IRUZID

Active material: Gidroxlorotiazid, Lisinopril
When ATH: C09BA03
CCF: Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.16.03
Manufacturer: BELUPO Pharmaceuticals & Cosmetics d.d. (Croatia)

Pharmaceutical form, composition and packaging

Pills of blue color, hexagonal, lenticular.

Excipients: mannitol, Calcium phosphate dihydrate, corn starch, pre-gelatinized starch, indigokarmin, magnesium stearate.

30 PC. – blisters (1) – packs cardboard.

Pills yellow color, hexagonal, lenticular.

Excipients: mannitol, Calcium phosphate dihydrate, corn starch, pre-gelatinized starch, iron oxide yellow (dye), magnesium stearate.

30 PC. – blisters (1) – packs cardboard.

Pills light pink, round, lenticular.

Excipients: mannitol, Calcium phosphate dihydrate, corn starch, pre-gelatinized starch, iron oxide red (dye), magnesium stearate.

30 PC. – blisters (1) – packs cardboard.

Pharmacological action

Antihypertensive combination preparation, containing an ACE inhibitor (Lisinopril) and diuretic (gidroxlorotiazid). It has antihypertensive and diuretic effect.

Lisinopril – ACE inhibitor. The mechanism of action is associated with inhibition of ACE activity, which leads to suppression of the formation of angiotensin II from angiotensin I and to the direct reduction of aldosterone release. It reduces the degradation of bradykinin, and increases the synthesis of prostaglandins. Reduces PR, FROM, preload, the pressure in the pulmonary capillaries, It causes an increase in cardiac output and increase exercise tolerance in patients with chronic heart failure. Lisinopril exerts vasodilating effects, wherein the artery expands to a greater extent, than veins. Some effects are explained by the influence on the tissue renin-angiotensin system. It improves blood flow to ischemic myocardium. Prolonged use reduces myocardial hypertrophy and arterial walls resistive type.

The use of ACE inhibitors in patients with heart failure increases the life expectancy; patients, myocardial infarction, without clinical symptoms of heart failure – to slow the progression of left ventricular dysfunction.

Antihypertensive effect observed after 6 hours after drug administration and persists for 24 no. The duration of action is also dependent on the dose of. The onset of action of the drug – through 1 no. The maximum effect is observed after 6-7 no. When hypertension effect observed in the first days after the start of treatment, stable operation is developed through 1-2 of the month.

With a sharp lifting of the drug has not been pronounced increase in blood pressure.

In addition to lowering blood pressure lisinopril reduces albuminuria. Patients with hyperglycemia helps normalize the function of the damaged glomerular endothelial.

Lisinopril does not affect the concentration of blood glucose in diabetic patients, and does not lead to increased incidence of hypoglycemia.

Gidroxlorotiazid – tiazidnый diuretic, diuretic effect which involves a violation of the reabsorption of sodium ions, Chlorine, Potassium, Magnesium, water in the distal nephron; delays excretion of calcium ions, Uric acid. It has antihypertensive effect due to the expansion of arterioles. Almost no effect on normal blood pressure. The diuretic effect develops in 1-2 no, reaches through 4 hours and lasts 6-12 no. The antihypertensive effect is manifested through 3-4 day, but in order to achieve optimum therapeutic effect may require 3-4 of the week.

The combination of lisinopril and hydrochlorothiazide exert an additive antihypertensive effect.

Pharmacokinetics

Lisinopril

Absorption

Absorption – 30% (6-60%). The bioavailability of lisinopril 25-50%. C_max in plasma is approximately 6-8 no. Food intake has no effect on the absorption of lisinopril.

Distribution

Weakly bound to plasma proteins. Lisinopril slightly penetrate the BBB and placenta.

Deduction

Lisinopril is not metabolised and is excreted unchanged in the urine.

T_1/2 – 12 no. The main part of lisinopril output during the initial phase α- (Effective T_1/2 – 12 no), followed by the remote terminal β-phase (about 30 no).

Gidroxlorotiazid

Absorption

After ingestion absorbed on 60-80%. C_max in plasma is approximately 1.5-3 no. suction change under the influence of food intake have no clinical significance.

Distribution

Hydrochlorothiazide accumulates in erythrocytes. In the phase of deducing the concentration of the erythrocytes in 3-9 times more, than in plasma. Plasma protein binding 40-70%.

Metabolism and excretion

Hydrochlorothiazide is metabolized to a very small extent.

Derivation of hydrochlorothiazide from plasma is biphasic: T_1/2 in the initial phase of α- 2 no, a terminal β-phase – about 10 no. Hydrochlorothiazide is excreted in the urine; 50-75% an oral dose – in unchanged form.

Testimony

- Arterial hypertension (patients, which shows the combination therapy).

Dosage regimen

The drug is prescribed inside of 1 tab. (10 mg + 12.5 mg or 20 mg + 12.5 mg) 1 time / day. If necessary, the dose can be increased to 20 mg + 25 mg 1 time / day.

