Diroton Plus capsules with modified release 1.5mg+20mg, 28pcs

Composition

Active ingredients:  indapamide – 1,500 mg, lisinopril dihydrate-21.776 mg (equivalent to lisinopril-20,000 mg). Excipients: lactose monohydrate – 84,000 mg, calcium hydrophosphate dihydrate – 106,244 mg, hypromellose (type 2208) – 49,500 mg, mannitol – 33,340 mg, corn starch – 24,300 mg, microcrystalline cellulose, type 102 – 9,000 mg, croscarmellose sodium – 6,000 mg, talc – 5,000 mg, magnesium stearate – 4,090 mg, colloidal silicon dioxide – 0.750 mg, opadray II white – 4,500 mg (contains: polyvinyl alcohol – 40.0%, titanium dioxide – 25.0%, macrogol-3350 – 20.20%, talc 14.80%), solid gelatin capsule – 76 mg (contains: iron oxide red dye – 0.5000%, crimson dye (Ponso 4R) – 0.2156%, titanium dioxide -0.8000%, gelatin – 83.9800%, water – 14.5000%).

Pharmacological action

Diroton® Plus is a combination drug with fixed doses of lisinopril and indapamide. Indapamide It is a sulfonamide derivative containing an indole ring Pharmacological properties of indapamide are similar to thiazide-like diuretics, which inhibit the reabsorption of sodium ions in the cortical segment of the Henle loop. This is accompanied by an increase in the excretion of sodium, chloride and potassium ions and, to a lesser extent, magnesium ions, which leads to increased diuresis and antihypertensive effect. In phase II and III clinical trials, the use of indapamide as monotherapy in doses that do not cause a pronounced diuretic effect caused a 24-hour antihypertensive effect. The antihypertensive activity of indapamide leads to an improvement in the elasticity index of large arteries and to a decrease in total peripheral and arteriolar resistance. Indapamide reduces left ventricular hypertrophy. In certain doses, the optimal therapeutic effect of thiazide and thiazide-like diuretics is achieved, however, with further increase in the dose, the frequency of side effects increases. Therefore, the dose should not be increased if the therapeutic effect is not achieved when using the drug at the recommended therapeutic doses. In short -, medium-and long-term studies involving patients with arterial hypertension, indapamide has been shown to be effective in the treatment of hypertension. :  

• It does not affect lipid metabolism, including the concentration of triglycerides, cholesterol, low-and high-density lipoproteins.
• it does not affect carbohydrate metabolism, including in patients with diabetes mellitus.

Lisinopril

It is an angiotensin-converting enzyme ACE inhibitor that inhibits the conversion of angiotensin I to angiotensin II. A decrease in the concentration of angiotensin II leads to a direct decrease in the secretion of aldosterone. Lisinopril inhibits bradykinin degradation and increases prostaglandin synthesis. Reduces total peripheral vascular resistance, blood pressure, preload, and pulmonary capillary pressure.

In patients with chronic heart failure, lisinopril increases the minute volume of blood and increases the tolerance of the myocardium to stress. Dilates the arteries to a greater extent than the veins. Some of the effects are explained by the effect on the tissue renin-angiotensin systems. With prolonged use, hypertrophy of the myocardium and arterial walls of the resistive type decreases.

Lisinopril improves blood supply to the ischemic myocardium.

In patients with chronic heart failure, ACE inhibitors increase life expectancy; in patients with a history of myocardial infarction without clinical manifestations of heart failure, lisinopril slows the progression of left ventricular dysfunction.

Lisinopril begins to act within 1 hour after ingestion. The maximum effect is achieved within 6-7 hours; the duration of the effect is 24 hours.

In patients with arterial hypertension, the effect appears within the first days after the start of treatment; a stable effect occurs within 1-2 months of treatment. Cases of marked increase in blood pressure (BP) after abrupt discontinuation of the drug have not been reported. Lisinopril reduces both blood pressure and albuminuria.

