Valsacor, pills 80mg+12.5mg, 30pcs

Composition

1 film-coated tablet contains:

Core:

Active ingredients:

Valsartan 80.00 mg

Hydrochlorothiazide 12.50 mg

Auxiliary substances:

Microcrystalline cellulose, croscarmellose sodium, povidone-K25, lactose monohydrate, magnesium stearate, colloidal silicon dioxide

Film shell: hypromellose 2910, titanium dioxide (E 171), macrogol-4000, iron oxide dye red (E 172), iron oxide dye yellow (E 172)

Pharmacological action

combined antihypertensive agent

(angiotensin II receptor antagonist + diuretic).

Clinical pharmacology

Valsacor ® H 80 is a combined antihypertensive drug consisting of an angiotensin II receptor antagonist (ARA II) and a thiazide diuretic.

Pharmacodynamics

Valsartan

Valsartan is a selective ARA II for oral use, of a non-protein nature.

Selectively blocks AT_-1receptors responsible for the vasopressor effect of angiotensin II. The consequence of AT1-receptor blockadeis an increase in the concentration of angiotensin II in blood plasma, which can stimulate unblocked AT2-receptors, which balances the vasopressor effects associated with the excitation_ofAT1-receptors. Valsartan has no agonistic activity against AT1receptors. Its affinityfor AT1 receptors is approximately 20,000 times higher than for AT2 receptors.

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

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

After ingestion of a single dose of valsartan, the antihypertensive effect develops within 2 hours, and the maximum decrease in blood pressure is achieved after 4-6 hours. The antihypertensive effect of valsartan persists for 24 hours after its use. With continuous use of valsartan, the maximum reduction in blood pressure, regardless of the dose, is achieved after 2-4 weeks and is maintained at the achieved level during long-term therapy. Concomitant use with hydrochlorothiazide (HCT) can achieve a significant additional reduction in blood pressure.

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

HCTZ

The point of application of thiazide diuretics is the 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 (Na+) and chlorine (Cl -) ions is suppressed. Suppression of the Na+ and Cl-co-transport systems seems to occur due to competition for Cl-binding sites in this system, which leads to an increase in Na+ and Cl – excretion to approximately the same extent.

As a result of diuretic action, there is a decrease in the volume of circulating blood (BCC), which increases the activity of renin, aldosterone secretion, excretion of potassium by the kidneys and, consequently, a decrease in the content of potassium in the blood serum. The relationship between renin and aldosterone is mediated by angiotensin II, so the decrease in serum potassium content with concomitant use of HCT with valsartan is less pronounced than with HCT monotherapy.

Pharmacokinetics

Valsartan

Suction

After oral use of valsartan, the maximum concentration (cmax) in blood plasma is reached within 2-4 hours. The average absolute bioavailability is 23%. When valsartan is taken with food, the area under the concentration-time curve (AUC) and_cmax in blood plasma decrease 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. The decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect of valsartan, so the drug can be taken regardless of the meal time.

Distribution

The volume of distribution₍vd) of valsartan at steady state after intravenous use was about 17 liters, which indicates that there is no pronounced distribution of valsartan in tissues. Valsartan actively binds to plasma proteins (94-97%), mainly albumin.

Metabolism

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

Deduction

Valsartan is excreted in two phases: a-phase with a half-life (T_1/2a) of less than 1 hour and b-phase with T_1/2b-about 9 hours. Valsartan is mainly excreted unchanged through the intestines (about 83%) and kidneys (about 13%). After intravenous use, 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_1/2 of valsartan is 6 hours.

The pharmacokinetics of valsartan in the therapeutic dose range is linear. No changes in pharmacokinetic parameters were observed with repeated use of valsartan. When taking valsartan 1 time a day, accumulation is insignificant. Plasma concentrations of valsartan are similar in men and women.

