Lisinopril

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LIZINOPRIL (LISINOPRIL)

Composition:

Active substance: lisinopril;

One tablet contains lisinopril dihydrate equivalent to lisinopril 5 mg or 10 mg or 20 mg;

Excipients: calcium hydrogen phosphate, mannitol (E 421), maize starch, magnesium stearate, colloidal anhydrous silicon dioxide.

Pharmaceutical form. Tablets.

Main physicochemical properties: white, flat cylindrical tablets with bevelled edges and a score line.

Pharmacotherapeutic group.

Angiotensin-converting enzyme (ACE) inhibitors.

ATC code C09A A03.

Pharmacological Properties

Pharmacodynamics

Lisinopril reduces plasma levels of angiotensin-II and aldosterone while simultaneously increasing the concentration of the vasodilator bradykinin. Lisinopril causes a reduction in peripheral vascular resistance and arterial blood pressure; cardiac output may increase with unchanged heart rate, and renal blood flow may also be enhanced.

Arterial blood pressure begins to decrease within 1 hour after oral administration of the drug, with maximum antihypertensive effect achieved within 6 hours. The duration of lisinopril's action (approximately 24 hours) is dose-dependent. With long-term treatment, the drug's efficacy does not diminish. Abrupt discontinuation of therapy does not lead to significant fluctuations in blood pressure (withdrawal syndrome).

Although the primary action of lisinopril is associated with the renin-angiotensin-aldosterone system, the drug is effective even in cases of arterial hypertension occurring with low renin levels.

In addition to direct reduction of arterial blood pressure, lisinopril reduces albuminuria due to changes in the histology and hemodynamics of the glomerular apparatus of the kidneys. In controlled clinical trials in patients with diabetes mellitus, no fluctuations in blood glucose levels or increased incidence of hypoglycemia were observed.

Lisinopril plays a positive role in restoring the function of damaged endothelium in patients with hyperglycemia.

Pharmacokinetics

Absorption

Following oral administration of lisinopril, maximum serum concentration (Cmax) is reached approximately 7 hours after dosing. Based on urinary excretion data, the average absorption rate of lisinopril is approximately 25% following doses of 5–80 mg. Inter-patient variability may range from 6% to 60%. Absolute bioavailability of lisinopril decreases to approximately 16% in patients with NYHA class II–IV heart failure. Food intake does not affect the absorption of lisinopril.

Distribution

Apart from binding to angiotensin-converting enzyme (ACE), lisinopril does not bind significantly to other plasma proteins. Animal studies indicate that lisinopril crosses the blood-brain barrier only to a minimal extent.

Elimination

Lisinopril is not metabolized and is excreted exclusively by the kidneys in unchanged form. After dose escalation, the effective half-life is 12.6 hours. The clearance of lisinopril is approximately 50 ml/min in healthy volunteers. Following the elimination of a significant amount of free active substance, a slower elimination phase follows for the fraction bound to ACE.

Hepatic impairment

In patients with hepatic cirrhosis, absorption of lisinopril is slowed by approximately 30% depending on the degree of hepatic dysfunction (as determined by urinary excretion). On the other hand, its elimination is reduced, leading to a 50% increase in lisinopril's effectiveness.

Renal impairment

Renal impairment reduces the elimination of lisinopril, which is primarily excreted by the kidneys. This reduction is clinically significant only when glomerular filtration rate is less than 30 ml/min. When creatinine clearance is between 30–80 ml/min, the mean area under the concentration-time curve (AUC) increases by only 13%. When creatinine clearance is between 5–30 ml/min, the mean AUC increases by 4.5 times compared to normal. Lisinopril can be removed by dialysis.

Heart failure

In patients with heart failure, the effect of lisinopril is increased (AUC increases by approximately 25%). On the other hand, the absolute bioavailability of lisinopril decreases to approximately 16% in patients with heart failure.

Pediatric population

The pharmacokinetic profile of lisinopril has been studied in patients aged 6 to 16 years with arterial hypertension and glomerular filtration rate below 30 ml/min/1.73 m². Following doses of 0.1 to 0.2 mg/kg, the steady-state plasma concentration of lisinopril achieved within 6 hours, as well as the extent of absorption based on urinary excretion, was approximately 28%. These values differ from those observed in adult patients. However, AUC and Cmax values in children from this study were comparable to those obtained in adults.

