Valsacor N80 - instructions for use, dose, side effects, contraindications

Excipients: microcrystalline cellulose 41.00 mg Croscarmellose sodium 2.375 mg Povidone K25 1.50 mg Lactose monohydrate 17.125 mg magnesium stearate 4.50 mg colloidal silica 1.00 mg.

Film sheath: 2.80 mg Hypromellose 2910, titanium dioxide (E171) 0.86 mg macrogol 4000 0.30 mg iron oxide red dye (E172) 0.03 mg iron oxide yellow dye (E172) 0.01 mg

Description:

Oval, biconvex tablets, covered with a film shell of pink color. View of the fracture: a white rough mass with a film shell of pink color.

Pharmacotherapeutic group:A combined hypotensive drug (angiotensin II receptor antagonist + diuretic)

ATX: & nbsp

C.09.D.A.03 Valsartan in combination with diuretics

C.09.D.A Angiotensin II antagonists in combination with diuretics

Pharmacodynamics:Valsacor® H 80 is a combined antihypertensive drug that contains an angiotensin II receptor antagonist (ARA II) and a thiazide diuretic.

Valsartan

Valsartan is a selective ARA II for oral administration, non-protein nature. Selectively blocks AT₁-receptors responsible for the vasopressor effect of angiotensin II. The consequence of the blockade AT₁-receptors is an increase in the concentration of angiotensin II in blood plasma, which can stimulate unblocked AT₂-receptors, which balances the vasopressor effects associated with excitation AT₁receptors. Valsartan has no agonistic activity against AT₁receptors. His affinity for AT₁-receptors are approximately 20 000 times higher than for AT₂receptors.

Valsartan does not inhibit angiotensin-converting enzyme (ACE), known as kininase II, which converts angiotensin I to angiotensin II and breaks down bradykinin. Due to the lack of influence on ACE, the effects of bradykinin and substance P are not potentiated. The frequency of development of dry cough is lower in patients treated with ARA II, compared with patients receiving ACE inhibitors. Valsartan does not interact and does not block the receptors of other hormones or ion channels involved in the regulation of the functions of the cardiovascular system.

In the treatment of hypertension (AH) valsartan lowers blood pressure (BP), without affecting the heart rate (heart rate).

After ingestion of a single dose of valsartan, the antihypertensive effect develops within 2 hours, and the maximum decrease in blood pressure is achieved in 4-6 hours. The antihypertensive effect of valsartan persists for 24 hours after its administration. With the constant use of valsartan, the maximum decrease in blood pressure, regardless of dose, is achieved after 2-4 weeks and is maintained at the achieved level during prolonged therapy.Simultaneous use with hydrochlorothiazide allows achieving a significant additional reduction in blood pressure.

Sudden abolition of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable clinical consequences.

Hydrochlorothiazide (HCTZ)

The point of application of the action of thiazide diuretics is distal convoluted renal tubules. When thiazide diuretics are applied to highly sensitive receptors of the distal tubules of the cortical layer of the kidneys, reabsorption of sodium ions (Na⁺) and chlorine (C1^-). Suppression of the co-transport system Na⁺ and C1,^-apparently, occurs due to competition for the binding sites C1^- in this system, which leads to an increase in excretion Na⁺ and C1^- approximately to the same extent. As a result of diuretic action, a decrease in the volume of circulating blood (BCC) is observed, which increases the activity of renin, the secretion of aldosterone, the excretion of potassium by the kidneys and, consequently, the decrease in the potassium content in the serum. The relationship between renin and aldosterone is mediated by angiotensin II, so a decrease in potassium in the serum with simultaneous use of HCTT with valsartan is less pronounced than with monotherapy of HCTT.

Pharmacokinetics:

Valsartan

Suction

After taking valsartan, the maximum concentration (C_mOh) in the blood plasma is achieved within 2-4 hours. The average absolute bioavailability is 23%. When taking valsartan with food, the area under the concentration-time curve (AUC) and C_mOhin blood plasma are reduced by 40% and 50%, respectively. However, 8 hours after taking valsartan, taken on an empty stomach and with food, its plasma concentrations are the same. Decrease AUC is not accompanied by a clinically significant decrease in the therapeutic effect of valsartan, so the drug can be taken regardless of the time of ingestion.

