Vanatex Kombi 80 mg / 12.5 mg tablet number 28

Vanatex Combi user manual

Composition

active ingredients: 1 coated tablet contains 80 mg of valsartan and 12.5 mg of hydrochlorothiazide or 160 mg of valsartan and 12.5 mg of hydrochlorothiazide, or 160 mg of valsartan and 25 mg of hydrochlorothiazide;

Excipients:

core: lactose, sodium croscarmellose, silicon dioxide colloid, magnesium stearate

80 mg / 12.5 mg tablet (Advantia Prime 171996BA01): hypromellose, macrogol 400, titanium dioxide (E 171), iron oxide red (E 72)

Sheath tablet 160 mg / 12.5 mg (Advantia Prime 172012BA01): hypromellose, macrogol 400, titanium dioxide (E 171), iron oxide red (E172), iron oxide yellow (E172), iron oxide black (E172);

Sheath tablet 160 mg / 25 mg (Advantia Prime 185998BA01): hypromellose, macrogol 400, titanium dioxide (E 171), iron oxide red (E172), iron oxide yellow (E172), iron oxide black (E172).

Dosage form

Film-coated tablets.

Pharmacological group

Blockers of angiotensin II receptors (AT-1 receptor blockers) and diuretics.

ATS code C09D A03.

Indications

Arterial hypertension in patients, blood pressure in them, respectively, is not regulated by monotherapy with valsartan or hydrochlorothiazide.

Contraindications

• Hypersensitivity to valsartan, hydrochlorothiazide, other drugs based on sulfonamide or to any of the auxiliary substances.
• Severe hepatic insufficiency, cirrhosis and cholestasis.
• Severe renal insufficiency (creatinine clearance
• Rack hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia.
• Pregnant women or women planning to become pregnant (see "Use during pregnancy or lactation").
• Simultaneous use of angiotensin receptor antagonists, or ACE inhibitors with aliskiren in patients with diabetes mellitus or renal dysfunction (glomerular filtration rate (SHGF)

Dosing and Administration

The recommended dose of Vanatex Kombi is 80 mg / 12.5 mg - 1 tablet once a day.

With insufficient reduction in blood pressure after 3-4 weeks of treatment, it is recommended to consider the possibility of continuing treatment with a dosage of 1 tablet of 160 mg / 12.5 mg once a day. Tablets 160 mg / 25 mg are prescribed for patients who do not achieve a sufficient reduction in blood pressure when using tablets 160 mg / 12.5 mg. If in the future when using 160 mg / 25 mg tablets arterial pressure is not enough to reduce, it is recommended to consider the possibility of continuing treatment with a dosage of 320 mg / 12.5 mg (to be able to receive such dosage should be used valsartan and hydrochlorothiazide in another dosage form). A dose of 320 mg / 25 mg is given to patients who do not achieve a sufficient reduction in blood pressure with a dose of 320 mg / 12.5 mg.

The maximum daily dose is 320 mg / 25 mg (2 tablets 160 / 12.5 mg).

The maximum antihypertensive effect is achieved within 2-4 weeks. Some patients may need 4-8 weeks of treatment.

Vanatex Kombi can be taken regardless of food intake, washed down with water.

Additional information for specific patient groups

Renal insufficiency

Patients with creatinine clearance> 10 ml / min do not need dose adjustment. The simultaneous use of valsartan with aliskiren in patients with impaired renal function (glomerular filtration rate (SHGF)

Due to the presence of hydrochlorothiazide, Vanatex Combi is contraindicated in patients with severe renal insufficiency.

Diabetes

The simultaneous use of Vaneatex Combi with aliskiren in patients with diabetes mellitus is contraindicated.

Liver failure

For patients with mild and moderate hepatic insufficiency without cholestasis, the dose of valsartan should not exceed 80 mg. Vanatex Combi is contraindicated in patients with severe hepatic insufficiency.

Elderly patients

Dose selection is not required for elderly patients.

Adverse Reactions

Side effects of valsartan / hydrochlorothiazide

From the side of metabolism and nutrition: infrequently - dehydration.