In patients with hyperglycemia, lisinopril promotes the restoration of impaired glomerular endothelial function.

In patients with diabetes mellitus, lisinopril does not affect the concentration of plasma glucose; taking the drug is not associated with an increased risk of hypoglycemia.

Indications

Essential arterial hypertension (patients requiring combination therapy).

Contraindications

• Hypersensitivity to lisinopril or other ACE inhibitors.
• Hypersensitivity to indapamide or other sulfonamide derivatives.
• Hypersensitivity to excipients of the drug.
• A history of angioedema, including angioedema associated with the use of ACE inhibitors.
• Hereditary or idiopathic angioedema.
• Severe renal insufficiency (creatinine clearance
• Hepatic encephalopathy or severe hepatic impairment.
• Hypokalemia.
• Simultaneous use of Diroton® Plus and drugs containing aliskiren in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR)
• Pregnancy or breastfeeding.
• Age up to 18 years (efficacy and safety have not been established).
• Lactose intolerance, galactosemia, glucose and galactose malabsorption syndrome.

Side effects

The frequency of adverse reactions is presented separately for lisinopril and indapamide. The following adverse drug reactions (NLR) have been reported with isolated use of lisinopril and indapamide. The frequency is defined as follows: Very often – 1/10 of appointments (>10%). Frequently – 1/100 appointments (>1% and >Infrequently – 1/1000 appointments (>0.1% and >Rarely – 1/10000 appointments (>0.01% and >Very rare – less than 1/10000 appointments (The frequency is unknown (the frequency cannot be estimated based on the available data). Within each frequency group, adverse reactions are presented in order of decreasing severity. Related to Indapamide

Most of the adverse reactions (laboratory and clinical changes) are dose-dependent. Disorders of the blood and lymphatic system: very rarely-thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

Nervous system disorders: rarely-asthenia, headache, paresthesia, dizziness; frequency unknown-syncope.

Disorders of the cardiovascular system: very rarely – arrhythmia, severe hypotension; frequency unknown-ventricular tachycardia of the “pirouette” type (life-threatening condition).

Gastrointestinal disorders: infrequently-vomiting; rarely-nausea, constipation, dry mouth; very rarely-pancreatitis.

Renal and urinary tract disorders: very rare – renal failure.

Liver and biliary tract disorders: very rare-impaired liver function; frequency unknown – in case of hepatic insufficiency, hepatic encephalopathy may develop; hepatitis.

Skin and subcutaneous tissue disorders: hypersensitivity reactions, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions.

Often-maculopapular rash; infrequently-hemorrhagic vasculitis; very rarely-angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; frequency unknown – possible deterioration in patients with acute systemic lupus erythematosus. Cases of photosensitivity reactions have been reported.

Influence on the results of laboratory and instrumental studies: frequency unknown-prolongation of the QT interval on the ECG; increased uric acid and glucose concentrations-in patients with gout and diabetes mellitus, treatment with thiazide and thiazide-like diuretics should be carried out with caution; increased activity of “liver” enzymes. In clinical trials, hypokalemia (less than 3.4 mmol/l of potassium in the blood plasma) was observed in 10% of patients and 3.2 mmol/l in 4% of patients after 4-6 weeks of treatment.

After 12 weeks, the potassium content in blood plasma decreased, on average, by 0.23 mmol / l; very rarely – hypercalcemia; frequency unknown-decrease in potassium content and development of hypokalemia, especially significant for patients at risk; hyponatremia, accompanied by hypovolemia, dehydration and orthostatic hypotension. Concomitant chloride reduction can lead to compensatory metabolic alkalosis, but its frequency and severity are insignificant.

Related to Lisinopril

The most common adverse reactions include dizziness, headache, fatigue, diarrhea, dry cough, and nausea.

Disorders of the blood and lymphatic system: rarely-decreased hemoglobin and hematocrit; very rarely-leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia; frequency unknown-erythrocytopenia.