Distribution

Volume of distribution (V_d) of valsartan in the equilibrium period after intravenous administration was about 17 liters, indicating that there was no pronounced valsartan distribution in the tissues. Valsartan actively binds to blood plasma proteins (94-97%), mainly with albumin.

Metabolism

Valsartan does not undergo significant biotransformation, only about 20% of the dose taken internally is excreted as metabolites. The hydroxyl metabolite is determined in blood plasma at low concentrations (less than 10% of AUC valsartan). This metabolite has no pharmacological activity.

Excretion

Valsartan is biphasic: α-phase with half-life (T_1/2α) is less than 1 hour and βphase with T_1/2_β - about 9 hours. Valsartan is excreted mainly unchanged through the intestine (about 83%) and kidneys (about 13%). After intravenous injection, the plasma clearance of valsartan is about 2 l / h, the renal clearance is 0.62 l / h (about 30% of the total clearance). T_1/2valsartan is 6 hours.

The pharmacokinetics of valsartan in the range of therapeutic doses is linear. With repeated use of valsartan, there were no changes in pharmacokinetic parameters. When taking valsartan once a day, cumulation is negligible. Plasma concentrations of valsartan are the same for men and women.

HCTZ

Suction

When ingested, HCTZ is absorbed rapidly. FROM_mOh in the blood plasma is achieved 2 hours after ingestion. In the therapeutic range of doses, the average value AUC increases in direct proportion to the increase in dose. Simultaneous intake with food can lead to an increase or decrease in systemic availability as compared to fasting, these changes are not clinically important.When administered, the absolute bioavailability of HCTZ is 70%.

Distribution

Visible V_d is 4-8 l / kg. Binding to blood plasma proteins (mainly with albumins) is about 40-70%. HCTZ accumulates in erythrocytes in a concentration about 3 times that of plasma.

Metabolism, excretion

HCTZ is eliminated almost unchanged. T_1/2 the final phase is 6-15 hours. With repeated use, the pharmacokinetics of HCTZ does not change. When receiving 1 time per day, the accumulation of HCTZ is negligible. More than 95% of the absorbed dose is excreted unchanged by the kidneys.

Valsartan / hydrochlorothiazide

With simultaneous use with valsartan, the system bioavailability of HCTZ is reduced by 30%, and the bioavailability of valsartan does not change significantly. The noted interaction does not affect the effectiveness of the combined use of valsartan and HCTZ. In controlled clinical trials, a distinct antihypertensive effect of this combination was found, which exceeded the effect of each component of the drug alone or the placebo effect.

Pharmacokinetics of special groups of patients

Patients of advanced age (over 65 years)

AUC Valsartan in some elderly patients is greater than that of young volunteers. These changes have no clinical significance. Presumably, in elderly patients with a normal level of blood pressure and hypertension, the systemic clearance of HCTZ is lower than in healthy young volunteers.

Patients with impaired renal function

In patients with impaired renal function with a creatinine clearance (CK) of 30-70 ml / min, dose adjustment of the preparation Valsacor® H 80 is not required. There are no data on the use of the drug in patients with severe renal dysfunction (QC less than 30 ml / min) and in patients on hemodialysis. Valsartan is not excreted by hemodialysis, in contrast to HCTZ.

In the presence of renal failure C_mOh and AUC HCTZ is increased, and the elimination rate is reduced. In patients with impaired renal function of mild and moderate severity T_1/2HCTZ is almost doubled.

Patients with impaired hepatic function

In patients with lungs (5-6 points on the Child-Pugh scale) or moderate (7-9 on the Child-Pugh scale), liver function impairment AUC Valsartan was 2 times more than in healthy volunteers.There is no data on the use of the drug Valsacor® H 80 in patients with severe impaired liver function (more than 9 on the Child-Pugh scale).

Disturbance of liver function does not have a significant effect on the pharmacokinetics of HCTZ, so correction of its dose in patients with impaired liver function is not required.

In patients with bile duct obstruction, the preparation Valsacor® H 80 should be used with caution.

