Expiration date: 09/2025

The composition and form of issue:

Tablets, film-coated 1 tablet contains active substance:

valsartan 40, 80 or 160 mg

other ingredients: microcrystalline crospovidone silicon dioxide colloidal magnesium stearate 

film cover 

for tablets 40 mg: Opadry TAN 03B34653 (hypromellose 6 CP titanium dioxide E171 macrogol 400 talc colorant iron oxide yellow E172 colorant iron oxide red E172 colorant iron oxide black E172) 

for tablets of 80 and 160 mg: Opadry PiNK 03B34654 (hypromellose 6 CP titanium dioxide E171 macrogol 400 talc colorant iron oxide yellow E172 colorant iron oxide red E172) 

in blister al/al 10 pieces in cartons of 3 blister.

Description pharmaceutical form:

Pills 40 mg: round biconvex shaped, film-coated light-brown color, engraved C73 on one side and scored on the other.

Tablets 80 mg: oblong, biconvex, film-coated pink, engraved C74 on one side and scored on the other.

Pills 160 mg: oblong, biconvex, film-coated pink, engraved with C75 on one side and scored on the other.

Pharmacokinetics:

Valsartan is rapidly absorbed after ingestion, however, the degree of absorption varies widely. Average absolute bioavailability is 23%. The pharmacokinetic curve is downward valsartan bieksponencialny character (T1/2 &alpha-phase less than 1 h and T1/2 &beta-phase of about 9 hours).

The pharmacokinetics of valsartan in the dose range investigated is linear.

When you re receiving valsartan inside changes in the pharmacokinetics of the drug are not observed, and when taking the drug once a day — its accumulation is negligible.

Tmax is 2 h.

Plasma concentrations of valsartan are similar in men and women. Valsartan is largely associated with serum proteins (94-97%), mainly albumin. Vss is low (about 17 l). Compared with hepatic blood flow (about 30 l/h), plasma clearance of the drug is relatively low (about 2 l/h).

After taking the drug inside 83% of the dose of the drug is excreted through the intestine and 13% in the kidneys, mainly unchanged. About 20% of the dose is excreted as metabolites. The main metabolite — Valerie-4-hydroxyvalerate. The enzymes involved in the metabolism of valsartan have not defined and do not refer to the isozymes of cytochrome P450.

When taking valsartan with food decreases the AUC by 48%. However, after 8 h after ingestion the plasma concentrations of valsartan, taken on an empty stomach and with food, the same. The reduction in AUC is not accompanied by a clinically significant reduction in therapeutic effect, so the drug can be used both before and after a meal.

Pharmacokinetics in special patient groups

Patients of advanced age. Some elderly patients the systemic exposure to valsartan was more expressed compared to patients of young age. The elderly patients we recommend the use of a lower starting dose of valsartan is 40 mg.

Patients with impaired renal function. Given that renal clearance accounts for only 30% of the value of total clearance in patients with impaired renal function (Cl creatinine clearance is 20-50 ml/min) is not required correction doses of the drug to patients with impaired kidney with Cl creatinine <20 ml/min, it is recommended to start treatment with a dose of 40 mg. the Degree of binding of valsartan with plasma protein is high, so its removal with hemodialysis is unlikely.

Patients with impaired liver function. About 70% of the absorbed valsartan dose is excreted through the intestine with the bile, mainly unchanged. Valsartan is not exposed to significant biotransformation, therefore, its systemic effect is not correlated with the degree of liver dysfunction. Therefore, in patients with hepatic insufficiency nobiliario of origin and in the absence of cholestasis is not required to change doses of valsartan. In patients with biliary cirrhosis or biliary obstruction AUC of valsartan is increased about 2 times compared with the levels in healthy volunteers.

Description pharmacological action:

Valsartan — antihypertensive drug, a specific antagonist of angiotensin II receptors. Selectively acts on the AT1-subtype receptors, which are responsible for the known effects of angiotensin II. The active hormone of the RAAS is angiotensin II, which is formed from angiotensin I with the participation of the APF. Angiotensin II binds to specific receptors located on cell membranes in various tissues. It has a wide range of physiological effects, including in particular both direct and indirect participation in regulating blood pressure. Being a powerful vasoconstrictor, angiotensin II causes direct Pressor response. In addition, he contributes to the delay of sodium ions in the body and stimulates the secretion of aldosterone.