HCTZ

Suction

When taken orally, HCT is absorbed quickly. Cmax in blood plasma

is reached 2 hours after oral use. In the therapeutic dose range, the average AUC increases in direct proportion to the dose increase. Concomitant use with food may lead to an increase or decrease in systemic availability compared to fasting, but these changes are not clinically relevant. When taken orally, the absolute bioavailability of HCTZ is 70%.

Distribution

The visible Vd is 4-8 l/kg. Binding to plasma proteins (mainly albumins) is about 40-70%. HCTZ accumulates in red blood cells at a concentration approximately 3 times higher than plasma.

Metabolism, excretion

of HCTZ is eliminated almost unchanged. T_1/2 of the final phase is

6-15 hours. With repeated use, the pharmacokinetics of HCTZ do not change. When taken once a day, the accumulation of HCTZ is insignificant. More than 95% of the absorbed dose is excreted unchanged by the kidneys.

Valsartan/ Hydrochlorothiazide

When used concomitantly with valsartan, the systemic bioavailability of

HCTZ decreases by 30%, and the bioavailability of valsartan does not change significantly.

This 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 of the drug components individually or the placebo effect.

Pharmacokinetics of special patient groups

Elderly patients (over 65 years of age)

The AUC of valsartan in some elderly patients is higher than in young volunteers. These changes are not clinically relevant.

Presumably, in elderly patients with normal blood pressure and hypertension, the systemic clearance of HCT is lower than in healthy young volunteers.

Patients with impaired renal function

In patients with impaired renal function with a creatinine clearance of 30-70 ml/min, no dose adjustment of Valsacor ® H 80 is required. There are no data on the use of the drug in patients with severe renal impairment (creatinine clearance less than 30 ml / min) and in patients undergoing hemodialysis. Valsartan is not eliminated by hemodialysis, unlike HCT.

In the presence of renal insufficiency_{, cmax} and AUC of HCT increase, and the rate of elimination decreases. In patients with mild to moderate renal impairment, T_1/2 HCT is almost twice as long.

Patients with impaired liver function

In patients with mild (Child-Pugh score 5-6) or moderate (Child-Pugh score 7-9) hepatic impairment, valsartan AUC was 2 times higher than in healthy volunteers. There are no data on the use of Valsacor ® H 80 in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale).

Impaired liver function does not significantly affect the pharmacokinetics of HCT, so no dose adjustment is required in patients with impaired liver function.

Valsacor® H 80 should be used with caution in patients with biliary tract obstruction.

Indications

Arterial hypertension (patients who are indicated for combination therapy).

Use during 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 the II-III trimesters of pregnancy, since use in the II-III trimesters of pregnancy can cause fetotoxic effects (decreased renal function, lack of water, slowing ossification of the fetal skull bones) and neonatal toxic effects (renal failure, hypotension, hyperkalemia). There are reports of spontaneous abortions, lack of water and impaired renal function in newborns whose mothers unintentionally received valsartan during pregnancy.

If the drug was still used in the II-III trimesters of pregnancy, then it is necessary to conduct an ultrasound examination of the kidneys and skull bones of the fetus.

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

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

HCTZ

Experience with HCT during pregnancy, especially in the first trimester, is limited. HCTZ passes through the placenta. When using thiazide diuretics in the II-III trimester of pregnancy, thrombocytopenia, impaired water and electrolyte balance, jaundice in the fetus or newborn may develop.

If pregnancy is confirmed, Valsacor® H 80 should be discontinued as soon as possible.

Breast-feeding period

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

Contraindications

• Hypersensitivity to valsartan, hydrochlorothiazide and other sulfonamide derivatives or any other components of the drug.
• Severe liver dysfunction (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis.
• Anuria, severe renal impairment (creatinine clearance less than 30 ml / min).
• Refractory hypokalemia, hyponatremia, hypercalcemia, and symptomatic hyperuricemia.
• Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus (DM) and/or with moderate or severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 of body surface area).
• Concomitant use with ACE inhibitors in patients with diabetic nephropathy.
• Pregnancy and pregnancy planning, breast-feeding period.
• Age up to 18 years (efficacy and safety in children have not been proven).
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, as Valsacor® H 80 contains lactose.

