Monopril, 20 mg tablets 28 pcs

Monopril is a hypotensive.

Pharmacodynamics

Fosinopril is an ester that is hydrolyzed in the body by enzymes into the active compound fosinoprilat. Due to the specific connection of the phosphinate group with ACE, it prevents the conversion of angiotensin I into the vasoconstrictor angiotensin II, which leads to vasodilation and reduction of aldosterone secretion.

The latter effect may lead to a slight increase in serum potassium ion concentration (0.1 mEq/L on average) and a decrease in sodium ion concentration and fluid volume. Fosinopril inhibits metabolism of bradykinin peptide, which has a potent vasodilatory effect, due to which the antihypertensive effect of the drug may be enhanced.

The decrease of BP is not accompanied with changes in BCC, cerebral and renal blood flow, blood supply of internal organs, skeletal muscles, skin, myocardial reflex activity. After oral administration the hypotensive effect develops within 1 hour, reaches its maximum after 3-6 hours and lasts for 24 hours.

In heart failure, the beneficial effects of Monopril^® are mainly achieved by inhibition of the renin-aldosterone system. Suppression of ACE results in reduction of both preload and postload on the myocardium.

The drug promotes exercise tolerance and reduces the severity of the course of heart failure.

Pharmacokinetics

After oral administration, absorption is approximately 30-40%. The degree of absorption is independent of food intake, but its rate may be slower. Hydrolytic conversion of fosinopril under the action of enzymes to fosinoprilate occurs primarily in the liver and gastrointestinal mucosa.

In impaired hepatic function, the rate of hydrolysis may be slowed and the degree of conversion does not change markedly. C_max in plasma is reached after approximately 3 h and is independent of the dose taken. Fosinoprilat binds ≥95% to blood proteins, has a relatively low volume of distribution and is insignificantly bound to cellular components of the blood.

Fosinopril is excreted from the body equally through the liver and kidneys. In patients with arterial hypertension with normal renal and hepatic function, the T_1/2 of fosinoprilat is approximately 11.5 h. In patients with heart failure, the T_1/2 value is 14 h. Fosinoprilat clearance in hemodialysis and peritoneal dialysis averages 2 and 7%, respectively, relative to urea clearance values.

In patients with impaired renal function (Cl creatinine <80 ml/min/1.73 m²) 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 markedly altered. Reduced renal excretion is compensated by increased hepatic excretion. Moderate increase of AUC values in plasma (less than twofold compared to the norm) is observed in patients with renal insufficiency of various degrees, including renal failure in the terminal stage (СІсreatinina <10 ml/min/1.73 m²).

In patients with impaired liver function (in alcoholic or biliary cirrhosis) the rate of hydrolysis of fosinopril may be reduced, but the degree of hydrolysis does not change markedly. Total clearance of fosinoprilat from these patients is about half that of patients with normal liver function.

Indications

Arterial hypertension, heart failure.

Pharmacological effect

Monopril is an antihypertensive.

Pharmacodynamics

Fosinopril is an ester that is hydrolyzed in the body by enzymes into the active compound fosinoprilate. Due to the specific connection of the phosphinate group with ACE, it prevents the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, which leads to vasodilation and a decrease in aldosterone secretion.

The latter effect may lead to a slight increase in serum potassium ion concentration (average 0.1 mEq/L) and a decrease in sodium ion concentration and fluid volume. Fosinopril inhibits the metabolism of the bradykinin peptide, which has a powerful vasodilating effect, due to which the antihypertensive effect of the drug may be enhanced.

A decrease in blood pressure is not accompanied by changes in blood volume, cerebral and renal blood flow, blood supply to internal organs, skeletal muscles, skin, or reflex activity of the myocardium. 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 Monopril® are achieved mainly through inhibition of the renin-aldosterone system. Suppression of ACE leads to a decrease in both preload and afterload on the myocardium.

The drug helps to increase tolerance to physical activity and reduce the severity of heart failure.

