Index of drugs

Treatment of spontaneous hypertension in adults. A fixed-dose drug is indicated for use in adult patients whose blood pressure is not adequately compensated by monotherapy with valsartan or hydrochlorothiazide.

1 tabl powl. contains 160 mg valsartan and 25 mg hydrochlorothiazide; tablets contain lactose.

Combined preparation containing an angiotensin II receptor antagonist - valsartan and a thiazide diuretic - hydrochlorothiazide. Valsartan is orally active and a 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, does not inhibit the activity of kinase II - an enzyme that converts angiotensin I to angiotensin II and breaks down bradykinin. Valsartan does not bind to and blocks other hormone receptors or ion channels that are important in cardiovascular regulation. In patients with hypertension, it causes a reduction in blood pressure without affecting the pulse rate. In the majority of patients, the onset of antihypertensive activity occurs within 2 hours, and the maximum reduction in blood pressure is achieved within 4-6 hours. The antihypertensive effect persists for 24 hours after the dose is taken. 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 (about 20%). It is excreted in faeces (83%) and urine (13%), mainly in unchanged form. T_0,5 is 6 hours. Hydrochlorothiazide is a thiazide diuretic. Increases the excretion of sodium and chlorides approximately equally. 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, C_max occurs after 2 h. It binds to plasma proteins at 40-70%. 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. 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 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. There are no data on the use of the product in kidney transplant patients. 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. 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: sodium deficient or dehydrated - risk of symptomatic hypotension, especially at the beginning of treatment (hyponatremia and / or circulating blood volume should be balanced before starting treatment); with impaired renal function (control of potassium, creatinine and uric acid levels in the blood); with mild or moderate hepatic dysfunction without cholestasis. During treatment, the concentration of electrolytes in the blood should be determined regularly (there is a risk of hypokalemia, hyponatremia, hypochlora alkalosis, hypomagnesaemia and slight hypercalcemia associated with the use of hydrochlorothiazide). Due to valsartan, concomitant use of potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes or other drugs that may increase potassium levels is not recommended. Thiazide may affect Glucose tolerance, so patients with diabetes may need to modify the dosage of oral antidiabetic agents and insulin. The use of thiazide diuretics may be associated with an increase in cholesterol and triglycerides and hyperuricemia. There have been reports of worsening or active systemic lupus erythematosus under the influence of thiazide diuretics. 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 or 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. There are no data on the safety and efficacy of the preparation in children <18 years - use in this age group is not recommended. Due to the lactose content, do not use the preparation in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

The use of the preparation in the first trimester of pregnancy is not recommended (there is a risk of teratogenic effect). 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 the newborn (renal failure, hypotension, hyperkalemia) - when exposure to the drug occurred from 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 in the II and III trimester may adversely affect fetal-placental perfusion and may cause fetal and neonatal effects such as jaundice, electrolyte imbalance and thrombocytopenia. Hydrochlorothiazide passes into breast milk. The preparation is not recommended during breastfeeding, especially when feeding newborns or premature babies.

Uncommon: dehydration, blurred vision, tinnitus, hypotension, cough, muscle pain, tiredness. Very rare: dizziness, diarrhea, joint pain. 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 potential adverse events when using a combination drug.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 skin rash, impotence; rare: thrombocytopenia, (sometimes with purpura), depression, sleep disturbances, headache, arrhythmia, constipation, discomfort in the gastrointestinal tract, intrahepatic cholestasis, jaundice,hypersensitivity to light; very rare: agranulocytosis, leukopenia, haemolytic anemia, bone marrow suppression, hypersensitivity reactions, respiratory failure (including inflammation and pulmonary edema), pancreatitis, necrotizing vasculitis and toxic epidermal necrolysis, skin reactions reminiscent of lupus erythematosus, activation of cutaneous form lupus erythematosus.

Orally. Adults: 1 tabl. once a day. Individual dose adjustments of individual components are recommended. In any case, the effects of gradually increasing the dose of individual components should be monitored to reduce the risk of hypotension and other adverse reactions. If there is a clinical justification for patients whose blood pressure is not adequately controlled with valsartan or hydrochlorothiazide monotherapy, a direct change from monotherapy to a fixed-dose combination may be considered, provided that the combined drug is administered in 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 any of the components to a maximum dose of valsartan / hydrochlorothiazide 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 (CCr≥ 30 ml / min). In patients with mild to moderate hepatic impairment without cholestasis, the maximum dose of valsartan is 80 mg per day.Way of giving. The tablets can be taken with or without water.