Index of drugs

Treatment of primary hypertension. A fixed-dose fixed dose formulation is indicated for use in adult patients whose blood pressure is not adequately controlled with irbesartan or hydrochlorothiazide monotherapy.

1 tabl powl. contains 150 mg or 300 mg irbesartan and 12.5 mg hydrochlorothiazide.

Combined preparation containing angiotensin II receptor antagonist - irbesartan and thiazide diuretic - hydrochlorothiazide. The combination of hydrochlorothiazide and irbesartan causes additive, dose-dependent, lowering of blood pressure over the therapeutic dose range. Irbesartan is a potent, selective antagonist of angiotensin II receptors (AT subtype₁). It blocks all actions of angiotensin II, regardless of the source or route of its synthesis. Selective antagonism towards AT₁ causes an increase in the concentration of renin and angiotensin II in the blood and a decrease in aldosterone. In patients without risk factors for electrolyte disturbances, irbesartan, in therapeutic doses, does not significantly affect the level of potassium in the blood. It is also not an ACE inhibitor, thanks to which it does not increase the effects of bradykinin-dependent effects. It does not require metabolic activation for its activity. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chloride in approximately similar amounts. The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity, increases aldosterone secretion, leading to increased potassium and bicarbonate loss in the urine and decreased potassium levels in the blood. When co-administered with valsartan and hydrochlorothiazide, the reduction in potassium in the blood is less pronounced than with hydrochlorothiazide alone. Following oral administration of irbesartan / hydrochlorothiazide, the absolute bioavailabilities are 60-80% and 50-80% for irbesartan and hydrochlorothiazide, respectively. Food does not affect the bioavailability of the drug. C_max occurs 1.5-2 hours after oral administration of irbesartan and 1-2.5 hours for hydrochlorothiazide. Irbesartan is associated with plasma proteins in approximately 96%, hydrochlorothiazide - approximately 68%. Irbesartan is metabolised in the liver, by conjugation with glucuronic acid and oxidation (with the participation of PRP2C9). Irbesartan and its metabolites are excreted in both bile (80%) and urine (20%). Final T_0,5 is 11-15 h. Hydrochlorothiazide is not metabolized, it is rapidly excreted by the kidneys. At least 61% of the oral dose is excreted unchanged within 24 hours.

Hypersensitivity to irbesartan, hydrochlorothiazide, other sulphonamide derivatives or to any of the excipients. Severe hepatic dysfunction, liver biliary cirrhosis and cholestasis. Severe renal impairment (creatinine clearance <30 ml / min). Resistance to hypokalemia, hypercalcemia. Co-administration with aliskiren in patients with diabetes or renal impairment (GFR <60 ml / min / 1.73 m²). II and III trimester of pregnancy.

Do not use the preparation in patients with primary hyperaldosteronism. Caution is required in patients with mild to moderate hepatic impairment; slight changes in fluid and electrolyte balance may cause these patients to develop hepatic coma. Caution should be exercised in patients with mild to moderate renal impairment (creatinine clearance 30-60 ml / min) - periodic monitoring of serum potassium, creatinine and serum uric acid levels is recommended; azotemia associated with the use of thiazide diuretics may occur in patients with impaired renal function. There is no experience regarding the use of the drug in patients after a recent kidney transplantation. In patients with bilateral renal artery stenosis or artery stenosis of the only functioning kidney, there is an increased risk of severe hypotension and renal failure during treatment.In patients whose vascular tone and renal function are dependent on the activity of the renin-angiotensin-aldosterone system - RAA (eg patients with severe congestive heart failure or with kidney disease, including renal artery stenosis), treatment with the preparation may cause a rapid reduction blood pressure, azotemia, oliguria or in rare cases - acute renal failure. Due to the risk of hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure), dual RAA blocking is not recommended (eg, by the combined use of an angiotensin II receptor antagonist with an ACE inhibitor or aliskiren); if the use of the RAA double block is absolutely necessary, it should only be carried out under the supervision of a specialist. At the same time, angiotensin II receptor antagonists and ACE inhibitors should not be used in patients with diabetic nephropathy. Because of the risk of hypotension, use caution in patients with a decreased intravascular volume and / or sodium depletion due to intense dehydrating treatment, reduced salt supply in the diet, diarrhea or vomiting - these deficiencies should be corrected before irbesartan is used. As with other antihypertensive agents, excessive hypotension in patients with ischemic cardiomyopathy or ischemic heart disease can lead to a heart attack or stroke. Particularly cautiously use in patients with aortic or mitral valve stenosis or hypertrophic cardiomyopathy with narrowing of the left ventricle outflow pathway. During treatment with the product, the concentration of electrolytes in the blood should be checked regularly. Although hypokalaemia may occur with thiazide diuretics, combination therapy with irbesartan may reduce the diuretic-induced hypokalemia. The risk of hypokalemia is greatest in patients with liver cirrhosis, in patients with increased diuresis, in patients receiving orally inadequate amounts of electrolytes and in patients treated concomitantly with corticosteroids or ACTH. On the other hand, irbesartan, a component of a combined preparation, can cause hyperkalaemia, especially if there is a renal dysfunction and / or heart failure and diabetes. Appropriate monitoring of serum potassium in patients at risk is recommended. Caution should be taken with the combined preparation of potassium-sparing diuretics or potassium supplements and potassium salt substitutes. There is no evidence that irbesartan could reduce or prevent the occurrence of diuretic induced hyponatremia. Hydrochlorothiazide may cause slight and transient hypercalcaemia; significant hypercalcemia may be evidence of concomitant hyperparathyroidism. The use of thiazide diuretics should be discontinued before performing tests to evaluate parathyroid function. The occurrence of a hypersensitivity reaction to hydrochlorothiazide is more likely in patients with allergy and asthma. In case of hypersensitivity reactions to light, it is recommended to discontinue the drug; if it is necessary to restart the diuretic therapy, it is recommended to protect the body against sunlight or artificial UV radiation. Co-administration of the preparation and lithium is not recommended. In patients with diabetes, the dose of insulin or oral antidiabetic agents may need to be adjusted during treatment with the preparation. It is not recommended for use in children and adolescents.

