Valsartan Medisorb 40 mg 30 coated tablets blister

Adults

• arterial hypertension;

• chronic heart failure (NYHA functional class II-IV), in adult patients receiving standard therapy with one or more drugs from the following pharmacotherapeutic groups: diuretics, cardiac glycosides, as well as ACE inhibitors or beta-blockers. The use of each of the listed drugs is not mandatory. Assessment of patients with CHF should include evaluation of kidney function.

• to improve survival in patients after an acute myocardial infarction complicated by left ventricular failure and/or left ventricular systolic dysfunction, with stable hemodynamic parameters.

• Children and adolescents

• arterial hypertension in children and adolescents aged 6 to 18 years.

Tablets should be taken orally, without chewing, regardless of food intake, with water.
Adults
Arterial hypertension:
The drug may be prescribed at a dose of 40 mg, 80 mg, 160 mg, 320 mg.
The recommended initial dose of the drug is 80 mg once daily, regardless of the patient's race, age, and gender. The antihypertensive effect develops within the first 2 weeks of treatment; maximum effect is observed after 4 weeks.
For patients who do not achieve an adequate therapeutic response, the daily dose may be increased to a maximum daily dose of 320 mg or additional diuretics may be required.
Chronic heart failure:
The recommended initial dose of the drug is 40 mg twice daily. The dose should be gradually increased over at least 2 weeks to 80 mg twice daily, and if well tolerated, to 160 mg twice daily. The maximum daily dose of the drug is 320 mg in 2 doses. A reduction in the dose of concurrently taken diuretics may be required.
To improve survival after acute myocardial infarction:
Treatment should begin within 12 hours after the myocardial infarction. The initial dose is 20 mg (1/2 of a 40 mg tablet) twice daily. Dose escalation is performed by titration (40 mg, 80 mg, 160 mg twice daily) over the following weeks, until the target dose of 160 mg twice daily is reached.
The maximum daily dose is 320 mg in 2 doses. Generally, it is recommended to reach a dose of 80 mg twice daily by the end of the second week of treatment. Achieving the maximum target dose of 160 mg twice daily is recommended by the end of the third month of therapy. Dose increases depend on the drug's tolerability during titration.
In case of developing arterial hypotension with clinical manifestations or renal function impairment, consideration should be given to reducing the dose. Assessment of patients' condition after myocardial infarction should include evaluation of renal function.
Children and adolescents aged 6 to 18 years
Arterial hypertension:
The recommended initial dose of valsartan for children and adolescents aged 6 to 18 years is 40 mg for children weighing less than 35 kg and 80 mg for children weighing more than 35 kg. The dose should be adjusted based on blood pressure reduction. The maximum recommended daily doses are reflected in the table below. Use of higher doses is not recommended.
Body weight Maximum recommended daily dose
< 35 kg 80 mg ≥ 35 kg < 80 kg 160 mg ≥ 80 kg ≤ 160 kg 320 mg Chronic heart failure and post-acute myocardial infarction: Valsartan is not recommended for the treatment of chronic heart failure and post-acute myocardial infarction in patients under 18 years of age. Use in patients over 65 years of age: No dose adjustment is required for elderly patients. Use in patients with renal function impairment: No dose adjustment is required for patients with renal function impairment. Currently, there is no data on the use of valsartan in patients with a glomerular filtration rate of less than 10 ml/min. Concurrent use of valsartan with aliskiren is contraindicated in patients with renal function impairment (glomerular filtration rate < 60 ml/min/1.73 m²). Use in patients with liver function impairment: In patients with mild to moderate non-biliary liver function impairment without cholestasis, valsartan should be used with caution, and the daily dose should not exceed 80 mg. In patients with severe liver function impairment (more than 9 points on the Child-Pugh scale), biliary cirrhosis, and cholestasis, the use of valsartan is contraindicated. Use in patients aged 6 to 18 years with renal function impairment: In patients aged 6 to 18 years with renal function impairment and a creatinine clearance of less than 30 ml/min, as well as in patients on hemodialysis, the use of valsartan has not been studied, therefore its use in this patient group is not recommended. In patients aged 6 to 18 years with a creatinine clearance of more than 30 ml/min, no dose adjustment is required. During the use of valsartan, renal function and plasma potassium levels should be closely monitored. Use in patients aged 6 to 18 years with liver function impairment: As with adult patients, the use of valsartan is contraindicated in patients aged 6 to 18 years with severe liver function impairment, biliary cirrhosis, and cholestasis. Experience with valsartan in patients with mild to moderate liver function impairment is limited. The dose should not exceed 80 mg in this patient group.