Immune system disorders: infrequently-skin rash, pruritus; rarely – angioedema of the facial region, angioedema of the extremities, lips, tongue, epiglottis and / or larynx; very rarely – interstitial angioedema; frequency unknown – fever, positive antinuclear antibody test result, increased erythrocyte sedimentation rate, eosinophilia, leukocytosis.

Mental disorders: infrequently-emotional lability; rarely-confusion.

Nervous system disorders: infrequently-paresthesia, drowsiness; rarely-asthenic syndrome; frequency unknown – twitching of the muscles of the limbs and face.

Cardiac disorders: infrequently-chest pain; rarely-tachycardia, bradycardia, increased symptoms of heart failure, atrioventricular conduction disorders, myocardial infarction, palpitation sensation.

Vascular disorders: often-marked decrease in blood pressure; rarely-orthostatic hypotension; frequency unknown-vasculitis.

Respiratory, thoracic and mediastinal disorders: very rare – bronchospasm; frequency unknown-shortness of breath.

Gastrointestinal disorders: infrequently-dyspepsia, dysgeusia, abdominal pain; rarely-dry mouth; very rarely-pancreatitis; frequency unknown-decreased appetite.

Liver and biliary tract disorders: very rarely – hepatic-cellular and cholestatic jaundice, hepatitis.

Skin and subcutaneous tissue disorders: infrequently-pruritus; rarely-urticaria, alopecia; very rarely-sweating; frequency unknown-photosensitization.

Musculoskeletal and connective tissue disorders: frequency unknown-myalgia, arthralgia/arthritis.

Renal and urinary tract disorders: often-impaired renal function; rarely-acute renal failure, uremia; very rarely-oliguria, anuria; frequency unknown-proteinuria.

Genital and breast disorders: infrequently-decreased potency.

Influence on the results of laboratory and instrumental studies: infrequently-hyperkalemia, hyponatremia; rarely-increased activity of “liver” enzymes, hyperbilirubinemia, increased creatinine and urea concentrations.

If any of the side effects listed in the instructions get worse, or you notice any other side effects that are not listed in the instructions, tell your doctor.

Interaction

Interactions with indapamide

Undesirable combination of medications 

Lithium preparations

With the combined use of indapamide and lithium preparations, it is possible to increase the content of lithium in blood plasma due to a decrease in excretion, which leads to intoxication. If necessary, combined use of diuretics with lithium preparations is possible, but it is necessary to carefully select the dose of drugs and regularly monitor the lithium content in blood plasma.

A combination of drugs that requires special attention

Medications that can cause pirouette-type arrhythmias:

• Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
• Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);
• Some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);
• Others: bepridil, cisapride, difemanil, erythromycin (intravenous), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (iv).

Increased risk of ventricular arrhythmia, in particular, cardiac arrhythmias such as “pirouette” (risk factor-hypokalemia). Determination of the potassium content in blood plasma and, if necessary, its correction before the combined use of indapamide and the above drugs is shown. It is necessary to monitor the patient’s clinical condition, the content of electrolytes in the blood plasma and ECG. Patients with hypokalemia should take medications that do not cause cardiac arrhythmias.

Nonsteroidal anti-inflammatory drugs (with systemic use), including selective COX-2 inhibitors, salicylates in high doses (>3 g / day).

It is possible to reduce the antihypertensive effect of indapamide.

With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration). Replacement of fluid loss and careful monitoring of renal function at the beginning of treatment is indicated.

Angiotensin-converting enzyme inhibitors

The use of ACE inhibitors in patients with reduced plasma sodium levels (especially in patients with renal artery stenosis) leads to severe hypotension and/or acute renal failure. Patients with arterial hypertension and a possible decrease in the sodium content in the blood plasma due to the appointment of diuretics are indicated:

• Discontinuation of diuretics three days before the appointment of ACE inhibitors. In the future, if necessary, it is possible to resume taking diuretics.
• Or the use of ACE inhibitors in smaller doses with a gradual increase in the dose if necessary.