Elderly patients

In elderly patients, lisinopril levels are generally higher due to impaired renal function; AUC is approximately 60% higher than in younger patients.

Clinical characteristics.

Indications.

• Essential hypertension.
• Heart failure (symptomatic treatment).
• Acute myocardial infarction (short-term treatment (6 weeks) of hemodynamically stable patients no later than 24 hours after acute myocardial infarction).
• Treatment of initial nephropathy in patients with type II diabetes mellitus and arterial hypertension.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
• Angioedema in medical history associated with previous treatment with other ACE inhibitors.
• Hereditary or idiopathic angioedema.
• Aortic or mitral valve stenosis or hypertrophic cardiomyopathy with hemodynamic impairment.
• Primary hyperaldosteronism.
• Renal artery stenosis (bilateral or unilateral).
• Cardiogenic shock.
• Condition with unstable hemodynamics after acute myocardial infarction.
• Use in patients undergoing hemodialysis with high-flux membranes (e.g., AN 69).
• Serum creatinine level > 220 μmol/L.
• Pregnancy or women planning to become pregnant (see section "Use during pregnancy or breastfeeding").

Interaction with other medicinal products and other forms of interaction.

Potassium-sparing diuretics and potassium supplements

Concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, and potassium-containing salt substitutes requires caution. Hyperkalemia in some cases may lead to impaired kidney function. For this reason, such combination therapy should be prescribed only under close medical supervision and with regular monitoring of serum potassium levels and renal function.

Diuretics

Concomitant use of diuretics with lisinopril generally produces an additive hypotensive effect. Particular caution should be exercised when adding lisinopril to the treatment regimen of patients already receiving diuretics, as a significant reduction in arterial pressure may occur due to decreased extracellular fluid volume and/or excessive excretion of sodium chloride from the body. In view of the above, the risk of symptomatic hypotension can be reduced by discontinuing diuretic therapy and increasing fluid or salt intake prior to initiating lisinopril dosing, as well as by starting treatment with low doses of ACE inhibitors.

Other antihypertensive agents

Concomitant use of other antihypertensive drugs may enhance the antihypertensive effect of lisinopril.

Concomitant use of nitroglycerin and other nitrates or other vasodilating agents may additionally reduce arterial pressure.

Nonsteroidal anti-inflammatory drugs (including acetylsalicylic acid at doses of 3 g/day)

Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of ACE inhibitors. Furthermore, increased serum potassium levels have been reported with concomitant use of NSAIDs and ACE inhibitors, which may lead to impaired renal function. This effect is usually reversible and is most likely to occur in patients with pre-existing renal impairment.

Acetylsalicylic acid, thrombolytic agents, β-blockers, nitrates

Lisinopril may be used concomitantly with acetylsalicylic acid (at cardiologic doses), thrombolytic agents, β-blockers, and/or nitrates under medical supervision.

Lithium preparations

ACE inhibitors may reduce lithium excretion, which may be accompanied by increased toxicity. Given this fact, concomitant use of lisinopril with lithium preparations is not recommended; however, if such combination therapy is necessary, serum lithium levels should be monitored regularly.

Antidiabetic agents

Concomitant use of antidiabetic agents with ACE inhibitors may enhance the hypoglycemic effect of insulin and sulfonylureas, increasing the risk of symptomatic hypoglycemia. However, improved glucose tolerance may reduce the required dose of insulin or sulfonylureas. This interaction typically manifests during the first week of combination therapy, particularly in patients with renal impairment.

Sympathomimetics

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors. Therefore, more careful monitoring of the patient's blood pressure is required to determine whether the desired therapeutic effect has been achieved.

Tricyclic antidepressants, neuroleptics, anesthetics

Concomitant use of tricyclic antidepressants, neuroleptics, or anesthetics may enhance the hypotensive effect of lisinopril.

Gold

Nitritoid reactions (symptoms of vasodilation, including flushing, nausea, dizziness, and arterial hypotension, which may be severe) following gold injections (e.g., sodium aurothiomalate) occur more frequently in patients concurrently receiving lisinopril.

Streptokinase

Lisinopril should be administered with caution to patients with acute myocardial infarction within 6–12 hours after administration of streptokinase (risk of arterial hypotension).

Concomitant use of lisinopril with narcotics, anesthetics, alcoholic beverages, and sedatives enhances the hypotensive effect.

Special precautions for use.