Composition per 1 tablet:
active ingredient: valsartan 40 mg;
excipients: lactose monohydrate (milk sugar); povidone K-30 (polyvinylpyrrolidone); potato starch; croscarmellose sodium; talc; magnesium stearate;
coating: - Opadry® II Pink: (hydroxypropyl methylcellulose 2910, lactose monohydrate, titanium dioxide, macrogol (PEG), iron oxide red dye, iron oxide yellow dye, aluminum lake of indigo carmine);

Round, biconvex tablets coated with a film, white with a pinkish tint. The core is white in cross-section.

• Hypersensitivity to valsartan or any of the components of the medication;

• Severe liver dysfunction (more than 9 points on the Child-Pugh scale), biliary cirrhosis, and cholestasis;

• Simultaneous use with aliskiren and medications containing aliskiren in patients with diabetes and/or moderate to severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m² body surface area);

• Simultaneous use with ACE inhibitors in patients with diabetic nephropathy;

• Age under 6 years - for the indication of arterial hypertension;

• Age from 6 to 18 years - for all indications except arterial hypertension (efficacy and safety not established);

• Pregnancy;

• Breastfeeding period;

• Lactose intolerance, lactase deficiency, or glucose-galactose malabsorption (the medication contains lactose).
Caution
Special caution should be exercised when administering the medication to patients with hereditary angioedema or angioedema due to prior treatment with angiotensin II receptor antagonists (ARAs) or ACE inhibitors.
Use with caution in patients with bilateral renal artery stenosis, stenosis of a single kidney artery, primary hyperaldosteronism, on a salt-restricted diet, in conditions associated with decreased circulating blood volume (including diarrhea, vomiting), in patients with creatinine clearance (CC) less than 10 ml/min (no clinical data), in patients aged 6 to 18 years with CC less than 30 ml/min, including those on hemodialysis, in patients with mild to moderate liver dysfunction of biliary and non-biliary origin without cholestasis, in patients with NYHA functional class III-IV heart failure whose kidney function depends on the renin-angiotensin-aldosterone system (RAAS), in patients with mitral or aortic stenosis, in patients with hypertrophic obstructive cardiomyopathy, as well as in patients after kidney transplantation.
Simultaneous use of ARAs with medications containing aliskiren is contraindicated in patients with diabetes and/or moderate to severe renal failure (GFR less than 60 ml/min/1.73 m² body surface area) and is not recommended in other patients.
Simultaneous use of ARAs with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
It is not recommended to use valsartan simultaneously with ACE inhibitors, as this combined therapy does not provide advantages over monotherapy with valsartan or an ACE inhibitor regarding all-cause mortality rates.
Use during pregnancy and breastfeeding
Pregnancy
The use of the medication is contraindicated during pregnancy.
Like any other medication that directly affects the RAAS, valsartan should not be used in women planning to become pregnant.
When prescribing any medication that affects the RAAS, the physician should inform women of childbearing age about the potential dangers of using these medications during pregnancy.
Given the mechanism of action of ARAs, the risk to the fetus cannot be excluded. The effects of ACE inhibitors (medications affecting the RAAS) on the fetus, if prescribed during the second and third trimesters of pregnancy, may lead to fetal damage and death. Retrospective data indicate that the use of ACE inhibitors in the first trimester of pregnancy increases the risk of giving birth to children with congenital defects. There are reports of spontaneous abortions, oligohydramnios, and renal function disorders in newborns whose mothers inadvertently took valsartan during pregnancy.
If pregnancy is detected during treatment with valsartan, the medication should be discontinued as soon as possible.
Breastfeeding period
It is unknown whether valsartan is excreted in breast milk; therefore, the use of the medication during breastfeeding is contraindicated.
Fertility
There are no data on the effect of the medication on human fertility. Animal studies did not observe any effects of valsartan on fertility.

