Index of drugs

Treatment of spontaneous hypertension in adults. A fixed-dose combination is indicated for patients whose blood pressure is not adequately controlled with 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 tablets contain lactose.

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 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%), mainly with albumin. 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. 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.

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 with renal function may depend on the activity of the renin-angiotensin-aldosterone system - RAA (eg patients with severe congestive heart failure), the preparation should not be used (risk of oliguria, azotemia and acute renal failure). 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. 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 it seems necessary to restart the treatment, it is recommended to protect the exposed body surface 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. Due to the lack of data on the safety and efficacy of the drug in children and adolescents, the use of the preparation in this age group is not recommended.

It is not recommended during the first trimester of pregnancy. In the second and third trimester, the use of the preparation is contraindicated. The administration of angiotensin II receptor antagonists in the second and third trimester causes fetal effects (decreased 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. 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. It is not recommended to use the product during breastfeeding. During breastfeeding, in particular newborns and premature babies, it is recommended to use other preparations with a better safety profile. Hydrochlorothiazide passes into breast milk.

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, hypochlora alkalosis. 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, frequency unknown - decrease in hemoglobin, hematocrit reduction, thrombocytopenia, hypersensitivity reactions (including serum sickness), hyperkalemia, hyponatraemia, diarrheal headache, vasculitis, increased liver enzymes, angioedema, 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 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. 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. No dose 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.