Patients with renal insufficiency at KK from 80 to 30 ml / min Iruzid^® It can be used only after titration of the individual components of the preparation. The recommended initial dose of lisinopril in uncomplicated renal insufficiency is 5-10 mg / day.

Upon receiving the starting dose Iruzida^® symptomatic hypotension may occur. Such cases are frequently observed in patients, which it was the loss of fluids and electrolytes due to prior treatment with diuretics. Therefore, you should stop taking the diuretic for 2-3 days before treatment Iruzidom^®.

Side effect

Most often noted dizziness, headache.

Cardio-vascular system: marked reduction in blood pressure, chest pain; rarely – orthostatic hypotension, tachycardia, bradycardia, symptoms of heart failure, violation of AV-conduction, myocardial infarction.

From the digestive system: nausea, vomiting, abdominal pain, dry mouth, dyspepsia, anorexia, change in taste, pancreatitis, hepatocellular or cholestatic hepatitis, jaundice.

From the central and peripheral nervous system: fatigue, mood lability, impaired concentration, paresthesia, drowsiness, jerking of the limbs and lips; rarely – asthenic syndrome, confusion.

The respiratory system: dry cough, dyspnoea, bronchospasm, apnea.

Dermatological reactions: increased perspiration, hair loss, photosensitivity.

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

With the genitourinary system: uremia, oligurija / anurija, impairment of renal function, acute renal failure, reduced potency.

Allergic reactions: angioneurotic edema of the face, limbs, lips, language, epiglottis and / or larynx, skin rash, itching, hives, fever, vasculitis, positive for antinuclear antibodies, increased erythrocyte sedimentation rate, eozinofilija.

Laboratory findings: hyperkalemia and / or hypokalemia, giponatriemiya, gipomagniemiya, chloropenia, hypercalcemia, hyperuricemia, giperglikemiâ, increased creatinine, hypercholesterolemia, hypertriglyceridemia, reduced glucose tolerance.

Other: arthralgia, arthritis, myalgia, worsening of gout, fever.

Contraindications

- Anurija;

- Severe renal insufficiency (CC < 30 ml / min);

- Angioedema (incl. a history of the use of ACE inhibitors);

- Hemodialysis using membranes vysokoprotochnyh;

- Hypercalcemia;

- Giponatriemiya;

- Porphyria;

- Prek, pechenochnaya coma;

- Diabetes (severe);

- Up to 18 years (efficacy and safety have not been established);

- Hypersensitivity to the drug, other ACE inhibitors and derivatives of sulfonamides.

FROM caution should be prescribed the drug for aortic stenosis, hypertrophic cardiomyopathy, bilateral renal artery stenosis, stenosis of the artery to a solitary kidney with progressive azotemia, if condition after kidney transplantation, renal failure (a creatinine clearance 30 ml / min), primary hyperaldosteronism, hypotension, hypoplasia of the bone marrow, giponatriemii (an increased risk of hypotension in patients, are on a salt-free diet or malosolevoy), under conditions, accompanied by a decrease in the bcc (incl. diarrhea, rvote), connective tissue diseases (systemic lupus erythematosus, scleroderma), diabetes, suppression of bone marrow hematopoiesis, podagre, hyperuricemia, hyperkalemia, CHD, cerebrovascular diseases (incl. with a circulation of cerebral insufficiency), severe chronic heart failure, hepatic insufficiency, elderly patients.

Pregnancy and lactation

Application Iruzida^® contraindicated during pregnancy. In the event of pregnancy treatment Iruzidom^® should as soon as possible to stop. ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (may be marked reduction of blood pressure, renal failure, hyperkalemia, skull hypoplasia, fetal death). Information about the negative impact of the drug on the fetus in the case of use in the I trimester of pregnancy is not. For newborns and babies, who underwent in utero effects of ACE inhibitors, should be closely monitored for early detection of significant decrease in blood pressure, oligurii, hyperkalemia.

No data on the penetration of lisinopril in breast milk, Hydrochlorothiazide passes into breast milk. During drug treatment Iruzid^® breastfeeding should be abolished.

Cautions

It should be taken into account, that the decrease in blood pressure occurs with a decrease in the bcc, caused by diuretic therapy, reducing the amount of salt in the food, dializom, diarrhea or vomiting. In patients with chronic heart failure with concurrent renal insufficiency with or without symptomatic hypotension may develop, which is often detected in patients with severe heart failure, as a consequence of the use of high doses of diuretics, hyponatremia or impaired renal function. In these patients, treatment should start under close medical supervision. Such tactics to be followed in the appointment of Iruzida^® patients with coronary artery disease, cerebrovascular insufficiency, in which the sharp decline in blood pressure can lead to heart attack or stroke. Transient hypotensive response is not a contraindication to receiving the next dose.

Prior to treatment should be possible to normalize the concentration of sodium and / or make up for the lost volume of liquid, carefully control action initial dose per patient.

