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.

Active ingredient

Composition

The active ingredient: fosinopril sodium 20 mg.

How to take, the dosage

Before initiating treatment of arterial hypertension, a review of prior antihypertensive drug therapy, the degree of BP elevation, salt and/or fluid restrictions, and other clinical circumstances should be performed. If possible, discontinue previous antihypertensive therapy several days before starting Monopril.

The recommended starting dose is 10 mg once daily. The dose should be adjusted according to the dynamics of BP decrease. The average dose is 10-40 mg once daily. If sufficient hypotensive effect is absent, additional prescription of diuretics is possible.

If treatment with Monopril is started against the background of current diuretic therapy, the initial dose should not exceed 10 mg with careful medical monitoring of the patient. In order to reduce the risk of arterial hypotension, diuretics should be discontinued 2-3 days before starting Monopril.

In chronic heart failure, the recommended starting dose is 10 mg once daily. Depending on the therapeutic effectiveness, the dose may be increased at weekly intervals up to a maximum of 40 mg once daily. Close medical supervision is required at the beginning of and during treatment. The development of arterial hypotension after the initial dose should not interfere with a careful adjustment of Monopril dose after effective relief of arterial hypotension. In case of heart failure, Monopril is recommended to be used in combination with a diuretic.

Interaction

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

In patients receiving Monopril concomitantly with lithium salts, there may be increased plasma lithium concentrations and the risk of lithium intoxication (use with caution at the same time).

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

When co-administration of Monopril with diuretics or in combination with a strict diet restricting salt intake or with dialysis, pronounced arterial hypotension may develop, especially in the first hour after taking the initial dose of fosinopril.

The co-administration of Monopril with potassium-saving diuretics (including spironolactone, amiloride, triamterene), with food supplements containing potassium, increases the risk of hyperkalemia (use with caution; frequent monitoring of serum potassium levels is required).

The bioavailability of Monopril does not change when co-administered with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propantelin, digoxin, acetylsalicylic acid and warfarin.

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

Special Instructions

If angioedema develops with Monopril, the drug should be stopped immediately. Patients should be warned that in case of edema on the face, eyes, lips and tongue, laryngeal spasm or difficulty in breathing, the drug should be stopped immediately and a physician should be consulted. In such cases, rapid injection of adrenaline solution (1:1000) and other emergency therapy measures are necessary.

We should use caution when prescribing the drug in patients receiving desensitization therapy, since there is a risk of anaphylactoid reactions.

There have also been reports of anaphylactoid reactions with Monopril during hemodialysis through highly permeable membranes as well as during LDL apheresis with adsorption on dextran sulfate. In such cases, another type of dialysis membrane or other drug treatment should be considered.

In rare cases, patients with uncomplicated arterial hypertension have developed arterial hypotension when using Monopril. Symptomatic arterial hypotension when using ACE inhibitors is most likely in patients after intensive treatment with diuretics and/or diet with limited salt content, as well as during renal dialysis. 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 may lead to oliguria or azotemia and, in rare cases, to acute renal failure and death. Therefore, when treating chronic heart failure with Monopril, patients should be carefully monitored, especially during the first 2 weeks of treatment, and any increase in the dose of fosinopril or diuretic.

Patients with normal or reduced BP who have previously received intensive diuretic therapy and with reduced sodium in the blood may need to reduce the diuretic dose. Arterial hypotension is not a contraindication for further use of Monopril. Some reduction in systemic BP is a common and desirable effect at the beginning of use of the drug in heart failure.

The extent of this decrease is maximal in the early stages of treatment and stabilizes within 1-2 weeks of therapy. BP usually returns to pre-treatment values with no decrease in therapeutic efficacy.

If marked jaundice and marked increase in liver enzyme activity appear during treatment with Monopril, the drug should be discontinued and appropriate treatment should be prescribed.
In hypertensive patients with renal artery stenosis of one or both kidneys as well as in concomitant use of diuretics without signs of renal vascular disease during treatment with ACE inhibitors, increase of blood urea nitrogen and serum creatinine levels is possible.

These effects are usually reversible and go away after discontinuation of treatment. Dose reduction of diuretic and/or Monopril may be required.In patients with severe chronic heart failure in whom renal function may depend on renin-angiotensin-aldosterone system activity, treatment with ACE inhibitors may lead to oliguria or progressive azotemia and in rare cases to acute renal failure and/or fatal outcome.

In patients with heart failure, with diabetes mellitus, simultaneously taking potassium-saving diuretics, potassium supplements and/or food salt substitutes containing potassium salts, or other drugs that increase potassium content in blood (e.g., heparin), use of ACE inhibitors increases the risk of hyperkalemia.

Because the excretion of fosinopril from the body is done in two ways, it is usually not necessary to decrease the dose of Monopril in the treatment of arterial hypertension and heart failure in patients with renal or hepatic impairment.

There is no difference in efficacy and safety of treatment with Monopril in patients aged 65 years or older and younger. However, in older patients, greater susceptibility to the drug cannot be excluded.

Control of laboratory parameters
During Monopril administration peripheral blood leukocyte counts should be determined periodically, paying attention to patients with impaired renal function, especially against a background of collagenoses (systemic lupus erythematosus or scleroderma), since it has been reported that leukocyte counts in the blood are rare.Because it has been reported that in rare cases ACE inhibitors cause agranulocytosis and suppression of bone marrow function more likely in this category of patients.

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

Contraindications

With caution:

Side effects

Cardiovascular system disorders:dizziness, palpitations, chest pain.

Respiratory system:cough.

Allergic reactions: skin rash, itching.

From the CNS and peripheral nervous system: feeling of fatigue, impaired sensitivity (including paresthesias).

Muscular system disorders: myalgia.

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

In general, adverse reactions when taking Monopril are mild and temporary in patients both young and old.

Overdose

Symptoms: Evident BP decrease, bradycardia, shock, water-electrolyte disturbance, acute renal failure, stupor.

treatment: the drug should be stopped, gastric lavage, sorbents (e.g. activated charcoal), vasopressors, infusion of 0.9% sodium chloride solution and further symptomatic and supportive treatment is indicated. The use of hemodialysis is ineffective.

Similarities