Side effects

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

very common ≥ 1/10

common ≥ 1/100 to < 1/10

uncommon ≥ 1/1000 to < 1/100

rare ≥ 1/10000 to < 1/1000

very rare < 1/10000

frequency unknown cannot be estimated based on available data.

When using a combination of valsartan/hydrochlorothiazide

Metabolic and nutritional disorders:

infrequently: dehydration.

Nervous system disorders:

common: headache;

uncommon: paresthesia;

very rare: dizziness;

frequency unknown: syncope.

Visual disturbances:

infrequently: reduced visual acuity.

Hearing disorders and labyrinth disorders:

infrequently: tinnitus.

Vascular disorders:

infrequently: marked decrease in blood pressure, peripheral edema.

Respiratory, thoracic and mediastinal disorders:

infrequently: cough;

frequency unknown: non-cardiogenic pulmonary edema.

Disorders of the gastrointestinal tract:

infrequently: nausea;

very rarely: diarrhea.

Musculoskeletal and connective tissue disorders:

infrequently: myalgia;

very rarely: arthralgia.

Kidney and urinary tract disorders:

frequency unknown: impaired renal function.

General disorders and disorders at the injection site:

infrequently: increased fatigue.

Laboratory and instrumental data:

frequency unknown: increased serum uric acid concentration, increased serum bilirubin concentration, increased serum creatinine concentration, hyponatremia, hypokalemia, neutropenia, increased serum residual urea nitrogen concentration.

When studying the clinical use of a fixed combination of valsartan/HCTZ in patients with hypertension, the following adverse events (AES) were observed without an obvious connection with taking the drug: abdominal pain, upper abdominal pain, anxiety, arthritis, asthenia, back pain, bronchitis (including acute), chest pain, postural dizziness, dyspepsia, shortness of breath, dry oral mucosa, nosebleeds, erectile dysfunction, gastroenteritis, headache, increased sweating, hypesthesia, flu-like state, insomnia, sprain, muscle spasms, muscle hypertonicity, nasal congestion, nasopharyngitis, nausea, neck pain, peripheral edema, otitis media, pain in the extremities, rapid heartbeat, pain in the larynx and pharynx, pyrexia, pollakiuria, hyperthermia, sinusitis, drowsiness, upper respiratory tract infections, urinary tract infections pathways, vertigo, viral infections, visual impairment.

The following are AES associated with the use of each component separately.

When using valsartan

Disorders of the blood and lymphatic system:

frequency unknown: decreased hemoglobin, decreased hematocrit, thrombocytopenia.

Immune system disorders:

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

Metabolic and nutritional disorders:

frequency unknown: increased serum potassium, hyponatremia.

Hearing disorders and labyrinth disorders:

infrequently: vertigo.

Vascular disorders:

frequency unknown: vasculitis.

Disorders of the gastrointestinal tract:

infrequently: abdominal pain.

Liver and biliary tract disorders:

frequency unknown: increased activity of “liver” enzymes.

Skin and subcutaneous tissue disorders:

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

Kidney and urinary tract disorders:

frequency unknown: renal failure.

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

When using thiazide diuretics, including HCT

Disorders of the blood and lymphatic system:

rare: thrombocytopenia, sometimes with purpura;

very rare: agranulocytosis, inhibition of bone marrow hematopoiesis, hemolytic anemia, leukopenia;

frequency unknown: aplastic anemia.

Immune system disorders:

very rare: hypersensitivity reactions.

Metabolic and nutritional disorders:

very common: hypokalemia, increased plasma lipids (especially with high doses of HCT);

often: hyponatremia, hypomagnesemia, hyperuricemia;

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

very rare: hypochloremic alkalosis.

Mental disorders:

rare: sleep disorders, depression.

Nervous system disorders:

rare: headache, dizziness, paresthesia.

