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

ACE inhibitor. 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 into angiotensin II, which is a potent vasoconstrictor. As a result of a decrease in angiotensin II concentration, a secondary increase in plasma renin activity occurs due to elimination of negative feedback during the release of renin and a direct decrease in aldosterone secretion.In addition, fosinoprilat, apparently, has an effect on the kinin-kallikrein system, preventing the breakdown of bradykinin.

Due to the vasodilator effect, reduces the overall peripheral resistance of the vessels (afterload), wedging pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases the minute volume of the heart and tolerance to the load.

After taking a single dose, the hypotensive effect reaches a maximum after 4-6 hours and lasts 24 hours (provides 24-hour blood pressure monitoring). Does not affect (in contrast to enalapril) the activity of neutral endopeptidase, which catalyzes, in particular, the cleavage of neurokinin A (one of the factors causing the appearance of dry cough) to inactive peptides.

Pharmacokinetics:After oral administration, it is slowly absorbed from the digestive tract. Admission with food can slow down, but not the degree of absorption. Metabolized in the liver and in the mucous membrane of the gastrointestinal tract by hydrolysis with the formation of fosinoprilata, due to pharmacologicalth activity of which hypotensive action is realized. The binding of fosinoprilata to plasma proteins is 97-98%.Fosinoprilat half-life is 11.5 hours. It is excreted by the kidneys - 44-50% and through the intestine - 46-50%.

Indications:Arterial hypertension (mono- and combination therapy), heart failure (auxiliary treatment).

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

IX.I10-I15.I15 Secondary Hypertension

IX.I30-I52.I50.9 Heart failure, unspecified

Contraindications:Hypersensitivityhypotension, severe renal failure, severe hyperkalemia, pregnancy, breast-feeding, lactose intolerance, lactase deficiency and glucose-galactose syndromemalabsorption, hereditary or idiopathic angioedemaedema, angioedemaedema on the background of treatment with ACE inhibitors in history, age under 18 years (safety and efficacy have not been studied), simultaneous use with aliskiren and aliskirenwith drugs in patients with diabetes mellitus and / or moderate and severe renal impairment (creatinine clearance less than 60 mL / min).

Carefully:Risk-benefit ratio evaluation is necessary in the following cases: severe autoimmune disease (systemic lupus erythematosus, scleroderma and other systemic collagenoses), bone marrow depression (leukopenia, thrombocytopenia), impaired cerebral or coronary circulation, severe heart failure, obliterating atherosclerosis of the lower limbs; aortic, mitral stenosis or other obstructive changes that hinder the flow of blood from the heart; diabetes mellitus, severe renal failure (serum creatinine level above 300 μmol / L) or hyperkalemia (more than 5.5 mmol / l), hyponatremia or sodium restriction in the diet, dialysis procedures, anesthesia and surgical interventions, dehydration, bilateral stenosis of the kidneys arteries or stenosis of the artery of a single kidney, the presence of a transplanted kidney, cirrhosis of the liver, hepatitis, chronic obstructive pulmonary disease, children (safety and efficacy not identified) and advanced age.

Pregnancy and lactation:

Contraindicated in pregnancy. Action category for the fetus by FDA - D.

For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

When administered orally, the initial dose is 10 mg once a 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 once a day.When administered with diuretics, the initial dose of fosinopril should not exceed 10 mg (with careful medical monitoring of the patient's condition).

The maximum daily intake for oral administration is 80 mg.

Side effects:

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): palpitation, arrhythmia, chest pain, angina pectoris, rhythm disturbances, myocardial infarction, orthostatic hypotension, hypertensive crisis, fainting, flushing of the face; sudden death, cardiopulmonary insufficiency, cardiogenic shock, brady or tachycardia (with heart failure); anemia (hemolytic and aplastic), a decrease in the level of hemoglobin or a decrease in hematocrit, leukocytosis, leuko- or neutropenia, thrombocytopenia, eosinophilia.

From the nervous system and sensory organs: asthenia, weakness, headache, dizziness, syncope, cerebrovascular disorders, tremor, paresthesia, mood and / or sleep, vision and memory disorders.

From the side organs of the digestive tract: dry mouth, impaired taste, decreased appetite, stomatitis, dysphagia, dyspepsia, nausea, vomiting, diarrhea / constipation, abdominal pain,pancreatitis, impaired liver function (cholestatic jaundice, fulminant liver necrosis with fatal outcome), change in the level of transaminases.

From the side skin integument: photosensitivity, urticaria, rash, itching, exfoliative dermatitis, bulez pemphigus and other hypersensitivity reactions.

From the side genitourinary system: edema, proteinuria, oliguria, renal failure, anuria.

From the side respiratory system: cough, rhinitis, sinusitis, laryngitis, pharyngitis, tracheobronchitis, bronchospasm.

From the side musculoskeletal system: myalgia, arthralgia, arthritis, convulsions.

Other: weight loss, fever, chills, development of infections, lymphadenopathy, hyperhidrosis, angioedema, increased concentration of creatinine, urea, hyperkalemia, hyponatremia, weakening of libido, impotence.

Overdose:

Symptoms: acute arterial hypotension, bradycardia, shock, disturbance of water-electrolyte balance, acute renal failure, stupor.

Treatment: reduction of dose or complete withdrawal of the drug; gastric lavage, transfer of the patient to a horizontal position with raised legs, the introduction of adsorbents and sodium sulfate within 30 minutes after ingestion.Carrying out measures to increase the volume of circulating blood (introduction of physiological solution, transfusion of other blood-substituting fluids), symptomatic therapy: epinephrine (subcutaneously or intravenously), antihistamines, hydrocortisone (intravenously).

