Iruzid (Hydrochlorothiazide + Lisinopril)

1 tablet contains:

Active ingredients:

 lisinopril,

hydrochlorothiazide; 

Excipients:

calcium phosphate dibasic,

mannitol,

corn starch,

pregelatinized corn starch,

magnesium stearate,

iron oxide yellow,

purified water.

Iruzid is a diuretic, antihypertensive.

Pharmacodynamics

Combined antihypertensive agent. It has antihypertensive and diuretic effects.

Lisinopril

ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease 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 an increase in exercise tolerance in patients with chronic heart failure. Expands arteries more than veins. Some of the effects are attributed to the effect on tissue renin-angiotensin systems.

With prolonged use, the severity of hypertrophy of the myocardium and the walls of resistive arteries decreases. Improves blood supply to the ischemic myocardium. ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow down the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure.

The antihypertensive effect begins after about 6 hours and lasts for 24 hours. The duration of the effect also depends on the dose. The onset of action is after 1 hour, the maximum effect is determined after 6–7 hours. In arterial hypertension, the effect is observed in the first days after the start of treatment, a stable effect develops after 1–2 months.

With a sharp withdrawal of the drug, there is no pronounced increase in blood pressure.

In addition to lowering blood pressure, lisinopril reduces albuminuria. In patients with hyperglycemia, it helps to normalize the function of the damaged glomerular endothelium.

Lisinopril does not affect the blood glucose concentration in patients with diabetes mellitus and does not lead to an increased incidence of hypoglycemia.

Hydrochlorothiazide

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

The antihypertensive effect occurs within 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.

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

Arterial hypertension (in patients for whom combination therapy is indicated).

The use of lisinopril during pregnancy is contraindicated. When pregnancy is established, taking Iruzid should be discontinued as early as possible.

Reception of inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (a pronounced decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull, intrauterine death are possible).

There is no data on the negative effects of the drug on the fetus when used during the first trimester. For newborns and infants who have been exposed to intrauterine exposure to ACE inhibitors, it is recommended to monitor for the timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia.

For the period of treatment with Iruzid, breastfeeding should be canceled.

• hypersensitivity to the drug, other ACE inhibitors and sulfonamide derivatives;
• anuria;
• severe renal failure (Cl creatinine <30 ml / min);
• angioneurotic edema (including a history with the use of ACE inhibitors);
• hemodialysis using high-flow membranes;
• hypercalcemia;
• hyponatremia;
• porphyria;
• precom;
• hepatic coma;
• severe forms of diabetes mellitus;
• age up to 18 years (efficacy and safety have not been established).

Precautions: aortic stenosis / hypertrophic cardiomyopathy; bilateral renal artery stenosis; stenosis of an artery of a solitary kidney with progressive azotemia; condition after kidney transplantation; renal failure (Cl creatinine> 30 ml / min); primary hyperaldosteronism; arterial hypotension; bone marrow hypoplasia; hyponatremia (increased risk of arterial 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; Ischemic heart disease; cerebrovascular diseases (including cerebrovascular insufficiency); severe chronic heart failure; liver failure; elderly age.

From the CVS: marked decrease in blood pressure, chest pain; rarely - orthostatic hypotension, tachycardia, bradycardia, the appearance of symptoms of heart failure, impaired AV conduction, myocardial infarction.

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

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

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

From the respiratory system: dyspnea, bronchospasm, apnea.

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

Allergic reactions: angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx, skin rashes, itching, fever, vasculitis, positive reactions to antinuclear antibodies, increased ESR, eosinophilia.

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

Laboratory indicators: hyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hypercalcemia, hyperuricemia, hyperglycemia, increased levels of urea and creatinine in the blood plasma; hyperbilirubinemia, hypercholesterolemia, hypertriglyceridemia, decreased glucose tolerance, increased hepatic transaminase activity, especially if there is a history of kidney disease, diabetes mellitus and renovascular hypertension.

Others: dry cough, arthralgia, arthritis, myalgia, fever, fetal malformation, exacerbation of gout.

With simultaneous use with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium - the risk of hyperkalemia increases, especially in patients with impaired renal function. Therefore, they can be co-administered only on the basis of the 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 - an increase in the hypotensive effect.

With simultaneous use with NSAIDs (indomethacin, etc.), estrogens - a decrease in the antihypertensive effect of lisinopril.

