Expiration date: 03/2025

The composition and form of issue:

Tablets, 1 tablet contains:

lisinopril dihydrate (in terms of lisinopril anhydrous) 10 mg

hydrochlorothiazide 12, 5 mg

auxiliary substances: mannitol, calcium phosphate dihydrate, starch corn starch pregelatinized magnesium stearate Indigo Carmine 

blistere in 30 PCs. in cardboard pack 1 blister.

Tablets, 1 tablet contains:

lisinopril dihydrate (equivalent to lisinopril anhydrous) 20 mg

hydrochlorothiazide 12, 5 mg

excipients: calcium mannitol phosphate dihydrate starch corn starch pre-gelatinized dye iron oxide yellow magnesium stearate 

blistere in 30 PCs. in cardboard pack 1 blister.

Tablets, 1 tablet contains:

lisinopril dihydrate (equivalent to lisinopril anhydrous) 20 mg

hydrochlorothiazide 25 mg

excipients: calcium mannitol phosphate dihydrate starch corn starch pre-gelatinized dye iron oxide red magnesium stearate 

blistere in 30 PCs. in cardboard pack 1 blister.

Description of dosage form:

Tablet 10 + 12, 5 mg: blue, biconvex, hexagonal tablets.

Tablets 20 + 12, 5 mg: yellow, biconvex, hexagonal tablets.

Tablets 20 + 25 mg: light pink, biconvex, round tablets.

Description of pharmacological action:

Hypotensive combined agent. It has antihypertensive and diuretic effect.

Lisinopril

ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. Reducing the content of angiotensin II leads to a direct reduction in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of PG. Reduces OPSS, blood PRESSURE, preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and increased tolerance to stress in patients with chronic heart failure. Dilates arteries to a greater extent than veins. Some effects are explained by the effect on tissue renin-angiotensin systems. With long-term use decreases the severity of myocardial hypertrophy and arterial walls resistive type. Improves blood flow to ischemic myocardium. ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who have suffered myocardial infarction without clinical manifestations of heart failure.

The antihypertensive effect starts in approximately 6 hours and persists for 24 h. the Duration of effect depends on dose. Onset of action through 1 h, the maximum effect is determined through 6-7 h. In arterial hypertension effect noted in the first days after the start of treatment, stable effect develops through 1-2 months.

With the abrupt withdrawal of the drug, there is no marked increase in blood PRESSURE.

In addition to reducing blood PRESSURE lisinopril reduces albuminuria. In patients with hyperglycemia contributes to the normalization of the function of the damaged glomerular endothelium.

Lisinopril does not affect the concentration of glucose in the blood of patients with diabetes and does not lead to an increase in cases of hypoglycemia.

Hydrochlorothiazide

Thiazide diuretic, the diuretic effect of which is associated with a violation of the reabsorption of ions of sodium, chlorine, potassium, magnesium, water in the distal nephron delays the excretion of calcium ions, uric acid. Has antihypertensive properties hypotensive effect develops due to the expansion of arterioles. Almost no effect on normal blood pressure. Diuretic effect occurs after 1-2 hours, reaches a maximum of 4 hours and lasts 6-12 hours.

Antihypertensive effect occurs after 3-4 days, but to achieve the optimal therapeutic effect may require 3-4 weeks.

Lisinopril and hydrochlorothiazide, if used simultaneously, have an additive antihypertensive effect.

Indications:

• Arterial hypertension (in patients, which shows the combined therapy).
  

Contraindications:

• hypersensitivity to the drug, other ACE inhibitors and sulfonamide derivatives
  
• anuria
  
• severe renal failure (CL creatinine < 30 ml/min.)
  
• angioedema (including a history of ACE inhibitors)
  
• hemodialysis using high-flow membranes
  
• hypercalcemia
  
• hyponatremia
  
• porphyria
  
• precoma
  
• hepatic coma
  
• severe forms of diabetes
  
• the age of 18 years (efficacy and safety not established).
  

With caution:

• aortic stenosis/hypertrophic cardiomyopathy
  
• bilateral renal artery stenosis
  
• stenosis of artery only kidneys with progressive azotemia
  
• condition after kidney transplantation
  
• renal failure (creatinine Cl >30 ml / min .)
  
