day at a time (the interval between dose increases should be at least a week). Treatment should begin under the supervision of a doctor.

Pharmacodynamics

The active substance of the drug Fozinopril VIVA PHARM - fosinopril - is an ester, which is hydrolyzed in the body under the action of esterases into the active compound fosinoprilat. Fosinopril, due to the specific connection of the phosphinate group with ACE, prevents the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, as a result of which vasopressor activity and aldosterone secretion are reduced. The latter effect can lead to a slight increase in the content of potassium ions in the serum (average 0.1 mEq/L) with a simultaneous loss of sodium ions and fluid from the body.

Fosinopril suppresses the metabolic degradation of bradykinin peptide, which has a powerful vasodepressor effect; Due to this, the antihypertensive effect of the drug may be enhanced.

In heart failure, the positive effects of the drug Fosinopril are achieved mainly through suppression of the renin-aldosterone system. Suppression of angiotensin-converting enzyme leads to a decrease in both preload and afterload on the myocardium. The drug improves symptoms and increases exercise tolerance, reduces the severity of heart failure and reduces the frequency of hospitalizations for heart failure.

Side effects

• lymphatic system and hematopoietic system: transient decrease in hemoglobin and hematocrit, leukopenia, eosinophilia, neutropenia, thrombocytopenia, lymphadenopathy, transient anemia, agranulocytosis;
• metabolism: exacerbation of gout, loss of appetite, hyperkalemia;
• central nervous system (CNS): headache, dizziness, mood lability, sleep disturbance, paresthesia, depression, drowsiness, tremor, taste disturbances, sleep disturbances, confusion, memory and speech disturbances, disorientation, anxiety, inappropriate behavior, imbalance, ischemia brain, hemorrhagic stroke;
• organ of vision: visual impairment;
• cardiovascular system: tachycardia, orthostatic hypotension, marked decrease in blood pressure, angina pectoris, arrhythmia, increased blood pressure, shock, peripheral edema, transient ischemia, hemorrhage, flushing of the facial skin, peripheral circulatory disorders, hypertensive crisis;
• respiratory system: dry cough, rhinitis, pharyngitis, shortness of breath, tracheobronchitis, sinusitis, pneumonia, bronchospasm, pulmonary infiltrates, nosebleeds, laryngitis, dysphonia, chest pain;
• digestive system: diarrhea, abdominal pain, nausea, vomiting, dry oral mucosa, constipation, taste disturbance, loss of appetite, pancreatitis, stomatitis, dysphagia, intestinal obstruction, angioedema of the intestine;
• liver and biliary tract: hepatitis, liver failure;
• skin and subcutaneous tissues: dermatitis, skin rash, angioedema, increased sweating, itching, urticaria, exfoliative dermatitis, ecchymosis;
• musculoskeletal system: myalgia, arthralgia, convulsions, arthritis, muscle weakness;
• urinary system: urinary disorders, proteinuria, development or worsening of symptoms of chronic renal failure, acute interstitial nephritis, acute renal failure;
• reproductive system: sexual dysfunction, prostate disorders;
• infectious and parasitic diseases: upper respiratory tract infections, viral infections;
• other: weakness, pain of unknown localization, fever, weight gain, sudden death;
• laboratory parameters: increased activity of liver transaminases, lactate dehydrogenase and alkaline phosphatase; hyperbilirubinemia, increased urea concentration, hypercreatininemia, hyperkalemia, slight increase in hemoglobin, hyponatremia, decreased hematocrit, hyponatremia.

Side effects of the drug Fozinopril

from the digestive system: rarely - nausea, vomiting, dyspepsia, increased activity of liver transaminases; cases of pancreatitis and hepatitis have been described; from the respiratory system: cough, rarely - pharyngitis, laryngitis, sinusitis, bronchospasm; from the cardiovascular system: palpitations, chest pain, rarely - orthostatic hypotension, collapse, hot flashes, arrhythmia; allergic and immunological reactions - skin rash, itching, photosensitivity, angioedema, myalgia, arthralgia; from the urinary system - proteinuria, oliguria, disorders of excretory function, accompanied by an increase in the concentration of creatinine and urea in the blood plasma; other reactions - dizziness, fatigue, impaired taste and other types of sensitivity.