Marked decrease in arterial pressure, accompanied by symptomatic hypotension, may occur in patients with hypovolemia and/or reduced extracellular fluid volume resulting from diuretic therapy, dietary salt restriction, or other forms of fluid loss (excessive sweating, prolonged vomiting, diarrhea, dialysis), as well as in patients with heart failure. In case of arterial hypotension, the patient should be placed in a supine position; intravenous infusion of fluids (administration of physiological saline) is recommended as an essential measure. Transient arterial hypotension is generally not a contraindication for further treatment; however, temporary discontinuation or dose reduction may be necessary.

If possible, hypovolemia and/or reduced extracellular fluid volume should be corrected before initiating lisinopril therapy, and the effect of the initial dose on arterial pressure should be carefully monitored. In patients with cerebrovascular disease or ischemic heart disease, a sudden initial drop in arterial pressure may precipitate stroke or myocardial infarction.

In patients with acute myocardial infarction, lisinopril is contraindicated if vasodilator therapy may worsen the patient's hemodynamic status (e.g., if systolic blood pressure is 100 mm Hg or lower) or in cases of cardiogenic shock. If systolic arterial pressure is 120 mm Hg or lower, low doses (2.5 mg/day) should be administered during the first 3 days after infarction. In case of arterial hypotension, maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg. If persistent arterial hypotension occurs (systolic arterial pressure below 90 mm Hg for more than 1 hour), treatment with this drug should be discontinued.

Aortic stenosis/hypertrophic cardiomyopathy

Like all vasodilating agents, ACE inhibitors should be used with caution in the presence of pre-existing outflow tract obstruction.

As with other ACE inhibitors, lisinopril is not recommended for administration to patients with mitral stenosis or impaired left ventricular outflow (in aortic stenosis or hypertrophic cardiomyopathy).

Renal function impairment

In patients with impaired renal function (creatinine clearance < 80 mL/min), the initial dose of lisinopril should be adjusted according to creatinine clearance values (see section "Dosage and administration") and clinical response to treatment. These patients require regular monitoring of serum potassium and creatinine levels.

In patients with heart failure, arterial hypotension occurring after initiation of ACE inhibitor therapy may lead to impaired renal function. Acute renal failure, usually reversible, has been reported in such cases.

In some patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney receiving ACE inhibitors, increases in blood urea nitrogen and serum creatinine have been observed, which are usually reversible upon discontinuation of therapy. This is particularly relevant in patients with pre-existing renal impairment. If renovascular hypertension is also present, the risk of severe hypotension and renal failure increases. Treatment of such patients should be initiated under close medical supervision, starting with low doses and careful dose titration. Since diuretic therapy may be a contributing factor to the above-mentioned effects, diuretics should be discontinued prior to lisinopril administration, and renal function should be monitored closely during the first weeks of lisinopril treatment.

Use in patients with transplanted kidney

There is no experience with the use of lisinopril in patients who have recently undergone kidney transplantation. Therefore, lisinopril therapy is not recommended.

Treatment should not be initiated in patients with acute myocardial infarction if renal function is at risk (serum creatinine level above 177 µmol/L and/or albuminuria above 500 mg/24 h). If renal function impairment develops during treatment (serum creatinine level above 265 µmol/L or more than twice the baseline level), the physician should consider discontinuing therapy.

Hypersensitivity, angioedema

Angioedema of the face, extremities, lips, tongue, pharynx, and/or larynx has been rarely reported in patients receiving ACE inhibitors, including lisinopril. Angioedema may develop during treatment in 0.1–1.0% of patients. In such cases, treatment must be discontinued immediately, and the patient should remain under medical supervision until complete resolution of symptoms.

Even with rapid and complete resolution of facial and lip swelling, antihistamines may be used to relieve symptoms. Angioedema involving the larynx may be fatal. Involvement of the tongue, glottis, or respiratory tract may cause airway obstruction; therefore, immediate appropriate treatment is required: subcutaneous injection of 0.3–0.5 mL of 0.1% epinephrine solution (0.3–0.5 mg epinephrine) or slow intravenous injection of 0.1 mL, administration of glucocorticoids, and antihistamines.

Surgery/anesthesia

During invasive surgery or general anesthesia with agents that may provoke arterial hypotension, lisinopril inhibits the formation of angiotensin II despite compensatory renin release. Arterial hypotension resulting from this mechanism can be corrected by volume expansion.