Patients with renal impairment
There is no experience of safe use of valsartan in patients with creatinine clearance (CC) less than 10 ml/min and in patients on hemodialysis; therefore, the use of Valsartan Medisorb in such patients should be approached with caution. In patients with CC greater than 10 ml/min, dose adjustment is not required.
The simultaneous use of ARB II with medications containing aliskiren is contraindicated in patients with diabetes and/or moderate to severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m² body surface area) and is not recommended in other patients.
The simultaneous use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Liver impairment
In patients with mild to moderate liver impairment without cholestasis, valsartan should be used with caution.
Hyperkalemia
When used simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or other medications that may cause hyperkalemia (e.g., heparin), caution should be exercised, and regular monitoring of potassium levels in plasma is required.
Kidney transplantation
There is no data on the safety of valsartan use in patients who have undergone kidney transplantation.
Sodium deficiency and/or decreased circulating blood volume (CBV)
In patients with significant sodium deficiency and/or decreased CBV, for example, those receiving high doses of diuretics, arterial hypotension may occur at the beginning of treatment with the drug in rare cases, accompanied by clinical manifestations. Before starting treatment with the drug, sodium levels and/or CBV should be corrected, including by reducing the diuretic dose.
Renal artery stenosis
Short-term use of the drug in patients with renovascular hypertension secondary to unilateral renal artery stenosis of a single kidney does not lead to significant changes in renal hemodynamics, serum creatinine concentration, or blood urea nitrogen. However, considering that other medications affecting the RAAS may cause an increase in urea and creatinine levels in serum in patients with bilateral or unilateral renal artery stenosis, monitoring of these parameters is recommended as a precaution.
Primary hyperaldosteronism:
The drug is ineffective for the treatment of arterial hypertension in patients with primary hyperaldosteronism, as this category of patients does not exhibit RAAS activation.
Aortic and mitral stenosis. Obstructive hypertrophic cardiomyopathy
As with other vasodilators, caution should be exercised when taking Valsartan Medisorb in patients with aortic and mitral stenosis and obstructive hypertrophic cardiomyopathy.
Pregnancy
The use of ARB II is contraindicated during pregnancy. Female patients planning to become pregnant should be prescribed alternative medications with a confirmed safety profile during pregnancy. If pregnancy is diagnosed during treatment with Valsartan Medisorb, it should be discontinued as soon as possible, and alternative treatment should be initiated.
Chronic heart failure/myocardial infarction recovery period:
In patients with chronic heart failure (CHF) or after a myocardial infarction, starting treatment with valsartan often results in a slight decrease in blood pressure; therefore, blood pressure should be monitored at the beginning of therapy. Provided that dosing recommendations are followed, there is usually no need to discontinue the drug due to arterial hypotension. Assessment of patients with CHF should include evaluation of renal function.
Due to RAAS inhibition, some patients may experience renal function impairment. In patients with CHF of functional class III-IV according to NYHA classification, whose renal function depends on the state of RAAS, treatment with ACE inhibitors and ARB II may be associated with oliguria and/or worsening azotemia and, in rare cases, acute renal failure and/or death. Therefore, in these patient categories, renal function should be assessed before starting valsartan and periodically during therapy.
Combination therapy for arterial hypertension:
For arterial hypertension, the drug can be used as monotherapy or in combination with other antihypertensive medications, particularly diuretics.
Combination therapy in the post-myocardial infarction period:
The drug may be used in combination with other medications used after a myocardial infarction, namely thrombolytics, acetylsalicylic acid as an antiplatelet agent, beta-blockers, and HMG-CoA reductase inhibitors (statins). In this patient category, the simultaneous use of the drug with ACE inhibitors is not recommended, as this combination therapy does not provide advantages over monotherapy with valsartan or an ACE inhibitor regarding overall mortality from any cause.
Combination therapy for CHF:
In CHF, the drug can be used both as monotherapy and in combination with other medications - diuretics, cardiac glycosides, as well as ACE inhibitors or beta-blockers. In this patient category, the use of triple combination therapy with ACE inhibitors, beta-blockers, and valsartan is not recommended.
Angioedema, including Quincke's edema:
Angioedema, including of the larynx and vocal cords leading to airway obstruction, and/or swelling of the face, lips, throat, and/or tongue, has occurred in patients receiving valsartan; some of these patients had a history of angioedema with other medications, including ACE inhibitors. The drug should be immediately discontinued if angioedema occurs, and resumption of the drug is prohibited.
Dual RAAS blockade
When treating with medications affecting the RAAS, especially in combination, there have been reports of significant blood pressure reduction, syncope, stroke, hyperkalemia, and changes in renal function (including acute renal failure) in sensitive patients. Caution should be exercised when combining ARB II, including valsartan, with other RAAS-blocking medications, such as ACE inhibitors or aliskiren.
The simultaneous use of ARB II with medications containing aliskiren is contraindicated in patients with diabetes and/or moderate to severe renal impairment (GFR less than 60 ml/min/1.73 m² body surface area) and is not recommended in other patients.
The simultaneous use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Other conditions stimulating RAAS (for a dose of 320 mg)
For patients whose renal function may depend on RAAS activity (e.g., patients with severe congenital heart failure), treatment with ACE inhibitors is associated with the manifestation of oliguria and/or progressive azotemia and, in rare cases, with acute renal failure and/or death. Since valsartan is an ARB II, it cannot be excluded that its use may be associated with renal function impairment.
Children and adolescents aged 6 to 18 years
Renal impairment
In patients aged 6 to 18 years with renal impairment and CC less than 30 ml/min, as well as in patients on hemodialysis, the use of valsartan has not been studied; therefore, the use of Valsartan Medisorb in this patient group is not recommended. In patients aged 6 to 18 years with CC greater than 30 ml/min, dose adjustment is not required. During treatment with Valsartan Medisorb, renal function and potassium levels in plasma should be closely monitored. These precautions should be particularly observed when taking valsartan in the context of elevated temperature or decreased CBV, as renal function impairment may develop in such cases.
Liver impairment
As with adult patients, the use of Valsartan Medisorb is contraindicated for patients aged 6 to 18 years with severe liver impairment, biliary cirrhosis, and cholestasis. Experience with valsartan in patients with mild to moderate liver impairment is limited. The dose should not exceed 80 mg in this patient group.
Effect on the ability to drive vehicles and operate machinery
Since therapy with the drug may lead to adverse effects such as dizziness or syncope, patients taking valsartan should exercise caution when driving vehicles and engaging in potentially hazardous activities.

