Vasar H 160 mg / 25 mg tablets No.90

Vasar H (VASAR H) user's manual

Composition

1 tablet contains

valsartan	80 mg,
hydrochlorothiazide	12.5 mg
or valsartan	160 mg,
hydrochlorothiazide	12.5 mg,
or valsartan	160 mg,
hydrochlorothiazide	25 mg,
or valsartan	320 mg,
hydrochlorothiazide	12.5 mg,
or
valsartan	320 mg,
hydrochlorothiazide	25 mg

auxiliary substances: lactose, microcrystalline cellulose, croscarmellose sodium, povidone K29-KZ2, talc, magnesium stearate, silicon dioxide colloid
shell tablet 80 / 12.5 mg Opadry II 85G34642 Pink (polyvinyl alcohol, talc, titanium dioxide (E 171), macrogol 3350, lecithin, iron oxide red (E172), iron oxide yellow (E172))
Sheath tablet 160 / 12,5 mg Opadry II 85G25455 Red (alcohol polyvinyl, talc, titanium dioxide (E 171), macrogol 3350, lecithin, iron oxide red (E172), colorant Sunset Yellow (E 110));
Tablets 160/25 mg Opadry II 85G23675 Orange (polyvinyl alcohol, talc, titanium dioxide (E 171), macrogol 3350, lecithin, iron oxide red (E172), iron oxide yellow (E172), iron oxide black (E 172)) ;
tablet shell 320 / 12.5 mg Opadry II pink 85G34643 (polyvinyl alcohol, talc, titanium dioxide (E 171), macrogol 3350, lecithin, iron oxide red (E172), iron oxide yellow (E172))
tablet shell 320/25 mg Opadry II yellow 85G32408 (polyvinyl alcohol, talc, titanium dioxide (E 171), macrogol 3350, lecithin, iron oxide yellow (E172)).

Dosage form

Film-coated tablets.

Basic physical and chemical properties:

tablets 80 / 12.5 mg - oval pink, biconvex with a film coating, with the logo "V" on one side and the logo "H" - on the other;
tablets 160 / 12.5 mg - oval red, biconvex with a film coating with the logo "V" on one side and the logo "H" - on the other;
tablets 160/25 mg - oval orange, biconvex with a film coating with the logo "V" on one side and the logo "H" - on the other;
tablets 320 / 12.5 mg - oval pink, biconvex with a film coating, with the logo "V" on one side and the logo "H" - on the other;
tablets 320/25 mg - oval biconvex tablets, covered with a film coating of yellow color, with a line of fracture from the sides of the tablet, the logo "H" on one side and the logo "V" and the fault line on the other.

Pharmacological group

Combined preparations of angiotensin II antagonists. Angiotensin II antagonists and diuretics. ATC Code C09D A03.

Pharmacological properties

Pharmacodynamics.

The active hormone renin-angiotensin (RAAS) is angiotensin II, formed from angiotensin I with the participation of the angiotensin-converting enzyme (ACE). Angiotensin II binds to specific receptors located on cell membranes in various tissues. It has a wide range of physiological effects, including both direct and indirect participation in the regulation of blood pressure. Being a potent vasoconstrictor, angiotensin II has a direct vasopressor effect. In addition, it promotes sodium retention and stimulates the secretion of aldosterone.

Valsartan is an active and specific antagonist of angiotensin II receptors, intended for oral administration. It acts selectively on the AT 1 receptor subtype, which is responsible for the effects of angiotensin II. Increased levels of angiotensin II due to blockade of AT 1 -receptors by valsartan can stimulate free AO 2 receptors, which balances the effect of AT 1 receptors. Valsartan does not have any partial agonist activity with respect to AO 1 receptors and has a much larger (approximately 20,000-fold) relationship with AO 1 receptors than with AO 2 receptors.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I into angiotensin II and breaks down bradykinin. There are no side effects due to bradykinin. In clinical studies where valsartan was compared to an ACE inhibitor, the incidence of dry cough was significantly lower (P <0.05) in patients treated with valsartan than in patients taking an ACE inhibitor (2.6% compared with 7.9% in accordance). Patients who had previously been treated with ACE inhibitors developed a dry cough, in valsartan, this complication was noted in 19.5% of cases, and in the treatment with thiazide diuretic - in 19% of cases, while in the group of patients treated with an ACE inhibitor , cough was observed in 68.5% of cases (P <0.05). Valsartan does not interact and does not block the receptors of other hormones or ion channels, which are known to play an important role in regulating the functions of the cardiovascular system.