Hemodialysis

Anaphylactoid reactions have been reported in patients undergoing dialysis with high-flux polyacrylonitrile membranes (e.g., AN 69) while concurrently taking an ACE inhibitor. This combination should be avoided, and consideration should be given to using an alternative dialysis membrane or a different class of antihypertensive agents.

Low-density lipoprotein (LDL) apheresis

Life-threatening anaphylactoid reactions (such as profound arterial hypotension, respiratory distress, vomiting, allergic skin reactions) may occur in patients receiving ACE inhibitors during LDL apheresis with dextran sulfate. Therefore, during LDL apheresis, ACE inhibitors used for the treatment of arterial hypertension or heart failure should be temporarily replaced with other agents.

Insect venom immunotherapy may cause anaphylactoid reactions in some patients taking ACE inhibitors. These life-threatening reactions can be avoided by temporarily discontinuing ACE inhibitors prior to desensitization.

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, thrombocytopenia, and anemia may develop during ACE inhibitor therapy in patients with arterial hypertension. These conditions are rarely observed in patients with normal renal function and in the absence of other complications. Neutropenia and agranulocytosis resolve after discontinuation of ACE inhibitor therapy. Lisinopril should be used with particular caution in patients with impaired renal function, especially in those with diseases affecting the vasculature of both kidneys and connective tissue (e.g., systemic lupus erythematosus or scleroderma), as well as during concomitant immunosuppressive therapy (e.g., corticosteroids, cytotoxic agents, antimetabolites). ACE inhibitor use in such patients may be associated with severe infections, which in some cases do not respond to intensive antibiotic treatment.

In such patients, periodic monitoring of blood leukocyte levels during lisinopril therapy is recommended, and patients should be advised to report any signs of infection.

Proteinuria

Isolated cases of proteinuria have been reported in patients, particularly those with reduced renal function or after high-dose lisinopril administration. Lisinopril should be used only after careful assessment of therapeutic benefit versus potential risk and with continuous monitoring of clinical and biochemical parameters in cases of clinically significant proteinuria (exceeding 1 g per day).

Ethnic characteristics (race)

ACE inhibitors cause angioedema more frequently in black patients than in white patients.

As with other ACE inhibitors, the efficacy of lisinopril is lower in black patients due to a higher prevalence of low-renin hypertension in this population compared to white patients.

Hepatic impairment

Very rarely, ACE inhibitors may accelerate the development of cholestatic jaundice or hepatitis, which may rapidly progress to necrosis and, in some cases, result in death. The underlying mechanism is unknown. If jaundice or marked elevation of liver enzymes occurs in patients taking lisinopril, the drug should be discontinued and alternative therapy initiated.

Hyperkalemia

Lisinopril therapy may be associated with hyperkalemia, particularly in patients with renal impairment and/or heart failure. Potassium supplementation or concomitant use of potassium-sparing diuretics is generally not recommended, as it may lead to significant increases in serum potassium levels. If concomitant use of these agents is unavoidable, frequent monitoring of serum potassium levels is recommended.

In elderly patients, the same doses may result in higher plasma concentrations; therefore, dosage should be determined with particular caution, taking into account the patient's renal function. Nevertheless, no significant differences in antihypertensive efficacy of lisinopril have been observed between younger and elderly patients.

Cough

Cough has been reported during ACE inhibitor therapy. The cough is typically dry and non-productive and resolves after discontinuation of treatment.

Diabetes mellitus

More careful monitoring of blood glucose levels is required during the first month of ACE inhibitor therapy, in addition to ongoing insulin or oral hypoglycemic agent treatment.

Lithium preparations

Concomitant use of lithium and lisinopril is not recommended.

Use during pregnancy or breastfeeding.

Pregnancy.

This medicinal product is contraindicated in pregnant women or women planning pregnancy. If pregnancy is confirmed during treatment with this medicinal product, administration should be discontinued immediately, and if necessary, replaced with another medicinal product approved for use during pregnancy.

It is known that prolonged exposure to ACE inhibitors during the second and third trimesters of pregnancy induces fetotoxicity (impaired renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia). If exposure to ACE inhibitors occurs during the second trimester of pregnancy, renal and skull bone function should be monitored by ultrasound.

Newborns whose mothers received lisinopril should be carefully monitored for arterial hypotension, oliguria, and hyperkalemia.

Breastfeeding.

Since information on the use of lisinopril during breastfeeding is lacking, lisinopril administration is not recommended.