With simultaneous use with lithium preparations, the excretion of lithium from the body slows down (increased cardiotoxic and neurotoxic effects of lithium).

With simultaneous use with antacids and cholestyramine - a decrease in absorption in the gastrointestinal tract.

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

Reduces the effect of oral contraceptives. Ethanol enhances the hypotensive effect of the drug. With the simultaneous administration of methyldopa, the risk of hemolysis increases.

In case of essential arterial hypertension, the drug is administered orally 1 tablet 1 time per day.

If necessary, the dose can be increased to 2 tablets once a 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 the individual components of the drug. The recommended initial dose of lisinopril for uncomplicated renal failure is 5-10 mg.

Prior diuretic therapy

Symptomatic hypotension may occur after taking the initial dose of Iruzid®. Such cases are more common in patients with fluid and electrolyte loss due to prior diuretic treatment. Therefore, it is necessary to stop taking diuretics 2-3 days before starting treatment with Iruzid

Symptoms: a  pronounced decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability.

Treatment:  symptomatic therapy, intravenous fluid administration, blood pressure control, therapy aimed at correcting dehydration and violations of the water-salt balance. Control of urea, creatinine and electrolytes in serum, as well as urine output.

Symptomatic hypotension

Most often, a pronounced decrease in blood pressure occurs with a decrease in fluid volume 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 or without concurrent renal failure, a marked decrease in blood pressure is possible. Hypotension is more common in patients with severe heart failure as a result of high doses of diuretics, hyponatremia, or impaired renal function. In such patients, treatment should be started under the strict supervision of a physician. Similar rules should be followed when prescribing patients with coronary artery disease or cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

A transient hypotensive reaction is not a contraindication for taking the next dose of the drug.

Before starting treatment, if possible, the sodium concentration should be normalized and / or the lost volume of fluid should be replenished, the effect of the initial dose of the drug on the patient should be carefully monitored.

Impaired renal function

In patients with chronic heart failure, a pronounced decrease in blood pressure after starting treatment with ACE inhibitors can lead to a further deterioration in renal function. Cases of acute renal failure have been reported. In patients with bilateral stenosis of the renal arteries or stenosis of an artery of a single kidney, who received ACE inhibitors, there was an increase in urea and creatinine in serum, usually reversible after discontinuation of treatment. More often, these changes occurred in patients with renal failure.

Hypersensitivity / Angioedema

Angioneurotic edema of the face, extremities, lips, tongue, epiglottis and / or larynx can occur during any period 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 the patient should be monitored until the symptoms completely regress. In cases where edema occurs only on the face and lips, it most often goes away without treatment, however, antihistamines may be prescribed.

Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis or larynx is covered, airway obstruction may occur, therefore appropriate therapy (0.3-0.5 ml of epinephrine (adrenaline) solution 1: 1000 s / c) and / or measures to ensure airway should be taken ways.

Patients who already 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.

Cough

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

Patients on hemodialysis

Anaphylactic reaction was also observed in patients who underwent hemodialysis using dialysis membranes with high permeability, who simultaneously take ACE inhibitors. In such cases, consider using a different type of dialysis membrane or other antihypertensive drug.

Surgery / General anesthesia

When using drugs that lower blood pressure in patients with extensive surgery or during general anesthesia, lisinopril can block the formation of angiotensin II. A pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by an increase in BCC.

Before surgery (including dental), the surgeon / anesthetist should be warned about the use of ACE inhibitors.

Serum potassium

In some cases, hyperkalemia was noted.

Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, taking potassium supplements or drugs that increase the concentration of potassium in the blood (such as 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, fluid and salt loss must be compensated for before starting 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 urinary calcium excretion and cause hypercalcemia. Severe hypercalcemia may be a symptom of latent hyperparathyroidism. It is recommended that treatment with thiazide diuretics be discontinued before the test to assess the function of the parathyroid glands.

During the period of drug treatment, regular monitoring of potassium, glucose, urea and lipids in blood plasma is required.

During the treatment period, it is not recommended to consume alcoholic beverages, because alcohol enhances the hypotensive effect of the drug.

Caution should be exercised when exercising, in hot weather (risk of dehydration and an excessive decrease in blood pressure due to a decrease in BCC).

Impact on the ability to drive a car or perform work that requires an increased speed of physical and mental reactions. During the treatment period, one should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions, because dizziness is possible, especially at the beginning of treatment.

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