Visual disturbances:

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

frequency unknown: acute attack of angle-closure glaucoma.

Cardiac disorders:

rare: arrhythmias.

Vascular disorders:

often: orthostatic hypotension (may increase with simultaneous use of ethanol, sedatives or painkillers).

Respiratory, thoracic and mediastinal disorders:

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

Disorders of the digestive system:

often: decreased appetite, moderate nausea and vomiting;

rarely: abdominal discomfort, constipation, diarrhea;

very rarely: pancreatitis.

Liver and biliary tract disorders:

rarely: intrahepatic cholestasis or jaundice.

Kidney and urinary tract disorders:

frequency unknown: impaired renal function, acute renal failure (ARF).

Skin and subcutaneous tissue disorders:

common: urticaria and other forms of skin rash;

rare: photosensitization;

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

frequency unknown: erythema multiforme.

Musculoskeletal and connective tissue disorders:

frequency unknown: muscle spasms.

Genital and breast disorders:

often: impotence.

General disorders and disorders at the injection site:

frequency unknown: hyperthermia, asthenia.

Interaction

Common drug interactions for valsartan and hydrochlorothiazide

Simultaneous use is not recommended

Lithium preparations

With simultaneous use of ACE inhibitors, ARA II or thiazide diuretics with lithium preparations, a reversible increase in the concentration of lithium in blood plasma and the development of intoxication were noted. The risk of toxic effects associated with the use of lithium preparations may further increase with concomitant use with Valsacor® H 80, since the renal clearance of lithium preparations decreases under the influence of thiazide diuretics. If concomitant use with lithium preparations is necessary, the concentration of lithium in the blood plasma should be carefully monitored.

Concomitant use with caution

Other antihypertensive drugs

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

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

It is possible to weaken the effect of pressor amines, which does not require discontinuation of the simultaneous use of valsartan and HCTZ.

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

Concomitant use of ARA II and HCTZ with NSAIDs may weaken the diuretic and antihypertensive effects. In conditions of hypovolemia, acute renal failure may develop, it is recommended to monitor renal function at the beginning of therapy, as well as to carry out adequate BCC replenishment in the patient.

Drug interactions for valsartan

Simultaneous use is contraindicated

Concomitant use of ARA II, including valsartan, with drugs containing aliskiren is contraindicated in patients with DM and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant use of ARA II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Simultaneous use is not recommended

Potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations, potassium-containing salt substitutes, and other drugs and substances that may cause an increase in serum potassium (for example, heparin)

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

Concomitant use with caution

Concomitant use of ARA II, including valsartan, with drugs that affect the RAAS, such as ACE inhibitors or aliskiren, increases the incidence of hypotension, hyperkalemia, and impaired renal function. It is necessary to monitor blood pressure, renal function, and the content of electrolytes in blood plasma in such patients.

Carrier proteins

In vitro studies on liver cultures have shown that valsartan is a substrate for the OATP1B1/OATP1B3 and MRP2 transporter proteins. Concomitant use of valsartan with OATP1B1/OATP1B3 transporter protein inhibitors (rifampicin, cyclosporin) or MRP2 (ritonavir) may increase systemic exposure to valsartan (_cmax and AUC). Caution should be exercised at the beginning of concomitant use with the above drugs or after their withdrawal.

No drug interaction

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

Drug interactions for HCT

Concomitant use with caution

Medications that affect the potassium content in blood plasma

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

Medicinalproducts capable of causing polymorphic ventricular tachycardia typea “pirouette“

Caution should be exercised when concomitantly using class IA and III antiarrhythmics and certain antipsychotic drugs (neuroleptics) with HCT, as there is a risk of developing pirouette-type arrhythmia against the background of possible hypokalemia. Monitoring of the potassium content in blood plasma is recommended.

Non-depolarizing peripheral muscle relaxants (tubocurarin)

HCTZ potentiates the action of muscle relaxants.

Hypoglycemic agents (for oral use and insulin)

With simultaneous use, it may be necessary to adjust the dose of hypoglycemic agents.