From the nervous system: very rarely - dizziness infrequently - paresthesia, hypoesthesia, unknown - fainting, insomnia.

From the side of the organ of vision : infrequently - blurred vision, visual impairment.

From the organs of hearing: infrequent - ringing in the ears, otitis media.

From the cardiovascular system: infrequently - arterial hypotension, tachycardia.

From the respiratory system: infrequently - cough; unknown - noncardiogenic pulmonary edema.

From the side of the digestive tract: very rarely diarrhea.

From the musculoskeletal system: infrequently - myalgia (pain in the muscles) is very rare - arthralgia.

From the side of the urinary system : unknown - renal dysfunction.

Common violations: infrequent fatigue.

Laboratory indices : unknown - an increase in uric acid in the serum, an increase in bilirubin and serum creatinine, hypokalemia, hyponatremia, an increase in the level of blood urea nitrogen, neutropenia.

Additional information on individual components

Inadvertent adverse reactions reported earlier, caused by one of the individual components, can also be a potential undesirable effect of Vanatex Combi.

Adverse reactions of valsartan.

On the part of the blood system and lymphatic system: unknown - reduced hemoglobin, reduced hematocrit, neutropenia, thrombocytopenia.

From the immune system: unknown - other allergic reactions / hypersensitivity reactions, including serum sickness.

From the side of metabolism and nutrition: unknown - an increase in potassium in the blood serum, hyponatremia.

From the organs of hearing: infrequently - dizziness (vertigo).

From the side of the cardiovascular system : it is unknown - vasculitis.

From the side of the digestive tract: rarely - pain in the abdomen.

From the side of the digestive system: unknown - an increase in liver function, including increased serum bilirubin levels.

From the skin and subcutaneous tissues : unknown - Quincke's edema (angioedema), rash, itching.

From the urinary system: unknown - renal failure and impaired renal function, increased serum creatinine levels.

On the part of the respiratory system: very rarely - bronchitis, infections of the upper respiratory tract.

Adverse reactions of hydrochlorothiazide

Hydrochlorothiazide has been widely used for many years, often at higher doses than at the doses that Vanatex Kombi intended. The following adverse reactions are reported in patients who received monotherapy with thiazide diuretics, including hydrochlorothiazide.

On the part of the blood system and lymphatic system : rarely - thrombocytopenia, sometimes with purpura, very rarely - agranulocytosis, leukopenia, hemolytic anemia, oppression of bone marrow function.

From the immune system: very rarely - allergic reactions (hypersensitivity reactions).

From the side of the psyche: rarely - depression, sleep disturbance.

From the nervous system: rarely - a headache.

From the cardiovascular system: rarely - cardiac arrhythmia; often - orthostatic hypotension.

On the part of the respiratory system : very rarely - labored breathing (dyspnea), including pneumonia and pulmonary edema.

From the digestive tract: often - loss of appetite, mild nausea and vomiting rarely - constipation, gastrointestinal discomfort; very rarely - pancreatitis.

From the liver and gallbladder: rarely - cholestasis, jaundice.

From the skin and subcutaneous tissues: often - hives and other types of rashes; rarely - photosensitivity; very rarely - necrotizing vasculitis and toxic epidermal necrolysis, systemic lupus erythematosus, reaction erythematosus, re-activation of cutaneous lupus erythematosus.

From the genitals and the breast: often - impotence.

Overdose

Symptoms. An overdose of valsartan can lead to a noticeable arterial hypotension, which in turn can lead to depression, circulatory collapse (vascular insufficiency), and / or shock (comma). In addition, such signs and symptoms can occur due to an overdose of hydrochlorothiazide: nausea, drowsiness, hypovolemia and electrolyte disorders associated with cardiac arrhythmias and muscle spasms.

Treatment . Therapeutic measures depend on the time of ingestion and the type and severity of the symptoms, the stabilization of the circulation is extremely important.