Indications:

Arterial hypertension (patients who are shown combined therapy).

Contraindications:

- Hypersensitivity to valsartan, hydrochlorothiazide and other sulfonamide derivatives or any other components of the drug;

- severe violations of the liver (more than 9 points on the scale Child-Pugh), biliary cirrhosis and cholestasis;

- anuria, severe renal dysfunction (CC less than 30 ml / min);

- refractory hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia;

- simultaneous application with aliskiren in patients with diabetes mellitus or moderate and severe renal dysfunction (CC less than 60 ml / min);

- pregnancy and pregnancy planning, the period of breastfeeding;

- age under 18 years (effectiveness and safety in children are not proven);

- lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, since the composition of the drug Valsakor® H 80 enters lactose.

Carefully:

- Simultaneous use of potassium-sparing diuretics, potassium preparations, potassium-containing food additives or other medications that can increase the potassium content in the blood serum (eg, heparin);

- conditions accompanied by water-electrolyte disorders: nephropathy with loss of salts and pererenal (cardiogenic) renal dysfunction, hypokalemia, hypomagnesemia, hypercalcemia;

- chronic heart failure (CHF) III-IV functional class by classification NYHA;

- pronounced hyponatremia and / or conditions accompanied by a decrease in bcc (including diarrhea, vomiting, therapy with high doses of diuretics);

- bilateral or unilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, condition after kidney transplantation;

- primary hyperaldosteronism;

- Stenosis of the aortic and / or mitral valve, hypertrophic obstructive cardiomyopathy (GOKMP);

- systemic lupus erythematosus (SLE);

- diabetes mellitus (DM);

- hypercholesterolemia;

- hypertriglyceridemia;

- an angle-closure glaucoma;

- in patients with hereditary angioedema, or angioneurotic edema on the background of previous therapy with ARA II or ACE inhibitors.

Pregnancy and lactation:

Pregnancy

Valsartan

The use of ARA II in the first trimester of pregnancy is not recommended. The use of ARA II is contraindicated in II-III trimester of pregnancy, because the use of II-III trimester of pregnancy can cause fetotoxic effects (decreased kidney function, low blood pressure, slowing ossification of the fetal bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). There are reports of spontaneous abortions, malnutrition and impaired renal function in newborns whose mothers during pregnancy were unintentionally receiving valsartan.

If nevertheless used the drug in II-III trimesters of pregnancy, it is necessary to conduct ultrasound examination of the kidneys and bones of the fetal skull.

When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile.

Newborns whose mothers received ARA II during pregnancy, need medical supervision, since there is a risk of developing arterial hypotension.

HCTZ

The experience of using HCTZ during pregnancy, especially the first trimester is limited. HCTZ penetrates the placenta. With the use of thiazide diuretics in II-III trimester of pregnancy may develop thrombocytopenia, a violation of the water-electrolyte balance, jaundice in the fetus or newborn.

With the confirmation of pregnancy, the preparation Valsacor® H 80 should be discontinued as soon as possible.

Breastfeeding period

There is no data on the isolation of valsartan in breast milk. HCTZ is excreted in breast milk in women. If you need to use the drug Valsacor® H 80 during lactation it is necessary to stop breastfeeding.

Dosing and Administration:

Before starting therapy with Valsacor® H 80, it is necessary to correct water-electrolyte disturbances (see the sections "With caution", "Special instructions").

Inside, once a day, every day, regardless of the time of food intake, the tablet should be swallowed whole and washed down with a sufficient amount of liquid.

The recommended daily dose is 1 tablet of the preparation Valsacor® H 80.

The dose of the drug Valsacor® H 80 is selected after previous titration of the doses of individual components of the drug. If the antihypertensive effect is insufficient, an increase in the dose of the drug (not earlier than 4-6 weeks) is possible by titrating the doses to the maximum daily dose in terms of valsartan 320 mg and up to the maximum daily dose for HCTZ 25 mg.

The maximum reduction in blood pressure is usually achieved within 2-4 weeks of therapy, but in some patients - for 4-8 weeks, which should be taken into account when titrating the dose.

Impaired renal function

Patients with mild to moderate renal dysfunction (CK ≥30 mL / min (0.5 mL / s)) do not need dose adjustment.