The affinity of valsartan for the AT1 receptor subtype is much higher (about 20,000) than to the AT2 receptor subtype.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Because there is no effect on ACE and there is no accumulation of bradykinin or substance P, it is unlikely that the use of antagonists of angiotensin II may be associated with cough. According to the results of clinical studies where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly lower (p<0.05) in patients treated with valsartan than in patients treated with ACE inhibitor (2.6 percent versus 7.9 percent, respectively). In a clinical study in patients who have had a dry cough during therapy with ACE inhibitors in history, the incidence of cough was 19.5% in patients receiving valsartan and 19% who received thiazide diuretics, compared with 68.5 per cent of patients who received therapy with ACE inhibitors (p<0.05). Valsartan does not bind or block other hormone receptors or ion channels, which play an important role in the regulation of SSS.

Hypertension

The use of valsartan in patients with hypertension leads to a decrease in blood pressure without changing heart rate. In most patients, after administration of a single dose of the drug beginning of the antihypertensive effect occurs within 2 h, while the maximum decrease in blood pressure is achieved within 4-6 hours and lasts for 24 hours after taking the drug inside.

When you re receiving valsartan of its antihypertensive effect stabiliziruemost regardless of dose, achieved within 2-4 weeks and maintained at that level during long-term therapy.

Discontinuation of the valsartan is not accompanied by a sharp rise in blood pressure or other undesirable clinical consequences.

Valsartan does not affect the concentration of total cholesterol, triglycerides, fasting glucose and uric acid in serum.

After myocardial infarction

In patients with acute myocardial infarction known congestive heart failure and/or systolic dysfunction of the left ventricle, the use of valsartan in combination therapy, including acetylsalicylic acid, &beta-blockers, ACE inhibitors, thrombolytics, and inhibitors of HMG-COA reductase leads to a reduction in deaths from cardiovascular causes after acute myocardial infarction and increased the time to cardiovascular events. Reduced frequency of hospitalizations for heart failure and recurrent myocardial infarction.

Indications:

• hypertension
  
• acute myocardial infarction — as part of combination therapy in patients with stable hemodynamic parameters with asymptomatic systolic dysfunction of the left ventricle and/or heart failure to reduce mortality in myocardial infarction.
  

Contraindications:

• hypersensitivity to valsartan or other components of the drug
  
• pregnancy
  
• lactation
  
• severe hepatic impairment (child-Pugh >9 points), cirrhosis of the liver, obstruction of the bile ducts (cholestasis)
  
• the age of 18 years (efficacy and safety not established).
  

With caution: arterial hypotension, hepatic failure (child-Pugh <9 points), renal failure (Cl creatinine <20 ml/min), including patients on hemodialysis after myocardial infarction hyponatremia the diet with restriction of sodium intake, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney status, accompanied by a decrease in BCC (W. diarrhea, vomiting), patients older than 75 years.

Application of pregnancy and breast-feeding:

The application of the product Northvan during pregnancy is contraindicated. Renal perfusion the fetus, which depends on the development of RAAS, starts functioning in the III trimester of pregnancy. Risk to the fetus increases when taking valsartan in II and III trimestrah.

Drugs acting on the RAAS, in the case of their application in II and III trimester of pregnancy can cause damage and fetal death. There are reports of spontaneous abortions, water scarcity and impaired renal function of the newborn in cases where pregnant women have taken valsartan.

Data on the allocation of valsartan with breast milk is not available. If necessary, the appointment of the drug, Northvan during lactation breastfeeding should be discontinued.

Side effects:

During clinical trials in patients with hypertension, adverse events were mild and were transient in nature. The incidence of adverse events was not associated with gender, age or race of patients.

The frequency of side effects is defined as follows: very common (&ge1/10) frequently (&GE. 1/100, <1/10) uncommon (&ge1/1000, <1/100) rare (&ge1/10000, <1/1000) very rare, including private messages (<1/10000).

Infection: often — viral infections, rarely — infection of the upper respiratory tract, pharyngitis, sinusitis very rare — rhinitis.

With the hematopoietic system: often — neutropenia very rarely — thrombocytopenia.