In the case of chronic heart failure, ACE inhibitors should be administered in lower doses with possible preliminary reduction in the dose of diuretics. In all cases, monitoring of renal function is indicated in the first week after use of an ACE inhibitor (blood creatinine concentration). Other drugs that may cause hypokalemia: amphotericin B (IV), gluco-and mineralocorticosteroids (with systemic use), tetracosactide, laxatives that stimulate intestinal motility.

Increased risk of hypokalemia (additive effect).

Regular monitoring of the potassium content in the blood plasma and, if necessary, its correction is indicated. Patients receiving cardiac glycosides require special attention. It is recommended to use laxatives that do not stimulate intestinal motility.

Baclofen

Increased antihypertensive effects have been reported.

Patients should receive fluid replacement and renal function monitoring at the beginning of treatment.

Cardiac Glycosides: 

Hypokalemia increases the toxic effects of cardiac glycosides. With the combined use of indapamide and cardiac glycosides, monitoring of the potassium content in blood plasma, as well as ECG, is indicated. If necessary, therapy should be corrected.

Drug combinations that require attention

Potassium-sparing diuretics (amiloride, spironolactone, triamterene) Combined use of potassium-sparing diuretics and indapamide is effective in some patients. Despite this, the risk of hypokalemia (especially in patients with diabetes mellitus and renal insufficiency) or hyperkalemia cannot be ignored.

It shows monitoring and, if necessary, correction of the potassium content in blood plasma, as well as ECG monitoring.

Metformin

Functional renal failure, which may occur with the use of diuretics, especially loop diuretics, increases the risk of lactic acidosis with the combined use of metformin.

Metformin should not be used if creatinine concentrations exceed 15 mg / l (135 mmol/l) in men and 12 mg/l (110 mmol/l) for women.

Iodine-containing radiopaque preparations

Dehydration with diuretics may increase the risk of acute renal failure, especially when using high-dose iodine-containing medications.

It is necessary to make up for the loss of fluid before prescribing iodine-containing radiopaque drugs.

Tricyclic antidepressants, antipsychotic drugs (neuroleptics) 

Drugs of this class enhance the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

Calcium Salts

When used in combination, the risk of hypercalcemia increases due to a decrease in the excretion of calcium by the kidneys.

Cyclosporine, tacrolimus

It is possible to increase the concentration of creatinine in blood plasma at an unchanged concentration of circulating cyclosporine, even with normal circulating blood volume and sodium content in blood plasma.

Corticosteroid medications, tetracosactide (for systemic use) 

Reduced antihypertensive effects (fluid and sodium retention caused by corticosteroids).

Interactions with lisinopril

Potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes

Concomitant use of lisinopril with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, and potassium-containing salt substitutes is associated with an increased risk of hyperkalemia, especially in patients with impaired renal function.

Diuretics

Concomitant use with other diuretics leads to a significant reduction in the risk of stroke. Other antihypertensive drugs

Combined use with other antihypertensive drugs leads to an additive effect.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of >3 g/day >

Combined use with nonsteroidal anti-inflammatory drugs (indomethacin, etc. ), estrogens and adrenal stimulants leads to a decrease in the antihypertensive effect of lisinopril.

Lithium 

Concomitant use with lithium preparations helps to slow down the elimination of lithium.

Antacids and cholestyramine

Concomitant use with antacids and cholestyramine leads to suppression of gastrointestinal absorption.

Ethanol

Ethanol enhances the effect of lisinopril.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin II receptor antagonists, ACE inhibitors, or aliskiren

Clinical studies have shown that double blockade of the RAAS in combination with ACE inhibitors, angiotensin II receptor blockers or aliskiren leads to an increased incidence of side effects such as hypotension, hyperkalemia and decreased renal function (including acute renal failure), compared with the use of only one drug that affects the RAAS.