In patients with arterial hypertension, the frequency of adverse events in controlled clinical studies was comparable to placebo. There is no data on the dependence of the frequency of any adverse events on dosage or duration of treatment, as well as on sex, age, or race. The safety profile of valsartan in patients with arterial hypertension aged 6 to 18 years did not differ from the safety profile of valsartan in adult patients.
Below are the adverse events observed during clinical studies and in clinical practice.
The frequency of side effects was assessed as follows: very common (≥1/10); common (≥1/100,

Symptoms: in case of overdose, the main manifestation is a pronounced decrease in blood pressure, which may lead to consciousness suppression, collapse, and/or shock.
Treatment: symptomatic, the nature of which depends on the time elapsed since the drug was taken and the severity of symptoms.
In case of accidental overdose, induce vomiting (if the drug was taken recently) or perform gastric lavage. In the event of a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution is necessary; the patient should be laid down with legs elevated for the required duration of therapy, and active measures should be taken to support cardiovascular function, including regular monitoring of heart and respiratory activity, circulating blood volume, and urine output. It is unlikely that valsartan can be removed from the body by hemodialysis.

It has been established that there are no clinically significant interactions with the following medications when valsartan is used as monotherapy: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
Double blockade of the RAAS when using ARBs, ACE inhibitors, or aliskiren
Simultaneous use of ARBs with medications containing aliskiren is contraindicated in patients with diabetes and/or moderate to severe renal impairment (GFR less than 60 ml/min/1.73 m² body surface area) and is not recommended for other patients.
Simultaneous use of ARBs with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended for other patients.
Simultaneous use of ARBs, including valsartan, with other medications affecting the RAAS is associated with an increased frequency of arterial hypotension, hyperkalemia, and renal function impairment compared to monotherapy. Monitoring of blood pressure, renal function, and electrolyte levels is recommended for patients taking valsartan and other medications affecting the RAAS.
Non-steroidal anti-inflammatory drugs (NSAIDs)
When used simultaneously with NSAIDs (including selective COX-2 inhibitors), a reduction in the antihypertensive effect of valsartan may occur. The use of ARBs simultaneously with NSAIDs may lead to worsening of renal function and increased plasma potassium levels. If simultaneous use of valsartan and NSAIDs is necessary, renal function should be assessed and any water-electrolyte balance disorders corrected before starting therapy.
Transport proteins
According to in vitro studies on liver cultures, valsartan is a substrate for the transport proteins OAT1B1 and MRP2. Simultaneous use of valsartan with inhibitors of the OAT1B1 transport protein (rifampicin, cyclosporine) and with the MRP2 transport protein inhibitor (ritonavir) may increase the systemic exposure of valsartan (Cmax and AUC).
Lithium preparations:
Simultaneous use of ACE inhibitors and ARBs with lithium preparations is associated with a reversible increase in serum lithium levels and an enhancement of its toxic effects; therefore, monitoring of serum lithium levels is recommended. The risk of toxic effects associated with the use of lithium preparations may be further increased when used simultaneously with valsartan and diuretics.
Potassium preparations and medications that can increase potassium levels
Simultaneous use of potassium-sparing diuretics (including spironolactone, eplerenone, triamterene, amiloride), potassium preparations or salts containing potassium, as well as other medications that can increase potassium levels (e.g., heparin, etc.) may lead to increased serum potassium levels and, in patients with heart failure, to increased plasma creatinine concentrations. If such combined treatment is deemed necessary, caution should be exercised, and regular monitoring of plasma potassium levels should be conducted.
Use in children and adolescents aged 6 to 18 years
In children and adolescents, arterial hypertension is often associated with renal function impairment. Caution is recommended when using valsartan simultaneously with other medications affecting the RAAS in this patient group, as this may lead to increased serum potassium levels. Regular monitoring of renal function and serum potassium levels should be conducted in patients in this group.