In patients with chronic heart failure, marked reduction in blood pressure after initiation of therapy with ACE inhibitors may result in further deterioration of renal function. Cases of acute renal failure. In patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, ACE inhibitor, It showed an increase of urea and creatinine in the serum, usually reversible upon discontinuation of treatment (frequently observed in patients with renal insufficiency).

Patients, taking ACE inhibitors, including lisinopril, rarely develop angioedema face, limbs, lips, language, epiglottis and / or larynx, and its development is possible at any time during treatment. In this case, treatment should cease as soon as possible and the patient be placed under observation until complete regression of symptoms. However, in cases, when swelling occurs only on the face and lips, and state returned to normal without treatment, possible appointment of antihistamines.

In the propagation of the language of angioedema, epiglottis and / or laryngeal airway obstruction may occur, why you should immediately conduct appropriate therapy (0.3-0.5 ml epinephrine / adrenaline / 1:1000 n / a) and / or measures to ensure airway. Patients, a history of angioedema have been, not related to previous treatment with an ACE inhibitor, It may be at increased risk of its development during treatment with an ACE inhibitor.

When using an ACE inhibitor cough celebrated (dry, long, which disappears after discontinuation of ACE inhibitor). In the differential diagnosis of cough and cough should be considered, resulting from the use of an ACE inhibitor.

It should be taken into account, that patients, simultaneously taking ACE inhibitors and hemodialysis using dialysis membranes with high permeability, can develop an anaphylactic reaction. In such cases, you should consider using another type of membrane dialysis or other antihypertensive.

When using drugs, lowering blood pressure, in patients with extensive surgery or during general anesthesia, lisinopril may block the formation of angiotensin II. Marked decrease in blood pressure, which is considered a consequence of this mechanism, You can eliminate the increase in BCC. Before surgery (including dentistry) must notify the surgeon / anesthesiologist on the use of ACE inhibitors.

In some cases, there is hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes, potassium supplementation or drugs, causing an increase in the potassium concentration in the blood (eg, Heparin), especially in patients with impaired renal function.

Patients, in which there is a risk of symptomatic hypotension and are at malosolevoy or salt-free diet with / without hyponatraemia, and in patients, who received high doses of diuretics, above the state before the start of treatment necessary to compensate (loss of fluids and salts).

Thiazide diuretics may affect glucose tolerance, therefore it is necessary to adjust the dose of hypoglycemic drugs, taken together with Iruzidom^®.

Thiazide diuretics may reduce urinary calcium excretion and cause hypercalcemia. Marked hypercalcaemia may be a sign of hidden hyperparathyroidism. It is recommended to discontinue treatment with thiazide diuretics in before the test to assess the function of the parathyroid glands.

During treatment Iruzidom^® requires regular monitoring of the level of potassium, Glucose, urea, lipids in the blood plasma.

During treatment is not recommended to drink alcohol, tk. Alcohol enhances the hypotensive effect of the drug.

Caution must be exercised during exercise, hot weather, tk. there is a risk of development of dehydration and excessive loss of blood pressure due to a decrease BCC.

Effects on ability to drive vehicles and mechanisms

During treatment should refrain from driving vehicles and Occupation potentially hazardous activities, require high concentration and speed of psychomotor reactions, tk. dizziness, especially at the beginning of treatment.

Overdose

Symptoms: marked reduction in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability.

Treatment: symptomatic therapy, aimed at correcting the dehydration (administering fluids) and violations of water-salt balance, in / in a liquid, BP control. Control should be carried urea, Electrolytes and creatinine in blood serum, and diuresis.

Drug Interactions

With simultaneous application Iruzida^® with potassium-sparing diuretics (spironolactone, triamterene, amilorid), potassium supplements, salt substitutes, containing potassium, increased risk of hyperkalemia, especially in patients with impaired renal function. Therefore, when the need for this combination is shown potassium control in serum and renal function.

With simultaneous application Iruzida^® with vasodilators, ʙarʙituratami, fenotiazinami, tricyclic antidepressants and ethanol, there is a growing anti-hypertensive action.

With simultaneous application Iruzida^® NSAIDs, estrogen reduced antihypertensive effect of lisinopril.

With simultaneous application Iruzida^® with lithium therapy slows lithium excretion, which leads to increased cardiotoxic and neurotoxic effects of lithium.

While the use of antacids and colestyramine reduced absorption Iruzida^® from the gastrointestinal tract.

Iruzid^® while applying enhances the neurotoxicity salicylates.

With simultaneous application Iruzid^® ters effect gipoglikemicakih oral drugs, norepinephrine, epinephrine and protivopodagricakih funds.

With simultaneous application Iruzid^® enhances the effects of (including side) cardiac glycosides, effects of peripheral muscle relaxants.

With simultaneous application Iruzid^® reduces the excretion of quinidine.

When applied simultaneously reduces the effect of oral contraceptives.

In an application with methyldopa increased risk of hemolysis.

Ethanol enhances the hypotensive effect of the drug.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at a temperature of 25 ° C. Shelf life - 2 year.