• primary hyperaldosteronism
  
• arterial hypotension
  
• bone marrow hypoplasia
  
• hyponatremia (increased risk of hypotension in patients on a low-salt or salt-free diet)
  
• hypovolemic conditions (including diarrhea, vomiting)
  
• connective tissue diseases (systemic lupus erythematosus, scleroderma)
  
• diabetes
  
• gout, hyperuricemia
  
• oppression of bone marrow hematopoiesis
  
• hyperkalemia
  
• CHD
  
• cerebrovascular diseases (including cerebrovascular insufficiency)
  
• severe chronic heart failure
  
• liver failure
  
• old age.
  

Use during pregnancy and breast-feeding:

The use of lisinopril during pregnancy is contraindicated. Upon determination of the pregnancy the drug you need to stop as early as possible. Taking inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (there may be a marked decrease in blood PRESSURE, renal failure, hyperkalemia, hypoplasia of the skull, intrauterine death). Data on the negative effects of the drug on the fetus in the case of use during the first trimester no. For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, it is recommended to monitor for the timely detection of a marked decrease in blood PRESSURE, oliguria, hyperkalemia.

For the period of treatment with the drug it is necessary to cancel breastfeeding.

Side effect:

The most common side effects are dizziness, headache.

Other side effects

From the cardiovascular system: a marked decrease in blood PRESSURE, chest pain rarely-orthostatic hypotension, tachycardia, bradycardia, the appearance of symptoms of heart failure, violation of AV conduction, myocardial infarction.

From the digestive tract: nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, taste change, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice.

On the part of the skin: urticaria, sweating, photosensitization, itching, hair loss.

On the part of the nervous system: lability of mood, impaired concentration, paresthesia, fatigue, drowsiness, convulsive twitching of the muscles of the limbs and lips rarely — asthenic syndrome, confusion.

The respiratory system: dyspnea, bronchospasm, apnea.

From the hematopoietic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decrease in hemoglobin, hematocrit, erythrocytopenia).

Allergic reactions: angioedema of the face, limbs, lips, tongue, epiglottis and/or larynx (see "Special instructions"), skin rashes, itching, fever, vasculitis, positive reactions to antinuclear antibodies, increased ESR, eosinophilia.

From the genitourinary system: uremia, oliguria / anuria, renal dysfunction, acute renal failure, decreased potency.

Laboratory findings: hyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hypercalcemia, hyperuricemia, hyperglycemia, increased levels of urea and creatinine in plasma hyperbilirubinemia, hypercholesterolemia, hypertriglyceridemia, reduced glucose tolerance, increased activity of hepatic transaminases, especially in the history of kidney disease, diabetes and renovascular hypertension.

Other: dry cough, arthralgia, arthritis, myalgia, fever, violation of fetal development, exacerbation of gout.

Drug interaction:

While the use of potassium-spiking diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium — increases the risk of hyperkalemia, especially in patients with impaired renal function. Therefore, they can be jointly prescribed only on the basis of an individual decision of the attending physician with regular monitoring of serum potassium levels and renal function.

With simultaneous use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol - increased hypotensive effect.

With simultaneous use with NSAIDs (indomethacin, etc.), estrogen — reducing the antihypertensive effect of lisinopril.

With the simultaneous use of drugs lithium — slows excretion of lithium from the body (strengthening of the cardiotoxic and neurotoxic action of lithium).

While the use of antacids and colestyramine-reduced absorption in the gastrointestinal tract.

The drug increases the neurotoxicity of salicylates, weakens the action of oral hypoglycemic drugs, norepinephrine, epinephrine and anti-podagric drugs, enhances the effects (including side) cardiac glycosides, the action of peripheral muscle relaxants, reduces the excretion of quinidine.

Reduces the effect of oral contraceptives. Ethanol increases the hypotensive effect of the drug. While taking methyldopa increases the risk of hemolysis.

Method of application and doses:

Inside.

1 table. Iruzid 10 mg + 12, 5 mg or 20 mg + 12, 5 mg 1 time per day. Sometimes, if necessary, the dose can be increased to Onusida 20 mg + 25 mg 1 time per day.

Dose for renal failure:

In patients with Cl creatinine from 30 to 80 ml / min, the drug can be used only after selecting the dose of individual components of the drug. The recommended initial dose of lisinopril in uncomplicated renal failure-5-10 mg.

Previous diuretic therapy:

Symptomatic hypotension may occur after taking the initial dose of the drug Iruzid. Such cases are more common in patients with loss of fluid and electrolytes due to previous treatment with diuretics. Therefore, it is necessary to stop taking diuretics 2-3 days before the start of treatment with Iruzid (see "Special instructions").