Impaired liver function

The maximum recommended daily dose of the drug is Valsacor^® H 80 in patients with mild (5-6 points on the Child-Pugh scale) or moderate (7-9 points on the Child-Pugh scale), a violation of the liver function without the phenomena of cholestasis - 1 tablet per day (80 / 12.5 mg).

Side effects:

Classification of the frequency of development of side effects of the World Health Organization (WHO):

very often ≥ 1/10

often from ≥ 1/100 to <1/10

infrequently from ≥ 1/1000 to <1/100

rarely from ≥ 1/10000 to <1/1000

very rarely <1/10000

frequency is unknown - can not be estimated from the available data.

When a combination of valsartan / hydrochlorothiazide

Disorders from the metabolism and nutrition:

infrequently: dehydration.

Impaired nervous system:

often: headache;

infrequently: paresthesia;

very rarely: dizziness;

frequency unknown: faint.

Disorders from the side of the organ of vision:

infrequently: decreased visual acuity.

Hearing disorders and labyrinthine disturbances:

infrequently: noise in the ears.

Vascular disorders:

infrequent: marked decrease in blood pressure, peripheral edema.

Disturbances from the respiratory system, chest and mediastinal organs:

infrequently: cough;

frequency unknown: noncardiogenic pulmonary edema.

Disorders from the gastrointestinal tract:

infrequently: nausea;

very rarely: diarrhea.

Disturbances from the musculoskeletal and connective tissue:

infrequently: myalgia;

very rarely: arthralgia.

Disorders from the kidneys and urinary tract:

frequency unknown: impaired renal function.

General disorders and disorders at the site of administration:

infrequently: increased fatigue.

Laboratory and instrumental data:

frequency is unknown: increasing the concentration of uric acid in serum, an increase in serum bilirubin concentration, elevated serum creatinine concentration in the serum, hyponatremia, hypokalemia, neutropenia, increasing the concentration of residual urea nitrogen in blood serum.

When studying the clinical application of fixed combination Valsartan / hydrochlorothiazide in hypertensive patients were observed following adverse events (AEs) with no obvious connection with drug intake: abdominal pain, pain in the upper abdomen, anxiety, arthritis, asthenia, back pain, bronchitis (in including acute), chest pain, postural dizziness, indigestion, shortness of breath, dryness of the oral mucosa, nasal bleeding, erectile dysfunction, gastroenteritis, headache, increased sweating, gipostezii, flu-like coc -being, insomnia, sprain, muscular spasms, muscular hypertonicity, nasal congestion, nasopharyngitis, nausea, neck pain, peripheral edema, otitis media, pain in extremities, palpitations, sore throat and pharynx, pyrexia, pollakiuria, hyperthermia,sinusitis, drowsiness, upper respiratory tract infections, urinary tract infections, vertigo, viral infections, visual impairment.

With the use of the combination valsartan / hydrochlorothiazide, the occurrence of AEs that occur both with valsartan and HCTZ in monotherapy and not detected in clinical trials is possible.

When valsartan is used

Violations from the blood and lymphatic system:

the frequency is unknown: a decrease in hemoglobin, a decrease in hematocrit, thrombocytopenia.

Immune system disorders:

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

Disorders from the metabolism and nutrition:

frequency is unknown: increased serum potassium, hyponatremia.

Hearing disorders and labyrinthine disturbances:

infrequently: vertigo.

Vascular disorders:

frequency unknown: vasculitis.

Disorders from the gastrointestinal tract:

infrequently: pain in the abdomen.

Disorders from the liver and bile ducts:

frequency is unknown: increased activity of "liver" enzymes.

Disturbances from the skin and subcutaneous tissues:

frequency unknown: angioedema, skin rash, skin itching, bullous dermatitis.

Disorders from the kidneys and urinary tract:

frequency unknown: renal failure.

The following AEs were observed in the study of clinical use of valsartan in patients with AH irrespective of their causal relationship with valsartan: arthralgia, asthenia, back pain, diarrhea, dizziness, headache, insomnia, decreased libido, nausea, edema, pharyngitis, rhinitis, sinusitis , upper respiratory tract infections, viral infections.