Overdose

Symptoms of an overdose of Fosinopril: marked decrease in blood pressure, cough, dizziness, anxiety, bradycardia, renal failure, water and electrolyte imbalance, tachycardia, temporary hyperventilation, stupor.

Treatment is carried out in a hospital setting, in the intensive care ward. Monitoring of electrolytes and creatinine levels is required. Within 30 minutes after taking the drug, you should perform a gastric lavage and start taking adsorbents and sodium sulfate. If there is a pronounced decrease in blood pressure, place the patient horizontally, raise the legs, and administer 0.9% sodium chloride solution and catecholamines intravenously. For bradycardia, atropine administration is required; in some cases, an artificial pacemaker may be required. Dialysis and peritoneal dialysis are ineffective.

special instructions

It is advisable to stop previously administered antihypertensive therapy several days before starting fosinopril. In a hospital setting, it should be started in patients with malignant arterial hypertension or concomitant decompensation of chronic heart failure. It is recommended to stop taking diuretics 2-3 days before starting fosinopril therapy. Before and during therapy, monitoring of renal function, creatinine, urea, blood pressure and electrolyte levels, and liver enzyme activity is necessary.

While taking Fozinopril, caution should be exercised during increased physical activity, as well as in hot weather, due to the increased risk of dehydration and hypotension.

Conditions encountered when taking ACE inhibitors:

• angioedema of the limbs, face, lips, tongue, mucous membranes, pharynx, larynx: this condition is usually reversible when the drug is stopped, but in some cases it can lead to airway obstruction and possibly death. Immediate discontinuation of the drug and symptomatic measures are recommended, for example, subcutaneous administration of a solution of epinephrine (adrenaline) (1:1000);
• swelling of the intestinal mucosa: symptoms disappear after discontinuation of the drug. Sometimes swelling of the intestinal mucosa occurs without nausea, vomiting and facial swelling, while C1-esterase activity is normal; its only symptom may be abdominal pain;
• anaphylactic reactions during dialysis using high-permeability membranes, and during apheresis of low-density lipoproteins with adsorption on dextran sulfate: it is advisable to consider the possibility of using dialysis membranes of a different type and the use of antihypertensive drugs of a different class;
• anaphylactic reactions during desensitization: desensitization should be carried out with extreme caution in patients taking ACE inhibitors; if signs of an anaphylactoid reaction appear, their use should be stopped immediately;
• neutropenia/agranulocytosis: it is recommended to monitor the number of leukocytes and leukocyte formula once a month at the beginning of treatment, especially in patients with impaired renal function, in the presence of systemic connective tissue diseases (systemic lupus erythematosus or scleroderma);
• arterial hypotension: most often occurs when diuretics are used along with ACE inhibitors, a diet with limited salt intake, and also during dialysis. After measures have been taken to restore circulating blood volume, the drug can be continued; a reduction in the dose of the diuretic may be necessary. In patients with CHF, taking ACE inhibitors can cause an excessive antihypertensive effect, which can lead to the development of oliguria and azotemia, as well as, in some cases, acute renal failure with a fatal outcome, and therefore this group of patients requires careful monitoring in the first 2 weeks taking Fosinopril, as well as with any increase in dose. However, a slight decrease in blood pressure when starting to take ACE inhibitors is normal for patients with CHF. Usually blood pressure returns to normal within 1–2 weeks without reducing the therapeutic effectiveness of the drug;
• hyperkalemia: when taking ACE inhibitors, there have been cases of increased potassium levels in the blood, especially in patients with renal failure, type 1 diabetes, in patients taking potassium-sparing diuretics or drugs that increase potassium levels in the blood serum (heparin, etc.);
• cough: taking ACE inhibitors can cause a persistent, non-productive cough that goes away on its own after discontinuation of the drug;
• general anesthesia, surgical operations: it is possible to enhance the antihypertensive effect of drugs used for general anesthesia, and therefore the surgeon and anesthesiologist should be warned about taking ACE inhibitors.