Metformin should be taken with caution, as lactic acidosis may develop due to renal failure while taking HCT.

Medications that affect the sodium content in blood plasma

When used concomitantly for a long time with antidepressants, anticonvulsants, antipsychotic (neuroleptic) drugs (for example, carbamazepine), etc., caution should be exercised, as the risk of hyponatremia increases. It is recommended to regularly monitor the sodium content in the blood plasma.

Cardiac Glycosides

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

N – and m-holinoblockers

N-and m-holinoblockers (atropine, biperiden) can increase the bioavailability of thiazide diuretics by reducing the peristaltic activity of the gastrointestinal tract (GIT) and slowing gastric emptying. Accordingly, stimulants of gastrointestinal motility (cisapride) may reduce the bioavailability of thiazide diuretics.

Anion exchange resins (colestyramine and colestipol)

The absorption of thiazide diuretics, including HCTZ, decreases with the simultaneous use of colestyramine and colestipol. Therefore, HCT should be taken 4 hours before or 4-6 hours after taking anion exchange resins.

Methyldopa

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

Vitamin D and calcium salts

Concomitant use of thiazide diuretics, including HCT, with vitamin D or calcium salts may lead to an increase in blood plasma calcium content as a result of increased calcium reabsorption.

Cyclosporine

Concomitant use of HCT and cyclosporine increases the risk of hyperuricemia and gout-like symptoms.

Radiopaque agents containing iodine

If hypovolemia develops while taking diuretics, the risk of acute renal failure increases. BCC should be filled before using products with a high iodine content (for example, X-ray contrast agents containing iodine).

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

When using HCT, the concentration of uric acid in the blood plasma may increase, which may require dose adjustment of medications for the treatment of gout (for example, increasing the dose of sulfinpyrazone and probenecid). Concomitant use with thiazide diuretics, including HCT, may increase the frequency of hypersensitivity reactions to allopurinol.

Amantadine

Concomitant use with thiazide diuretics, including HCT, increases the risk of side effects of amantadine.

Beta-blockers and diazoxide

Concomitant use with thiazide diuretics, including HCT, increases the risk of hyperglycemia.

Cytotoxic drugs (cyclophosphamide, methotrexate)

Concomitant use with thiazide diuretics, including HCT, reduces the excretion of cytotoxic drugs by the kidneys, which leads to potentiation of their myelosuppressive effect.

Ethanol, barbiturates and narcotic drugs

Concomitant use with thiazide diuretics, including HCT, may potentiate the development of orthostatic hypotension.

How to take, course of use and dosage

Before starting therapy with Valsacor® H 80, it is necessary to correct water and 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 Valsacor ® H 80.

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

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

Impaired renal function

Patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml / min (0.5 ml / sec)) no dose adjustment is required.

Impaired liver function

The maximum recommended daily dose of Valsacor ® H 80 in patients with mild (Child-Pugh score 5-6) or moderate (Child-Pugh score 7-9) hepatic impairment without cholestasis is 1 tablet per day (80/12.5 mg).

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. An overdose of HCT may cause the following symptoms: nausea, drowsiness, decreased BCC, cardiac arrhythmias, and muscle spasms caused by a violation of the water-electrolyte balance.

Treatment: It is symptomatic and depends on the time that has elapsed since taking the drug, and on the severity of symptoms. In case of early diagnosis of overdose, it is recommended to induce vomiting and / or flush the stomach. Hemodynamic parameters should be stabilized. With a marked decrease in blood pressure, it is necessary to transfer the patient to a horizontal position with legs raised up and replenish the BCC (intravenously inject 0.9% sodium chloride solution) under the control of hemodynamic and diuresis indicators. Valsartan is not eliminated by hemodialysis, as it binds significantly to plasma proteins. HCTZ is eliminated by hemodialysis.

Description

Oval, biconvex tablets, covered with a film-coated pink color.

View at the break: white rough mass with a pink film shell.