Overdose:

Symptoms: marked decrease in blood PRESSURE, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: symptomatic therapy, IV fluid, blood PRESSURE control, therapy aimed at correcting dehydration and violations of water-salt balance. Control of urea, creatinine and serum electrolytes, as well as diuresis.

Special instruction:

Symptomatic hypotension

Most often, a marked decrease in blood PRESSURE occurs with a decrease in the volume of fluid caused by diuretic therapy, a decrease in the amount of salt in food, dialysis, diarrhea or vomiting (see "Interaction" and "Side effects"). In patients with chronic heart failure with simultaneous renal failure or without it, may be a marked decrease in blood PRESSURE. Hypotension is more common 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 begin under the strict supervision of a doctor. Such rules should be followed when appointing patients with coronary artery disease or cerebrovascular insufficiency, in which a sharp decrease in blood PRESSURE can lead to myocardial infarction or stroke.

A transient hypotensive response is not a contraindication to receiving the next dose.

Before treatment, if possible, it is necessary to normalize the concentration of sodium and / or fill the lost volume of fluid, carefully monitor the effect of the initial dose of the drug on the patient.

Impaired renal function

In patients with chronic heart failure, a marked decrease in blood PRESSURE after treatment with ACE inhibitors can lead to further deterioration of renal function. Cases of acute renal failure were noted. Patients with bilateral renal artery stenosis or renal artery stenosis, receiving ACE inhibitors, there was an increase in urea and serum creatinine, usually reversible after discontinuation of treatment. These changes were more common in patients with renal insufficiency.

Hypersensitivity/Angioneurotic edema

Angioedema of the face, limbs, lips, tongue, epiglottis and/or larynx can occur at any time of treatment, rarely observed in patients treated with ACE inhibitors, including lisinopril. In this case, treatment with lisinopril should be stopped as soon as possible and patients should be monitored until complete regression of symptoms. In cases where swelling occurs only on the face and lips, it often goes without treatment, but it is possible to prescribe antihistamines.

Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis or larynx are covered, airway obstruction may occur, so appropriate therapy (0, 3-0, 5 ml of epinephrine (adrenaline) 1:1000 p/K) and/or measures to ensure airway patency should be taken immediately.

Patients who have a history of angioedema, not associated with previous treatment with ACE inhibitors, may be at increased risk of its development during treatment with ACE inhibitor.

Cough

With the use of ACE inhibitors was noted to cough. Dry, prolonged cough that disappears after discontinuation of treatment with ACE inhibitor. In the differential diagnosis of cough, it is necessary to take into account the cough caused by the use of ACE inhibitor.

Patients on hemodialysis

Anaphylactic reaction was also noted in patients subjected to hemodialysis using dialysis membranes with high permeability, which simultaneously take ACE inhibitors. In such cases it is necessary to consider the possibility of using a different type of dialysis membrane or a different antigipertenzivnogo preparation.

Surgery/General anesthesia

When using drugs that reduce blood pressure, patients with extensive surgery or during General anesthesia, lisinopril may block the formation of angiotensin II. The marked decrease in blood PRESSURE, which is considered a consequence of this mechanism, can be eliminated by increasing the BCC.

Before surgery (including dental surgery) it is necessary to warn the surgeon/anesthesiologist about the use of ACE inhibitors.

Potassium in serum

In some cases, hyperkalemia was noted.

Risk factors for hyperkalemia include kidney failure, diabetes, potassium supplementation, or drugs that cause an increase in the concentration of potassium in the blood (e.g. heparin), especially in patients with impaired renal function.

In patients who are at risk of symptomatic hypotension (on a low-salt or salt-free diet) with or without hyponatremia, as well as in patients who received high doses of diuretics, the loss of fluid and salts must be compensated before treatment.

Metabolic and endocrine effects

Thiazide diuretics can affect glucose tolerance, so it is necessary to adjust the dose of antidiabetic drugs.

Thiazide diuretics can reduce the excretion of calcium in the urine and cause hypercalcemia. Severe hypercalcemia may be a symptom of latent hyperparathyroidism. It is recommended to stop treatment with thiazide diuretics before the test to assess the function of the parathyroid glands.

During treatment with the drug requires regular monitoring of plasma potassium, glucose, urea and lipids.

During treatment, it is not recommended to drink alcoholic beverages, because alcohol increases the hypotensive effect of the drug.

Caution should be exercised when exercising, hot weather (risk of dehydration and excessive reduction of blood PRESSURE due to lower BCC).

Impact on the ability to drive and operate machinery

During treatment should refrain from driving and engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions, as possible dizziness, especially at the beginning of treatment.