Lisinopril, tablets 20 mg 30 pcs

Lisinopril

Indications

Essential and renovascular arterial hypertension (as monotherapy or in combination with other antihypertensive drugs).

Chronic heart failure (as part of combination therapy).

Acute myocardial infarction (in the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevent left ventricular dysfunction and heart failure).

Diabetic nephropathy (to reduce albuminuria in patients with insulin-dependent diabetes mellitus with normal blood pressure and in patients with non-insulin-dependent diabetes mellitus with arterial hypertension).

Pharmacological effect

Pharmacotherapeutic group: Agents acting on the renin-angiotensin system; angiotensin-converting enzyme (ACE) inhibitors

Pharmacological action

ACE inhibitor. The mechanism of antihypertensive action is associated with inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II (which has a pronounced vasoconstrictor effect and stimulates the secretion of aldosterone in the adrenal cortex). As a result of a decrease in the formation of angiotensin II, there is a secondary increase in plasma renin activity due to the elimination of negative feedback on renin release and a direct decrease in aldosterone secretion. Decreased aldosterone secretion may contribute to increased potassium concentrations.

Lisinopril reduces peripheral vascular resistance, reduces blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in minute volume of blood and an increase in myocardial tolerance to stress in patients with chronic heart failure (CHF). Dilates arteries more than veins. Some effects are explained by effects on tissue RAAS. With long-term use, this leads to the reverse development of myocardial hypertrophy and pathological remodeling in the cardiovascular system. Improves endothelial function and blood supply to ischemic myocardium.

ACE inhibitors extend life expectancy in patients with CHF and slow down the progression of left ventricular dysfunction in patients who have suffered a myocardial infarction without clinical manifestations of heart failure.

Lisinopril reduces albuminuria. In patients with hyperglycemia, it helps to normalize the function of damaged glomerular endothelium. 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 oral administration, lisinopril is slowly and incompletely absorbed from the gastrointestinal tract. Absorption averages 25%, with high variability – 6-60%. Bioavailability – 29%. Cmax in plasma is reached after approximately 7 hours. Plasma protein binding is negligible. It is excreted unchanged in the urine. In patients with normal renal function, T1/2 is 12 hours.

Lisinopril is eliminated from the body during hemodialysis.

Special instructions

Most often, a pronounced decrease in blood pressure occurs when there is a decrease in blood volume caused by diuretic therapy, decreased salt intake, dialysis, diarrhea or vomiting. In patients with CHF with or without simultaneous renal failure, a pronounced decrease in blood pressure is possible.

For patients with coronary artery disease or cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke, lisinopril should be prescribed only under the strict supervision of a physician. Transient arterial hypotension is not a contraindication to the next dose of lisinopril.

When using lisinopril, some patients with CHF, but with normal or low blood pressure, may experience a decrease in blood pressure, which is usually not a reason to discontinue treatment.

In CHF, severe arterial hypotension that occurs can lead to deterioration of renal function. In some cases, in the presence of CHF with normal or low blood pressure, lisinopril can also cause an additional decrease in blood pressure. This effect is not a contraindication for further use of lisinopril.

In patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney, an increase in plasma urea nitrogen and serum creatinine concentrations was observed in some cases during treatment with ACE inhibitors. These changes were almost always reversible and disappeared after discontinuation of the ACE inhibitor. These complications are especially typical for patients with existing renal dysfunction. If a patient has renovascular hypertension, the risk of severe hypotension and renal failure increases. In this category of patients, treatment should begin with lower doses of lisinopril under medical supervision.

Because simultaneous use of diuretics is an additional risk factor for the development of arterial hypotension; they should be discontinued and renal function monitored during the first week.

Increases in plasma urea nitrogen and serum creatinine concentrations have also been observed in patients with arterial hypertension without concomitant renal impairment, especially with simultaneous use of lisinopril and diuretics. These changes were mild in severity, and the indicators returned to normal after discontinuation of lisinopril or a diuretic.

In patients with acute myocardial infarction, lisinopril therapy should not be started if there are signs of renal dysfunction, expressed as an increase in plasma creatinine clearance above 177 µmol/l and/or proteinuria above 500 mg/day. If renal dysfunction develops while taking lisinopril (creatinine clearance in the blood plasma is above 265 µmol/l or doubles compared to the values ​​before the start of therapy), then it is necessary to consider the possibility of discontinuing lisinopril. Treatment with lisinopril in acute myocardial infarction is carried out against the background of standard therapy (thrombolytics, acetylsalicylic acid (as an antiplatelet agent), beta-blockers). Lisinopril can be used with nitroglycerin solution for intravenous administration or with sublingual nitroglycerin.