Interaction:

Allopurinol. Increases (mutually) the risk of neutropenia. Against the background of allopurinol, the probability of Stevens-Johnson syndrome increases.

Acetylsalicylic acid reduces hyponatremic and hypotensive effects of fosinopril (a consequence of inhibition of prostaglandin synthesis in the kidneys with a decrease in renal blood flow and sodium and liquid retention).

Bumetanide with simultaneous use increases the hypotensive effect of fosinopril. Sharing fosinopril and bumetanide in combination with a strict diet that limits salt intake or with dialysis can lead to a marked decrease in blood pressure, especially in the first hour after taking the initial dose of fosinopril.

Verapamil. With simultaneous application verapamil enhances the hypotensive effect of fosinopril.

Hydrochlorothiazide. Strengthens (mutually) the effect.

Digoxin. Bioavailability of fosinopril with simultaneous application with digoxin does not change.

Ibuprofen. With simultaneous application ibuprofen can reduce the antihypertensive effect of fosinopril, especially in patients with hypertension and / or low renin level in the blood plasma.

Indapamide. Strengthens (mutually) the hypotensive effect, reduces the loss of potassium.

Ketorolac. Against the background of ketorolac, the hypotensive effect is weakened (due to the inhibition of renal prostaglandins with decreased renal blood flow and sodium and liquid retention), the risk of impairment of renal function is increased, especially in patients with hypovolemia.

Magnesium hydroxide. Simultaneous use of magnesium hydroxide can reduce the absorption of fosinopril, so an interval of at least 2 hours is necessary.

Meloksikam. Against the background of meloxicam, the hypotensive effect is weakened (a consequence of inhibition of renal prostaglandins with decreased renal blood flow and sodium and liquid retention); joint use may increase the risk of impaired renal function, especially in patients with hypovolemia.

Methyldopa. Fosinopril enhances (mutually) the hypotensive effect.

Metoclopramide. Bioavailability of fosinopril with simultaneous application with metoclopramide does not change.

Naproxen. On the background of naproxen, the hypotensive effect of fosinopril is weakened (a consequence of inhibition of renal prostaglandins with a decrease in renal blood flow and sodium and liquid retention). Joint use increases the risk of impaired renal function, especially in patients with hypovolemia.

Nimodipine. Strengthens (mutually) the hypotensive effect.

Nitroglycerine. Strengthens (mutually) the hypotensive effect.

Nifedipine. With simultaneous application nifedipine enhances the hypotensive effect of fosinopril. Bioavailability of fosinopril with simultaneous application with nifedipine does not change.

Piroxicam. Against the backdrop of piroxicam, the hypotensive effect is weakened (a consequence of inhibition of renal prostaglandins with a decrease in renal blood flow and a delay in sodium and liquid); joint use may increase the risk of impaired renal function, especially in patients with hypovolemia.

Procainamide. Fosinopril increases the risk of developing leukopenia with concomitant use with procainamide.

Propranolol. With simultaneous application propranolol enhances the hypotensive effect of fosinopril. Bioavailability of fosinopril with simultaneous application with propranolol does not change.

Risperidone. With simultaneous application risperidone enhances the hypotensive effect of fosinopril.

Risperidone. Strengthens (mutually) antihypertensive effect.

Simethicone. Simultaneous use of simethicone can reduce the absorption of fosinopril: use these drugs should be at intervals of at least 2 hours.

Spironolactone. It inhibits the release of aldosterone, significantly increases the risk of hyperkalemia. Against the background of spironolactone, the hypotensive effect is enhanced.

Terazosin. Fosinopril strengthens (mutually) hypotensive effect, possibly a sharp drop in blood pressure; at a combined appointment it is necessary to lower the dose.

Triamterene. With the simultaneous use of fosinopril and triamterene, the risk of hyperkalemia increases: a control of the potassium content in the blood plasma is necessary. In patients with heart failure, diabetes mellitus, simultaneously taking triamterene fosinopril increases the risk of increasing the concentration of potassium ions in the blood serum.

Furosemide with simultaneous use increases the hypotensive effect of fosinopril. Sharing fosinopril and furosemide in combination with a strict diet that limits salt intake or with dialysis can lead to a marked decrease in blood pressure, especially in the first hour after taking the initial dose of fosinopril.

Chlorthalidone with simultaneous use increases the hypotensive effect of fosinopril. Sharing fosinopril and chlorthalidone in combination with a strict diet that limits salt intake or with dialysis can lead to a marked decrease in blood pressure, especially in the first hour after taking the initial dose of fosinopril. Bioavailability of fosinopril with simultaneous application with chlorthalidone does not change.

Celecoxib. With simultaneous application celecoxib can reduce the antihypertensive effect of fosinopril, especially in patients with hypertension and / or low renin level in the blood plasma.

Cyclosporine. With simultaneous use with fosinopril ciclosporin increases the risk of hyperkalemia.

Etacrynic acid. In the initial period of joint therapy with fosinopril, you should stop taking etakrinovojacid or reduce the dose of fosinopril to avoid severe arterial hypotension. On the background of fosinopril, the hypokalemic effect of ethacrynic acid decreases.

Ethanol. With simultaneous use with ethanol, the hypotensive effect of fosinopril is enhanced; For the duration of treatment should be excluded the use of alcoholic beverages.

Special instructions:

In patients with left ventricular hypertrophy, prolonged use of fosinopril leads to a decrease in left ventricular mass and a decrease in the thickness of the interventricular septum. After abolition of fosinopril there is no sharp increase in blood pressure.

Do not require a special correction of the dosage regimen of fosinopril in elderly patients. Safety of use in children is not established.

Care must be taken when driving vehicles or doing other work that requires increased attention, as dizziness is possible, especially after the initial dose of fosinopril.

Instructions

Fosinopril (Fosinoprilum)