Irumed, tablets 20 mg 30 pcs

Pharmacotherapeutic group: angiotensin converting enzyme inhibitor (ACE)

ATX code: C09AA03

Pharmacological Properties

Pharmacodynamics

ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. The decrease in angiotensin II leads to a direct decrease in the release of aldosterone.

Decreases bradykinin degradation and increases prostaglandin synthesis. Reduces total peripheral vascular resistance, blood pressure (BP), preload, pulmonary capillary pressure, causes an increase in the minute blood volume and increases myocardial exercise tolerance in patients with chronic heart failure. Dilates arteries to a greater extent than veins. Some effects are explained by the effect on tissue renin-angiotensin systems. Long-term use reduces myocardial hypertrophy and resistive arterial wall hypertrophy. It improves the blood supply to the ischemic myocardium.

The ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure. Onset of action is within 1 hour.

The maximal effect is determined after 6-7 hours, the duration -24 hours. With arterial hypertension the effect is noted in the first days after the start of treatment, the stable effect develops after 1-2 months. At acute withdrawal of the drug, no pronounced increase in BP has been observed. In addition to BP reduction, lisinopril reduces albuminuria. In patients with hyperglycemia, it normalizes the function of the damaged glomerular endothelium. Lisinopril does not affect blood glucose concentration in diabetic patients and does not lead to increased incidence of hypoglycemia.

Pharmacokinetics

After oral administration about 25% of lisinopril is absorbed from the gastrointestinal tract. Food intake does not affect absorption of the drug. Absorption averages 30%, bioavailability 29%. After oral administration maximum concentration of lisinopril in plasma is reached after 6-8 hours.

Weakly bound to plasma proteins.

Metabolism.Lisinopril is not biotransformed in the body.

The elimination half-life is 12 hours. Lisinopril weakly penetrates through the blood-brain barrier.

Indications

Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs).
Chronic heart failure (as part of combination therapy for the treatment of patients taking digitalis and/or diuretics).
Early treatment of acute myocardial infarction as part of combination therapy (in the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevent left ventricular dysfunction and heart failure).
Diabetic nephropathy (reduction of albuminuria in insulin-dependent patients with normal blood pressure and non-insulin-dependent patients with arterial hypertension).

Pharmacological effect

PHARMACOTHERAPEUTIC GROUP: angiotensin converting enzyme (ACE) inhibitor

ATX CODE: C09AA03

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

An ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone.

Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces total peripheral vascular resistance, blood pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and an increase in myocardial tolerance to stress in patients with chronic heart failure. Dilates arteries more than veins. Some effects are explained by effects on tissue renin-angiotensin systems. With long-term use, hypertrophy of the myocardium and the walls of resistive arteries decreases. Improves blood supply to ischemic myocardium.

ACE inhibitors prolong life expectancy in patients with chronic heart failure and slow the progression of left ventricular dysfunction in patients who have suffered a myocardial infarction without clinical manifestations of heart failure. Onset of action – after 1 hour

The maximum effect is determined after 6-7 hours, duration -24 hours. In arterial hypertension, the effect is observed in the first days after the start of treatment, a stable effect develops after 1-2 months. When the drug was abruptly discontinued, no pronounced increase in blood pressure was observed. In addition to lowering blood pressure, lisinopril reduces albuminuria. In patients with hyperglycemia, it helps to normalize the function of damaged glomerular endothelium. Lisinopril does not affect the concentration of glucose in the blood in patients with diabetes and does not lead to an increase in cases of hypoglycemia.

Pharmacokinetics

After taking the drug orally, about 25% of lisinopril is absorbed from the gastrointestinal tract. Eating does not affect the absorption of the drug. Absorption averages 30%, bioavailability – 29%. After oral administration, the maximum concentration of lisinopril in the blood plasma is achieved after 6-8 hours.

Weakly binds to blood plasma proteins.

Metabolism. Lisinopril is not biotransformed in the body.

The half-life is 12 hours. Lisinopril poorly penetrates the blood-brain barrier.

Special instructions

Symptomatic hypotension

Most often, a pronounced decrease in blood pressure occurs with a decrease in fluid volume caused by diuretic therapy, reducing salt in food, dialysis, diarrhea or vomiting (see INTERACTIONS WITH OTHER MEDICINES AND SIDE EFFECTS). In patients with chronic heart failure with or without concurrent renal failure, symptomatic arterial hypotension may develop.

It was more often detected in patients with severe heart failure, as a result of the use of large doses of diuretics, hyponatremia or impaired renal function. In such patients, treatment should be started under the strict supervision of a physician (with caution in selecting the dose of the drug and diuretics).