The use of lisinopril is not recommended in patients who have suffered acute myocardial infarction if systolic blood pressure does not exceed 100 mm Hg.

When drugs that lower blood pressure are used in patients undergoing major surgery or during general anesthesia, lisinopril may block the formation of angiotensin II secondary to compensatory renin release. Before surgery (including dental surgery), stop taking lisinopril 24 hours in advance and inform the surgeon/anesthesiologist about the use of an ACE inhibitor.

It is assumed that the simultaneous use of ACE inhibitors and insulin, as well as hypoglycemic drugs for oral administration, may lead to the development of hypoglycemia. The greatest risk of development is observed during the first weeks of combination therapy, as well as in patients with impaired renal function. Patients with diabetes require careful glycemic control, especially during the first month of ACE inhibitor therapy.

Before starting treatment, it is necessary to compensate for the loss of fluid and salts. In patients with risk factors for the development of symptomatic arterial hypertension (patients on a salt-restricted diet with or without hyponatremia, patients with hypovolemia, or receiving diuretic therapy), these conditions should, if possible, be corrected before starting treatment with lisinopril. Risk factors for the development of hyperkalemia include chronic renal failure, diabetes mellitus and the concomitant use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, or amiloride), potassium supplements or salt substitutes containing potassium ions, as well as the use of drugs that are associated with an increase in plasma potassium levels (for example, heparin). Periodic monitoring of potassium levels in blood plasma is recommended.

Angioedema of the face, extremities, lips, tongue, mucous membranes, epiglottis and/or larynx has been observed with the use of ACE inhibitors, incl. drugs containing lisinopril. This side effect can occur at any stage of therapy. In such cases, it is necessary to urgently discontinue the use of lisinopril and prescribe adequate therapy. The patient should be under medical supervision until the symptoms of edema completely resolve. It should be borne in mind that even in cases where only swelling of the tongue is noted, the patient should be under medical supervision, since therapy with antihistamines and corticosteroids may not be sufficient.

Patients who have previously undergone respiratory surgery are at higher risk of developing angioedema of the larynx or tongue.

Patients who have had angioedema not associated with taking ACE inhibitors are at greater risk of developing this complication when taking ACE inhibitors. It should be taken into account that the use of ACE inhibitors in patients of the Negroid race entails a higher risk of developing angioedema. The effectiveness of ACE inhibitors in reducing blood pressure in patients of the Black race is lower than in representatives of other races. This effect may be associated with a pronounced predominance of low-renin status in patients of the Negroid race with arterial hypertension.

Patients taking ACE inhibitors during hymenoptera venom desensitization procedures may very rarely develop life-threatening anaphylactoid reactions. This can be avoided by temporarily stopping ACE inhibitor treatment before each desensitization procedure.

The dry cough that appears with the use of ACE inhibitors is non-productive, persistent and disappears after cessation of treatment. In the differential diagnosis of cough, its possible connection with ACE inhibitors should be taken into account.

Very rarely, there have been cases of the development of a syndrome that began with the development of cholestatic jaundice, progressed to fulminant necrosis and, in some cases, led to death. The mechanism of development of this syndrome is not clear. The use of lisinopril in patients with signs of jaundice or a significant increase in liver transaminases should be discontinued and appropriate monitoring of laboratory parameters and the patient’s condition should be carried out.

There have been cases of neutropenia/agranulocytosis, thrombocytopenia and anemia while taking ACE inhibitors. Such cases are quite rare in patients with normal renal function. Neutropenia and agranulocytosis disappear after discontinuation of ACE inhibitors. Lisinopril should be used with extreme caution in patients with systemic connective tissue diseases, those receiving immunosuppressive therapy, treatment with allopurinol or procainamide, or these risk factors concurrently, especially in patients with impaired renal function. In some cases, such patients may develop infectious diseases that are resistant to antibacterial therapy. If the drug is used in such patients, regular monitoring of blood leukocytes should be carried out.