Impact on the ability to drive vehicles and complex mechanisms

Caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require rapid psychomotor reactions due to the risk of side effects, such as dizziness.

Special instructions for the use of the drug Fozinopril

Prescribe with caution to patients with renovascular hypertension, heart failure, patients on hemodialysis, as well as patients with hypovolemia and/or reduced plasma osmolarity of any etiology due to the increased risk of developing side effects from the kidneys. In order to reduce the risk of arterial hypotension, diuretics should be discontinued 2-3 days before fosinopril is prescribed and the water and electrolyte balance should be corrected. In patients with left ventricular hypertrophy, long-term use of fosinopril leads to a decrease in left ventricular mass and a decrease in the thickness of the interventricular septum. After discontinuation of fosinopril, no withdrawal syndrome (sharp increase in blood pressure) is observed. The safety and effectiveness of fosinopril in pediatric practice has not been established. No special adjustment of the fosinopril dosage regimen is required in elderly patients. Women of reproductive age receiving fosinopril should use reliable contraception.

Use during pregnancy and lactation

The use of Fosinopril during pregnancy is contraindicated due to its teratogenic and fetotoxic effects. If pregnancy occurs while taking the drug, it should be stopped immediately and switched to an alternative treatment that is safe during pregnancy. The patient should be informed of the risk to the fetus, and a thorough ultrasound examination should be performed to identify fetal abnormalities.

In newborns whose mothers took ACE inhibitors during pregnancy, oliguria, arterial hypotension, and hyperkalemia were observed.

If it is necessary to take Fozinopril during lactation, breastfeeding should be discontinued.

Instructions:

Clinical and pharmacological groups

01.024 (ACE inhibitor) 01.048 (Antihypertensive drug)

pharmachologic effect

ACE inhibitor. It is a prodrug from which the active metabolite fosinoprilat is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II, which is a powerful vasoconstrictor. As a result of a decrease in the concentration of angiotensin II, a secondary increase in plasma renin activity occurs due to the elimination of negative feedback during the release of renin and a direct decrease in aldosterone secretion. In addition, fosinoprilat appears to have an effect on the kinin-kallikrein system, inhibiting the breakdown of bradykinin.

Thanks to its vasodilating effect, it reduces roundabout percentage (afterload), wedge pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases cardiac output and exercise tolerance.

Pharmacokinetics

When taken orally, it is slowly absorbed from the gastrointestinal tract. Taking with food may reduce the rate, but not the extent, of absorption. Metabolized in the liver and in the mucous membrane of the gastrointestinal tract by hydrolysis with the formation of fosinoprilat, due to the pharmacological activity of which a hypotensive effect is realized. The binding of fosinoprilat to plasma proteins is 97-98%. T1/2 of fosinoprilat is 11.5 hours. It is excreted by the kidneys - 44-50% and through the intestines - 46-50%.

Dosage

When taken orally, the initial dose is 10 mg 1 time/day. In the future, the dose is set depending on the dynamics of blood pressure; if necessary, the dose can be increased to 20-40 mg 1 time / day. When prescribed during diuretic therapy, the initial dose of fosinopril should be no more than 10 mg (with careful medical monitoring of the patient's condition).

The maximum daily dose when taken orally is 80 mg.

Drug interactions

When used simultaneously with antacids, the absorption of fosinopril may be increased.

When used simultaneously with antihypertensive drugs, the antihypertensive effect may be enhanced.

When used simultaneously with diuretics, severe arterial hypotension may develop.

When used simultaneously with potassium-sparing diuretics and potassium preparations, it is possible to increase the concentration of potassium in the blood plasma.

When used simultaneously with lithium carbonate, it is possible to increase the concentration of lithium in the blood plasma and increase the risk of developing intoxication.

When used simultaneously with drugs used in anesthesia and analgesics, the antihypertensive effect may be enhanced.

When used simultaneously with acenocoumarol, a case of bleeding has been described.

When used simultaneously with indomethacin and other NSAIDs (acetylsalicylic acid), the effectiveness of ACE inhibitors may decrease.