Therapeutic measures depend on the prescription of the excessive dose, as well as the type and severity of the symptoms, while the primary measure is the normalization of hemocirculation.

If the drug has been taken recently, you should induce vomiting. If after the use of the drug has passed a long time, it is necessary to give the patient a sufficient amount of activated carbon.

With arterial hypotension, the patient should be placed in a horizontal position and immediately restore the water-salt balance by introducing an isotonic saline solution.

Valsartan can not be removed from the body by hemodialysis due to its binding to plasma proteins, but to remove hydrochlorothiazide from the body, hemodialysis is effective.

Use during pregnancy or lactation

Pregnancy

Valsartan

The use of angiotensin II receptor antagonists (Arai) is contraindicated throughout the gestation period.

Epidemiological data on the risk of teratogenic effects due to the use of ACE inhibitors during the first trimester of pregnancy are not convincing, but a slight increase in risk can not be ruled out. Because there are no controlled epidemiological risk data for the use of angiotensin II receptor antagonists, the risk of teratogenic effects may exist for this class of drugs. Except when continuing therapy is considered necessary, patients planning a pregnancy should be prescribed an alternative antihypertensive therapy with an established safety profile for use during pregnancy. If pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately and, if necessary, another drug approved for use in pregnant women.

It is known that the use of angiotensin II receptor antagonists during the II and III trimesters of pregnancy induces fetotoxicity in a person (weakening of kidney function, oligohydroamnion, delayed ossification of the skull bones) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia).

If Arai was used with AI trimester of pregnancy, it is recommended to perform an ultrasound examination to check the function of the kidneys and the condition of the bones of the skull.

The condition of newborns whose mothers used Arai should be carefully checked for the development of arterial hypotension.

Hydrochlorothiazide

There is limited experience with the use of hydrochlorothiazide in pregnancy, especially in the first trimester of pregnancy. The introduction of a thiazide diuretic into the uterine cavity led to the development of thrombocytopenia in the fetus or newborn, as well as the development of other undesirable phenomena. Hydrochlorothiazide penetrates the placenta. Given the pharmacological mechanism of action of hydrochlorothiazide for its use in the II and III trimesters, it can lead to a threat of fetoplacental perfusion and can cause such violations in the fetus and newborn as jaundice, electrolyte imbalance and thrombocytopenia.

Lactation

Because of the lack of information on the use of valsartan during the breastfeeding period, Vanatex Kombi is not recommended for use during this period.

Hydrochlorothiazide penetrates into breast milk. Therefore, it is not recommended to use Vanatex Kombi during lactation. If pregnancy is detected during treatment, the drug should be discontinued as soon as possible.

Children

Safety and efficacy of Vanatex Combi for children are not established.

Application features

Changes in the concentration of electrolytes. Caution should be exercised when using Vanatexso Combi together with potassium salts, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that can increase potassium levels (eg, heparin). Reported cases of hypokalemia in the treatment of thiazide diuretics. It is recommended to check the content of potassium in serum often.

Treatment with thiazide diuretics is often associated with the occurrence of hyponatremia and hypochloraemic alkalosis.Thiazides increase the excretion of magnesium in the urine, which as a result can lead to hypomagnesemia.

Patients with a deficiency in the body of sodium and / or volume of circulating blood (BCC). In patients with severe sodium deficiency and / or circulating blood volume in the body, such as those receiving high doses of diuretics, in rare cases, symptomatic hypotension may occur at the start of Vanatex Combi therapy. Therefore, before starting therapy with the drug should be corrected the content of sodium and / or the volume of circulating blood.

In case of hypotension, the patient should be placed in the supine position and, if necessary, a saline infusion.Treatment can be continued immediately after the stabilization of blood pressure.

Patients with severe chronic heart failure or other conditions with increased activity of renin-angiotensin-

In patients whose kidney function is dependent on the activity of renin-angiotensin (for example, in patients with severe congestive heart failure), treatment with ACE inhibitors is associated with oliguria and / or progressive azotemia and rarely with acute renal failure. The use of Vaneatex Combi in patients with severe chronic heart failure is unreasonable.