If any symptoms of infection (eg, sore throat, fever) appear, the patient should consult a doctor immediately, as they may be a manifestation of neutropenia.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or surgery. Symptoms disappeared after stopping the ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Impact on the ability to drive vehicles and machinery

During the treatment period, you should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as weakness or dizziness may develop, especially at the beginning of the course of treatment.

Active ingredient

Lisinopril

Composition

Active substance: lisinopril

Excipients: lactose monohydrate (milk sugar) – 138 mg, microcrystalline cellulose (MCC-101 Premium) – 20 mg, corn starch – 18.61 mg, povidone K25 – 6 mg, pregelatinized starch – 5 mg, calcium stearate – 1.5 mg.

Pregnancy

Contraindicated for use during pregnancy and lactation (breastfeeding). If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.

Contraindications

Hypersensitivity to lisinopril and other ACE inhibitors; history of angioedema, incl. against the background of the use of ACE inhibitors; hereditary angioedema or idiopathic angioedema; pregnancy; breastfeeding period; age under 18 years (efficacy and safety have not been established); hemodialysis or hemofiltration using high-flux, high-permeability dialysis membranes (eg, AN69); apheresis of low-density lipoproteins using dextran sulfate; desensitizing therapy to the venom of hymenoptera insects (bees, wasps); simultaneous use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate or severe renal impairment (creatinine clearance less than 60 ml/min); simultaneous use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy; concomitant use with neutral endopeptidase inhibitors (for example, with drugs containing sacubitril) due to the high risk of developing angioedema.

With caution: renal dysfunction; bilateral renal artery stenosis or stenosis of the artery of a single kidney; condition after kidney transplantation; azotemia; hyperkalemia; aortic stenosis, mitral stenosis; hypertrophic obstructive cardiomyopathy; primary hyperaldosteronism; arterial hypotension; cerebrovascular diseases (including cerebrovascular insufficiency); IHD; coronary insufficiency, autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma); inhibition of bone marrow hematopoiesis; hypovolemic conditions (including as a result of diarrhea, vomiting); diet with limited salt; old age (over 65 years); use in patients of the Negroid race; simultaneous use with drugs containing aliskiren or angiotensin II receptor antagonists (with double blockade of the RAAS there is an increased risk of developing arterial hypotension, hyperkalemia and renal failure); diabetes mellitus.

Side Effects

From the hematopoietic system: rarely – decreased hemoglobin, decreased hematocrit; very rarely – suppression of bone marrow function, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia, lymphadenopathy.

From the immune system: infrequently – angioedema (face, lips, tongue, larynx or epiglottis, upper and lower extremities); rarely – a syndrome including an increase in ESR, arthralgia and the appearance of antinuclear antibodies, urticaria; very rarely – autoimmune diseases, intestinal neurotic edema.

From the endocrine system: rarely – syndrome of impaired ADH secretion.

From the mental point of view: infrequently – mood lability; rarely – anorexia; frequency unknown – depression, confusion.

From the nervous system: often – dizziness, headache; uncommon – paresthesia, sleep disturbance (drowsiness/insomnia); rarely – confusion, frequency unknown – convulsive twitching of the muscles of the limbs and lips.

From the organ of vision: rarely – visual impairment.

From the organ of hearing and labyrinthine disorders: infrequently – vertigo.

From the cardiovascular system: often – orthostatic hypotension; uncommon – marked decrease in blood pressure, acute myocardial infarction, tachycardia, palpitations; rarely – aggravation of the severity of symptoms and the course of CHF, impaired AV conduction, chest pain, cerebrovascular accident in patients at “high risk” due to a pronounced decrease in blood pressure, Raynaud’s syndrome, vasculitis.

From the respiratory system: often – dry cough; infrequently – rhinitis; very rarely – sinusitis, dyspnea, bronchospasm, allergic alveolitis/eosinophilic pneumonia.

From the digestive system: often – nausea, vomiting, diarrhea; rarely – dry mouth, dyspepsia, abdominal pain, changes in taste; very rarely – pancreatitis.

From the liver and biliary tract: rarely – hepatocellular or cholestatic jaundice, hepatitis.

From the urinary system: often – impaired renal function; rarely – uremia, acute renal failure; very rarely – oliguria, anuria; frequency unknown – proteinuria.