How to take, course of use and dosage

Inside. The drug Diroton® Plus, you can take it regardless of food intake. Dosage As a general rule, fixed-dose combination medications should not be used for initial therapy. The drug Diroton® Plus is prescribed to adult patients who have achieved adequate control of arterial hypertension while taking lisinopril and indapamide, which the patient takes simultaneously in the same doses as in the combined drug. The recommended dose is 1 capsule per day, preferably in the morning, at the same time every day. The maximum daily dose is 1 capsule. If dose adjustment is necessary, indapamide and lisinopril should be administered separately. Special groups of patientspatients with impaired renal function on the background of therapy with Diroton® Plus, it is necessary to monitor kidney function, as well as the content of potassium and sodium in the blood plasma. In case of deterioration of renal function, the drug Diroton® Plus, it should be canceled and replaced with individually selected drugs. Children and teenagers (Safety and efficacy of Diroton® Plus in children and adolescents is not established. Elderly patients (>65 years)This medication should be used with caution in elderly patients. It is necessary to monitor the concentration of creatinine in the blood plasma and assess its compliance with age, body weight and gender.

Overdose

Overdose of indapamide No toxic effects of indapamide were observed in overdose, even in very high doses (up to 40 mg, i. e. 27 times higher than the therapeutic dose). Symptoms of acute intoxication of the drug depend primarily on the water-electrolyte imbalance (hyponatremia, hypokalemia). Clinical manifestations of overdose may include nausea, vomiting, decreased blood pressure, seizures, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia). Emergency measures include removing the drug from the body, gastric lavage, and / or taking activated charcoal to restore water and electrolyte balance. Lisinopril overdose Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability. Treatment: symptomatic therapy, intravenous use of 0.9% sodium chloride solution and vasopressors (in the absence of contraindications), blood pressure control, water-electrolyte balance control. Hemodialysis is possible

Special instructions

If you are hospitalized, tell your doctor that you are taking Diroton Plus. If you forgot to take Diroton® Plus, wait and take the next dose at the usual time. Do not take two capsules to make up for a missed dose. When using the drug Diroton® Plus, you need to take into account special instructions regarding individual components of the drug. Related to Indapamide

Impaired liver function

When prescribing thiazide and thiazide-like diuretics to patients with impaired liver function, hepatic encephalopathy may develop, especially in the presence of an electrolyte imbalance. In this case, it is necessary to stop using diuretics. Photosensitization

Photosensitization has been reported with thiazide and thiazide-like diuretics. With the development of photosensitization during therapy, the withdrawal of these drugs is indicated. If it is necessary to continue treatment, it is recommended to protect the skin from sunlight or artificial UV radiation.

Water-electrolyte balance

Blood plasma sodium content

The sodium content in the blood plasma should be determined before starting treatment. During the entire period of therapy, regular monitoring of this parameter is indicated. All diuretics can cause hyponatremia, which can sometimes have very serious consequences.

Constant monitoring of the sodium content in the blood plasma is necessary, since at the beginning of therapy such a decrease may not be accompanied by the appearance of pathological symptoms. Sodium monitoring should be carried out especially carefully in patients with cirrhosis of the liver and in elderly patients.

Potassium content in blood plasma

Against the background of therapy with thiazide and thiazide-like diuretics, a sharp decrease in the content of potassium in blood plasma is possible, as well as the development of hypokalemia. It is necessary to minimize the risk of hypokalemia (/l) in the following groups of patients: elderly patients, debilitated patients, patients receiving combination therapy with other progivoarrhythmic drugs and drugs that can prolong the QT interval, patients with cirrhosis of the liver, peripheral edema and ascites, coronary insufficiency, heart failure.

In such patients, hypokalemia increases the toxic effects of cardiac glycosides and increases the risk of arrhythmias. In addition, patients with an extended QT interval should be considered a high-risk group, regardless of whether they have the above conditions or the influence of medications.

Hypokalemia, also known as bradycardia, is a condition that contributes to the development of severe arrhythmias and, in particular, heart rhythm disorders that can lead to death. Regular monitoring of the potassium content in blood plasma in these groups of patients is indicated, starting from the first week of treatment. If hypokalemia is detected, appropriate therapy is indicated.

