Valz (Tablets) Instructions for Use

ATC Code

C09CA03 (Valsartan)

Active Substance

Valsartan (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Angiotensin II receptor antagonist

Pharmacotherapeutic Group

Angiotensin II receptor antagonist

Pharmacological Action

Valsartan is an active, specific angiotensin II receptor antagonist intended for oral administration. It selectively blocks the AT₁ receptor subtype, which is responsible for the effects of angiotensin II. The consequence of AT₁ receptor blockade is an increase in the plasma concentration of angiotensin II, which may stimulate unblocked AT₂ receptors. Valsartan does not have any significant agonistic activity towards AT₁ receptors. The affinity of valsartan for the AT₁ receptor subtype is approximately 20,000 times higher than for the AT₂ receptor subtype.

There are no data indicating that Valsartan interacts with or blocks other hormone receptors or ion channels that are important in the regulation of cardiovascular function.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and causes the degradation of bradykinin; this reduces the likelihood of cough occurring when taking Valz.

In comparative clinical studies of valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower (p<0.05) in patients receiving Valsartan (in 2.6% of patients receiving Valsartan, and in 7.9% receiving an ACE inhibitor). In a clinical study, the incidence of dry cough with valsartan and a thiazide diuretic in patients with dry cough during previous ACE inhibitor therapy was 19.5% and 19.0%, respectively, compared to 68.5% of patients who received an ACE inhibitor (p<0.05).

Use for arterial hypertension in patients over 18 years of age

Treatment of patients with arterial hypertension with valsartan results in a reduction in blood pressure, not accompanied by a change in heart rate.

After a single oral dose of the drug, the onset of the antihypertensive effect is observed within 2 hours in most patients, and the maximum reduction in blood pressure is achieved within 4-6 hours, persisting for more than 24 hours. With repeated use of the drug, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy. A significant additional reduction in blood pressure is achieved with the simultaneous use of the drug with hydrochlorothiazide.

Abrupt discontinuation of valsartan is not accompanied by a significant increase in blood pressure or other adverse reactions (AR). 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 of age

When valsartan is used for 2 years in patients who started taking it within 12 hours to 10 days after an acute myocardial infarction (complicated by left ventricular failure and/or left ventricular systolic dysfunction), it reduces the rates of all-cause mortality, cardiovascular mortality and increases the time to first hospitalization due to worsening of chronic heart failure (CHF), recurrent myocardial infarction, sudden cardiac arrest and stroke (non-fatal). 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 of age

When valsartan (at an average daily dose of 254 mg) was used for 2 years in patients with CHF of functional class II (62%), III (36%) and IV (2%) according to the NYHA classification with a left ventricular (LV) ejection fraction of less than 40% and an internal LV diastolic diameter of more than 2.9 cm/m², receiving standard therapy, including ACE inhibitors (93%), diuretics (86%), digoxin (67%) and beta-blockers (36%), a significant reduction in the all-cause mortality rate (by 33%), cardiovascular mortality and morbidity associated with CHF (time to first cardiovascular event) was observed, which were assessed by the following indicators: death, sudden death with resuscitation, hospitalization due to worsening 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 all-cause mortality was observed against the background of valsartan treatment, but the rates of cardiovascular mortality and morbidity associated with CHF were reduced by 18.3%.

Overall, the use of valsartan leads to a reduction in the number of hospitalizations for CHF, a slowing of the progression of CHF, an improvement in the NYHA functional class of CHF, an increase in left ventricular ejection fraction, as well as a reduction in the severity of signs and symptoms of heart failure and an improvement in quality of life compared to placebo.

Use in patients over 18 years of age with arterial hypertension and impaired glucose tolerance

When using valsartan and lifestyle changes, a statistically significant reduction in the risk of developing diabetes mellitus was observed in this category of patients. Valsartan did not affect 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 in age, sex and race.

Use in children and adolescents from 6 to 18 years of age for arterial hypertension

In children and adolescents from 6 to 18 years of age, Valsartan provides a dose-dependent, smooth reduction in blood pressure. When using valsartan, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2 weeks and is maintained at the achieved level during long-term therapy.

Pharmacokinetics

Absorption

After oral administration of the drug, the C_max of valsartan in plasma is reached within 2-4 hours. The mean value of absolute bioavailability is 23%. When valsartan is taken with food, the AUC decreases by 48%, although, starting from approximately the 8th hour after drug administration, the plasma concentrations of valsartan are the same both when taken on an empty stomach and when taken with food. However, the decrease in AUC is not accompanied by a clinically significant reduction in the therapeutic effect, so Valsartan can be taken regardless of meal time.