Special instructions

The simultaneous use of potassium-sparing diuretics, potassium supplements, potassium-containing supplements or other drugs capable of increasing the potassium content in the blood serum (e. g., heparin), state, accompanied by water-electrolyte disorders: nephropathy with the loss of salts and prerenal (cardiogenic) with impaired renal function, hypokalemia, hypomagnesemia, hypercalcemia, chronic heart failure (CHF) III-IV functional class NYHA classification, moderately severe violations of the liver without signs of cholestasis, severe hyponatremia and/or the state, accompanied by a decrease in BCC (including diarrhea, vomiting, therapy with high doses of diuretics, bilateral or unilateral renal artery stenosis or stenosis of the artery to a solitary kidney, condition after kidney transplantation, primary aldosteronism, stenosis of aortic and/or mitral valve disease, hypertrophic obstructive cardiomyopathy (HACMP), systemic lupus erythematosus (SLE), non-melanoma skin cancer (NMRC) in history (see “Special instructions”), obstructive disease of the biliary tract, diabetes, hypercholesterolemia, hypertriglyceridemia, angle-closure glaucoma, in patients with hereditary angioedema or angioedema in the background of previous therapy with ARA II or ACE inhibitors.

Contraindicated in children under 18 years of age (efficacy and safety in children have not been proven).

Impaired renal function

Patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml / min (0.5 ml / sec)) no dose adjustment is required.

Impaired liver function

The maximum recommended daily dose of Valsacor ® H 80 in patients with mild (Child-Pugh score 5-6) or moderate (Child-Pugh score 7-9) hepatic impairment without cholestasis is 1 tablet per day (80/12.5 mg).

Double blockade of the RAAS

Concomitant use of ARA II, including valsartan, with drugs containing aliskiren is contraindicated in patients with DM and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant use of ARA II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Impaired renal function

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

Condition after undergoing a kidney transplant

The safety of Valsacor® H 80 in patients who have recently undergone a kidney transplant has not been established.

Aortic and/or mitral valve stenosis, HOCMP

Valsacor ® H 80 should be used with caution in patients with hemodynamically significant aortic and/or mitral valve stenosis or with HOCMP.

Impaired liver function

Valsacor ® H 80 is not used in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale). In patients with mild to moderate hepatic impairment without cholestasis, Valsacor ® H 80 should be used with caution.

Violations of the water-electrolyte balance

Hypokalaemia, hyponatremia and hypochloremic alkalosis, hypomagnesaemia (due to increased renal excretion of magnesium) and hypercalcaemia (due to decreased renal excretion of calcium) have been reported with thiazide diuretics, including HCT. When using Valsacor® H 80, it is recommended to regularly monitor the content of electrolytes in the blood serum, especially potassium.

Hyponatremia and / or decreased BCC

In patients with severe hyponatremia and / or with a reduced BCC (for example, when taking high doses of diuretics), in rare cases, a pronounced decrease in blood pressure with clinical manifestations may occur at the beginning of therapy with Valsacor® H 80. Therefore, at the beginning of treatment, it is necessary to correct the sodium content in the blood serum and / or replenish the BCC.

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

Severe CHF (NYHA functional class III-IV) or other diseases associated with RAAS stimulation

In patients whose renal function depends on the condition of the RAAS (for example, with CHF of NYHA functional class III-IV), ACE inhibitor therapy may be accompanied by oliguria and / or progressive azotemia, in rare cases – acute renal failure. It is impossible to exclude the development of impaired renal function due to the suppression of RAAS activity while taking Valsacor ® H 80. Therapy with Valsacor ® H 80 should be carried out with caution, under the control of renal function.

Primary hyperaldosteronism

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

Renal artery stenosis

In patients with unilateral or bilateral renal artery stenosis 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 blood plasma.

Systemic lupus erythematosus

When using thiazide diuretics (including HCT), cases of exacerbation and worsening of connective tissue diseases (for example, SLE) have been described.