Since it can not be ruled out that due to the suppression of renin-angiotensin-using, the Vanatexu Combi can also be associated with impaired renal function, Vanatex Kombi should not be used in such patients.

Stenosis of the renal artery. Do not apply the drug to patients with unilateral or bilateral stenosis of the renal artery or stenosis caused by a single kidney, as these patients can increase the levels of urea and creatinine plasma

Primary hyperaldosteronism

Do not use Vanatex Combi with patients with primary hyperaldosteronism, since their renin-angiotensin system is not activated.

Stenosis of the aortic and mitral valve, hypertrophic obstructive cardiomyopathy

As with the use of other vasodilators, patients with stenosis of the aortic and mitral valve or hypertrophic obstructive cardiomyopathy (GOCM) require special care.

Impaired renal function. For patients with mild to moderate renal impairment (creatinine clearance ≥ 30 mL / min), dose adjustment is not required.

It should be used with caution VANATEX Combi in severe renal failure (creatinine clearance

Kidney transplantation

Currently, there is no experience regarding the safety of the drug to patients who have recently undergone kidney transplantation.

Violation of the function of the liver. For patients with minor and moderate impairment of liver function without cholestasis, dose adjustment is not required. However, the Vanatex Combi should be used with caution. Diseases of the liver do not significantly alter the pharmacokinetics of hydrochlorothiazide.

Systemic lupus erythematosus. It has been reported that thiazide diuretics enhance or activate manifestations of systemic lupus erythematosus.

Other metabolic disorders. Thiazide diuretics can alter glucose tolerance and raise serum cholesterol, triglycerides and uric acid levels. For patients with diabetes, a dose adjustment of insulin or oral antidiabetic drugs may be required.Thiazides can reduce the excretion of calcium in the urine and cause a fickle and insignificant increase in serum calcium in the absence of calcium metabolism disorders. Significant hypercalcemia may indicate that the patient has background hyperparathyroidism. It is necessary to stop the use of thiazides before performing tests to assess the function of parathyroid glands.

Photosensitivity

It has been reported that photosensitivity occurs when thiazide diuretics are used. If the photosensitivity reaction occurs during treatment, it is recommended to stop. If repeated use of a diuretic is deemed necessary, it is recommended to protect the exposed skin from sunlight or artificial ultraviolet radiation.

Pregnancy

During pregnancy, angiotensin II receptor antagonists should not be started. If only continued therapy with angiotensin II receptor antagonists is not considered necessary, patients planning a pregnancy should be transferred to alternative types of antihypertensive treatment, have an established safety profile for use during pregnancy. When pregnancy is detected the treatment of angiotensin II receptor antagonists should be stopped immediately, and, if necessary, to start alternative therapy.

General recommendations

Caution must be exercised when using the drug in patients with hypersensitivity to other angiotensin II receptor antagonists in the anamnesis. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients with allergy and asthma.

angioedema

Occurrence Quincke's edema (including edema of the larynx and the glottis, resulting in airway obstruction and / or swelling of face, mouth, pharynx, and / or language) was observed in patients treated with valsartan, some of these patients had a history of angioneurotic edema in the use of other drugs, including the use of other angiotensin II receptor antagonists. In the case of angioneurotic edema treatment of angiotensin II receptor antagonists should be stopped immediately. Contraindicated re-use of the preparation.

acute glaucoma

Application hydrochlorothiazide, sulfonamide been associated with the occurrence of idiosyncratic reactions, which may lead to acute myopia and transition acute angle-closure glaucoma. It noted a sharp decline in visual acuity and eye pain. These symptoms usually occur within a few hours a week while taking the drug. Untreated glaucoma can lead to irreversible vision loss.

Should immediately stop using the product. It may require medical or surgical treatment. Factor in the risk of developing acute angle-closure glaucoma is an allergic response to the use of a sulfonamide or penicillin.

For elderly patients, a dose adjustment is required.