Pharmacokinetics

After oral administration, absorption is approximately 30–40%. The extent of absorption is independent of food intake, but its rate may be slower. The hydrolytic conversion of fosinopril under the action of enzymes into fosinoprilat occurs mainly in the liver and mucous membrane of the gastrointestinal tract.

If liver function is impaired, the rate of hydrolysis may be slowed down, but the degree of conversion does not change noticeably. Cmax in blood plasma is reached after approximately 3 hours and does not depend on the dose taken. Fosinoprilat is ≥95% protein bound, 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 patients with arterial hypertension with normal renal and liver function, T1/2 of fosinoprilat is approximately 11.5 hours. In patients with heart failure, the T1/2 value is 14 hours. The clearance of fosinoprilat during hemodialysis and peritoneal dialysis averages 2 and 7%, respectively, in relation to the clearance values ​​of urea.

In patients with impaired renal function (Cl creatinine < 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 do not change significantly. Reduced excretion through the kidneys is compensated by increased excretion through the liver. A moderate increase in plasma AUC values ​​(less than double the normal value) is observed in patients with varying degrees of renal failure, including end-stage renal failure (Clcreatinine < 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.

Special instructions

If angioedema develops while taking Monopril, the drug should be discontinued immediately. Patients should be warned that if swelling appears in the face, eyes, lips and tongue, spasm of the laryngeal muscles or difficulty breathing, they should immediately stop taking the drug and consult a doctor. In such cases, rapid subcutaneous injection of adrenaline solution (1:1000) and other emergency treatment measures are necessary.

Caution must be exercised when prescribing the drug to patients receiving desensitizing therapy, because there is a risk of developing anaphylactoid reactions.

Anaphylactoid reactions have also been reported while taking Monopril during hemodialysis through highly permeable membranes, as well as during LDL apheresis with adsorption on dextran sulfate. In such cases, the use of a different type of dialysis membrane or other drug treatment should be considered.

In rare cases, arterial hypotension developed in patients with uncomplicated arterial hypertension when using Monopril. Symptomatic hypotension with the use of ACE inhibitors is most likely in patients after intensive treatment with diuretics and/or a salt-restricted diet, as well as during renal dialysis. A temporary hypotensive reaction is not a contraindication for the use of the drug after measures to hydrate the body.

In chronic heart failure with or without concomitant renal failure, treatment with ACE inhibitors may cause excessive antihypertensive effects, which can lead to oliguria or azotemia, and in rare cases, acute renal failure and death. Therefore, when treating chronic heart failure with Monopril, it is necessary to carefully monitor the patient’s condition, especially during the first 2 weeks of treatment, as well as with any increase in the dose of fosinopril or a diuretic.

Patients with normal or low blood pressure who have previously received intensive diuretic therapy and low sodium levels in the blood may require a reduction in the diuretic dose. Arterial hypotension is not a contraindication for further use of the drug Monopril. Some reduction in systemic blood pressure is a common and desirable effect when starting the drug for heart failure.

The degree of this reduction is maximum in the early stages of treatment and stabilizes within 1-2 weeks of therapy. Blood pressure usually returns to values ​​characteristic of the period before treatment, without a decrease in therapeutic effectiveness.

If, during treatment with Monopril, noticeable jaundice and a marked increase in the activity of liver enzymes appear, the drug should be discontinued and appropriate treatment prescribed.
In case of arterial hypertension in patients with renal artery stenosis of one or both kidneys, as well as with the simultaneous use of diuretics without signs of renal vascular disease, an increase in the level of blood urea nitrogen and serum creatinine during treatment with ACE inhibitors is possible.

These effects are usually reversible and disappear after treatment is stopped. A dose reduction of the diuretic and/or Monopril may be required. In patients with severe chronic heart failure, in whom renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors may lead to oliguria or progressive azotemia and, in rare cases, acute renal failure and/or death.

In patients with heart failure or diabetes mellitus who are simultaneously taking potassium-sparing diuretics, potassium dietary supplements and/or salt substitutes containing potassium salts, or other drugs that increase potassium levels in the blood (for example, heparin), the use of ACE inhibitors increases the risk of developing hyperkalemia.