Blood plasma calcium content

Thiazide and thiazide-like diuretics have been reported to reduce the excretion of calcium by the kidneys, which leads to a slight temporary increase in the content of calcium in the blood plasma. Hypercalcemia with clinical manifestations may be the result of previously undiagnosed hyperparathyroidism. In this case, it is necessary to cancel diuretics before examining the function of the parathyroid glands.

Blood plasma glucose

Glucose control is indicated in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

Patients suffering from gout may have an increased frequency of attacks or exacerbation of the course of gout.

Diuretics and kidney function

Thiazide and thiazide-like diuretics are most effective in patients with normal or slightly reduced renal function (adult plasma creatinine The concentration of creatinine in blood plasma in elderly patients is estimated depending on age, body weight and gender.

At the beginning of treatment, patients show a decrease in glomerular filtration rate due to hypovolemia, which may be associated with the loss of water and sodium ions due to the action of diuretics. In this regard, it is possible to increase the concentration of uric acid and creatinine in the blood plasma.

In the absence of impaired renal function, such transient functional renal failure usually passes without complications, but the general condition of patients may worsen in the presence of renal failure.

Athletes

Since indapamide is a part of the drug Diroton® Plus, a positive result of a doping test in athletes is possible.

Lactose

The drug contains lactose, so it should not be taken in patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Related to Lisinopril

Symptomatic arterial hypotension

The most common significant decrease in blood pressure is associated with hypovolemia caused by the use of diuretics, a decrease in the amount of salt in food, dialysis, diarrhea or vomiting.

Patients with chronic heart failure, regardless of whether it is associated with renal failure, may develop hypotension. Patients with severe heart failure have been found to develop this condition more frequently due to high-dose diuretics, hyponatremia, or impaired renal function.

In such patients, careful medical monitoring is required (careful selection of doses of lisinopril and diuretics is indicated). The same guidelines apply to patients with coronary heart disease and cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to a myocardial infarction or stroke.

With a significant decrease in blood pressure, the patient should take a horizontal position; an intravenous injection of 0.9% sodium chloride solution is possible.

Transient hypotensive reactions are not a contraindication to the use of the next dose of lisinopril.

In patients with chronic heart failure with normal or reduced blood pressure, the use of lisinopril can lead to a decrease in blood pressure; this usually does not serve as a reason for discontinuing the drug. If hypotension is associated with clinical manifestations, consideration should be given to reducing the dose or discontinuing lisinopril.

In patients at risk of developing symptomatic hypotension (with a low-salt or salt-free diet), regardless of the presence of hyponatremia, as well as in patients receiving high-dose diuretics, it is necessary to achieve compensation for these conditions (hypovolemia or lack of sodium) before starting treatment. Control of the effect of the initial dose of lisinopril on blood pressure is shown.

Acute myocardial infarction

Standard treatment (thrombolytics, acetylsalicylic acid, beta-blockers) is recommended.

Lisinopril can be used in combination with intravenous nitroglycerin or transdermal nitroglycerin.

In patients with acute myocardial infarction and the risk of further deterioration of hemodynamics, worsening of symptoms after the appointment of vasodilators, lisinopril therapy should not be initiated.

These patients include patients with systolic blood pressure In patients with systolic blood pressure In patients with systolic blood pressure In patients with persistent arterial hypotension (systolic blood pressure 

Impaired renal function

In patients with chronic heart failure, a significant decrease in blood pressure during the use of ACE inhibitors may lead to an aggravation of renal dysfunction.

Cases of acute renal failure have been reported.

Patients with bilateral renal artery stenosis or stenosis of the renal artery of a single kidney during the use of ACE inhibitors showed an increase in the concentration of urea and serum creatinine; usually such disorders were temporary and stopped after discontinuation of therapy. They were more common in patients with renal insufficiency.

