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 80 mg valsartan and 12.5 mg hydrochlorothiazide or 160 mg valsartan and 12.5 mg hydrochlorothiazide or 160 mg valsartan and 25 mg hydrochlorothiazide. The 80 mg + 12.5 mg tablets contain sunset yellow.

Antihypertensive 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 hrs, maximum pressure reduction is achieved within 4-6 h and persists for 24 h. During repeated administration, the maximum reduction in blood pressure is usually achieved within 4 weeks and persists during long-term treatment. In patients with hypertension, type 2 diabetes and microalbuminuria, urinary albumin excretion is reduced. 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. Thiazides affect the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chlorides. The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity, increases aldosterone secretion, increases urinary potassium loss. When co-administered with valsartan and hydrochlorothiazide, the reduction in potassium in the blood is less pronounced than with hydrochlorothiazide alone. The bioavailability of hydrochlorothiazide is 60-80%. It binds to plasma proteins at 40-70%. Over 95% of the absorbed 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 liver dysfunction, liver biliary cirrhosis, cholestasis. Resistance-resistant hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia. Severe renal impairment (creatinine clearance <30 ml / min), anuria. 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 heart failure or other conditions associated with stimulation of the renin-angiotensin-aldosterone system (RAA) and in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery supplying one kidney. Do not use the preparation in patients with primary hyperaldosteronism due to inhibition of RAA activity. Particularly cautiously use in patients with aortic valve stenosis, mitral valve or hypertrophic cardiomyopathy with left ventricular outflow tract obstruction and in patients with mild to moderate hepatic dysfunction without cholestasis and patients who have previously experienced hypersensitivity reactions to other angiotensin receptor blockers II.The occurrence of a hypersensitivity reaction to hydrochlorothiazide is more likely in patients with allergy and asthma. There are no data on the safety of the preparation in patients who have recently had a kidney transplant. The use of valsartan in children and adolescents under 18 years is not recommended (no data on safety and efficacy in this age group). Patients with diabetes who take thiazide diuretics may need to adjust their insulin dose or oral antidiabetic medicines. Treatment with the product should be discontinued if a photosensitivity reaction occurs and if it is necessary to resume therapy with a diuretic, protection of the exposed body surface from sunlight or artificial UV radiation is recommended. Co-administration of potassium supplements, potassium-sparing diuretics, potassium-containing potassium substitutes or other drugs that may increase potassium levels (eg heparin) is not recommended, if combined treatments should be monitored for potassium levels. 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. Table. 80 mg + 12.5 mg contain an orange sunset which may cause allergic reactions.

The preparation is not recommended in the first trimester and is contraindicated in the second and third trimester of pregnancy. Patients planning pregnancy should be switched to alternative antihypertensive treatments with an established safety profile during pregnancy. If pregnancy is diagnosed, treatment should be discontinued immediately and, if appropriate, alternative therapy should be started. Exposure to the drug in the II and III trimester exerts a toxic effect on the fetuses (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and newborns (renal failure, hypotension, hyperkalemia). In the case of exposure to the drug from the second trimester of pregnancy, ultrasound check of renal function and development of the skull is recommended. Infants whose mothers used the medicine should be closely monitored for hypotension. Hydrochlorothiazide crosses the placenta. Its use in the second and third trimester of pregnancy may adversely affect fetal-placental perfusion and may cause such effects in the fetus and newborn, such as jaundice, electrolyte imbalance and thrombocytopenia. There is no information on the use of valsartan during breast-feeding. Hydrochlorothiazide is excreted in breast milk. The use of the preparation during breastfeeding is not recommended. Alternative medicines with a better established safety profile are preferred during breastfeeding, especially when feeding newborns or premature babies.

Adverse reactions associated with the combination of valsartan / hydrochlorothiazide. Uncommon: dehydration; paresthesia; blurred vision; tinnitus; hypotension; cough; muscle pain; fatigue. Very rare: dizziness; diarrhea; arthralgia. Frequency unknown: fainting; non-cardiac pulmonary edema; impaired renal function; increase in uric acid, bilirubin, serum creatinine and urea nitrogen, hypokalemia, hyponatremia, neutropenia. Side effects associated with the use of valsartan. Uncommon: dizziness, abdominal pain. Frequency unknown: decrease in hemoglobin, hematocrit reduction, thrombocytopenia; other hypersensitivity / allergic reactions, including serum sickness; increase in serum potassium; vasculitis; increase in liver enzymes; angioedema, rash, pruritus; kidney failure.Adverse reactions associated with the use of hydrochlorothiazide. Common: orthostatic hypotension; loss of appetite, mild nausea and vomiting; urticaria and other forms of rash; impotence.Rare: thrombocytopenia, sometimes with purpura; depression, sleep disorders, headache, arrhythmias; constipation, discomfort in the digestive tract; intrahepatic cholestasis or jaundice; hypersensitivity to light. Very rare: agranulocytosis, leukopenia, haemolytic anemia, bone marrow suppression; hypersensitivity reactions; respiratory failure with inflammation and pulmonary edema; inflammation of the pancreas; necrotizing vasculitis and toxic epidermal necrolysis, cutaneous plaque-like reactions, activation of dermal lupus erythematosus.

Orally. Adults: the recommended dose is 1 tablet. 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 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 should be assessed, and if blood pressure can not be controlled, the dose can be increased by increasing the dose of each component to a maximum of 320 mg / 25 mg. The antihypertensive effect is clearly noticeable within 2 weeks. In most patients, the maximum effect is observed within 4 weeks, in some patients 4 to 8 weeks of treatment are required. This should be taken into account when adjusting the dose. In patients with mild to moderate hepatic dysfunction without cholestasis, doses higher than 80 mg valsartan should not be used daily. No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml / min) and in elderly patients.
The preparation can be taken regardless of meals; should be administered with water.