Allergic reactions: very rarely — hypersensitivity reactions (angioedema, skin rash, itching, serum sickness, vasculitis).

The laboratory parameters: often — hyperkalemia rarely — a decrease in hemoglobin and hematocrit, neutropenia, thrombocytopenia, hypercreatininemia, hyperbilirubinemia, elevated liver transaminases and urea nitrogen in serum.

CNS: rarely, fainting, insomnia, fatigue, asthenia, decreased libido dizziness very rare: headache, light and transient violation of taste sensitivity.

On the part of the organ of hearing: infrequent — vertigo.

From the CCC: often — heart failure, expressed lower AD, ortostatical gipotenzia, peripheral edema.

The respiratory system: rarely — cough, epistaxis.

From the digestive system: rare — diarrhea, abdominal pain very rare — nausea.

Hepatobiliary system: very rarely — infringements of function of a liver.

From the side of musculoskeletal system: rarely — pain in the back is very rarely — arthralgia, myalgia.

From the urinary system: very rarely — loss of kidney function, renal failure.

The incidence of side effects when using the drug, Northvan after myocardial infarction: rarely — hyperkalemia, syncope, orthostatic hypotension, heart failure very rare — the decline of renal function, renal failure.

Drug interactions:

As valsartan is not exposed to significant metabolism, you should not expect and significant drug interactions associated with induction or inhibition of cytochrome P450.

Clinically significant pharmacokinetic interactions with other drugs is not observed. The drugs tested in clinical trials include cimetidine, warfarin, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.

With simultaneous use of drugs lithium and ACE inhibitors have been reported reversible increase in lithium levels in the blood plasma and increased toxicity. In very rare cases these changes were observed while taking the drug lithium and antagonists of a receptor of angiotensin II. Should be used with caution drugs lithium drug Northvan. If this combination is required then it is recommended to monitor the lithium levels in the blood plasma.

The simultaneous appointment kalisberegath dioretikov (spironolactone, triamteren, amiloride), potassium supplements and potassium supplements can lead to an increase in the potassium content in the blood plasma.

At simultaneous reception of antagonists of a receptor of angiotensin II with NSAIDs, including selective COX-2 inhibitors, acetylsalicylic acid (>3 g/day) and other nonselective NSAIDs may decrease antihypertensive effects of valsartan.

The simultaneous use of antagonists of the receptor of angiotensin II and NSAIDs increases the risk of renal dysfunction, including acute renal failure, and increased potassium content in the blood plasma, especially in patients with impaired renal function. With simultaneous use caution, especially in elderly patients. After the start of combination therapy, and the treatment needed to control BCC and renal function.

The results of in vitro studies valsartan is a substrate for hepatic transporters MRP2 and ?ATP1B1.

Method of application and dose:

Inside.

Regardless of the meal, the multiplicity of reception — 1-2 times a day.

Hypertension/ For most patients, the recommended dose of Northvan is 80 mg 1 time per day, regardless of age, gender or race of the patient. Hypotensive effect occurs within 2 weeks of therapy and the maximum effect is observed after 4 weeks of treatment.

Some patients who fail to achieve target BP, the dose may be increased to 160 mg per day. Further strengthening of the hypotensive effect can be achieved either by increasing the dose of Northian to a maximum of 320 mg per day, or by adding to drug therapy, Northvan thiazide diuretics.

Northvan, may also be used in conjunction with other antihypertensive agents.

Patients older than 75 years. Start treatment with a lower dose, component of 40 mg 1 time per day.

Patients with impaired renal function. In patients with impaired renal function (Cl creatinine <20 ml/min) or on hemodialysis, it is recommended to start treatment with a lower dose, component of 40 mg 1 time per day. In patients with impaired renal function (Cl creatinine 20-50 ml/min) correction starting dose is not required.

Patients with reduced BCC. For patients with reduced BCC (for example on treatment with high doses of diuretics and when the amount of diuretic cannot be reduced), the initial dose of the drug, Northvan is 40 mg 1 time per day.

Patients with impaired liver function. Patients with hepatic impairment mild or moderate (child-Pugh <9 points) the recommended starting dose is 40 mg 1 time per day. Maximum daily dose of 80 mg should Not be exceeded daily dose of 80 mg.