Similar rules must be followed when prescribing to patients with coronary heart disease or cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke. If a pronounced decrease in blood pressure develops, place the patient in a supine position and, if necessary, inject a 0.9% sodium chloride solution intravenously. A transient hypotensive reaction is not a contraindication for taking the next dose of the drug.

When using the drug, some patients with chronic heart failure, but with normal or low blood pressure, may experience a decrease in blood pressure, which is usually not a reason to stop treatment. If arterial hypotension becomes symptomatic, it is necessary to reduce the dose of the drug or discontinue treatment with the drug.

In acute myocardial infarction

The use of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers) is indicated. IRUMED® can be used in conjunction with intravenous nitroglycerin or with the use of transdermal nitroglycerin systems.

Treatment with lisinopril should not be initiated in patients with acute myocardial infarction who are at risk of further severe hemodynamic deterioration after use of vasodilators.

These are patients with a systolic blood pressure of 100 mm Hg. or lower or with cardiogenic shock. During the first 3 days after a heart attack, the dose should be reduced if systolic blood pressure is 120 mm Hg. or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg if systolic blood pressure is 100 mmHg or lower. If arterial hypotension persists (systolic blood pressure less than 90 mm Hg for more than 1 hour), IRUMED® should not be used further.

Renal dysfunction

In patients with chronic heart failure, a pronounced decrease in blood pressure after initiation of treatment with ACE inhibitors may lead to a further deterioration of renal function. Cases of acute renal failure have been reported.

In patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney who received ACE inhibitors, there was an increase in serum urea and creatinine, usually reversible after discontinuation of treatment. It was more common in patients with renal failure.

Lisinopril is not used for acute myocardial infarction in patients with severe renal dysfunction, as defined by a change in serum creatinine concentration exceeding 177 mmol/l and/or proteinuria exceeding 500 mg/day.

If renal dysfunction develops during the use of the drug (serum creatinine concentration exceeding 265 mmol/l or doubling the value before treatment), the physician should assess the need for further use of Irumed®.

Hypersensitivity/Angioedema
Angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx, which may occur during any period of treatment, has rarely been reported in patients treated with an ACE inhibitor, including lisinopril. In this case, treatment with the drug should be stopped as soon as possible and the patient should be monitored until the symptoms completely regress.

In cases where swelling occurs only on the face and lips, the condition most often resolves without treatment, but antihistamines may be prescribed. Angioedema with laryngeal edema can be fatal.

Swelling of the tongue, epiglottis or larynx can cause airway obstruction, so appropriate therapy (0.3-0.5 ml of 1:1000 epinephrine (adrenaline) solution subcutaneously) and/or measures to ensure airway patency should be immediately carried out. It was noted that in patients of the Negroid race taking ACE inhibitors, angioedema developed more often than in patients of other races. Patients who have a history of angioedema not associated with previous treatment with ACE inhibitors may be at increased risk of developing it during treatment with an ACE inhibitor (see also CONTRAINDICATIONS).

Anaphylactoid reactions during desensitization to Hymenoptera
In patients taking ACE inhibitors during desensitization to Hymenoptera, it may, extremely rarely, develop dangerous for; life anaphylactoid reaction. This can be avoided by temporarily stopping ACE inhibitor treatment before each desensitization.

Patients on hemodialysis
Anaphylactoid reactions have also been observed in patients undergoing hemodialysis with a high-permeability membrane (eg AN 69®) who are simultaneously taking ACE inhibitors. In such cases, the use of a different type of dialysis membrane or another antihypertensive agent should be considered.

Cough

Cough has been reported when using an ACE inhibitor. The cough is dry and prolonged, which disappears after stopping treatment with an ACE inhibitor. In the differential diagnosis of cough, cough caused by the use of an ACE inhibitor must also be taken into account.

Surgery/General anesthesia

When using blood pressure lowering agents in patients undergoing major surgery or during general anesthesia, lisinopril may block the formation of angiotensin II, secondary to compensatory release of renin. The pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by increasing the volume of circulating blood.
Before surgery (including dental surgery), the surgeon/anesthetist should be informed about the use of an ACE inhibitor.

Serum potassium

In some cases, hyperkalemia was observed. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, and concomitant use of potassium-sparing diuretics (spironolactone, triamterene, or amiloride), potassium supplements, or salt substitutes containing potassium, especially in patients with impaired renal function. If the simultaneous use of lisinopril and the above-mentioned drugs is considered necessary, they should be used with caution, regularly monitoring serum potassium.