With the use of thiazide diuretics, including HCTZ

Violations from the blood and lymphatic system:

rarely: thrombocytopenia, sometimes with purpura;

very rarely: agranulocytosis, oppression of bone marrow hematopoiesis, hemolytic anemia, leukopenia;

frequency unknown: aplastic anemia.

Immune system disorders:

very rarely: hypersensitivity reactions.

Disorders from the metabolism and nutrition:

very often: hypokalemia, increase in the concentration of lipids in the blood plasma (especially against the background of high doses of HCTZ);

often: hyponatremia, hypomagnesemia, hyperuricemia;

rarely: hypercalcemia, hyperglycemia, glucosuria and worsening of SD;

Very rarely: hypochloraemic alkalosis.

Disorders of the psyche:

rarely: sleep disturbance, depression.

Impaired nervous system:

rarely: headache, dizziness, paresthesia.

Disorders from the side of the organ of vision:

rarely: visual impairment (especially in the first few weeks of treatment);

frequency unknown: acute attack of angle-closure glaucoma.

Heart Disease:

rarely: arrhythmias.

Vascular disorders:

often: orthostatic hypotension (may be intensified with simultaneous use with ethanol, sedatives or anesthetics).

Disturbances from the respiratory system, chest and mediastinal organs:

very rarely: respiratory distress syndrome, including pulmonary edema and pneumonitis.

Disorders from the digestive system:

often: decreased appetite, mild nausea and vomiting;

rarely: abdominal discomfort, constipation, diarrhea;

very rarely: pancreatitis.

Disorders from the liver and bile ducts:

rarely: intrahepatic cholestasis or jaundice.

Disorders from the kidneys and urinary tract:

frequency unknown: impaired renal function, acute renal failure.

Disturbances from the skin and subcutaneous tissues:

often: urticaria and other forms of skin rash;

rarely: photosensitization;

very rarely: necrotizing vasculitis and toxic epidermal necrolysis, lupus-like reactions, exacerbation of cutaneous manifestations of SLE;

frequency unknown: erythema multiforme.

Disturbances from the musculoskeletal and connective tissue:

frequency unknown: muscle spasms.

Violations of the genitals and breast:

often: impotence.

Common disorders and disorders together:

frequency unknown: hyperthermia, asthenia.

Overdose:

Symptoms: the main expected manifestation of valsartan overdose is a marked decrease in blood pressure, which can lead to impaired consciousness, collapse and / or shock. In case of an overdose of HCTT, the following symptoms may develop: nausea, drowsiness, decreased BCC, cardiac arrhythmias and muscle spasms caused by a disturbance of the water-electrolyte balance.

Treatment: is symptomatic and depends on the time elapsed since the time of taking the drug, and on the severity of the symptoms. In the case of early diagnosis of overdose, it is recommended to induce vomiting and / or rinse the stomach. It is necessary to stabilize the parameters of hemodynamics. With a pronounced decrease in blood pressure, it is necessary to move the patient to a horizontal position with the legs raised upwards and make up for the BCC (intravenously administer a 0.9% solution of sodium chloride) under the control of the parameters of hemodynamics and diuresis. Valsartan is not excreted by hemodialysis, since it binds significantly to plasma proteins. HCTZ is excreted by hemodialysis.

Interaction:

General drug interactions for valsartan and hydrochlorothiazide

Simultaneous use is not recommended

Lithium preparations

With simultaneous use of ACE inhibitors, APA II or thiazide diuretics with lithium preparations, a reversible increase in the concentration of lithium in the blood plasma and the development of intoxication were noted. The risk of toxic manifestations associated with the use of lithium drugs may be further increased with simultaneous use with the preparation of Valsacor® H 80, as the renal clearance of lithium preparations is reduced by thiazide diuretics.If it is necessary to simultaneously apply with lithium preparations, the concentration of lithium in the blood plasma should be carefully monitored.

Use with caution at the same time

Other antihypertensive drugs

It is possible to increase the antihypertensive effect when used simultaneously with other drugs that lower blood pressure (for example, ACE inhibitors, beta adrenoblockers, slow calcium channel blockers (BCCC), guanethidine, methyldopa, vasodilators, direct renin inhibitors, APA II).