The administration of the drug to patients with arterial hypertension leads to a decrease in blood pressure, without affecting the pulse rate.

In most patients after taking a single dose of the drug, the onset of antihypertensive activity is noted within 2:00, and the maximum decrease in blood pressure is achieved within 4-6 hours. The antihypertensive effect persists for more than 24 hours after taking a single dose. With regular use of the drug, the maximum therapeutic effect is usually achieved within 2-4 weeks and maintained at the achieved level during prolonged therapy. Combination with hydrochlorothiazide effectively reduces blood pressure.

The point of action of thiazide diuretics is the cortex of distal convoluted renal tubules, where the receptors are located, are highly sensitive to the action of diuretics, and where the transport of Na and Cl ions is suppressed. The mechanism of action of thiazides is associated with the suppression of the pump Na + Cl -, which, obviously, is due to competition for transport spaces Cl -. As a result, the excretion of sodium and chlorine ions increases approximately equally. Due to the diuretic action, a decrease in the volume of circulating plasma is observed, as a result of which the activity of renin, the secretion of aldosterone, excretion in the urine of potassium and, consequently, the decrease in the concentration of potassium in the serum are increased. The relationship between renin and aldosterone is mediated by angiotensin II, so the appointment of an angiotensin II receptor antagonist will reduce potassium losses associated with the use of a thiazide diuretic.

Pharmacokinetics.

Valsartan. After taking the drug inside, the absorption of valsartan and hydrochlorothiazide occurs quickly, however, the degree of absorption varies widely. The average bioavailability of Vasari H is 23%. The pharmacokinetic curve of valsartan has a downward multiexponential character (t 1/2 α <1 h and t 1/2 β almost 9:00).

In the range of doses studied, the kinetics of valsartan is linear. With repeated use of the drug, no changes in the kinetic parameters were noted. When taking the drug once a day, cumulation is negligible. The concentration of plasma in women and men was the same. Valsartan largely binds to blood plasma proteins (94-97%), mainly with albumin. The volume of distribution during the equilibrium period is low (about 17 liters). In comparison with the hepatic blood flow (about 30 l / h), the clearance of valsartan is relatively slow (about 2 l / h). The amount of valsartan that is excreted with feces is 70% (of the amount taken internally), and almost 30% is excreted in the urine, mostly unchanged.

In appointing valsartan with food, the area under the concentration-time curve (AUC) decreases by 48%, although starting at about 8:00 after taking the drug, the plasma concentration, both in the case of fasting, and in the case of admission with food are the same. However, a decrease in AUC is not accompanied by a significant decrease in the therapeutic effect.

Hydrochlorothiazide. The absorption of hydrochlorothiazide after ingestion occurs quickly (t max - approximately 2:00).The pharmacokinetics of the preparation in the phases of distribution and elimination is described in the general bi-exponential descending curve; the half-life of the final phase is 6-15 hours. In the therapeutic dose range, the average AUC increases in direct proportion to the dose increase. With repeated appointments, the pharmacokinetics of hydrochlorothiazide does not change; at appointment once a day cumulation is insignificant.

Bioavailability of hydrochlorothiazide when ingested is 60-80%.

It is excreted in the urine with more than 95% of the dose in unchanged form and about 4% in the form of hydrolyzate - 2-amino-4-chloro-m-benzene disulfonamide.

With the simultaneous use of hydrochlorothiazide with food, both the increase and decrease in its systemic bioavailability were noted compared with the corresponding index when administered on an empty stomach.

The range of these changes is insignificant and has no clinical significance.