Distribution

The V_d of valsartan at steady state after intravenous administration was about 17 L, indicating no significant distribution of valsartan into tissues. Valsartan is largely bound to serum proteins (94-97%), mainly albumin.

Metabolism

Valsartan is not subject to significant metabolism (about 20% of the orally administered dose is determined as metabolites). The hydroxyl metabolite is detected in plasma at low concentrations (less than 10% of the AUC of valsartan). This metabolite is pharmacologically inactive.

Excretion

Valsartan is excreted in two phases: an alpha-phase with a T_1/2 of less than 1 hour and a beta-phase with a T_1/2 of about 9 hours. Valsartan is excreted mainly unchanged through the intestines (about 83%) and by the 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 T_1/2 of valsartan is 6 hours.

Pharmacokinetics in specific patient groups

Patients with CHF

In this category of patients, the time to reach C_max and T_1/2 are similar to those in healthy volunteers. The increase in AUC and C_max is directly proportional to the increase in the drug dose (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 of age

In some patients over 65 years of age, the systemic bioavailability of valsartan is higher than in younger patients, but this has not been found to have any clinical significance.

Patients with impaired renal function

There is no correlation between renal function and the systemic bioavailability of valsartan. In patients with impaired renal function and a creatinine clearance of more than 10 ml/min, no dose adjustment of the drug is required. There are currently no data on use in patients on hemodialysis. Valsartan is highly bound to plasma proteins, so its removal by hemodialysis is unlikely.

Patients with impaired liver function

In patients with mild to moderate hepatic impairment, the bioavailability (AUC) of valsartan is doubled compared to healthy volunteers. However, no correlation is observed between the AUC values of valsartan and the degree of hepatic impairment. The use of the drug in patients with severe hepatic impairment has not been studied.

Patients from 6 to 18 years of age

The pharmacokinetic properties of valsartan in children and adolescents from 6 to 18 years of age do not differ from the pharmacokinetic properties of valsartan in patients over 18 years of age.

Indications

Adults

• Arterial hypertension;
• Chronic heart failure (NYHA functional class II-IV) in 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 the condition of patients with CHF should include an assessment of renal function;
• To improve survival of patients after acute myocardial infarction, complicated by left ventricular failure and/or left ventricular systolic dysfunction, in the presence of stable hemodynamic parameters.

Children and adolescents

• Arterial hypertension in children and adolescents from 6 to 18 years of age.

ICD codes

Dosage Regimen

Tablets

The drug is taken orally regardless of meal time. The tablets should be swallowed without chewing, with water.

Adults

Arterial hypertension

The drug may be prescribed at a dose of 80 mg, 160 mg, 320 mg.

The recommended initial dose of Valz is 80 mg once daily, regardless of the patient’s race, age and sex. The antihypertensive effect is noted within the first 2 weeks of treatment; the maximum effect develops after 4 weeks. For those patients in whom an adequate therapeutic response is not achieved, the daily dose of Valz can be increased to 160 mg, and also to the maximum daily dose of 320 mg; diuretic agents may be additionally prescribed.

Chronic heart failure

The drug may be prescribed at a dose of 40 mg, 80 mg, 160 mg.

The recommended initial dose of Valz is 40 mg twice daily. The dose of the drug 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 is 320 mg in 2 divided doses. This may require a reduction in the dose of concurrently used diuretics. Assessment of the condition of patients with CHF should include an assessment of renal function.

Improving survival of patients after myocardial infarction

The drug may be prescribed at a dose of 40 mg, 80 mg, 160 mg.

Treatment is started within 12 hours after myocardial infarction with an initial dose of 20 mg (1/2 tab. of 40 mg) twice daily, followed by an increase in dose (40 mg, 80 mg, 160 mg twice daily) over the next few weeks, until the target dose of 160 mg twice daily is reached.

Achieving a dose of 80 mg twice daily is recommended by the end of the 2nd week of treatment. Achieving the maximum target dose of 160 mg twice daily is recommended by the end of the 3rd month of therapy with Valz. Dose escalation depends on drug tolerance during the dose titration period.

In case of development of arterial hypotension accompanied by clinical manifestations, or impaired renal function, a dose reduction should be considered.

Assessment of the condition of patients in the period after myocardial infarction should include an assessment of renal function. The maximum daily dose is 320 mg in 2 divided doses.

Dose adjustment in elderly patients (over 65 years) is not required.

In patients with impaired renal function with creatinine clearance greater than 10 ml/min, no dose adjustment is required. Concurrent use of valsartan with aliskiren is contraindicated in patients with impaired renal function (eGFR <60 ml/min/1.73 m²). There are currently no data on the use of the drug in patients with creatinine clearance less than 10 ml/min.

Concurrent use of Valz with aliskiren is contraindicated in patients with type 2 diabetes.