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

It is possible to weaken the action of pressor amines, which does not require the cessation of simultaneous application of valsartan and HCTZ.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2)

With the simultaneous use of APA II and HCTT with NSAIDs, a decrease in diuretic and antihypertensive action is possible. In hypovolemic conditions, it is possible to develop acute renal failure (ARF), it is recommended to monitor renal function at the beginning of therapy, and adequate replenishment of BCC in the patient.

Drug Interactions for valsartan

Simultaneous use is contraindicated

The simultaneous use of ARA II, including valsartan, with aliskirenom is contraindicated in patients with diabetes mellitus or moderate and severe renal dysfunction (CC less than 60 ml / min).

Simultaneous use is not recommended

Potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations, potassium-containing substitutes for edible salt and other medicines and substances, which can cause an increase in serum potassium (for example, heparin)

If it is necessary to simultaneously apply with drugs that affect the potassium content, it is recommended to monitor the potassium content in the blood plasma.

Use with caution at the same time

With the simultaneous use of ARA II, including valsartan, with drugs that affect the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors or aliskiren the incidence of arterial hypotension, hyperkalemia, and renal dysfunction increase.

It is necessary to monitor blood pressure, kidney function, the content of electrolytes in the blood plasma in such patients.

Protein-carriers

Research in vitro on liver cultures showed that valsartan is a substrate for the OATP1B1 / OATP1B3 carrier proteins andMRP2. Simultaneous use of valsartan with inhibitors of the carrier protein OATP1B1/OATP1B3 (rifampicin, ciclosporin) orMRP2 (ritonavir) can increase the systemic exposure of valsartan (C_mOh and AUC). Caution should be exercised at the beginning of simultaneous use with the above drugs or after their withdrawal.

Lack of drug interaction

There were no clinically significant interactions with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, HCTZ, amlodipine and glibenclamide.

Drug Interactions for HCTZ

Use with caution at the same time

Drugs affecting the content of potassium in blood plasma

When used simultaneously with "loop" diuretics, glucocorticosteroids (GCS), adrenocorticotropic hormone (ACTH), amphotericin B, benzathine benzylpenicillin, carbenoxolone, laxatives, acetylsalicylic acid or its derivatives the risk of decreasing potassium levels in blood plasma and hypokalemia increases. In this case, it is recommended to monitor the potassium content in the blood plasma.

Drugs that can cause a polymorphic ventricular tachycardia such as "pirouette"

With simultaneous application antiarrhythmic drugs IA and III classes and some antipsychotics (neuroleptics) with HCTZ should be cautious, since there is a risk of arrhythmia such as "pirouette" against the background of possible hypokalemia. It is recommended to control the content of potassium in the blood plasma.

Muscle relaxants nondepolarizing the peripheral action (tubocurarine)

HCTZ potentiates the action of muscle relaxants.

Hypoglycemic agents (for ingestion and insulin)

With simultaneous use, a dose adjustment of hypoglycemic agents may be required.

Metformin should be taken with caution, as possible the development of lactic acidosis, induced by renal failure against the background of taking HCTZ.

Drugs affecting the sodium content in blood plasma

With prolonged simultaneous use with antidepressants, anticonvulsant, antipsychotic (neuroleptic) drugs (for example, carbamazepine) and so on, care should be taken, as the risk of developing hyponatremia increases. It is recommended to regularly monitor the sodium content in the blood plasma.

Cardiac glycosides

Hypokalemia and hypomagnesemia with thiazide diuretics may contribute to the development of cardiac arrhythmias in patients receiving cardiac glycosides.

H- and m-holinoblokatary

H- and m-holinoblokatory (atropine, biperidene) can increase the bioavailability of thiazide diuretics by reducing the peristaltic activity of the gastrointestinal tract (GI tract) and slowing the emptying of the stomach. Accordingly, GI motility stimulants (cisapride) may reduce the bioavailability of thiazide diuretics.

Anion exchange resins (colestramine and colestipol)

Absorption of thiazide diuretics, including HCTZ, decreases with simultaneous application of colestyramine and colestipol. Therefore, HCTZ should be taken within 4 hours or 4-6 hours after the intake of anion-exchange resins.

