Index of drugs

Treatment of spontaneous hypertension in adults. The drug is indicated for use in patients whose blood pressure is not sufficiently controlled by monotherapy with valsartan or hydrochlorothiazide.

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 ACE inhibitor (kinase II) - an enzyme that converts angiotensin I to 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 the circulatory system. In patients with hypertension, it causes a reduction in blood pressure without affecting the pulse rate. C_max in the blood occurs after 2-4 h. Bioavailability is 23%. It is strongly bound to plasma proteins (94-97%). It is metabolized to a small extent to pharmacologically inactive hydroxymetabolite. It is excreted mainly in unchanged form with faeces (83%) and urine (13%). T_0,5 is 6 hours. 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 and increases urinary excretion of potassium. When co-administered with valsartan and hydrochlorothiazide, the reduction in potassium in the blood is less pronounced than with hydrochlorothiazide alone. The absolute bioavailability of hydrochlorothiazide is 60-80% after oral administration. The systemic availability of hydrochlorothiazide is reduced by approximately 30% when co-administered with valsartan. Over 95% of the absorbed hydrochlorothiazide dose is 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.

Do not use the preparation in patients with severe chronic heart failure; with unilateral or bilateral stenosis of the renal artery or stenosis of the artery supplying the only kidney; with primary hyperaldosteronism. Particularly cautiously use in patients with aortic or mitral valve stenosis or hypertrophic cardiomyopathy with narrowing of the left ventricle outflow pathway. Caution use in patients with sodium deficiency or dehydrated (hyponatraemia and / or hypovolaemia should be compensated before initiating therapy); with mild to moderate hepatic dysfunction without cholestasis (dosage adjustment needed); with diabetes (the dose of insulin or oral antidiabetic medicines may need to be adjusted); with impaired renal function (control of potassium, creatinine and uric acid in the blood). There are no data on the use of the product in kidney transplant patients. 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.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. 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. During treatment with the product, the concentration of electrolytes in the blood should be checked regularly. There are no data on the safety and efficacy of the preparation in children and adolescents <18 years - use in this age group is not recommended.

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. Valsartan 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 valsartan 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.

Uncommon: dehydration, paresthesia, blurred vision, tinnitus, hypotension, coughing, muscle aches, fatigue. Very rare: dizziness, diarrhea, arthralgia. Frequency unknown: fainting, non-cardiac pulmonary edema, renal dysfunction, increased uric acid, bilirubin and creatinine in the blood, hypokalaemia, hyponatremia, increased blood urea nitrogen, neutropenia. Undesirable effects on individual components may be a potential adverse event when using a combined preparation, even if not observed in clinical trials. Valsartan - uncommon: dizziness, abdominal pain; frequency unknown: decrease in hemoglobin, hematocrit reduction, thrombocytopenia, hypersensitivity reactions (including serum sickness), hyperkalemia, vasculitis, increased liver enzymes, angioneurotic edema, rash, pruritus, renal failure. Hydrochlorothiazide - often: orthostatic hypotension, loss of appetite, nausea, vomiting, urticaria and other forms of rash, impotence; rarely: thrombocytopenia (sometimes with purpura), depression, sleep disturbances, headache, arrhythmia, constipation, discomfort in the digestive tract, intrahepatic cholestasis or jaundice, hypersensitivity reactions to light; very rare: agranulocytosis, leukopenia, hemolytic anemia, bone marrow suppression, hypersensitivity reactions, respiratory failure with pulmonary inflammation and edema, pancreatitis, necrotizing vasculitis and toxic epidermal necrolysis, cutaneous lupus-like reactions, activation of dermal lupus erythematosus. Thiazide diuretics, including hydrochlorothiazide, can alter Glucose tolerance and increase levels of cholesterol, triglycerides and uric acid in the blood.

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 may be considered in patients whose blood pressure is not adequately controlled with monotherapy with valsartan or hydrochlorothiazide, 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.Special groups of patients. No dose adjustment is necessary in elderly patients and 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.