Index of drugs

Treatment of spontaneous hypertension in adults. A fixed-dose formulation is indicated for the treatment of patients whose blood pressure is not adequately controlled during monotherapy with valsartan or hydrochlorothiazide.

1 tabl powl. contains 80 mg, 160 mg or 320 mg of valsartan and 12.5 or 25 mg of hydrochlorothiazide.

Antihypertensive drug 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 pressure drop is achieved within 4-6 h and persists for 24 h. During repeated administration, the maximum reduction in blood pressure is usually achieved within 2-4 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 any of the excipients. Severe liver dysfunction, cirrhosis and cholestasis. Treatment-resistant hypokalemia, hyponatraemia, 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.

The drug should not be used in patients with severe chronic heart failure (lack of experience) and in patients with other diseases associated with increased activity of the renin-angiotensin-aldosterone system - RAA (risk of renal dysfunction), and in patients with unilateral or bilateral stenosis of the renal artery or stenosis of the artery supplying the only kidney (risk of increased urea and serum creatinine) and patients with primary hyperaldosteronism (risk of inhibiting the activity of the renin-angiotensin system). Special caution is recommended in patients with aortic stenosis, mitral valve or hypertrophic cardiomyopathy with narrowing of the left ventricle outflow pathway. So far, there is no experience regarding the safety of the medicine in patients with kidney transplantation.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. Caution should be exercised in patients with mild to moderate hepatic impairment, without cholestasis. Hydrochlorothiazide may affect Glucose tolerance and increase serum cholesterol, triglycerides and uric acid - patients with diabetes may need to change their insulin dose or oral hypoglycaemic agents. Thiazides may reduce the excretion of Calcium in the urine, resulting in recurrent and slight increase in serum Calcium, thiazides should be discontinued before performing parathyroid tests. If a hypersensitivity reaction occurs during treatment, discontinuation of treatment is recommended, and if there is a continuation of treatment, places exposed to sunlight or UVA rays should be protected. Caution should be exercised in patients who have previously experienced hypersensitivity reactions to other angiotensin II receptor blockers. Due to the lack of data on safety and efficacy, it is not recommended for children under 18 years of age.

The use of the drug in the first trimester is not recommended, and in the second and third trimester is contraindicated. During the second and third trimesters, valsartan has toxic effects on fetal development (decreased renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). Hydrochlorothiazide may adversely affect fetal-placental perfusion and may cause fetus and newborn - jaundice, electrolyte imbalance and thrombocytopenia. In case of exposure to angiotensin II receptor antagonists from the second trimester of pregnancy, ultrasound check of renal function and development of the skull is recommended. Children whose mothers took the drug during pregnancy should be carefully monitored for hypotension. Patients planning pregnancy should be treated with other antihypertensive agents with an established safety profile for use in pregnancy. If pregnancy is diagnosed, valsartan should be discontinued immediately and, if appropriate, alternative therapy should be used. Breast-feeding is not recommended during treatment.

Adverse reactions associated with the combination of valsartan / hydrochlorothiazide. Uncommon: dehydration; paresthesia; blurred vision; tinnitus; hypotension; cough; muscular pains; fatigue. Very rare: dizziness; diarrhea; arthralgia. Frequency unknown: fainting; non-cardiac pulmonary edema; kidney problems; increased uric acid, bilirubin, serum creatinine and urea nitrogen, hypokalemia, hyponatremia, neutropenia. Side effects associated with the use of valsartan. Uncommon: labyrinth-like dizziness, abdominal pain. Not known: decreased hemoglobin, decreased hematocrit, thrombocytopenia; other hypersensitivity / allergic reactions, including serum sickness; increased 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, headaches, arrhythmias; constipation, gastrointestinal discomfort; intrahepatic cholestasis or jaundice; hypersensitivity to light. Very rare: agranulocytosis, leukopenia, hemolytic anemia, bone marrow suppression; hypersensitivity reactions; respiratory failure, including inflammation and pulmonary edema; inflammation of the pancreas; necrotizing vasculitis and toxic epidermal necrolysis, skin lupus erythematosus-like reactions, re-activation of cutaneous lupus erythematosus.

Oral: 1 tabletonce a day. It is recommended to gradually increase the dose of individual ingredients. If the blood pressure control is not sufficient, the dose may be increased by increasing the dose of any of the ingredients to a maximum dose of valsartan / hydrochlorothiazide 320 mg / 25 mg. In any case, an increase in the dose of individual components should be monitored to reduce the risk of hypotension and other side effects. The hypotensive effect is revealed within 2 weeks. In patients with mild to moderate hepatic impairment, without cholestasis, the dose of valsartan should not exceed 80 mg. The drug can be taken regardless of meals, tabl. drink with water.