Use during pregnancy and lactation

Use during pregnancy is contraindicated. Fosinopril is excreted in breast milk. If it is necessary to use fosinopril during lactation, the issue of stopping breastfeeding should be decided. During treatment, women of childbearing age should use reliable contraception.

Side effects

From the cardiovascular system: palpitations, chest pain, orthostatic arterial hypotension, fainting, hot flashes, arrhythmias.

From the digestive system: nausea, vomiting, dyspeptic symptoms, increased activity of liver transaminases, pancreatitis, hepatitis.

From the side of the central nervous system: dizziness, feeling of fatigue, disturbance of taste and other types of sensitivity.

From the urinary system: proteinuria, oliguria, increased concentrations of creatinine and urea in the blood plasma.

From the respiratory system: cough, pharyngitis, sinusitis, bronchospasm are possible.

From the musculoskeletal system: myalgia, arthralgia.

Allergic reactions: skin rash, itching, photosensitivity, angioedema.

Indications

Arterial hypertension (including in the form of monotherapy).

Contraindications

Pregnancy, lactation (breastfeeding), increased sensitivity to ACE inhibitors.

special instructions

Use with caution in cases of renovascular hypertension, heart failure, hyperkalemia, a history of angioedema, hypovolemia and/or reduced plasma osmolarity of various etiologies, as well as in patients on hemodialysis. 2-3 days before starting treatment with fosinopril, it is recommended to discontinue previous diuretic therapy, with the exception of patients with malignant or difficult-to-treat hypertension. In such cases, fosinopril therapy should be started immediately, at a reduced dose, with close medical supervision and careful dose escalation.

In patients with left ventricular hypertrophy, long-term use of fosinopril leads to a decrease in left ventricular mass and a decrease in the thickness of the interventricular septum. After discontinuation of fosinopril, no sharp increase in blood pressure was observed.

No special adjustment of the fosinopril dosage regimen is required in elderly patients. Safety of use in children has not been established.

Impact on the ability to drive vehicles and operate machinery

Caution is required when driving vehicles or performing other work that requires increased attention, because Dizziness may occur, especially after the initial dose of fosinopril.

Drug interactions

• Antacids: reduce the absorption of fosinopril. It is recommended to maintain an interval between taking these drugs of at least 2 hours;
• lithium salts: the risk of developing lithium intoxication increases, and therefore, when taking them together, careful monitoring of the lithium content in the blood serum is necessary;
• nonsteroidal anti-inflammatory drugs (NSAIDs) (indomethacin, acetylsalicylic acid at a dose of 3 g/day or more, selective cyclooxygenase-2 inhibitors): can reduce the antihypertensive effect of fosinopril, especially in patients with arterial hypertension and low renin activity in the blood plasma. In patients over 65 years of age, with hypovolemia and impaired renal function, these drugs can lead to deterioration of renal function, including acute renal failure, and therefore patients taking NSAIDs and fosinopril need careful monitoring of renal function;
• diuretics, low-salt diet, dialysis: risk of a pronounced decrease in blood pressure, especially in the first hour after taking the initial dose of the drug;
• potassium-sparing diuretics containing trimethoprim: the risk of hyperkalemia increases;
• mTOR enzyme inhibitors (temsirolimus, sirolimus, everolimus): the risk of angioedema increases;
• sulfonylurea derivatives, insulin: their hypoglycemic effect increases;
• allopurinol, cytotoxic drugs, immunosuppressants, procainamide: risk of developing leukopenia;
• estrogens: reduce the antihypertensive effect of fosinopril;
• drugs for general anesthesia, antihypertensive drugs, narcotic analgesics: enhance the antihypertensive effect of fosinopril;
• chlorthalidone, nifedipine, propranalol, hydrochlorothiazide, cimetidine, metoclopramide, propantheline bromide, digoxin, warfarin: do not affect the bioavailability of fosinopril;
• Aliskiren: Concomitant use is contraindicated in patients with diabetes mellitus and moderate to severe renal impairment. Prescribing these drugs in combination is allowed only in individual cases, and with regular monitoring of renal function.