Photosensitivity

Cases of photosensitivity development during HCT treatment are described. In case of development of photosensitivity symptoms, it is recommended to stop therapy. If it is necessary to continue therapy, it is recommended to protect exposed areas of the body from exposure to sunlight and ultraviolet (UV) rays.

NMRC

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between HCT intake and an increased risk of NSCLC-basal cell carcinoma and squamous cell carcinoma. The risk of developing NSCLC increased with an increase in the total (accumulated) dose of HCT. A possible mechanism for the development of NSCLC is the photosensitizing effect of HCT.

Patients taking HCT alone or in combination with other medications should be aware of the risk of developing NSCLC. Such patients are advised to have their skin examined regularly to identify any new suspicious lesions, as well as changes to existing skin lesions.

All suspicious skin changes should be reported to your doctor immediately. Suspicious skin areas should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

In order to minimize the risk of developing NSCLC, patients should be advised to take preventive measures, such as limiting exposure to sunlight and UV rays, as well as using appropriate protective equipment.

In patients with a history of NSCLC, it is recommended to reconsider the use of HCT.

Other metabolic disorders

Thiazide diuretics, including HCT, can cause changes in glucose tolerance and increase the concentration of cholesterol, triglycerides and uric acid in blood plasma.

Patients with diabetes may need to adjust the dose of insulin or hypoglycemic agents for oral use.

Thiazide diuretics reduce the excretion of calcium by the kidneys and may cause a slight increase in the content of calcium in the blood plasma in the absence of concomitant disorders of calcium metabolism. Severe hypercalcemia associated with the use of a thiazide diuretic may indicate hyperparathyroidism. Thiazide diuretics, including HCT, should be discontinued prior to parathyroid function testing.

The HCTZ anti-doping test

can give a positive result during doping control.

Hypersensitivity reactions

Hypersensitivity reactions associated with the use of HCT were most often observed in patients with a history of allergic reactions and bronchial asthma.

When using valsartan, patients have developed angioedema, including laryngeal and vocal cord edema leading to airway obstruction, and/or swelling of the face, lips, pharynx, and / or tongue. Some of these patients had a history of angioedema due to the use of other medications, including ACE inhibitors. If angioedema develops, Valsacor® H 80 should be discontinued immediately and treatment should not be resumed.

Acute attack of angle-closure glaucoma

Cases of transient myopia and acute angle-closure glaucoma have been reported with the use of HCT. Symptoms include a sudden onset, a sharp decrease in visual acuity, or pain in the eye, usually occurring between a few hours and a week after starting therapy. Untreated angle-closure glaucoma can lead to permanent vision loss.

First of all, it is necessary to cancel the use of HCT as soon as possible. If intraocular pressure remains uncontrolled, emergency medical or surgical treatment may be required. A history of allergic reactions to sulfonamides or penicillin may be a risk factor for acute angle-closure glaucoma.

Special information on excipients

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

Due to the possibility of dizziness or weakness during the use of Valsacor® H 80, caution should be exercised when driving vehicles and working with other technical devices that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Film-coated tablets,80 mg + 12.5 mg

During production at JSC “KRKA, D. D., Novo Mesto”, Slovenia:

7,10,14 or 15 tablets in a blister (contour cell package) made of combined PVC/PE/PVDC material and aluminum foil.

4,8,12 or 14 blisters (contour cell packages) of 7 tablets, or 3,6 or 9 blisters (contour cell packages) of 10 tablets, or 2,4,6 or 7 blisters (contour cell packages) of 14 tablets, or 2,4 or 6 blisters (contour cell packages) of 15 tablets are placed in a cardboard pack together with the instructions for use.

During production at KRKA-RUS LLC, Russia:

7,10,14 or 15 tablets in a contour cell package (blister) made of a combined PVC/PE/PVDC material and aluminum foil.

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

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children.

Shelf

life is 5 years.

Do not use the drug after the expiration date.

Active ingredient

Valsartan, Hydrochlorothiazide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension