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

Active ingredient

Composition

one tablet contains the active ingredient:

lisinopril dihydrate in terms of lisinopril anhydrous 20 mg,

and excipients:

mannitol,

calcium phosphate dihydrate,

corn starch,

pregelatinized corn starch,

iron oxide yellow dye (E 172),

iron oxide red dye (E 172),

colloidal silicon dioxide,

magnesium stearate.

How to take, the dosage

Ingestion.
The drug should be taken once a day in the morning, before or after meals, preferably at the same time.

In essential hypertension, IRUMED® is prescribed in an initial dose of 10 mg daily. The maintenance dose is 20 mg per day. The maximum daily dose is 40 mg. It may take 2-4 weeks of treatment to achieve the full effect of the drug (this should be taken into account when increasing the dose). If the use of the drug in the maximum dose does not produce a sufficient therapeutic effect, additional prescription of another antihypertensive agent is possible.

In patients who have previously received diuretics, it is necessary to cancel them 2-3 days before the start of the drug. If diuretics cannot be withdrawn, the starting dose of lisinopril should not exceed 5 mg daily.

In renovascular hypertension or other conditions with increased function of renin-angiotensin-aldosterone system the drug IRUMED® is prescribed in initial dose of 2.5-5 mg per day with monitoring of blood pressure, renal function and serum potassium concentration.

The maintenance dose is adjusted according to BP.

Interaction

In concomitant use with potassium-saving diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium – the risk of hyperkalemia increases, especially in patients with impaired renal function. In concomitant use with diuretics – pronounced BP reduction.

In concomitant use with other antihypertensive drugs – additive effect.

When used concomitantly with nonsteroidal anti-inflammatory drugs (indomethacin, etc.), estrogens, as well as adrenostimulants – reduction of hypotensive effect of lisinopril.

In concomitant use with mucilage – delayed excretion of lithium from the body, with antacids and colestyramine – reduced absorption in the gastrointestinal tract. Alcohol increases the effect of the drug.

Special Instructions

Symptomatic hypotension

Particularly pronounced BP decrease occurs with a decrease in fluid volume caused by diuretic therapy, salt reduction in food, dialysis, diarrhea, or vomiting (see INTERACTION WITH OTHER MEDICINES AND SIDE EFFECTS). In patients with chronic heart failure with concomitant renal failure or without it symptomatic arterial hypotension may develop.

It has been detected more frequently in patients with severe stage of heart failure, as a consequence of using high doses of diuretic, hyponatremia or impaired renal function. In such patients the treatment should be started under strict medical supervision (choose the dose of drug and diuretics with caution).

Similar rules should be observed when prescribing to patients with coronary heart disease, cerebrovascular insufficiency, in whom a sharp decrease of BP may lead to myocardial infarction or stroke. In case of pronounced BP decrease the patient should be placed in the supine position and, if necessary, 0.9% sodium chloride solution should be administered intravenously. Transient hypotensive reaction is not a contraindication for the next dose of the drug.

When using the drug in some patients with chronic heart failure but with normal or decreased BP a decrease in BP may/should be noted, which is usually not a reason to discontinue treatment. If arterial hypotension becomes symptomatic, reduction of the drug dose or discontinuation of treatment with the drug is necessary.

In acute myocardial infarction

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

The treatment with lisinopril should not be initiated in patients with acute myocardial infarction who are at risk of further serious hemodynamic deterioration following the use of vasodilators.

These are patients with a systolic BP 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 BP is 120 mmHg or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg if systolic BP is 100 mm Hg or lower. If arterial hypotension persists (systolic BP less than 90 mmHg for more than 1 hour), IRUMED® should not be used further.

Renal dysfunction

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

In patients with bilateral renal artery stenosis or artery stenosis of the single kidney receiving ACE inhibitors, there have been increased serum urea and creatinine, usually reversible after discontinuation of treatment. It occurred more frequently in patients with renal insufficiency.

Lisinopril is not used in acute infarction in patients with severe renal dysfunction established by changes 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 (a serum creatinine concentration greater than 265 mmol/L or a doubling of the pre-treatment values), the physician should evaluate the need for further use of IRUMED®.

Angioneurotic edema
Angioneurotic edema of the face, extremities, lips, tongue, epiglottis and/or larynx, which may occur at any time during treatment, has rarely been noted in patients treated with an ACE inhibitor, including lisinopril. In such a case, treatment with the drug should be discontinued as soon as possible and the patient should be monitored until symptoms have completely regressed.

In cases of edema of the face and lips only, the condition usually resolves without treatment, but antihistamines may be prescribed. Angioedema with laryngeal edema can be fatal.

The swelling of the tongue, epiglottis or larynx may 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 given immediately. It has been noted that patients of the Negro race taking ACE inhibitors developed angioedema more frequently than patients of other races. Patients who already have a history of angioedema unrelated to previous treatment with ACE inhibitors may have an increased risk of developing it during treatment with an ACE inhibitor (see also CONTRAINDICATIONS).