Valsartan / hydrochlorothiazide. With simultaneous use with valsartan, the systemic bioavailability of hydrochlorothiazide is reduced by about 30%. Simultaneous administration of hydrochlorothiazide does not significantly affect the kinetics of valsartan. However, this interaction does not affect the effectiveness of combined use of valsartan and hydrochlorothiazide. In controlled clinical trials, the distinct antihypertensive effect of this combination was found, which exceeded the effect of each of the components separately, as well as the placebo effect.

Pharmacokinetics in selected patient groups.

Patients of advanced age. In some elderly patients, the systemic effect of valsartan was somewhat more pronounced than in young patients, but it was not clinically significant.

Limited data suggest that in elderly patients, both healthy and those suffering from hypertension, systemic clearance of hydrochlorothiazide is lower than in healthy volunteers.

Patients with impaired renal function. Patients with a creatinine clearance of 30-70 ml / min do not need dose adjustment.

There is no data on the use of Vasari H in patients with severe renal impairment (creatinine clearance <30 mL / min) and patients on hemodialysis. Valsartan has a high degree of binding to plasma proteins and is not excreted in hemodialysis;Hydrochlorothiazide, on the contrary, is excreted from the body during hemodialysis.

The withdrawal of hydrochlorothiazide by the kidneys occurs by passive filtration and active secretion into the lumen of the renal tubules. The state of kidney function plays a big role in the pharmacokinetics of hydrochlorothiazide, which is understandable, given that this drug is excreted by the kidneys.

Violation of the function of the liver. The systemic effect of valsartan in patients with mild (n = 6) and moderately expressed (n = 5) violations of liver function was 2 times greater than in healthy volunteers. Data on the use of valsartan in patients with severe impairment of liver function.

Diseases of the liver do not significantly affect the pharmacokinetics of hydrochlorothiazide, so a reduction in its dose is not required.

Indications

Essential arterial hypertension in patients whose blood pressure is not appropriately regulated by monotherapy.

Contraindications

Hypersensitivity to the components of the drug or to other derivatives of sulfonamides, as well as to peanuts or soy.
Severe violations of the liver, cirrhosis and cholestasis.
Anuria, severe renal dysfunction (creatinine clearance <30 mL / min).
Refractory hypokalemia, hyponatremia, hypercalcemia, symptomatic hyperuricemia.
Simultaneous use of angiotensin receptor antagonists (APA), including valsartan, or ACE inhibitors (ACE) with aliskiren in patients with diabetes mellitus or renal dysfunction (GFR <60 mL / min / 1.73 m 2).
Pregnant women or women planning to become pregnant (see "Use during pregnancy or lactation").

Interaction with other drugs and other interactions

Interactions associated with both valsartan and hydrochlorothiazide

Simultaneous use is not recommended

Lithium

Reversible increase in the concentration of lithium in the blood plasma and manifestations of toxicity were recorded with simultaneous use of ACE inhibitors and thiazides, including hydrochlorothiazide. Due to the lack of experience in the simultaneous use of valsartan and lithium, this combination is not recommended. If it is necessary to use this combination, it is recommended to carefully monitor the level of lithium in the blood plasma.

Simultaneous application, which requires caution

Other antihypertensive drugs

Vasar H can enhance the action of other drugs with antihypertensive properties (eg, guanethidine, methyldopy, vasodilators, ACE inhibitors, angiotensin receptor antagonists, beta-blockers, calcium channel blockers and dopamine reuptake inhibitors).

Pressor amines (for example, noradrenaline, epinephrine)

It is possible to reduce the reaction to pressor amines, is not sufficient to exclude their use.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of COX-2, acetylsalicylic acid> 3 g / day and nonselective NSAIDs

NSAIDs can reduce the antihypertensive effect of both angiotensin II antagonists and hydrochlorothiazide when used concomitantly. In addition, the simultaneous administration of Vasar H and NSAIDs can lead to impaired renal function and potassium levels in the blood plasma. Thus, it is recommended to monitor the function of the kidneys at the beginning of treatment, as well as adequate hydration of the patient.

