Treatment of spontaneous hypertension in adults. A fixed-dose drug is indicated for use in patients whose blood pressure is not adequately compensated during treatment with valsartan or hydrochlorothiazide monotherapy.
Combined preparation containing an angiotensin II receptor antagonist - valsartan and a thiazide diuretic - hydrochlorothiazide. Valsartan is an active 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. Valsartan does not bind or block other hormone receptors and 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. Cmax 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%). T0,5 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. T0,5 is 6-15 hours.
Contraindications:
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.
Precautions:
Do not use the preparation in patients with severe congestive heart failure or other diseases associated with increased activity of the renin-angiotensin-aldosterone system; with unilateral or bilateral stenosis of the renal artery or stenosis of the artery of the sole active kidney; with primary hyperaldosteronism. The concomitant use of valsartan with potassium-sparing diuretics, potassium replacers containing potassium or other products that may increase potassium levels (including heparin) is not recommended. The potassium concentration should be monitored. 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. Due to the risk of hypokalemia, hyponatremia, hypochloraemic alkalosis, hypomagnesaemia and hypercalcaemia, the concentration of electrolytes in the blood should be determined regularly during treatment with hydrochlorothiazide. Particularly cautiously use in patients with aortic valve stenosis, mitral valve or hypertrophic narrowing cardiomyopathy. Caution in patients with sodium and / or dehydrated sodium deficiency (sodium and fluid deficiencies should be corrected before starting treatment, patients should be monitored for fluid and electrolyte imbalance during treatment); with impaired renal function (control of potassium, creatinine and uric acid levels in the blood); with mild or moderate hepatic dysfunction without cholestasis; with diabetes (you may need to adjust your insulin dose or oral antidiabetic medicines). Hydrochlorothiazide may alter Glucose tolerance and increase serum cholesterol, triglyceride and uric acid levels. 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; Hypersensitivity reactions to hydrochlorothiazide are more likely to occur in patients with allergies or asthma. Hydrochlorothiazide may cause slight and recurrent hypercalcaemia without overt disturbances of Calcium metabolism; significant hypercalcemia may indicate hyperparathyroidism. The use of thiazide diuretics should be discontinued before performing tests to evaluate parathyroid function. In case of hypersensitivity reactions to light, it is recommended to discontinue the drug; if it is necessary to resume therapy with a diuretic, it is recommended to protect the body against sunlight or artificial UVA radiation. There have been reports of worsening or active systemic lupus erythematosus under the influence of thiazide diuretics. There are no data on the safety and efficacy of the preparation in children under 18 - use in this age group is not recommended.
Pregnancy and lactation:
The preparation is not recommended during the first trimester of pregnancy (there is a risk of teratogenic effects). In the second and third trimester, the use of the preparation is contraindicated. Administration of angiotensin II receptor antagonists in the second and third trimester causes toxic effects on the fetus (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. Infants 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 interfere with fetal-placental blood flow and induce fetus and newborn, among others jaundice, electrolyte disturbances and thrombocytopenia. It is not recommended to use the product during breastfeeding. During breastfeeding, in particular newborns and premature babies, other preparations with a more favorable safety profile should be used. If the preparation is used during breastfeeding, the lowest possible dose should be used. Hydrochlorothiazide passes into breast milk.
Side effects:
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 levels of uric acid, bilirubin, creatinine and urea nitrogen in the blood, hypokalemia, hyponatremia, neutropenia.Side effects associated with the use of valsartan. Uncommon: abdominal pain. Not known: hemoglobin decreased, hematocrit reduced, thrombocytopenia; other hypersensitivity reactions or allergic reactions, including serum sickness; hyperkalemia, hyponatremia; dizziness of peripheral origin; vasculitis; increased values of liver function; angioedema, rash, pruritus; kidney failure.Adverse reactions associated with the use of hydrochlorothiazide. Common: orthostatic hypotension; loss of appetite, mild nausea, vomiting; urticaria and other forms of skin rash; impotence. Rare: thrombocytopenia, sometimes with purpura; depression, sleep disorders; headaches; Heart arythmia; constipation, discomfort in the abdomen; intrahepatic cholestasis, jaundice; hypersensitivity to light. Very rare: agranulocytosis, leukopenia, haemolytic anemia, bone marrow suppression; hypersensitivity reactions; respiratory failure, including inflammation and pulmonary edema; inflammation of the pancreas; necrotizing vasculitis and toxic epidermal necrolysis; skin reactions reminiscent of lupus erythematosus, recurrence of dermal lupus erythematosus.
Dosage:
Orally. Adults: 1 tabl. once a day. Individual doses of individual components of the preparation are recommended. The dose of individual substances should be gradually increased to reduce the risk of hypotension and other side effects.If there is a clinical justification, a direct change in monotherapy can be considered for treatment with a fixed-dose combination in patients whose blood pressure is not adequately controlled with valsartan or hydrochlorothiazide alone, provided the dose is given at a dose that has been previously chosen for each component individually. After the start of therapy, the clinical response to treatment should be assessed. If the blood pressure is still unbalanced, the dose can be increased by increasing the dose of each ingredient up to a maximum dose of 320 mg valsartan + 25 mg hydrochlorothiazide. Antihypertensive effect is noticeable within 2 weeks. In the majority of patients, the maximum effect is observed within 4 weeks, in some patients within 4-8 weeks. No dosage adjustment is necessary in patients with creatinine clearance ≥30 ml / min and in patients Elderly. In patients with mild or moderate hepatic impairment without cholestasis, the maximum daily dose of valsartan is 80 mg. The tablets can be taken with or without water.
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