Anaphylactoid reactions during hymenoptera desensitization
Patients taking ACE inhibitors during hymenoptera desensitization may, very rarely, experience a life-threatening anaphylactoid reaction. This can be avoided by temporarily stopping ACE inhibitor treatment before each desensitization.

Patients on hemodialysis
Anaphylactoid reactions have also been reported in patients on hemodialysis with a high permeability membrane (e.g. AN 69®) who take ACE inhibitors simultaneously. In such cases, another type of dialysis membrane or another antihypertensive agent should be considered.

Cough

Cough has been noted when using an ACE inhibitor. Cough is dry and prolonged, which disappears after discontinuation of ACE inhibitor treatment. In differential diagnosis of cough, cough caused by ACE inhibitor use must also be considered.

Surgery/General Anesthesia

Lisinopril may block angiotensin II formation secondary to compensatory renin release when BP lowering agents are used in patients undergoing major surgery or during general anesthesia. A pronounced decrease in BP, which is considered a consequence of this mechanism, can be corrected by increasing circulating blood volume.
Before surgical intervention (including dental surgery), the surgeon/anesthesiologist should be informed about the use of an ACE inhibitor.

Serum potassium

Hyperkalemia has been noted in some cases. Risk factors for development of hyperkalemia include renal insufficiency, diabetes mellitus and concomitant use of potassium-saving diuretics (spironolactone, triamterene or amiloride), potassium drugs or substitute salts containing potassium, especially in patients with impaired renal function. If concomitant use of lisinopril and the above-mentioned agents is considered necessary, they should be used with caution and serum potassium should be monitored regularly.

In patients who are at risk of symptomatic hypotension (being on low-salt or no-salt diet) with or without hyponatremia, as well as in patients who received high doses of diuretics, the above mentioned conditions should be compensated before initiation of therapy (loss of fluid and salts). The effect of the initial dose of IRUMED® on blood pressure should be monitored.

The effect on the ability to drive vehicles and mechanisms.

There are no data about the effect of the drug IRUMED® administered in therapeutic doses on the ability to drive and operate vehicles, but it should be noted that dizziness may occur and therefore caution should be exercised when driving vehicles.

Contraindications

Hypersensitivity to lisinopril or other ACE inhibitors, history of angioedema, including from use of ACE inhibitors, hereditary Quincke’s edema or idiopathic edema, age under 18 years (effectiveness and safety not established), pregnancy, lactation.

WARNING

Aortic stenosis, cerebrovascular disease (including cerebrovascular insufficiency), coronary heart disease, coronary artery disease, severe autoimmune systemic connective tissue disease (including systemic lupus erythematosus, scleroderma), suppression of medullary hematopoiesis, diabetes mellitus, hyperkalemia, bilateral renal artery stenosis, single renal artery stenosis, conditions after renal transplantation, renal failure, azotemia, primary aldosteronism, hypertrophic obstructive cardiomyopathy, arterial hypotension, diet with salt restriction, conditions accompanied by decreased circulating blood volume (includingincluding diarrhea, vomiting), elderly age.

Side effects

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

Cardiovascular system: marked BP decrease, chest pain, rarely – orthostatic hypotension, tachycardia, bradycardia, worsening of symptoms of heart failure, atrioventricular conduction disorder, myocardial infarction, palpitations.

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

Hematopoietic system disorders: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decreased concentration of hemoglobin, hematocrit, erythrocytopenia).

Laboratory parameters: hyperkalemia, hyponatremia, rarely – increase of “liver” enzymes activity, hyperbilirubinemia, increased levels of urea and creatinine.

Respiratory system: dyspnea, bronchospasm.

Gastrointestinal tract: dry mouth, anorexia, dyspepsia, changes in taste, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

Skin disorders: urticaria, increased sweating, itching, alopecia, photosensitization.

Hyrogenital system disorders: renal dysfunction, oliguria, anuria, acute renal failure, uremia, proteinuria, decreased potency.

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

Others: myalgia, arthralgia/arthritis, vasculitis.

Overdose

Symptoms: expressed BP decrease, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.

treatment: symptomatic therapy, intravenous 0.9% sodium chloride solution and, if possible, vasopressors, BP control, fluid and electrolyte balance. Hemodialysis may be used (see DISCUSSIONS – Patients on hemodialysis).

Pregnancy use

The use of lisinopril during pregnancy is contraindicated.

If pregnancy is established, treatment should be discontinued as soon as possible. Administration of ACE inhibitors by pregnant women in the second and third trimesters may cause fetal and neonatal death.

In newborns and infants who have had intrauterine exposure to ACE inhibitors should be closely monitored for the timely detection of marked decreases in blood pressure, oliguria, and hyperkalemia. Newborns may develop skull bone hypoplasia, oligohydramnios, skull and facial bone deformities, pulmonary hypoplasia, and fetal renal development disorders.

Lisinopril penetrates through the placenta. There are no data on permeation of lisinopril into breast milk. Breastfeeding should be stopped during treatment with the drug.

Similarities