From the skin and subcutaneous tissues: infrequently – skin itching, rash, rarely – psoriasis, very rarely – pemphigus, toxic epidermal necrolysis (Lyell’s syndrome), erythema multiforme, Stevens-Johnson syndrome, cutaneous pseudolymphoma.

From the musculoskeletal system: rarely – myalgia, arthralgia/arthritis.

From the genital organs and mammary gland: infrequently – sexual dysfunction; rarely – gynecomastia.

From laboratory parameters: infrequently – increased concentration of urea in the blood plasma, hypercreatininemia, hyperkalemia, increased activity of liver transaminases, rarely – hyperbilirubinemia, hyponatremia; very rarely – an increase in ESR, an increase in the titer of antinuclear antibodies, a decrease in glucose concentration.

General reactions: rarely – fever, asthenia, fatigue, alopecia, impaired fetal development; very rarely – increased sweating.

Interaction

When used concomitantly with antihypertensive agents, additive antihypertensive effects are possible.

When used simultaneously with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium supplements, table salt substitutes containing potassium, the risk of developing hyperkalemia increases, especially in patients with impaired renal function.

With the simultaneous use of ACE inhibitors and NSAIDs, the risk of developing renal dysfunction increases, and hyperkalemia is rarely observed.

When used simultaneously with loop diuretics and thiazide diuretics, the antihypertensive effect is enhanced. The occurrence of severe arterial hypotension, especially after taking the first dose of a diuretic, appears to be due to hypovolemia, which leads to a transient increase in the hypotensive effect of lisinopril. Increased risk of kidney dysfunction.

When used concomitantly with indomethacin, the antihypertensive effect of lisinopril is reduced, apparently due to inhibition of prostaglandin synthesis under the influence of NSAIDs (which are believed to play a role in the development of the hypotensive effect of ACE inhibitors).

When used simultaneously with insulin, hypoglycemic agents and sulfonylurea derivatives, hypoglycemia may develop due to increased glucose tolerance.

When used simultaneously with clozapine, the concentration of clozapine in the blood plasma increases.

When used simultaneously with lithium carbonate, the concentration of lithium in the blood serum increases, accompanied by symptoms of lithium intoxication.

Lisinopril slows the elimination of lithium drugs, which may increase the risk of side effects. Therefore, when used together, it is necessary to regularly monitor the lithium content in the blood plasma.

A case of the development of severe hyperkalemia in a patient with diabetes mellitus during concomitant use with lovastatin has been described.

The simultaneous use of lisinopril with beta-blockers, slow calcium channel blockers, diuretics, tricyclic antidepressants/neuroleptics and other antihypertensive drugs increases the severity of the hypotensive effect.

Antacids and cholestyramine reduce the absorption of lisinopril in the gastrointestinal tract.

When used together with insulin and oral hypoglycemic agents, the risk of hypoglycemia increases.

When used simultaneously with NSAIDs, COX-2 inhibitors and acetylsalicylic acid (at a dose of more than 3 g/day), estrogens, and sympathomimetics, the hypotensive effect of lisinopril is reduced. NSAIDs and ACE inhibitors increase plasma potassium and may impair renal function. This effect is usually reversible.

The use of lisinopril in combination with acetylsalicylic acid as an antiplatelet agent, thrombolytics and/or nitrates is not contraindicated.

When used simultaneously, ethanol enhances the effect of lisinopril.

With the simultaneous use of ACE inhibitors and gold preparations for intravenous administration (sodium aurothiomalate), a symptom complex has been described, including facial flushing, nausea, vomiting and decreased blood pressure.

Concomitant use with selective serotonin reuptake inhibitors may lead to severe hyponatremia.

Combined use with allopurinol, procainamide, and cytostatics may increase the risk of developing leukopenia.

When used simultaneously with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and patients with moderate and/or severe renal impairment (creatinine clearance less than 60 ml/min), the risk of developing hyperkalemia, deterioration of renal function and an increase in the incidence of cardiovascular morbidity and mortality increases.

In elderly patients and patients with impaired renal function, concomitant use of ACE inhibitors with sulfamethoxazole/trimethoprim was accompanied by severe hyperkalemia, which is believed to be caused by trimethoprim, therefore the drug should be used with caution with drugs containing trimethoprim, regularly monitoring plasma potassium levels.

Storage conditions

In a place protected from light, at a temperature not exceeding 25°C.

Shelf life

3 years.

Manufacturer

Ozon, Russia