Irumed®
Symptomatic hypotension
Most often, a pronounced decrease in blood pressure occurs with a decrease in circulating blood volume (CBV) caused by diuretic therapy, a decrease in sodium chloride in food, dialysis, diarrhea or vomiting. In patients with CHF and with or without renal failure, a pronounced decrease in blood pressure is possible. It is more often detected in patients with severe CHF, as a result of the use of large doses of diuretics, hyponatremia or impaired renal function. In such patients, treatment should be started under strict medical supervision (with caution in selecting the dose of the drug and diuretics). The same recommendations apply to patients with coronary heart disease and cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke.
Transient arterial hypotension is not a contraindication for taking the next dose of the drug. When using lisinopril, some patients with chronic heart failure, but with normal or reduced blood pressure, may experience a decrease in blood pressure, which is usually not a reason to discontinue treatment.
Before starting treatment with lisinopril, if possible, the circulating blood volume should be replenished and/or the sodium content in the blood serum should be normalized, and the condition of patients at increased risk of developing symptomatic hypotension should be carefully monitored at the beginning of treatment and during dose adjustment. If arterial hypotension develops, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of saline.
In case of renal artery stenosis (especially with bilateral stenosis or in the presence of stenosis of the artery of a single kidney), as well as with circulatory failure due to lack of sodium and/or fluid, the use of lisinopril can lead to impaired renal function, acute renal failure, which is usually irreversible even after discontinuation of the drug.
Arterial hypotension in acute myocardial infarction
In acute myocardial infarction, the use of lisinopril is contraindicated in cardiogenic shock and severe arterial hypotension (systolic blood pressure less than 100 mm Hg), since in such patients the use of a vasodilator can significantly worsen hemodynamic parameters. In patients with low systolic blood pressure (> 100 mm Hg and ≤ 120 mm Hg) low doses of lisinopril (2.5 mg once daily) should be used during the first 3 days after acute myocardial infarction. In case of arterial hypotension (systolic blood pressure ≤100 mm Hg), the maintenance dose of lisinopril is temporarily reduced to 5 mg per day, if necessary - to 2.5 mg per day. In case of prolonged pronounced decrease in blood pressure (systolic blood pressure below 90 mm Hg for more than 1 hour), the use of lisinopril should be discontinued.
In acute myocardial infarction, treatment with lisinopril should not be initiated in patients with signs of renal dysfunction, defined as a serum creatinine concentration greater than 177 μmol/L and/or proteinuria greater than 500 mg/24 hours. In case of development of renal dysfunction during therapy with lisinopril (serum creatinine concentration exceeding 265 µmol/l or twice the corresponding value before the start of treatment), the physician should consider the advisability of discontinuing lisinopril.
Mitral stenosis/ aortic stenosis/ hypertrophic obstructive cardiomyopathy
Lisinopril, like other ACE inhibitors. should be used with caution in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis.
Renal dysfunction
In patients with impaired renal function (creatinine clearance less than 80 ml/min), the initial dose of lisinopril should be changed in accordance with the clinical clearance (see section "Dosage and Administration"). Regular monitoring of potassium levels and creatinine concentrations in blood plasma is a mandatory treatment strategy for such patients.
In patients with CHF, arterial hypotension can lead to deterioration of renal function. Cases of acute renal failure, usually reversible, have been reported in such patients.
In some patients with bilateral renal artery stenosis or solitary renal artery stenosis treated with ACE inhibitors, increases in serum urea and creatinine concentrations were observed, usually reversible upon discontinuation of treatment. This is especially likely in patients with kidney failure. In the case of concomitant renovascular hypertension, there is an increased risk of developing severe arterial hypotension and renal failure. In such patients, treatment should be initiated under close medical supervision at low doses and the dose titrated carefully.
Since treatment with diuretics may contribute to the development of the above conditions, the diuretic should be discontinued and renal function should be monitored during the first weeks of lisinopril therapy.
In some patients with arterial hypertension without significant preexisting renovascular hypertension, an increase in serum urea and creatinine concentrations was observed, usually slight and transient, especially in cases where lisinopril was used concomitantly with a diuretic. This is especially likely in patients with pre-existing renal failure. A dose reduction and/or discontinuation of the diuretic and/or lisinopril may be required.
Kidney transplant
There is no experience with the use of lisinopril in patients who have recently undergone kidney transplantation.
Hypersensitivity reactions/angioedema
Angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx has been reported rarely in patients treated with ACE inhibitors, including Irumed®. Angioedema may occur at any time during treatment. In such cases, the drug should be immediately discontinued, appropriate treatment should be prescribed, and medical supervision should be provided until symptoms completely resolve. Even in cases of tongue swelling not accompanied by respiratory failure, patients may require long-term observation as treatment with antihistamines and corticosteroids may not be sufficient.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. When such symptoms appear, emergency treatment is required: administration of epinephrine (0.3-0.5 ml of epinephrine (adrenaline) solution 1:1000 subcutaneously, administration of glucocorticosteroids, antihistamines) and/or ensuring free patency of the airways. The patient should be under medical supervision until symptoms disappear completely and permanently.
In rare cases, intestinal edema (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. Diagnosis is made using abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after stopping the ACE inhibitors. The possibility of developing intestinal edema must be taken into account when carrying out the differential diagnosis of abdominal pain in patients taking ACE inhibitors.
Patients with a history of angioedema not associated with ACE inhibitors may be at greater risk of developing angioedema during ACE inhibitor therapy.
In black patients taking ACE inhibitors. Angioedema was observed more often than in representatives of other races.
An increased risk of angioedema was observed in patients concomitantly taking ACE inhibitors and drugs such as mTOR inhibitors (temsirolimus, sirolimus, everolimus), dipeptidyl peptidase type IV inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin), estramustine, neutral endopeptidase inhibitors (racecadotril). , sacubitril) and tissue plasminogen activators.
The simultaneous use of ACE inhibitors with sacubitril is contraindicated due to the increased risk of angioedema.
Anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom
In patients taking ACE inhibitors during desensitization with Hymenoptera (hymenoptera) venom, a life-threatening anaphylactoid reaction is extremely rare. It is necessary to temporarily stop treatment with an ACE inhibitor before starting a course of desensitization.
Anaphylactoid reactions during low-density lipoprotein apheresis (LDL apheresis)
In patients taking ACE inhibitors, anaphylactoid reactions may develop during LDL apheresis using dextran sulfate. The development of these reactions can be prevented by temporarily discontinuing the ACE inhibitor before each LDL apheresis procedure.
Hemodialysis using high-flow membranes
Anaphylactoid reactions may occur during simultaneous hemodialysis using high-flow membranes (including AN69®). A different type of dialysis membrane or another antihypertensive agent should be considered.
Liver dysfunction
In rare cases, while taking ACE inhibitors, a syndrome of development of cholestatic jaundice with transition to fulminant liver necrosis, sometimes with death, was observed. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of liver enzymes occurs while taking ACE inhibitors, you should stop taking the drug, and the patient should be under appropriate medical supervision.
Neutropenia / agranulocytosis / thrombocytopenia / anemia
While taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Neutropenia and agranulocytosis are reversible and disappear after discontinuation of the ACE inhibitor. Lisinopril should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function. Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When using lisinopril in such patients, periodic monitoring of the leukocyte content in the blood (blood test with leukocyte count) is recommended. Patients should be warned to report any signs of infectious disease (eg, sore throat, fever) to their physician.
Ethnic differences
It should be taken into account that patients of the Negroid race have a higher risk of developing angioedema. Like other ACE inhibitors, lisinopril is less effective in lowering blood pressure in black patients. This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.
Surgical interventions / general anesthesia
Before surgery (including dental surgery), the doctor/anesthesiologist should be informed about the use of an ACE inhibitor. During extensive surgical interventions, as well as when using other drugs that cause a decrease in blood pressure, lisinopril, by blocking the formation of angiotensin II, can cause a pronounced, unpredictable decrease in blood pressure. If arterial hypotension develops, it should be corrected by increasing the volume of blood volume.
Cough
A dry cough has been reported when using ACE inhibitors. 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.
Hyperkalemia
Hyperkalemia may develop during therapy with ACE inhibitors, including lisinopril. Risk factors for the development of hyperkalemia are renal failure, old age (over 65 years), diabetes mellitus, some concomitant conditions (dehydration, decreased blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene or amiloride), as well as potassium preparations, potassium-containing table salt substitutes and other drugs that increase the level of potassium in the blood plasma (for example, heparin). The use of potassium supplements/preparations, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms.
If simultaneous use of lisinopril and the drugs listed above containing potassium or increasing the potassium content in the blood plasma is necessary, caution should be exercised and the potassium content in the blood serum should be regularly monitored.
Patients with diabetes mellitus
When using lisinopril in patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of therapy.
Lithium preparations
As a rule, the simultaneous use of lithium and lisinopril is not recommended.
Ethanol
During the treatment period, it is not recommended to drink alcoholic beverages, since ethanol enhances the antihypertensive effect of ACE inhibitors.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
Cases of hypotension, syncope, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in susceptible patients, especially when multiple drugs that affect the RAAS are used concomitantly.
The simultaneous use of ACE inhibitors with medicinal products containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.
Concomitant use of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
In cases where the simultaneous administration of two drugs acting on the RAAS is necessary, their use should be carried out under the supervision of a physician with extreme caution and with regular monitoring of renal function, blood pressure and electrolyte levels in the blood plasma.
Combination therapy
In acute myocardial infarction, the use of standard therapy (thrombolytics, acetylsalicylic acid as an antiplatelet agent, beta-blockers) is indicated. Lisinopril can be used in conjunction with intravenous or therapeutic transdermal nitroglycerin systems.
Elderly age
In elderly patients, the use of standard doses of lisinopril results in higher plasma concentrations of lisinopril. Therefore, special care is required when determining the dose, despite the fact that no differences in the antihypertensive effect of lisinopril were identified in elderly and young patients.
Irumed, 20 mg, tablets, 30 pcs.
Symptomatic hypotension.
Most often, a pronounced decrease in blood pressure occurs with a decrease in fluid volume caused by diuretic therapy, a decrease in salt content in food, dialysis, diarrhea or vomiting (see “Interactions” 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 in patients with coronary artery disease and 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, the patient should be placed in the “lying” position and, if necessary, a 0.9% sodium chloride solution should be administered 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 Irumed®.
In acute myocardial infarction.
The use of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers) is indicated. Irumed® can be used in conjunction with intravenous administration or with the use of transdermal nitroglycerin systems.
Treatment with lisinopril should not be used in patients with acute myocardial infarction (at risk of further serious hemodynamic deterioration after use of vasodilators). These are patients with SBP - 100 mm Hg. or lower or cardiogenic shock. During the first 3 days after myocardial infarction, the dose should be reduced if SBP is 120 mm Hg. or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg if SBP is 100 mmHg. or lower.
If arterial hypotension persists (SBP less than 90 mmHg for more than 1 hour), treatment with Irumed should be discontinued.
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 levels, usually reversible after discontinuation of treatment. This was more common in patients with renal failure.
Lisinopril is not used for acute myocardial infarction in patients with severe renal dysfunction, as determined by measuring serum creatinine concentrations greater than 177 mmol/L and/or proteinuria greater than 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, is rarely observed in patients treated with an ACE inhibitor, including lisinopril. In this case, treatment should be stopped as soon as possible and the patient should be monitored until complete regression of symptoms. 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 may cause airway obstruction, so appropriate therapy (0.3–0.5 ml of 1:1000 SC epinephrine solution) 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 hymenopterans.
In patients taking ACE inhibitors, a life-threatening anaphylactoid reaction may extremely rarely occur during desensitization to hymenopterans. 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 using high-permeability membranes (for example AN 69®), who are simultaneously taking ACE inhibitors. In such cases, the use of a different type of dialysis membrane or another antihypertensive drug should be considered.
Cough.
When using ACE inhibitors, a dry, prolonged cough was noted, which disappears after stopping treatment with ACE inhibitors. 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 used in patients undergoing major surgery or during general anesthesia, lisinopril may block the formation of angiotensin II secondary to compensatory renin release. A pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by increasing the volume of blood volume. 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 the level of potassium in the blood serum.
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-mentioned conditions (loss of fluid and salts) must be compensated and monitored before starting treatment 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 Irumed®, used in therapeutic doses, on the ability to drive vehicles and machines, however, it must be taken into account that dizziness may occur.