Lisinopril is contraindicated in patients with acute myocardial infarction and severe renal impairment (serum creatinine >177 mmol/l and/or proteinuria >500 mg/day). If renal dysfunction develops during treatment (serum creatinine concentration >265 mmol/l or doubling compared to baseline), lisinopril should be discontinued.

Allergic reactions, angioedema

Angioedema of the face, extremities, lips, tongue, epiglottis, and/or larynx has been reported in rare cases with the use of ACE inhibitors, including lisinopril. In such cases, immediate withdrawal of lisinopril is required; monitoring of the patient’s condition is indicated until the symptoms are fully resolved. Usually, angioedema of the face and lips is temporary and does not require treatment; however, antihistamines may be prescribed.

Angioedema of the larynx may be the cause of death. Swelling of the tongue, epiglottis, or larynx can lead to secondary airway obstruction. In this case, it is necessary to immediately inject 0.3-0.5 ml of 1:1000 epinephrine solution subcutaneously, and also ensure patency of the respiratory tract.

Angioedema was reported to occur more frequently in patients treated with ACE inhibitors of the black race than in patients of other ethnic groups.

Patients with a history of angioedema that is not associated with ACE inhibitors have a higher risk of developing angioedema when using ACE inhibitors.

Anaphylactic reactions associated with hymenopteran venom desensitization In very rare cases, patients taking ACE inhibitors may develop life-threatening anaphylactic reactions during desensitization with hymenopteran venom, so it is necessary to temporarily cancel ACE inhibitors before desensitization.

Patients undergoing hemodialysis

Anaphylactic reactions have also occurred in patients undergoing hemodialysis using high-permeability dialysis membranes (for example, AN69) with concomitant use of ACE inhibitors. In such patients, the use of other dialysis membranes or other antihypertensive drugs is indicated.

Cough

ACE inhibitor therapy can cause coughing, which should be taken into account when making a differential diagnosis. Prolonged dry cough usually stops after ACE inhibitors are discontinued.

Surgical interventions/general anesthesia

The use of antihypertensive drugs during volumetric surgery or during general anesthesia may lead to inhibition of angiotensin II formation due to compensatory renin secretion. A significant decrease in blood pressure associated with this effect can be prevented by increasing the volume of circulating blood.

Patients taking ACE inhibitors should inform the surgeon / anaesthetist before performing surgery (including dental procedures).

Blood plasma potassium levels

Cases of hyperkalemia have been reported.

Risk factors for hyperkalemia include renal failure, diabetes mellitus, therapy with potassium-sparing diuretics (spironolactone, triamterene and amiloride), the use of potassium preparations and potassium-based salt substitutes, especially in patients with impaired renal function. If the combined use of lisinopril and these drugs is necessary, regular monitoring of the potassium content in blood plasma is indicated.

Double blockade of the RAAS

Simultaneous use of ACE inhibitors has been proven. angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure). Therefore, it is not recommended to prescribe ACE inhibitors, angiotensin II receptor blockers, or aliskiren for dual RAAS blockade.

If there are absolute indications for double blockade of the RAAS, it should be carried out under the careful supervision of a specialist with frequent monitoring of blood pressure, renal function and electrolyte content.

ACE inhibitors and angiotensin II receptor blockers should not be used simultaneously in patients with diabetic nephropathy.

Influence on the ability to drive vehicles and mechanisms

There are no data on the effect of lisinopril on the ability to drive vehicles and work with mechanisms. However, you should consider the possibility of dizziness. In this regard, care must be taken when driving vehicles and working with mechanisms.

Indapamide does not cause psychomotor dysfunction, however, in some patients with a decrease in blood pressure, various individual reactions may develop, especially at the beginning of therapy or when an additional antihypertensive drug is prescribed to the main treatment regimen. In this case, the ability to drive vehicles and work with mechanisms may be reduced.

Storage conditions

Store at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Indapamide, Lisinopril

Conditions of release from pharmacies

By prescription

Dosage form

Capsules