Ability to affect reaction speed when driving or operating machinery.

Due to the possibility of dizziness and fatigue, lisinopril may affect the ability to drive vehicles or operate machinery, especially at the beginning of treatment. Therefore, patients should refrain from driving or operating machinery until individual response to the drug is established.

Dosage and Administration.

Take once daily at the same time each day, regardless of food intake.

Essential Hypertension.

Initial dose. The recommended initial dose is usually 10 mg. In patients with a highly active renin-angiotensin-aldosterone system (particularly those with renovascular hypertension, excessive sodium chloride excretion and/or dehydration, cardiac decompensation, or severe arterial hypertension), an excessive reduction in arterial pressure may occur after the first dose. Therefore, such patients should be under medical supervision at the beginning of treatment, and the recommended initial dose should be 2.5*-5 mg.

Patients with renal impairment also require a reduced initial dose (see table).

Maintenance dose. The usual effective maintenance dose is 20 mg once daily. If the desired therapeutic effect is not achieved within 2–4 weeks of treatment, the dose may be increased further. The maximum daily dose should not exceed 80 mg.

If patients are taking diuretics, these should be discontinued 2–3 days before starting lisinopril therapy. If this is not possible, the initial dose of lisinopril should not exceed 5 mg daily, and medical supervision after the first dose is recommended due to the possible development of symptomatic hypotension (maximum effect occurs approximately 6 hours after drug administration).

Arterial hypotension may develop at the beginning of lisinopril therapy, particularly in patients already receiving diuretics. Since dehydration and/or excessive sodium chloride excretion may occur in these patients, lisinopril should be used with caution.

Heart Failure.

Lisinopril may be used concomitantly with diuretics and/or digitalis preparations. If possible, the dose of diuretic should be reduced prior to initiating therapy. The initial daily dose of lisinopril is 2.5* mg, which may be gradually increased to a maintenance dose of 5–20 mg daily.

The recommended dose increment after 2 weeks should not exceed 10 mg.

The maximum daily dose of lisinopril is 35 mg/day.

Before initiating lisinopril therapy and during treatment, arterial pressure, renal function parameters, and serum potassium and sodium concentrations should be monitored regularly to avoid the development of arterial hypotension and associated renal dysfunction.

Diabetic Nephropathy.

The daily dose for non-insulin-dependent diabetic patients with arterial hypertension is 10 mg as a single daily dose. If necessary, the dose may be increased to 20 mg daily to achieve optimal diastolic pressure (should be below 90 mm Hg).

Acute Myocardial Infarction.

When lisinopril is used within the first 24 hours after myocardial infarction, the initial dose should be 5 mg daily. After 24 hours, another 5 mg dose is administered; after 48 hours, 10 mg is given, followed by a maintenance dose of 10 mg daily. The treatment course lasts 6 weeks. If needed, treatment should follow the standard regimen for such cases, including administration of thrombolytic agents, acetylsalicylic acid, and β-blockers.

In cases of low systolic pressure (≤120 mm Hg) or within the first 3 days after myocardial infarction, a low dose (2.5* mg daily) is indicated. Subsequently, if the patient's condition allows, treatment may continue with higher doses. If arterial hypotension develops (systolic pressure ≤100 mm Hg), the maintenance dose should be reduced to 5 mg daily, and if necessary, further reduced temporarily to 2.5* mg daily.

Indications for discontinuing lisinopril therapy include persistent arterial hypotension when systolic pressure remains below 90 mm Hg one hour after drug administration.

If heart failure develops, dosing instructions provided in the relevant section should be followed.

* If a 2.5 mg dose is required, lisinopril in the appropriate strength or dosage form should be used.

Patients with Impaired Renal Function.

Since lisinopril is eliminated via the kidneys, the initial dose depends on creatinine clearance. The maintenance dose depends on clinical response and should be adjusted based on regular monitoring of renal function parameters and serum potassium and sodium concentrations.

* Lisinopril may be discontinued during dialysis.

The dose and frequency of administration of the medicinal product are determined according to the parameters of arterial pressure reduction.

The maximum dose of lisinopril is 40 mg/day.

Use in elderly patients

Clinical studies have not revealed differences in the efficacy or safety of lisinopril treatment depending on age. Since impaired renal function is often observed in elderly patients, the dose should be adjusted according to that recommended for renal insufficiency.