Since fosinopril is eliminated from the body in two ways, a reduction in the dose of Monopril is usually not required when treating arterial hypertension and heart failure in patients with impaired renal or hepatic function.

There are no differences in the effectiveness and safety of treatment with Monopril in patients aged 65 years and older and young patients. However, in older patients, greater susceptibility to the drug cannot be ruled out.

Control of laboratory parameters
While taking Monopril, the number of leukocytes in the peripheral blood should be periodically determined, paying attention to patients with impaired renal function, especially against the background of collagen diseases (systemic lupus erythematosus or scleroderma), because In rare cases, ACE inhibitors have been reported to cause agranulocytosis and bone marrow suppression is more likely to occur in this category of patients.

Use in pediatrics
The safety and effectiveness of Monopril in children have not been established.

Active ingredient

Fosinopril

Composition

Active ingredient: fosinopril sodium 20 mg.

Contraindications

hypersensitivity to fosinopril or any other substance included in the drug;
history of angioedema, incl. and after taking other ACE inhibitors;
pregnancy;
lactation period;
age under 18 years (efficacy and safety have not been established).

With caution:

renal failure;
hyponatremia (risk of dehydration, arterial hypotension, chronic renal failure);
bilateral renal artery stenosis or stenosis of the artery of a single kidney;
aortic stenosis;
condition after kidney transplantation;
desensitization;
systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma) – increased risk of developing neutropenia or agranulocytosis;
hemodialysis;
cerebrovascular diseases (including cerebrovascular insufficiency);
IHD; chronic heart failure stage III–IV. (according to NYHA classification);
diabetes mellitus;
inhibition of bone marrow hematopoiesis;
hyperkalemia;
in elderly patients;
gout;
on a salt-restricted diet;
conditions accompanied by a decrease in blood volume (including diarrhea, vomiting, previous treatment with diuretics).

Side Effects

From the cardiovascular system: dizziness, palpitations, chest pain.

From the respiratory system: cough.

Allergic reactions: skin rash, itching.

From the central nervous system and peripheral nervous system: feeling of fatigue, sensory disturbances (including paresthesia).

From the musculoskeletal system: myalgia.

From the digestive system: nausea, vomiting, dyspepsia, impaired taste sensitivity.

As a rule, adverse reactions when taking the drug Monopril are mild and temporary in both young and older patients.

Interaction

The simultaneous use of antacids (including aluminum hydroxide, magnesium hydroxide, simethicone) may reduce the absorption of fosinopril (Monopril and these drugs should be taken at least 2 hours apart).

In patients receiving Monopril simultaneously with lithium salts, there may be an increase in the concentration of lithium in the blood plasma and the risk of developing lithium intoxication (use with caution at the same time).

When prescribing Monopril, it should be taken into account that indomethacin and other NSAIDs (including acetylsalicylic acid) may reduce the antihypertensive effect of ACE inhibitors, especially in patients with low-renin hypertension.

When using Monopril together with diuretics or in combination with a strict diet that limits salt intake, or with dialysis, severe arterial hypotension may develop, especially in the first hour after taking the initial dose of fosinopril.

When Monopril is used together with potassium-sparing diuretics (including spironolactone, amiloride, triamterene), with food additives containing potassium, the risk of developing hyperkalemia increases (use with caution at the same time; frequent monitoring of serum potassium levels is required).

The bioavailability of Monopril does not change when combined with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propantheline, digoxin, acetylsalicylic acid and warfarin.

ACE inhibitors may enhance the antihypertensive effect of drugs used for general anesthesia.

Overdose

Symptoms: marked decrease in blood pressure, bradycardia, shock, impaired fluid and electrolyte status, acute renal failure, stupor.

Treatment: the drug should be stopped, gastric lavage, sorbents (for example, activated carbon), vasopressors, infusion of 0.9% sodium chloride solution, and then symptomatic and supportive treatment are indicated. The use of hemodialysis is ineffective.

Storage conditions

The drug should be stored in a dry place at room temperature.

Shelf life

3 years

Manufacturer

ICN Polfa Rzeszow AD, Poland