In patients with mild to moderate non-biliary hepatic impairment without cholestasis, the drug should be used with caution, the daily dose should not exceed 80 mg. The use of Valz is contraindicated in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis.

Children and adolescents

Arterial hypertension

The recommended initial dose of Valz in children and adolescents aged 6 to 18 years is 40 mg once daily for a child’s body weight less than 35 kg and 80 mg once daily for a child’s body weight greater than 35 kg. The dose should be adjusted based on blood pressure reduction.

Maximum recommended daily doses are shown in the table below. The use of the drug in higher doses is not recommended.

Valz is not recommended for the treatment of CHF and after acute myocardial infarction in patients under 18 years of age.

The use of the drug has not been studied in patients aged 6 to 18 years with impaired renal function with creatinine clearance <30 ml/min, as well as in patients on hemodialysis, therefore its use in this group of patients is not recommended. In patients aged 6 to 18 years with creatinine clearance greater than 30 ml/min, no dose adjustment is required. During treatment with Valz, renal function and serum potassium levels should be carefully monitored.

As for adult patients, the use of Valz is contraindicated for patients aged 6 to 18 years with severe hepatic impairment, biliary cirrhosis and cholestasis. Experience with the use of valsartan in patients with mild to moderate hepatic impairment is limited. A dose of 80 mg should not be exceeded in this group of patients.

Adverse Reactions

In patients with arterial hypertension in controlled clinical studies, the frequency of adverse reactions (AR) was comparable to placebo. There are no data on the dependence of the frequency of any AR on the dose or duration of treatment, or on the sex, age or race of the patient. The safety profile of Valz in patients with arterial hypertension aged 6 to 18 years does not differ from the safety profile of valsartan in adult patients.

The following ARs have been observed in clinical studies, as well as during the use of the drug in clinical practice.

The following criteria were used to assess the frequency of adverse reactions: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, but <1/1000); very rare (<1/10,000), including isolated reports. Within each frequency group, ARs are presented in order of decreasing importance.

For all ARs identified in clinical practice and in the analysis of laboratory parameters (the frequency of which cannot be determined), the gradation “frequency unknown” was used.

*an increase in serum potassium concentration (frequency unknown) was noted based on post-marketing studies.

Also, in the course of clinical studies of valsartan in patients after acute myocardial infarction and/or with CHF, the following ARs were observed, for which a causal relationship with its intake has not been established: arthralgia, abdominal pain, back pain, asthenia, insomnia, decreased libido, neutropenia, peripheral edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infections, viral infections.

If any of the adverse reactions listed in the instructions worsen, or any other adverse reactions not listed in the instructions are noticed, you should inform your doctor.

Contraindications

• Hypersensitivity to any of the components of the drug;
• Pregnancy;
• Breastfeeding period;
• Severe hepatic impairment (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis;
• Age under 6 years – for the indication of arterial hypertension;
• Age under 18 years – for other indications;
• Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR less than 60 ml/min/1.73 m² body surface area);
• Concomitant use with ACE inhibitors in patients with diabetic nephropathy;
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the drug contains lactose monohydrate).

With caution

Special caution should be exercised when using the drug in patients with hereditary angioedema, or angioedema during previous therapy with angiotensin II receptor antagonists (ARAs) or ACE inhibitors. Use with caution in bilateral renal artery stenosis; stenosis of the artery of a solitary kidney; primary hyperaldosteronism; when following a diet with restricted salt intake; in conditions accompanied by sodium deficiency in the body and/or reduced blood volume (including diarrhea and vomiting); in patients with creatinine clearance less than 10 ml/min, in patients aged 6 to 18 years with creatinine clearance less than 30 ml/min, including those on hemodialysis; with mild and moderate hepatic impairment of biliary and non-biliary origin without cholestasis (< 9 points on the Child-Pugh scale), in patients with CHF functional class III-IV (NYHA), whose renal function depends on the state of the RAAS, with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, and in patients after kidney transplantation. Exercise caution with concomitant use of ARAs, including Valz, with other agents blocking the RAAS, such as ACE inhibitors or aliskiren.

Use in Pregnancy and Lactation

Pregnancy

Risk Summary

As with any other drug affecting the RAAS, the use of Valz is contraindicated during pregnancy. Given the mechanism of action of ARAs, a risk to the fetus cannot be excluded. It is known that the use of ACE inhibitors (a specific class of drugs acting on the RAAS) in the second and third trimesters of pregnancy leads to fetal injury and death. According to retrospective analysis, the use of ACE inhibitors in the first trimester of pregnancy is associated with a potential risk of fetal malformations. Cases of spontaneous abortion, oligohydramnios, and impaired renal function in newborns have been described with unintentional use of valsartan during pregnancy. If pregnancy is diagnosed during treatment with Valz, the drug should be discontinued as soon as possible.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Hypertension in pregnancy increases the risk of preeclampsia, gestational diabetes, preterm delivery, and delivery complications (e.g., need for cesarean section, development of postpartum hemorrhage). With hypertension, the risk of intrauterine growth retardation and intrauterine fetal death increases.