Methyldopa

Individual cases of development of hemolytic anemia are described with simultaneous application of methyldopa and HCTZ.

Vitamin D and calcium salts

The simultaneous use of thiazide diuretics, including HCTT, with vitamin D or calcium salts can lead to an increase in the calcium content in the Plasma blood as a result of increased reabsorption of calcium.

Cyclosporin

With the simultaneous use of HCTT and cyclosporine, the risk of hyperuricemia and symptoms similar to that of gout is increasing.

Radiocontrast agents containing iodine

With hypovolemia, which has developed against the background of taking diuretics, the risk of developing acute renal failure increases. BCC should be replenished before using high iodine (eg radiocontrast agents containing iodine).

Medicines for the treatment of gout (probenecid, sulfinpyrazone and allopurinol)

When using HCTT, an increase in the concentration of uric acid in the blood plasma is possible, which may require correction of the doses of medicines for the treatment of gout (for example, an increase in the dose of sulfinpyrazone and probenecid). Simultaneous use with thiazide diuretics, including HCTZ, can lead to an increase in the frequency of hypersensitivity reactions to allopurinol.

Amantadine

Simultaneous use with thiazide diuretics, including HCTZ, increases the risk of developing side effects of amantadine.

Beta-blockers and diazoxide

Simultaneous use with thiazide diuretics, including HCTT, increases the risk of developing hyperglycemia.

Cytotoxic drugs (cyclophosphamide, methotrexate)

Simultaneous use with thiazide diuretics, including HCTT, reduces the excretion of cytotoxic drugs by the kidneys, which leads to potentiation of their myelosuppressive action.

Ethanol, barbiturates and narcotic drugs

Simultaneous use with thiazide diuretics, including HCTZ, can potentiate the development of orthostatic hypotension.

Special instructions:

Impaired renal function

In patients with impaired renal function (QC greater than 30 ml / min), no dose change is required. When using the drug Valsacor® H 80 in patients with impaired renal function, it is recommended to regularly monitor the potassium content, the concentration of creatinine and uric acid in the blood plasma.

Condition after kidney transplantation

The safety of the use of the preparation Valsacor® H 80 in patients who have recently undergone kidney transplantation,not installed.

Stenosis of aortic and / or mitral valves, GOKMP

Preparation Valsacor^® H 80 should be used with caution in patients with hemodynamically significant stenosis of the aortic and / or mitral valves or with GOKMP.

Impaired liver function

Preparation Valsacor^® H 80 is not used in patients with severe impaired liver function (more than 9 on the Child-Pugh scale). In patients with mild or moderate impairment of liver function without cholestasis, the preparation Valsacor® H 80 should be used with caution.

Violations of the water-electrolyte balance

With the use of thiazide diuretics, including HCTZ, there have been cases of hypokalemia, hyponatremia and hypochloraemic alkalosis, hypomagnesemia (as magnesium excretion by the kidneys increases) and hypercalcemia (as the excretion of calcium by the kidneys decreases). It is recommended that the content of electrolytes in the blood serum, in particular potassium, be regularly monitored when Valsacor® H 80 is used.

Hyponatremia and / or decrease in BCC

In patients with severe hyponatraemia and / or with reduced BCC (eg, when taking high doses of diuretics), in rare cases at the beginning of therapy with the drug

Valsacor® H 80 may have a marked decrease in blood pressure with clinical manifestations. Therefore, at the beginning of treatment, a correction of the sodium content in the blood serum and / or replenish the BCC should be performed.

In case of a marked decrease in blood pressure, the patient should be moved to a horizontal position with raised legs, and, if necessary, an intravenous infusion of 0.9% sodium chloride solution. After stabilization of blood pressure treatment with Valsakor^® H 80 can be continued.

Chronic heart failure severe (III-IV functional class by classification NYHA) or other diseases accompanied by RAAS stimulation

In patients whose renal function depends on the state of RAAS (for example, with CHF III-IV functional class by classification NYHA), therapy with ACE inhibitors may be accompanied by oliguria and / or progressive azotemia, in rare cases - ARF. It is impossible to exclude the development of renal dysfunction due to the suppression of RAAS activity against the background of the drug Valsacor® H 80. Therapy with Valsacor® H 80 should be performed with caution under the control of kidney function.