In patients at risk of symptomatic hypotension (those on a low-salt or salt-free diet) with or without hyponatremia, as well as in patients who have received high doses of diuretics, the above conditions must be compensated for (loss of fluid and salts) before starting treatment. It is necessary to monitor the effect of the initial dose of IRUMED® on blood pressure.

Impact on the ability to drive vehicles and machinery.

There is no data on the effect of the drug IRUMED®, used in therapeutic doses, on the ability to drive vehicles and machines, however, it must be taken into account that dizziness may occur, so care must be taken when driving vehicles.

Active ingredient

Lisinopril

Composition

one tablet contains the active substance:

lisinopril dihydrate in terms of lisinopril anhydrous 20 mg,

as well as excipients:

mannitol,

calcium phosphate dihydrate,

corn starch,

pregelatinized corn starch,

iron oxide yellow dye (E 172),

red iron oxide dye (E 172),

colloidal silicon dioxide,

magnesium stearate.

Pregnancy

The use of lisinopril during pregnancy is contraindicated.

When pregnancy is established, treatment should be stopped as soon as possible. Taking ACE inhibitors by pregnant women in the second and third trimesters can cause fetal and neonatal death.

For newborns and infants who have been exposed in utero to ACE inhibitors, it is recommended to conduct careful monitoring for timely detection of a pronounced decrease in blood pressure, oliguria, and hyperkalemia. Newborns may develop hypoplasia of the skull bones, oligohydramnios, deformation of the bones of the skull and face, hypoplasia of the lungs, and impaired development of the fetal kidneys.

Lisinopril crosses the placenta. There is no data on the penetration of lisinopril into breast milk. During treatment with the drug, breastfeeding should be discontinued.

Contraindications

Hypersensitivity to lisinopril or other ACE inhibitors, history of angioedema, including from the use of ACE inhibitors, hereditary angioedema or idiopathic edema, age under 18 years (efficacy and safety have not been established), pregnancy, lactation.

WITH CAUTION

Aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), coronary heart disease, coronary insufficiency, severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), suppression of bone marrow hematopoiesis, diabetes mellitus, hyperkalemia, bilateral renal artery stenosis, stenosis of the artery of a single kidney, condition after transplantation kidneys, renal failure, azotemia, primary aldosteronism, hypertrophic obstructive cardiomyopathy, arterial hypotension, salt-restricted diet, conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting), old age.

Side Effects

The most common side effects: dizziness, headache, fatigue, diarrhea, dry cough, nausea.

From the cardiovascular system: marked decrease in blood pressure, chest pain, rarely – orthostatic hypotension, tachycardia, bradycardia, worsening symptoms of heart failure, impaired atrioventricular conduction, myocardial infarction, rapid heartbeat.

From the central nervous system: mood lability, confusion, paresthesia, drowsiness, convulsive twitching of the muscles of the limbs and lips, rarely – asthenic syndrome.

From the hematopoietic system: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decreased hemoglobin concentration, hematocrit, erythrocytopenia).

Laboratory indicators: hyperkalemia, hyponatremia, rarely – increased activity of liver enzymes, hyperbilirubinemia, increased levels of urea and creatinine.

From the respiratory system: dyspnea, bronchospasm.

From the digestive tract: dry mouth, anorexia, dyspepsia, taste changes, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

From the skin: urticaria, increased sweating, itching, alopecia, photosensitivity.

From the genitourinary system: impaired renal function, oliguria, anuria, acute renal failure, uremia, proteinuria, decreased potency.

Allergic reactions: angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx, skin rashes, itching, fever, positive antinuclear antibody test results, increased erythrocyte sedimentation rate (ESR), eosinophilia, leukocytosis. In very rare cases – interstitial angioedema.

Other: myalgia, arthralgia/arthritis, vasculitis.

Interaction

When used simultaneously with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, the risk of developing hyperkalemia increases, especially in patients with impaired renal function. When used simultaneously with diuretics, there is a pronounced decrease in blood pressure.

When used simultaneously with other antihypertensive drugs, there is an additive effect.

When used simultaneously with nonsteroidal anti-inflammatory drugs (indomethacin, etc.), estrogens, and adrenergic stimulants, the hypotensive effect of lisinopril is reduced.

With simultaneous use of fusion – slowing down the excretion of lithium from the body, with antacids and cholestyramine – reduce absorption in the gastrointestinal tract. Alcohol enhances the effect of the drug.

Overdose

Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: symptomatic therapy, intravenous administration of 0.9% sodium chloride solution and, if possible, the use of vasopressors, control of blood pressure, water and electrolyte balance. Hemodialysis may be used (see SPECIAL INSTRUCTIONS – Patients on hemodialysis).

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Manufacturer

Belupo, medicines and cosmetics d.d., Croatia