Index of drugs

Treatment of spontaneous hypertension in adults. A fixed-dose combination is indicated for use in patients whose blood pressure is not adequately controlled with valsartan or hydroquinoriosidic monotherapy.

1 tabl powl. contains 160 mg valsartan and 25 mg hydrochlorothiazide.

Combined preparation containing an angiotensin II receptor antagonist - valsartan and a thiazide diuretic - hydrochlorothiazide. Valsartan is an active, potent and specific angiotensin II receptor antagonist. It acts selectively on the AT receptor subtype₁by blocking the effects of angiotensin II. It has no agonist activity towards the AT receptor₁, is also not an inhibitor of angiotensin convertase (kininase II) - an enzyme that converts angiotensin I into angiotensin II and breaks down bradykinin. Therefore, unlike ACE inhibitors, the likelihood of coughing is low. Valsartan does not bind or block other hormone receptors or ion channels that play a role in the regulation of cardiovascular function. In patients with hypertension, it causes a reduction in blood pressure without affecting the pulse rate. The onset of action occurs within 2 h, the maximum reduction of pressure is achieved within 4-6 h and persists for 24 h. In patients with hypertension, type 2 diabetes and microalbuminuria, the elimination of albumin in the urine. Valsartan is absorbed quickly after oral administration, bioavailability is 23%. It is strongly bound to plasma proteins (94-97%), mainly with albumin. It is excreted mainly in unchanged form with bile (83%) and urine (13%), to a small extent it is metabolized to pharmacologically inactive hydroxymetabolite. T_0,5 is 6 hours. Hydrochlorothiazide is a thiazide diuretic. The mechanism of action of antihypertensive thiazides has not been fully understood. 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. Hydrochlorothiazide is not metabolised in the human body and is almost completely excreted unchanged in the urine. T_0,5 is 6-15 hours.

Hypersensitivity to valsartan, hydrochlorothiazide, other sulfonamide derivatives or other ingredients of the preparation. Severe hepatic dysfunction, liver biliary cirrhosis and cholestasis. Severe renal impairment (creatinine clearance <30 ml / min), anuria. Treatment-resistant hypokalemia, hyponatraemia, hypercalcemia and symptomatic hyperuricemia. II and III trimester of pregnancy.

In rare cases, symptomatic hypotension may occur at the beginning of treatment in patients with hyponatremia and / or in dehydration, eg due to high doses of diuretics. Sodium deficiency and / or volume of circulating blood should be corrected before starting treatment. In patients in whom renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg patients with severe congestive heart failure) and those treated with ACE inhibitors, the preparation (risk of oliguria, azotemia and acute renal failure) should not be used. It must not be used in the treatment of hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery supplying the sole kidney, because the concentration of urea and creatinine in the blood may be increased. It should not be used in patients with primary hyperaldosteronism due to inhibition of the renin-angiotensin system in these patients. Particularly cautiously use in patients with aortic or mitral valve stenosis or hypertrophic cardiomyopathy with narrowing of the left ventricle outflow pathway.There is no experience regarding the safety of the preparation in patients who have recently had a kidney transplant. Use with caution in patients with mild to moderate hepatic dysfunction without cholestasis. In case of hypersensitivity reactions to light, it is recommended to discontinue the drug; if re-initiation of the drug appears to be necessary, it is recommended to protect the body from sunlight or artificial UV radiation. Caution should be exercised in patients who have previously experienced hypersensitivity reactions to other angiotensin II receptor antagonists. The occurrence of a hypersensitivity reaction to hydrochlorothiazide is more likely in patients with allergy and asthma. Due to the lactose content, patients with rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take the drug. The product contains lecithin - if you are hypersensitive to peanut or soya, do not take the medicine. Due to the lack of data on the safety and efficacy of the drug in children under 18 years of age, the use is not recommended in this age group.

It is not recommended during the first trimester of pregnancy. In the second and third trimester, the use of the preparation is contraindicated. Administration of the preparation during the second and third trimester of pregnancy results in toxic effects on the fetus (deterioration of fetal renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). If the exposure to angiotensin II receptor antagonists has occurred since the second trimester of pregnancy, ultrasound examination of the kidneys and the skull is recommended. Newborns whose mothers have taken drugs from the angiotensin II receptor antagonists should be observed for hypotension. Thiazides cross the placental barrier and may cause, among others, electrolyte abnormalities in the fetus, fetal icterus or newborn or neonatal thrombocytopenia. It is not recommended to use the product during breastfeeding. During breastfeeding, in particular newborns and children born prematurely, it is recommended to use other preparations with a better safety profile. Thiazides are excreted in breast milk and can inhibit lactation.

Uncommon (≥1 / 1000, <1/100): dehydration, paraesthesia, blurred vision, tinnitus, hypotension, cough, muscle aches, fatigue. Very rare (<1 / 10,000): dizziness, diarrhea, arthralgia. In addition, fainting, non-cardiac pulmonary edema, renal dysfunction, increased uric acid, bilirubin and creatinine in the blood, hypokalemia, increased blood urea nitrogen, neutropenia, hyponatremia, hypochloraemia alkalosis, hypercalcaemia were observed. Undesirable effects on individual components may be potential adverse events when using the product, even if they were not observed in clinical trials. Valsartan: uncommon - abdominal pain of unknown frequency - decrease in hemoglobin, decrease in hematocrit value, thrombocytopenia, hypersensitivity reactions (including serum sickness), hyperkalemia, vasculitis, increased liver enzymes, angioneurotic edema, rash, pruritus. Hydrochlorothiazide: often - orthostatic hypotension, loss of appetite, nausea, vomiting, urticaria and other forms of rash, impotence, rarely - thrombocytopenia (sometimes with purpura), depression, sleep disorders, headache, arrhythmias, constipation, discomfort in the gastrointestinal tract , intrahepatic cholestasis or jaundice, photosensitivity reactions, very rarely - agranulocytosis, leukopenia, hemolytic anemia, bone marrow suppression, hypersensitivity reactions, respiratory failure with inflammation and pulmonary edema, pancreatitis, necrotizing vasculitis and toxic epidermal necrolysis, cutaneous reactions Lupus-like, activating the skin form of Lupus Erythematosus.

Orally. Adults. The recommended dose is 1 tablet. once a day. Individual dose adjustments of individual product components are recommended. If there is a clinical justification, a direct change from monotherapy to fixed-dose combination therapy can be considered in patients whose blood pressure is not adequately controlled with valsartan or hydrochlorothiazide alone, provided that the formulation is administered at a dose that has been previously selected for each component individually. After initiation of therapy, the clinical response to treatment with the preparation should be evaluated and if the blood pressure can not be controlled, the dose can be increased by increasing the dose of each component to a maximum dose of 320 mg / 25 mg. The antihypertensive effect is noticeable within 2 weeks.In the majority of patients, the maximum effect is observed within 4 weeks, in some patients from 4 to 8 weeks. No dosage adjustment is necessary in patients with mild or moderate renal impairment (creatinine clearance> 30 ml / min). In patients with mild to moderate hepatic impairment without cholestasis, the maximum dose of valsartan is 80 mg per day.
The tablets can be taken with or without water.