Valsartan is an active specific angiotensin II receptor antagonist (ARA) intended for oral administration. It selectively blocks AT1 subtype receptors, which are responsible for the effects of angiotensin II. The blockade of AT1 receptors results in an increase in plasma concentrations of angiotensin II, which may stimulate unblocked AT2 receptors. Valsartan has no significant agonistic activity towards AT1 receptors. The affinity of valsartan for AT1 receptors is approximately 20,000 times higher than for AT2 receptors. Valsartan does not interact with or block receptors of other hormones or ion channels that are important in regulating cardiovascular function.

The likelihood of developing a cough when using valsartan is very low, which is associated with the lack of effect on angiotensin-converting enzyme (ACE), responsible for the degradation of bradykinin. A comparison of valsartan with an ACE inhibitor showed that the incidence of dry cough was significantly (p < 0.05) lower in patients receiving valsartan than in those receiving the ACE inhibitor (2.6% vs. 7.9%, respectively). In the group of patients who previously developed a dry cough while being treated with an ACE inhibitor, this complication was noted in 19.5% of cases when treated with valsartan, and in 19.0% of cases when treated with a thiazide diuretic, while in the group receiving ACE inhibitor treatment, cough was observed in 68.5% of cases (p < 0.05).Use in arterial hypertension in patients over 18 years old When treating patients with arterial hypertension with valsartan, a decrease in blood pressure (BP) is observed, without changes in heart rate (HR). After oral administration of a single dose of the drug, the onset of antihypertensive action is noted within 2 hours for most patients, and maximum BP reduction is achieved within 4-6 hours. After taking the drug, the antihypertensive effect lasts for more than 24 hours. With repeated administration of the drug, maximum BP reduction, regardless of the dose taken, is usually achieved within 2-4 weeks and is maintained at that level during long-term therapy. In the case of combining the drug with hydrochlorothiazide, a significant additional reduction in BP is achieved.Abrupt discontinuation of valsartan is not accompanied by a sharp increase in BP or other adverse events. In patients with arterial hypertension, type 2 diabetes, and nephropathy taking valsartan at a dose of 160-320 mg, a significant reduction in proteinuria (36-44%) is noted.Use after acute myocardial infarction in patients over 18 years old When the drug is used for 2 years in patients who started treatment between 12 hours and 10 days after an acute myocardial infarction (complicated by left ventricular failure and/or left ventricular systolic dysfunction), reductions in overall mortality, cardiovascular mortality, and an increase in the time to first hospitalization due to exacerbation of chronic heart failure, recurrent myocardial infarction, sudden cardiac arrest, and stroke (without fatal outcome) are observed. The safety profile of valsartan in patients with acute myocardial infarction is similar to that in other conditions.Chronic heart failure (CHF) in patients over 18 years old When valsartan (at an average daily dose of 254 mg) is used for 2 years in patients with CHF functional classes II (62%), III (36%), and IV (2%) according to the NYHA classification with left ventricular ejection fraction (LVEF) less than 40% and internal diastolic diameter of the left ventricle greater than 2.9 cm/m², receiving standard therapy including ACE inhibitors (93%), diuretics (86%), digoxin (67%), and beta-blockers (36%), a significant reduction (by 27.5%) in the risk of hospitalization due to exacerbation of CHF is noted.In patients not receiving ACE inhibitors, a significant reduction in overall mortality (by 33%), cardiovascular mortality, and morbidity related to CHF (time to the first cardiovascular event) is observed, evaluated by the following indicators: death, sudden death with resuscitation, hospitalization due to exacerbation of CHF, intravenous administration of inotropic or vasodilator drugs for 4 or more hours without hospitalization (by 44%). In the group of patients receiving ACE inhibitors (without beta-blockers), no reduction in overall mortality is observed during valsartan treatment; however, cardiovascular mortality and morbidity related to CHF decrease by 18.3%.Overall, the use of valsartan leads to a reduction in the number of hospitalizations due to CHF, slowing the progression of