The use of the preparation in the first trimester of pregnancy is not recommended. Use in the second and third trimester of pregnancy is contraindicated. Irbesartan used in the second and third trimester of pregnancy is toxic to fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and newborn (renal failure, hypotension, hyperkalemia) - when exposure to irbesartan has occurred since the second trimester of pregnancy, it is recommended an ultrasound examination of the fetus skull and kidneys; children whose mothers took the drug during pregnancy should be closely monitored for hypotension. Hydrochlorothiazide crosses the placental barrier and may cause effects in the fetus and newborn, such as electrolyte disturbances, jaundice, and thrombocytopenia. It is not recommended to use the product during breastfeeding.

Common: increased levels of blood urea nitrogen (BUN), creatinine and creatine kinase, dizziness, nausea, vomiting, impaired urination, fatigue. Uncommon: decreases in potassium and sodium in the blood, syncope, hypotension, tachycardia, edema, orthostatic dizziness, diarrhea, limb edema, flushing, sexual dysfunction, changes in libido. Not known: headache, tinnitus, cough, dyspepsia, taste disorder, renal dysfunction (including isolated cases of renal failure in patients with risk factors), arthralgia, myalgia, hyperkalemia, hypersensitivity reactions (angioneurotic edema, rash, urticaria ), hepatitis, abnormal liver function. Undesirable effects on individual components may be a potential adverse event when using a combined preparation, even if not observed in clinical trials: irbesaratan - uncommon: chest pain; hydrochlorothiazide - frequency unknown: electrolyte imbalance (including hypokalemia, hyponatremia, hypomagnesaemia), hyperuricemia (or gout), glycosuria, hyperglycaemia, increased cholesterol and triglycerides in the blood, arrhythmias, aplastic anemia, myelosuppression, neutropenia , agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia, dizziness, paresthesia, feeling of emptiness, anxiety, transient blurred vision, seeing in yellow colors, respiratory distress syndrome (including pneumonia and pulmonary edema), pancreatitis, anorexia, diarrhea , constipation, gastric irritation, salivary gland inflammation, loss of appetite, interstitial nephritis, anaphylactic reactions, toxic epidermal necrolysis, cutaneous lupus-like reactions, cutaneous lupus erythematosus, photosensitivity reaction, rash, nettle ka, muscle weakness, muscle cramps, orthostatic hypotension, fever, jaundice (intrahepatic jaundice), depression, sleep disorders.

Orally. Adults: 1 tabl. once a day. It is recommended to individually adjust the dose of individual components of the preparation. If there is a clinical justification, a direct change from monotherapy to a fixed-dose combination of 150 mg / 12.5 mg may be considered in patients whose blood pressure is not adequately controlled by either hydrochlorothiazide or irbesartan 150 mg monotherapy; 300 mg / 12.5 mg in patients not adequately controlled by irbesartan 300 mg or a combined 150 mg / 12.5 mg formulation; 300 mg + 25 mg in patients not adequately controlled by the combined preparation 300 mg + 12.5 mg. Higher doses than 300 mg irbesartan + 25 mg hydrochlorothiazide once daily are not recommended. If necessary, the combined preparation can be used with another antihypertensive drug.Special groups of patients. No dosage adjustment is necessary for patients with renal impairment with a creatinine clearance ≥30 ml / min, in patients with mild to moderate hepatic impairment and in elderly patients.
The tablets can be taken with or without food, with water.