Use in patients with kidney transplant

There is no experience with the use of lisinopril immediately after kidney transplantation; therefore, treatment with Lisinopril is not recommended in such patients.

Children

The drug is not administered to children.

Overdose

Data on overdose in humans are limited. Symptoms associated with overdose of ACE inhibitors may include arterial hypotension, circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, restlessness, and cough.

Treatment: Symptomatic therapy. In addition to general measures aimed at removing lisinopril from the body (gastric lavage, administration of adsorbents, and potassium sulfate within 30 minutes after lisinopril intake), continuous monitoring and correction of vital signs in an intensive care unit are required. Continuous monitoring of serum electrolyte levels and serum creatinine concentration is necessary.

Recommended treatment for overdose includes intravenous administration of normal saline solution and fluid volume repletion. If these measures do not achieve the desired effect, intravenous administration of catecholamines is required. Treatment with angiotensin II should also be considered.

Bradycardia may be treated with atropine. Pacemaker insertion should be considered in cases of treatment-resistant bradycardia.

Lisinopril can be removed from systemic circulation by hemodialysis. During dialysis, the use of high-flux polyacrylonitrile membranes should be avoided.

Adverse Reactions

Adverse effects are generally mild and transient; discontinuation of treatment is required only in extreme cases.

Blood system: Bone marrow suppression, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia, lymphadenopathy.

Immune system: Autoimmune disorders, angioedema.

Endocrine system: Syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Metabolic disturbances: Hypoglycemia.

Nervous system: Dizziness, headache, paresthesia, vertigo, taste disturbances, syncope.

Psychiatric disorders: Mood changes, sleep disturbances, confusion, depression.

Cardiovascular system: Palpitations, tachycardia; myocardial infarction may occur as a complication of excessive arterial hypotension in high-risk patients; orthostatic reactions (including arterial hypotension); cerebrovascular disorders may occur as a complication of excessive arterial hypotension in high-risk patients; Raynaud's phenomenon.

When lisinopril is administered to patients with acute myocardial infarction, second- or third-degree atrioventricular block, severe arterial hypotension and/or renal dysfunction may occur, particularly within the first 24 hours; in isolated cases – cardiogenic shock.

Respiratory system: Cough, rhinitis, bronchospasm, sinusitis, allergic alveolitis, eosinophilic pneumonia.

Gastrointestinal tract: Vomiting, diarrhea, nausea, abdominal pain, dyspepsia, dry mouth, pancreatitis, intestinal angioneurotic edema.

Hepatobiliary system: Hepatocellular or cholestatic jaundice, hepatitis, hepatic failure.

Skin: Rash, pruritus, hypersensitivity/angioedema (face, extremities, lips, tongue, glottis and/or larynx), urticaria, alopecia, psoriasis, increased sweating, bullous eruption, toxic epidermal necrolysis, Stevens-Johnson syndrome, polymorphic erythema, cutaneous pseudolymphoma (a complex of symptoms which may include one or several of the following: sensation of heat, muscle and joint pain, arthritis, vasculitis, eosinophilia, leukocytosis and/or positive antinuclear antibodies, increased erythrocyte sedimentation rate (ESR), photosensitization). If a severe skin reaction develops, lisinopril treatment should be discontinued immediately and medical advice should be sought without delay.

Urinary system: Renal function impairment, uremia, acute renal failure, oliguria/anuria.

Reproductive system: Impotence, gynecomastia.

General disorders: Chest pain, fatigue, asthenia.

Laboratory findings: Increased blood urea nitrogen and serum creatinine levels, increased liver enzyme activity, hyperkalemia, increased hematocrit, decreased hemoglobin levels, increased serum bilirubin, hyponatremia.

Regarding the safety of lisinopril-containing drugs, the following adverse reactions have also been reported: impaired balance, disorientation, olfactory disturbances, glossitis, syncope, muscle spasms, dyspnea, upper respiratory tract infections, decreased appetite, constipation, skin hyperemia, proteinuria.

Safety data obtained from clinical trials indicate that lisinopril is generally well tolerated in pediatric patients with arterial hypertension, and the safety profile in this age group is comparable to that observed in adult patients.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets per blister; 1, 2, or 3 blisters per carton.

Prescription status.

Prescription only.

Manufacturer.

ASTRAFARM LLC.

Manufacturer's address and location of business activity.

6, Kyivska Street, Vyshneve, Kyiv-Sviatoshyn District, Kyiv Region, 08132, Ukraine.