CHF, improving the functional class of CHF according to the NYHA classification, increasing the severity of signs and symptoms of heart failure, and improving quality of life compared to placebo.Use in patients over 18 years old with arterial hypertension and impaired glucose tolerance When valsartan and lifestyle changes are used, a statistically significant reduction in the risk of developing diabetes is noted in this category of patients. Valsartan had no effect on the frequency of fatal outcomes due to cardiovascular events, myocardial infarction, and non-fatal ischemic attacks, on hospitalizations due to heart failure or unstable angina, arterial revascularization, in patients with impaired glucose tolerance and arterial hypertension, differing by age, sex, and race.In patients receiving valsartan, the risk of developing microalbuminuria was significantly lower than in patients not receiving this therapy. The recommended starting dose of valsartan in patients with arterial hypertension and impaired glucose tolerance is 80 mg once daily. If necessary, the dose may be increased to 160 mg.Use in children and adolescents aged 6 to 18 years with arterial hypertension In children and adolescents aged 6 to 18 years, valsartan provides a dose-dependent, smooth reduction in BP. When valsartan is used, maximum BP reduction, regardless of the dose taken, is usually achieved within 2 weeks and is maintained at that level during long-term therapy.Absorption After oral administration, the maximum concentration (Cmax) of valsartan in 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) decreases by 48%, although starting from approximately 8 hours after administration, the plasma concentration of valsartan is the same whether taken fasting or with food. However, the reduction in AUC is not accompanied by a clinically significant decrease in therapeutic effect, so valsartan can be taken regardless of the timing of meals. Distribution The volume of distribution (Vd) of valsartan at steady state after intravenous administration was about 17 L, indicating a lack of significant distribution of valsartan in tissues. Valsartan is largely bound to serum proteins (94-97%), primarily to albumins. Metabolism Valsartan is not significantly metabolized, with only about 20% of the orally administered dose excreted as metabolites. The hydroxyl metabolite is detected in plasma at low concentrations (less than 10% of valsartan AUC). This metabolite is pharmacologically inactive. Excretion Valsartan is excreted in a biphasic manner: the α-phase with a half-life (T1/2α) of less than 1 hour and the β-phase with a T1/2β of about 9 hours. Valsartan is primarily excreted unchanged through the intestines (about 83%) and kidneys (about 13%). After intravenous administration, the plasma clearance of valsartan is about 2 L/h, and its renal clearance is 0.62 L/h (about 30% of total clearance). The T1/2 of valsartan is 6 hours. Pharmacokinetics in Special Patient Groups Patients with CHF: In this patient group, the achievement of Cmax and T1/2 is similar to that in healthy volunteers. The increase in AUC and Cmax is directly proportional to the increase in the dose of the drug (from 40 mg to 160 mg twice daily). The accumulation factor averages 1.7. After oral administration, the clearance of valsartan was approximately 4.5 L/h. The age of patients with CHF did not affect the clearance of valsartan. Patients over 65 years old: In some patients over 65 years old, the systemic bioavailability of valsartan is higher than that in younger patients; however, this is not clinically significant. Patients with renal impairment: There is no correlation between renal function and systemic bioavailability of valsartan. In patients with renal impairment and a glomerular filtration rate greater than 10 mL/min, dose adjustment is not required. Currently, there is no data on the use in patients undergoing hemodialysis. Valsartan has a high degree of binding to plasma proteins, so its removal by hemodialysis is unlikely. Patients with hepatic impairment: In patients with mild to moderate hepatic impairment, the bioavailability (AUC) of valsartan is increased twofold compared to healthy volunteers. However, there is no correlation between valsartan AUC values and the degree of hepatic impairment. The use of the drug in patients with severe hepatic impairment has not been studied. Patients aged 6 to 18 years The pharmacokinetic properties of valsartan in children and adolescents aged 6 to 18 years do not differ from those in patients over 18 years old.