Children and adolescents. The safety and efficacy of the drug, Northvan in children and adolescents under the age of 18 years not installed.

Patients after myocardial infarction. Therapy may be initiated in the first 12 h after acute myocardial infarction in an initial dose of 20 mg (1/2 table. 40 mg) 2 times a day, may gradual increase in dose, Northvan (40 mg, 80 mg) for several weeks until the maximum dose of 160 mg 2 times per day, subject to tolerability.

When identifying arterial hypotension or renal dysfunction should consider reducing the drug dose.

Northvan can be used in patients receiving standard therapy after myocardial infarction, including acetylsalicylic acid, &beta-adrenergic blockers, inhibitors of HMG-COA reductase.

In applying the drug, Northvan after myocardial infarction in patients with impaired renal function (Cl creatinine 20-50 ml/min) is not required correction doses of the drug.

Currently, there are no data on the use of drugs after myocardial infarction in patients with severe renal insufficiency (creatinine concentration >221 µmol/l). For this reason, Northvan should be used in these patients with caution, with appropriate assessment of renal function (see "precautions").

Overdose:

Symptoms: in spite of the lack of sufficient data, most expected manifestation of overdose would be tachycardia and a marked decrease in blood pressure, which can lead to collapse and/or shock.

Treatment: no specific antidote if the drug passed recently, you should induce vomiting, do gastric lavage, intake of activated carbon in marked decrease in blood pressure usual treatment is on/in the introduction 0.9% solution of sodium chloride. Hemodialysis is ineffective.

Precautions:

Hyponatremia and a decrease in BCC

In patients with severe deficits of sodium and/or reduced BCC, for example, receiving high doses of diuretics, in rare cases after initiation of therapy drug Northvan may experience severe hypotension. Patients in whom the dose of diuretic cannot be reduced with the goal of correction of sodium and/or BCC, the recommended starting dose of Northiana is 40 mg.

Renal artery stenosis

Short-term use of valsartan in patients with renovascular hypertension secondary to unilateral renal artery stenosis did not cause any significant changes of hemodynamic parameters of the kidney, the concentration of serum creatinine or urea nitrogen of the blood. However, because the use of other drugs that act on the RAAS can increase the concentration of urea and creatinine in blood serum, as a precaution it is recommended that monitoring of these indicators and the monitoring of this group of patients.

Liver failure

Based on the pharmacokinetic data, which demonstrate a significant increase in the concentration of valsartan in plasma in patients with arterial hypertension with concomitant light-to-moderate hepatic insufficiency (child-Pugh <9 points), it is recommended the use of lower doses of the drug, Northvan (see "Method of application and dosage"). These patients should not exceed the daily dose of 80 mg. The question of the use of doses higher than 80 mg twice daily should be considered only if the clinical benefits are likely to exceed the potential risks associated with increased antihypertensive action of the drug, Northvan (see "Method of application and dosage"). Patients with severe hepatic insufficiency (child-Pugh >9 points), liver cirrhosis, obstruction of biliary tracts drug use, Northvan contraindicated (see "Contraindications").

Violation of kidney function

Due to the suppression of activity in the RAAS, it was reported the increase of urea, creatinine in serum, and impaired renal function, including acute renal failure (very rarely), which was observed especially in patients with existing impaired renal function or in patients with severe chronic heart failure.

On the background of simultaneous supplementation of potassium is necessary to control the content of potassium in serum, especially in patients with impaired renal function or advanced age (see "Side effects", "Interaction").

Condition after myocardial infarction

The application of the product Northvan in patients after myocardial infarction usually leads to some decrease in blood pressure, but subject to recommendations for dosing regimen the drug, Northvan due to arterial hypotension usually is not necessary.

Care should be taken when administering the drug, Northvan in patients after myocardial infarction (see "Method of application and dosage").

Due to suppress the activity of RA in predisposed patients can expect the kidneys. Assessment of patients after myocardial infarction should always include assessment of renal function.

Combination with hydrochlorothiazide allows to achieve significant additional blood pressure reduction.

Effects on ability to drive or to perform work requiring high speed physical and mental reactions. Northvan on the ability to drive vehicles and use of technical means was conducted. However, be careful, because during the treatment may occur dizziness or fatigue.