Interactions associated with valsartan

Double blockade of renin-angiotensin (RAAS) ARA, ACE inhibitors or aliskeren

In the case of simultaneous use of ARA, including valsartan, with other agents, blocking RAAS, such as ACE inhibitors or aliskeren, caution is necessary.

The simultaneous use of angiotensin receptor antagonists (APA), including valsartan, or ACE inhibitors (ALF) with aliskiren in patients with diabetes mellitus or renal dysfunction (GFR <60 ml / min / 1.73 m 2) is contraindicated.

Simultaneous use is not recommended

Potassium-sparing diuretics, potassium-containing food additives, salt preparations for replacement therapy, containing potassium and other substances that can raise the level of potassium

In the case of the drug, affects the level of potassium in combination with valsartan, it is recommended to monitor the level of potassium in the blood plasma.

Conveyors

In vitro data show that valsartan is a substrate for the hepatic uptake transporter of OATP1B1 / OATP1B3 and the efflux hepatic transporter MRP2. The clinical significance of these data has not been fully elucidated. Simultaneous use of inhibitors of the absorption transporter (eg, rifampin cyclosporin) or eflusx transporters (eg ritonavir) can lead to an increase in systemic exposure to valsartan. Beginning or ending with simultaneous treatment with such medicines, it is recommended to exercise the necessary care.

Lack of interaction

In the studies of valsartan drug interaction, there was no clinically significant interaction between valsartan and any of the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide. Digoxin and indomethacin can interact with the hydrochlorothiazide component of the drug (see Hydrochlorothiazide-related interactions).

Interactions associated with hydrochlorothiazide

Simultaneous application, which requires caution

Medicinal products, the use of which is associated with potassium loss and hypokalemia

The hypokalemic effect of hydrochlorothiazide can be enhanced by the simultaneous administration of diuretics, corticosteroids, laxatives, ACTH, amphotericin, carbenoxolone, penicillin G, salicylic acid and derivatives.

If there is a need to prescribe these drugs with a combination of hydrochlorothiazide and valsartan, it is recommended to monitor the level of potassium in the blood plasma.

Medicines that can induce ventricular tachycardia of the "pirouette" type

Given the risk of hypokalemia, hydrochlorothiazide should be used with caution at the same time as drugs that can induce ventricular pirouette tachycardia, in particular antiarrhythmic agents of Class I and III, and also with some antipsychotic agents.

Drugs affecting the level of sodium in the blood serum

Hyponatremic effect of diuretics can be strengthened in case of simultaneous administration of such drugs as antidepressants, antipsychotics, antiepileptic drugs and the like. Care should be taken in the case of long-term use of these medicines.

Medications that can cause bidirectional tachycardia (torsades de pointes)

Antiarrhythmic drugs Ia class (quinidine, hydroquinidine, disopyramide).
Antiarrhythmic drugs of the III class (amiodarone, sotalol, dofetilida, ibutilid).
Some antipsychotics (eg thioridazine, chlorpromazine, levomepromazine, trifluoperazine, tsiamemazin, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol).
Other (eg, bepridil, cisapride, difemanil, erythromycin w / w, halofantrine, Ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine w / w).
Due to the risk of hypokalemia hydrochlorothiazide should be used with caution in conjunction with drugs that may lead to a 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. The simultaneous use of thiazides with calcium salts may cause hypercalcemia in patients prone to hypercalcemia (eg, patients with hyperparathyroidism, malignant tumors or vitamin D-mediated condition) due to the reinforcement tubular calcium reabsorption.

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

The simultaneous use of thiazide diuretics, including hydrochlorothiazide, with beta blockers may 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 level of uric acid in the blood plasma. It may be necessary to increase the dose of probenecid or sulfinpirazona. The simultaneous use of thiazide diuretics including hydrochlorothiazide , may increase the frequency of hypersensitivity reactions to allopurinol.

Anticholinergics (eg, 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. Conversely, one can expect that prokinetic drugs such as cisapride, can reduce the bioavailability of the thiazide type diuretics.

Amantadine

Thiazides, including hydrochlorothiazide, may increase the risk of side effects of amantadine.

Ion exchange resins

Absorption of thiazide diuretics, including hydrochlorothiazide, is reduced under the influence of cholestyramine or colestipol. This can result in sub-therapeutic effects of thiazide diuretics. However, the time reception shift hydrochlorothiazide and resin so as to take hydrochlorothiazide not less than 4:00 to or 4-6 hours after ingestion of the resin, can minimize the risk of interaction.

Cytotoxic agents (eg, cyclophosphamide, methotrexate)

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

Nondepolarizing skeletal muscle relaxants (eg, tubocurarine)

Thiazides, including hydrochlorothiazide, increase the effect of skeletal muscle relaxants like curare derivatives.

Cyclosporin

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

Alcohol, anesthetics and sedatives

In the case of simultaneous use of thiazide diuretics from drugs that can also lower blood pressure (eg by reducing the activity of the sympathetic nervous system or the central line vasodilatory action) may potentiate orthostatic hypotension.

methyldopa

Received isolated reports of haemolytic anemia in patients who receive 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.

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.

Features of the application

Changes in electrolytes. Care must be taken when used in conjunction with Vazario N potassium salts, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that may increase the level of potassium (e.g., heparin). It reported cases of hypokalemia during treatment with thiazide diuretics. Frequently check the content of potassium in the blood serum.

When the use of thiazide diuretics may cause hyponatremia and alkalosis gipohloremichesky. Thiazides increase the urinary excretion of magnesium, which can result in hypomagnesemia.

Patients deficient in the body of sodium and / or blood volume (CBV). Patients with severe deficiency of sodium and / or circulating blood volume in the body, such as those receiving high doses of diuretics, in rare cases, after the beginning of therapy with symptomatic hypotension may occur. Therefore, before starting therapy with this drug should carry out the correction contents in the body of sodium and / or blood volume.

In the case of hypotension patients should be placed in the supine position and, if necessary, an infusion of saline. Treatment can be continued immediately after the blood pressure has stabilized.

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

In patients whose kidney function is dependent on the activity of the renin-angiotensin (e.g., patients with severe congestive heart failure), treatment with ACE inhibitors is associated with oliguria and / or progressive azotemia, rarely - with acute renal failure. Use of the drug in patients with severe chronic heart failure is unfounded.

Since there can not be ruled out that due to the suppression of the renin-angiotensin-use of the drug can also be associated with renal dysfunction, Vazario H should not be used in such patients.

Renal artery stenosis. Should not be applied to patients with unilateral or bilateral renal artery stenosis or stenosis caused by solitary kidney, since such patients may increase the level of blood plasma urea and creatinine.

Primary hyperaldosteronism

Do not apply Vazario H patients with primary hyperaldosteronism as their renin-angiotensin system is activated.

Stenosis of the aortic and mitral valve, hypertrophic obstructive cardiomyopathy

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

Impaired renal function.For patients with mild and moderate renal impairment (creatinine clearance of> 30 ml / min) correction dose is not required. Periodic monitoring of potassium in serum creatinine and uric acid is recommended for use of the drug in patients with impaired renal function.

The simultaneous use of the angiotensin II receptor antagonists, including valsartan, ACE inhibitors or aliskiren patients with diabetes or impaired renal function (GFR <60 mL / min / 1.73 m 2) is contraindicated.

kidney transplantation

Currently, there is no experience regarding the safety of the drug in patients who have recently performed a kidney transplant.

Violation of the function of the liver.In patients with mild and moderate hepatic impairment without cholestasis Vazario H should be used with caution (see. "Dosing and dose"). Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, since minor alterations of fluid and electrolyte balance can provoke hepatic coma.

Systemic lupus erythematosus. It was reported that thiazide diuretics enhance or activate the manifestations of systemic lupus erythematosus.

Other metabolic disorders. Thiazide diuretics may alter glucose tolerance and raise the level of cholesterol, triglycerides and uric acid in the blood serum. For diabetic patients may require adjustment of the dose of insulin or oral antidiabetic drugs. Thiazides may decrease the urinary excretion of calcium and unstable and cause a slight increase in serum calcium in the absence of disturbances of calcium metabolism. A significant hypercalcemia may indicate the presence of the patient background hyperparathyroidism. Discontinue use of thiazides before the test to assess the function of the parathyroid glands.

photosensitivity

Reported cases of photosensitivity at the use of thiazide diuretics. If photosensitivity reaction occurs during treatment, it is recommended to discontinue treatment. If the re-use of the diuretic is deemed necessary, it is recommended to protect exposed skin from sunlight or ultraviolet radiation.

Pregnancy

During pregnancy should not start the application of angiotensin II receptor antagonists. Unless continued therapy of angiotensin II receptor antagonists is not considered essential, patients planning a pregnancy should be transferred to alternative antihypertensive treatment, have established safety profile for use in pregnancy. When pregnancy is detected the treatment of angiotensin II receptor antagonists should be stopped immediately, and, if necessary, to start alternative therapy.

Are common

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

angioedema

On the occurrence of angioedema (including swelling of the larynx and glottis, causing airway obstruction and / or swelling of the face, lips, throat and / or tongue) have been reported in patients treated with valsartan, some of these patients had a history of angioedema the use of other drugs, including the use of other angiotensin II receptor antagonists. With the development of angioedema 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. This symptoms usually lasts for several hours a week while taking the drug. Untreated glaucoma can lead to irreversible vision loss.

Should immediately stop using the product as quickly as possible. You may need medical or surgical treatment. Factor in the risk of developing acute angle-closure glaucoma is an allergic reaction to the use of sulfonamide or penicillin.

For elderly patients, a dose adjustment is required.

Hydrochlorothiazide may reduce the level of protein-bound iodine in the blood plasma. Hydrochlorothiazide is capable of increasing the serum concentration of free bilirubin.

Dual blockade of the renin-angiotensin (RAAS)

With simultaneous use of ACE inhibitors, angiotensin receptor blockers II or aliskiren increased risk of hypertension, hyperkalemia and decrease in renal function (including acute renal failure), however for the possible development of dual blockade of the RAAS, the simultaneous use of these drugs is not recommended (see. Section "Interaction with other drugs, and other kinds of interactions "). If such a combination is shown completely, it is recommended specialist supervision and frequent monitoring of blood pressure, renal function and electrolyte in these patients.

ACE inhibitors, angiotensin II receptor blockers do not simultaneously apply a patient with diabetic nephropathy.

Galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

You should not use this drug to patients with rare congenital problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Lecithin. Do not use this drug to patients with intolerance peanut or soybean.

Hypersensitivity.

Tablets Vazario H 160 / 12.5 mg contain Sunset yellow FCF (E110), which may cause hypersensitivity reactions.

Use during pregnancy or breast-feeding

valsartan

The drug should not be used for pregnant women or women trying to conceive. If during treatment with this agent confirmed the pregnancy, its use must be stopped immediately and replaced with another drug approved for use in pregnant women.

It is known that the use of angiotensin II receptor antagonists for trimesters II and III in humans causes fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).

If the use of angiotensin II receptor antagonists has occurred, starting with the AI trimester of pregnancy, it is recommended to perform ultrasound monitoring of kidney and skull function.

Infants whose mothers have received angiotensin II receptor antagonists require careful monitoring of hypotension.

Hydrochlorothiazide

The experience with hydrochlorothiazide during pregnancy is limited.

Studies on animals are inadequate. Hydrochlorothiazide penetrates the placenta. Based on the pharmacological mechanisms of action of hydrochlorothiazide, its use during the II and III trimesters of pregnancy can lead to a violation of the fetoplacental blood circulation and cause in the fetus and newborn such effects as jaundice, electrolyte balance disorder and thrombocytopenia.

The period of breastfeeding.

It is not recommended to use the drug during lactation. There is no information on the use of valsartan during breastfeeding, and hydrochlorothiazide penetrates into breast milk. Thiazides in high doses cause diuresis, which can suppress the production of milk. During breastfeeding it is advisable to use alternative therapies with better established safety profiles, especially during the feeding of a newborn or premature baby.

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 doctor), it is forbidden to drive and perform work, which can lead to an accident. Later the degree of prohibition is determined by the doctor.

Dosing and Administration

The recommended dose of Vasar H is 1 tablet of 80 mg / 12.5 mg per 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 per day. Tablets 160 mg / 25 mg administered to patients who do not achieve a sufficient reduction in blood pressure when using tablets 160 mg / 12.5 mg. If further when using 160 mg / 25 mg tablets arterial pressure is not enough, it is recommended to consider the possibility of continuing treatment with a dosage of 320 mg / 12.5 mg. Tablets 320 mg / 25 mg appoint a patient who does not achieve a sufficient reduction in blood pressure when using tablets 320 mg / 12.5 mg.

The maximum daily dose is 320 mg / 25 mg.

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

The drug Vasar H can be used regardless of food intake. Tablets should be washed down with a small amount of water.

In patients with minor and moderate impairment of renal function (creatinine clearance> 30 ml / min), dose adjustment is not required.

In patients with mild and moderate hepatic impairment of non-biliary origin and without cholestasis, the dose of valsartan should not exceed 80 mg.

Children

The drug Vazar H is not recommended for use in children due to the lack of data on safety and efficacy.

Overdose

An overdose of valsartan can cause severe hypotension, which in turn can lead to depression, development of vascular insufficiency and / or shock.

In case of an overdose with hydrochlorothiazide, the following signs and symptoms may appear: nausea, drowsiness, hypovolemia, electrolyte balance disturbance, and as a result, arrhythmia and muscle spasms. The most characteristic signs and symptoms of overdose are also tachycardia, arterial hypotension, shock, weakness, confusion, dizziness, muscle spasm, paresthesia, exhaustion, impaired consciousness, vomiting, thirst, polyuria, oliguria, anuria, alkalosis, elevated blood urea nitrogen level mainly kidney failure).

Treatment. Therapeutic measures depend on how long a large dose has been taken, as well as the type of 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.

When hypotension should put the patient in a horizontal position and immediately ensure the restoration of 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.

Adverse Reactions

Unwanted side reactions are given under the headings by frequency: very often (1/10) often (1/100, <1/10); infrequently (1/1000, <1/100) rarely (1/10000, <1/1000); very rarely (<1/10000), is unknown (can not be estimated based on available data).

Within each group, the incidence of adverse reactions is given in order of severity.

The frequency of unwanted reactions of valsartan / hydrochlorothiazide

Metabolic disorders

infrequently dehydration.

neurological disorders

very seldom dizziness

infrequently paresthesia;

unknown: fainting.

From the side of the organs of sight

infrequently blurred vision.

From the organs of hearing and vestibular apparatus

infrequently: ringing in the ears.

cardiovascular disorders

infrequently: arterial hypotension.

On the part of the respiratory system, the organs of the chest and the mediastinum, cough is infrequent;

unknown: noncardiogenic pulmonary edema.

Gastrointestinal disorders very rarely diarrhea.

From the musculoskeletal system and connective tissue: infrequently myalgia

very rarely: arthralgia.

From the urinary system

unknown: impaired renal function.

General disorders and reactions at the injection site

infrequently increased fatigue.

Study

Unknown: increased uric acid in the plasma, increased bilirubin and creatinine in the plasma, hypokalemia, hyponatremia, increased urea nitrogen in the blood, neutropenia.

The following reactions were observed during clinical trials in hypertensive patients, regardless of their causal relationship with the study drug: abdominal pain, abdominal pain in the upper abdomen, anxiety, arthritis, back pain, bronchitis, acute bronchitis, chest pain, dizziness, dyspepsia, dyspnea, dry mouth, nosebleeds, impotence, gastroenteritis, headache, increased sweating, hypoesthesia, influenza, insomnia, sprains, muscle spasms, muscle strain, nausea, nasal congestion, stagnant me sinusitis, drowsiness, tachycardia, upper respiratory tract infections, urinary tract infections, vertigo, peritoneal infections, nasal congestion, swelling in the paranasal sinuses, neck pain, edema, peripheral edema, otitis media, pain in the extremities, palpitation, pharyngolaryngeal pain, pollakiuria, fever, nasopharyngitis, sinusitis, drowsiness, tachycardia , viral infections, visual impairment. It is not known whether these effects had a causal relationship with therapy.

Additional information on individual components

Undesirable reactions, previously occurred when using each component separately, can be potential side effects also with the use of Vasar H, even if they have not been observed in clinical trials or during the postmarketing period of application of this combination.

The frequency of unwanted reactions of valsartan

On the part of the blood and lymphatic system

unknown: a decrease in hemoglobin, a decrease in hematocrit, thrombocytopenia.

From the immune system

unknown: other hypersensitivity reactions / allergic reactions, including serum sickness.

Metabolic disorders

unknown: increased potassium in plasma, hyponatremia.

From the organs of hearing and vestibular apparatus

infrequently vestibular dizziness (vertigo).

cardiovascular disorders

unknown: vasculitis.

Gastrointestinal disorders

infrequently: pain in the abdomen.

From the digestive system

unknown: an increase in liver function.

From the skin and subcutaneous tissue

unknown angioedema, rash, itching, bullous dermatitis.

From the urinary system

unknown: renal failure.

The following reactions were observed during clinical trials in hypertensive patients, regardless of their causal relationship with the study drug: arthralgia, asthenia, back pain, diarrhea, dizziness, headache, insomnia, decreased libido, nausea, edema, pharyngitis, rhinitis, sinusitis , inflammation of the upper respiratory tract, viral infections.

The frequency of undesired reactions of hydrochlorothiazide

Hydrochlorothiazide is widely used for many years, often at high doses than those contained in Vasar H. The following adverse reactions have been reported in patients receiving thiazide diuretics, including hydrochlorothiazide, as monotherapy:

With metabolism, metabolism

very often hypokalemia, when high doses are used, an increase in blood lipid levels

often: hyponatremia, hypomagnesemia, hyperuricemia;

rarely hypercalcaemia, hyperglycemia, glucosuria and the metabolism of diabetic patients;

very rarely hypochloremic alkalosis.

On the part of the blood and lymphatic system

rarely thrombocytopenia, sometimes with purpura;

very rarely agranulocytosis, leukopenia, hemolytic anemia, oppression of bone marrow function

unknown: aplastic anemia.

From the immune system

very rarely a hypersensitivity reaction.

mental disorders

rarely depression, sleep disturbance.

neurological disorders

rarely: headache, dizziness, paresthesia.

From the side of the organs of sight

infrequently blurred vision in the first few weeks after initiation of treatment;

unknown: acute glaucoma.

cardiac disorders

rarely cardiac arrhythmia.

cardiovascular disorders

often: postural hypotension, which can be exacerbated by the use of alcohol, anesthetics, sedatives.

On the part of the respiratory system, the organs of the thorax and the mediastinum

very rarely respiratory failure, including pneumonia and pulmonary edema.

Gastrointestinal disorders

often: loss of appetite, mild nausea and vomiting

rarely constipation, a feeling of gastrointestinal discomfort, diarrhea

very rarely pancreatitis.

With the digestive system

rarely intrahepatic cholestasis, jaundice.

From the skin and subcutaneous tissue

often hives and other types of rash;

rarely photosensitization;

very rarely necrotizing vasculitis and toxic epidermal necrolysis, skin reactions like lupus erythematosus, reactivation of lupus erythematosus;

unknown: erythema multiforme.

From the side of the reproductive system and mammary glands

often impotence.

From the urinary system

unknown: acute renal failure, renal impairment.

General disorders and reactions at the injection site

unknown: fever, increased fatigue.

From the side of the musculoskeletal system and connective tissue

unknown: muscle spasms.

Shelf life

For dosing 80 / 12,5 mg, 160 / 12,5 mg, 160/25 mg - 4 years.

For dosing 320 / 12,5 mg, 320/25 mg - 2 years.

Storage conditions

Store in the original packaging at a temperature not higher than 25 ° С. Keep out of the reach of children.

Packaging

10 tablets in a blister, 3 blisters or 9 blisters in a cardboard box.

Category of leave

On prescription.