Primary hyperaldosteronism

The drug Valsacor® H 80 is not effective for the treatment of hypertension in patients with primary hyperaldosteronism due to the lack of activation of RAAS.

Stenosis of the renal artery

In patients with unilateral or bilateral stenosis of the renal artery or stenosis of the artery of a single kidney, the drug should be used with caution, since it is possible to increase the concentrations of creatinine and urea in the blood plasma.

Systemic lupus erythematosus

With the use of thiazide diuretics (including HCTZ), cases of exacerbations and worsening of the course of connective tissue diseases (for example, SLE) are described.

Other metabolic disorders

Thiazide diuretics, including HCTT, can cause a change in glucose tolerance and an increase in the concentration of cholesterol, triglycerides and uric acid in the blood plasma.

Patients with diabetes may require a dose adjustment of insulin or hypoglycemic agents for oral administration.

Thiazide diuretics reduce the excretion of calcium by the kidneys and can cause a slight increase in calcium in the blood plasma in the absence of concomitant disorders of calcium metabolism.Expressed hypercalcemia on the background of the use of a thiazide diuretic may indicate hyperparathyroidism. Before the study of parathyroid function, thiazide diuretics, including HCTZ, should be discontinued.

Photosensitivity

The cases of development of photosensitivity against the background of HCTT are described. In the case of development of photosensitivity manifestations, it is recommended to stop therapy. If it is necessary to continue therapy, it is recommended to protect open areas of the body from exposure to sunlight and ultraviolet rays.

Anti-doping test

HCTZ can give a positive result in the conduct of doping control.

Hypersensitivity reactions

Reactions of hypersensitivity against the background of the use of HCTZ were most often observed in patients with allergic reactions and bronchial asthma in the anamnesis. With the use of valsartan, patients developed angioedema, including edema of the larynx and vocal cords, leading to airway obstruction, and / or edema of the face, lips, throat and / or tongue; in some of these patients, a development of angioedema was observed in the history of the use of other drugs, including ACE inhibitors.If angioedema develops, immediately stop taking Valsacor® H 80 and do not resume treatment with the drug.

Acute attack of angle-closure glaucoma

Against the backdrop of the use of HCTZ, there were cases of transient myopia and acute development of closed-angle glaucoma. Symptoms include a sudden onset, a sharp decrease in visual acuity, or pain in the eye, usually occur between a few hours and a week after the start of therapy. An untreated, closed-angle glaucoma can lead to persistent loss of vision.

First and foremost, it is necessary, as soon as possible, to cancel the use of HCTZ. If intraocular pressure remains uncontrolled, emergency medical or surgical treatment may be required. A risk factor for the development of acute, closed-angle glaucoma may be the presence in the patient of an anamnesis of allergic reactions to sulfonamides or penicillin.

Special information on excipients

Preparation Valsacor^® H 80 contains lactose, therefore, it should not be used in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf. and fur:

In connection with the possibility of dizziness or weakness on the background of the use of the drug Valsakor^® H 80 should be careful when driving vehicles and working with other technical devices that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets coated with a film membrane, 80 mg + 12.5 mg.

Packaging:

For 7, 10, 14 or 15 tablets in a blister (contour acrylic packaging) from the combined material PVC / PE / PVDC - aluminum foil.

For 4, 8, 12 or 14 blisters (contour cell packs (7 tablets)), or 3, 6 or 9 blisters (contour cell packs (10 tablets)), or 2, 4, 6 or 7 blisters (14 tablets)), or 2, 4 or 6 blisters (contour cell packs (15 tablets each)) are placed in a cardboard box together with instructions for use.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

At the production of JSC "Krka, dd, Novo mesto", Slovenia

3 years.

When produced at OOO KRKA-RUS, Russia

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001731/10

Date of registration:05.03.2010 / 21.11.2014

Expiration Date:Unlimited

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp20.01.2017

Illustrated instructions

Instructions

Valsacor® H80 (Valsacor® H80)