Hydrochlorothiazide may reduce the level of protein-bound iodine in the plasma krovi.Gidrohlorotiazid able to increase the concentration of free bilirubin in the serum.

Doping control

It should be borne in mind that this drug may cause a positive reaction in the anti-doping controls.

Excipients

Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose malabsorption syndrome should not take this drug.

The ability to influence the reaction rate when driving vehicles or other mechanisms

At the beginning of the drug (the period is determined individually by the physician) is forbidden to drive a car and do the work, which could lead to an accident. Later, the degree of prohibition is determined by your doctor.

Interaction with other drugs and other interactions

Interactions related to both valzartanom and hydrochlorothiazide

Simultaneous use is not recommended

Lithium. Reversible increases lithium concentration in plasma and toxicity were recorded while the use of ACE inhibitors and thiazides, including hydrochlorothiazide. this combination is not recommended due to lack of experience simultaneous use of valsartan and lithium. If necessary, use of such a combination is recommended to closely monitor the lithium level in blood plasma.

Simultaneous application requiring caution

Other antihypertensive drugs

Vanateks Combi can enhance the effect of other drugs and antihypertensive properties (e.g., ACE inhibitors, beta blockers, calcium channel blockers).

Pressor amines (e.g., norepinephrine, epinephrine)

Possible decreased response to pressor amines, it is not sufficient to exclude their use.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid> 3 g / day and nonselective NSAIDs
NSAIDs may attenuate the antihypertensive effect such as antagonists of angiotensin II, and while the use of hydrochlorothiazide. In addition, simultaneous Vanateksu Combination and NSAIDs may lead to deterioration of renal function and potassium levels in the blood plasma. Thus, it is recommended monitoring of renal function at the beginning of treatment and adequate hydration of the patient.

Interactions related to valzartanom

Simultaneous use is not recommended

Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that can increase the level of potassium

If the application of a drug which affects the level of potassium is considered necessary in combination with valsartan, recommended potassium monitoring of blood plasma.

The lack of interaction

In studies of drug interactions valsartan were noted clinically significant interactions valsartan and any of the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide. Digoxin and indomethacin can interact with gidrohlorotiazidnim component Vanateksu Combi (cm. "Interactions associated with hydrochlorothiazide").

Interactions related to hydrochlorothiazide

Simultaneous application requiring caution

Medications which application is associated with hypokalemia and potassium loss (e.g., with concomitant administration of diuretics, corticosteroids, laxatives, ACTH, amphotericin, carbenoxolone, penicillin G, salicylic acid and derivatives).

If there is a need for the appointment of these drugs with a combination of valsartan and hydrochlorothiazide, it is recommended to monitor the level of potassium in the plasma. These drugs may enhance the effect of hydrochlorothiazide on the level of potassium in the plasma.

Medications that can cause bidirectional tachycardia (torsades de pointes)

• Class Ia antiarrhythmic drugs (e.g., quinidine, gidrohinidin, disopyramide)
• Class III antiarrhythmics (amiodarone, sotalol, dofetilide, ibutilide)
• Some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, tsiamemazin, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol)
• Other (e.g., bepridil, cisapride, difemanil, erythromycin, halofantrine, Ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine i.v.).

Due to the risk of hypokalemia hydrochlorothiazide should be used with caution in conjunction with drugs that can cause bidirectional tachycardia (torsades de pointes).

digitalis glycosides

Thiazide-induced hypokalemia or hypomagnesemia may occur as a side effect, which contributes to the development of cardiac arrhythmias induced by digitalis preparations.

calcium salts and vitamin D

The use of thiazide diuretics including hydrochlorothiazide, simultaneously with vitamin D or calcium salts can increase the calcium level in the blood plasma.

Antidiabetics (oral drugs and insulin)

Treatment thiazide may influence the glucose tolerance. Dose adjustment may be required antidiabetic drug.

Caution is advised to use metformin because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.

Beta-blockers and diazoxide

Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta-blockers increase the risk of hyperglycemia. Thiazide diuretics including hydrochlorothiazide may enhance the hyperglycemic effect of diazoxide.

Drugs used in the treatment of gout (probenecid, sulfinpyrazone and allopurinol)

It may be necessary to dose adjustment of drugs that promote the excretion of uric acid, as hydrochlorothiazide may enhance the uric acid level in plasma. It may be necessary to increase the dose of probenecid or sulfinpirazona.Odnovremennoe use of thiazide diuretics including hydrochlorothiazide, may increase the frequency of hypersensitivity reactions to allopurinol.

Anticholinergics (e.g., atropine, biperiden)

The bioavailability of thiazide diuretics may be increased by anticholinergic agents, probably due to the decrease in motility of the gastrointestinal tract and gastric emptying rate.

amantadine

Thiazides, including hydrochlorothiazide, increase the risk of adverse effects caused by amantadine.

Resins cholestyramine and colestipol

Absorption of thiazide diuretics including hydrochlorothiazide, disrupted in the presence of anionic resins.

Cytotoxic agents (e.g., cyclophosphamide, methotrexate)

Thiazides, including hydrochlorothiazide, may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects.

Nedepolyarizuvalni skeletal muscle relaxants (such as tubocurarine)

Thiazides, including hydrochlorothiazide, increase the effect of curare derivatives.

Cyclosporin

The simultaneous appointment of cyclosporine may increase the risk of hyperuricemia and complications such as gout.

Alcohol, anesthetics and sedatives

May occur potentiation of orthostatic hypotension.

methyldopa

Obtained from the Department Yelnia reports of hemolytic anemia in patients who were prescribed concomitant treatment with methyldopa and hydrochlorothiazide.

carbamazepine

Patients receiving hydrochlorothiazide simultaneously with carbamazepine may develop hyponatremia. Such patients should be informed about the possibility of giponatriemichnoi reaction and observe properly for their condition.

Contrast agents containing iodine

In the case of diuretic-induced dehydration there is an increased risk of acute renal failure, especially when high doses of the drug containing iodine. It is necessary to carry out an adequate replenishment of fluid loss in a patient prior to use.

Pharmacological properties

Valsartan is an orally active and specific antagonist of angiotensin II (Ang II) receptor. It acts selectively on the AT 1 subtype receptor which is responsible for the well-known action of angiotensin II. Increased levels of Ang II in the blood plasma after receptor blockade AO 1 valzartanom can stimulate non-blocking receptor AT 2, which is likely to neutralize the action of receptor AO 1. Valsartan does not exhibit partial agonist activity on the receptor AO 1 and has a significantly greater affinity to the receptor AO 1 than AT 2 receptor .Valsartan not inhibit ACE (also known as kinase II), which converts Ang I into Ang II and destroys bradykinin. In clinical trials where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly less (P <0.05) in patientstaking valsartan than those who were treated with ACE inhibitors (2.6% compared with 7.9%). In the clinical study, patients with a history of dry cough during treatment with ACE inhibitors, 19.5% of the subjects treated with valsartan, and 19% of those taking thiazide diuretics, cough were compared with 68.5% of patients treated with ACE inhibitor (P <0.05).

Purpose of valsartan in hypertensive patients leads to reduced blood pressure without affecting the heart rate. In most patients, after a single oral dose of antihypertensive activity begins to occur within 2:00, and the maximum reduction in blood pressure is achieved within 4-6 hours. The hypotensive effect lasts for 24 hours after ingestion. Repeated dose dosage formulation the maximum reduction in blood pressure at any dose generally is achieved within 2-4 weeks and is maintained for a prolonged treatment. In combination with hydrochlorothiazide achieved significant additional lowering of blood pressure.

Patients with high blood pressure, diabetes type II and microalbuminuria has been shown that valsartan decreased excretion of albumin in the urine.

It was concluded that 160-320 mg of valsartan results in a clinically significant decrease UAE in patients with hypertension and type II diabetes.

hydrochlorothiazide

Venue thiazide diuretics, primarily - renal distal convoluted kanaltsy.Bylo demonstrated that the kidney cortex is a high affinity receptor that is the primary site of action binder thiazide diuretics and transporting inhibition of sodium chloride (NaCl) in the distal convoluted tubules. The mechanism of action is inhibition of thiazides Na + Cl - transporter -odnospryamovanogo possibly by competing for the Cl - site, affects the mechanisms of reabsorption of electrolytes directly - increasing sodium excretion, and chloride in approximately the same degree, and indirectly by a diuretic effect reducing the volume of blood plasma subsequent increase in plasma renin activity, aldosterone, potassium loss in the urine and decrease in serum potassium. The renin-aldosterone link is mediated by angiotensin II,however, while taking valsartan potassium lowering serum less pronounced than with hydrochlorothiazide monotherapy.

Pharmacokinetics.

Systemic bioavailability of hydrochlorothiazide is reduced by about 30% while the use of valsartan. The simultaneous use of hydrochlorothiazide has no significant effect on the kinetics of valsartan. This interaction does not affect the effectiveness of the combined application of valsartan and hydrochlorothiazide, since during controlled clinical studies have found a clear antihypertensive effect of the combination that exceeds the effect of the active substances separately, as well as a placebo effect.

valsartan is

suction

After taking valsartan separately, the maximum concentration of valsartan in the blood plasma is reached within 2-4 hours. The average bioavailability is 23%. Food reduces the impact by about 50%.

distribution

The equilibrium volume of valsartan distribution after intravenous administration is about 17 liters, indicating that valsartan does not divide widely in tissues. Valsartan largely binds to blood plasma proteins (94-97%), mainly from serum albumin.

Metabolism

Valsartan is NOT metabolized to a large extent, because only about 20% of the dose is recovered as metabolites.

Excretion

Valsartan demonstrates the kinetics of the baganoexponential decay (t1α

hydrochlorothiazide

suction

After intake hydrochlorothiazide absorption is rapid (t max about 2 h) with similar absorption characteristics in both suspensions and tablets. Bioavailability of hydrochlorothiazide is 60-80% after taking the drug.

distribution

The kinetics of the distribution and excretion is usually described by the function of bi-exponential decay. The expected volume of distribution is 4-8 l / kg.

Disseminated hydrochlorothiazide binds to plasma proteins (40-70%), mainly serum albumin.

Excretion

As for hydrochlorothiazide,> 95% of the absorbed dose is excreted unchanged in the urine. Kidney clearance consists of passive filtration and active secretion in the renal tubules. The half-life is 6-15 hours.

Special patient groups

elderly patients

Limited data indicate that the total clearance of hydrochlorothiazide is reduced in both healthy volunteers and in elderly patients with high blood pressure compared to young healthy volunteers.

renal insufficiency

When used in the recommended dose of Vanatex Combi, dose adjustment is not necessary for patients with creatinine clearance of 30-70 ml / min.

There are no data on the use of Vanatex Combi in patients with severe renal insufficiency (creatinine clearance

Renal clearance of hydrochlorothiazide consists of passive filtration and active secretion in the renal tubules. As expected for the drug, which is excreted almost exclusively by the kidneys, renal function significantly affects the kinetics of hydrochlorothiazide.

liver failure

During the pharmacokinetic study of patients with mild (n = 6) and moderate (n = 5) liver dysfunction, the effect of valsartan was greater by approximately 2-fold compared with healthy volunteers.

There are no data on the use of valsartan in patients with severe liver dysfunction. Diseases of the liver do not significantly affect the pharmacokinetics of hydrochlorothiazide.

Basic physical and chemical properties

80 mg / 12.5 mg pink, oblong, biconvex tablets, film-coated

160 mg / 12.5 mg tan, oblong, biconvex tablets, film-coated

160 mg / 25 mg: light brown, oblong, biconvex tablets, coated

film shell.

Shelf life

3 years.

Storage conditions

Store in a dry, protected from light place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Packaging

For 14 tablets, covered with a film sheath, in a blister, 2 blisters in a cardboard box.

Category of leave

On prescription.