Fetal/Neonatal Adverse Reactions

Oligohydramnios in pregnant women taking drugs affecting the RAAS in the second and third trimesters can lead to impaired fetal renal function, resulting in anuria and renal failure, fetal lung hypoplasia, fetal skeletal deformations, including skull hypoplasia, arterial hypotension, and fetal death.

In case of unintentional use of ARA drugs during pregnancy, consideration should be given to appropriate fetal monitoring.

Newborns whose mothers were treated with ARAs should be closely observed for the development of arterial hypotension.

Valsartan

In studies of embryo-fetal development in mice, rabbits, and rats, fetotoxicity was observed, which was associated with maternal toxicity in rats when valsartan was administered at a daily dose of 600 mcg/kg/day, which is approximately 18 times the maximum recommended human daily dose based on mg/kg body weight (calculation assumes a daily dose of 320 mg orally for a patient weighing 60 kg), and in rabbits when valsartan was administered at a daily dose of 10 mg/kg, which is approximately 0.6 times the maximum recommended human daily dose based on mg/kg body weight (calculation assumes a daily dose of 320 mg orally for a patient weighing 60 kg). No maternal toxicity or fetotoxicity was observed in mice at daily doses up to 600 mg/kg, which is approximately 9 times the maximum recommended human daily dose based on mg/kg body weight (calculation assumes a daily dose of 320 mg orally for a patient weighing 60 kg).

Breastfeeding

It is not known whether valsartan passes into breast milk. Preclinical studies have shown that valsartan is excreted in the milk of lactating rats. The use of the drug during breastfeeding is contraindicated.

Patients of Reproductive Potential

As with any other drug that has a direct effect on the RAAS, Valz should not be prescribed to women planning pregnancy. When choosing any drug affecting the RAAS, the physician should inform the female patient of reproductive potential about the potential risk of using the drug during pregnancy.

Fertility

There are no data on the effect of the drug on human fertility. In animal studies, no effects of valsartan on fertility were observed.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis.

In patients with mild to moderate hepatic impairment of non-biliary origin without cholestasis, the drug should be used with caution, the daily dose should not exceed 80 mg.

Use in Renal Impairment

In patients with renal impairment, no dose adjustment of the drug is required. Currently, there are no data on the use of the drug in patients with a creatinine clearance rate of less than 10 ml/min, so it should be prescribed with caution.

Pediatric Use

Contraindicated in children under 6 years of age for the indication of arterial hypertension; for other indications, contraindicated under 18 years of age.

Geriatric Use

No dose adjustment is required in elderly patients.

Special Precautions

Patients with Renal Impairment

Concomitant use of angiotensin II receptor antagonists, including Valz, or ACE inhibitors with aliskiren and drugs containing aliskiren should be avoided in patients with diabetes mellitus and moderate to severe renal impairment (GFR <60 ml/min/1.73 m²).

Hyperkalemia

When used concomitantly with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that may cause an increase in blood potassium levels (e.g., heparin), caution should be exercised and regular monitoring of blood potassium levels should be performed.

Kidney Transplantation

There are no data on the safety of Valz in patients who have undergone kidney transplantation.

Sodium Deficiency and/or Reduced Blood Volume

In patients with severe sodium deficiency and/or reduced blood volume, for example, those receiving high doses of diuretics, arterial hypotension accompanied by clinical manifestations may rarely develop at the beginning of treatment with the drug. Before starting treatment with Valz, sodium levels in the body should be corrected and/or blood volume should be replenished, including by reducing the dose of the diuretic.

In case of a pronounced decrease in blood pressure, the patient should be placed in a supine position with legs elevated, and if necessary, intravenous infusion of 0.9% sodium chloride solution should be performed.

After blood pressure stabilizes, treatment with Valz can be continued.

Renal Artery Stenosis

Short-term use of the drug in patients with renovascular hypertension secondary to unilateral stenosis of the artery of a solitary kidney does not lead to any significant changes in renal hemodynamics, serum creatinine concentration, or blood urea nitrogen. However, since other drugs affecting the RAAS may cause an increase in serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney, monitoring of these parameters is recommended as a precaution.

Primary Hyperaldosteronism

The drug is not effective for the treatment of arterial hypertension in patients with primary hyperaldosteronism, since activation of the RAAS is not noted in this category of patients.

CHF/Post-Myocardial Infarction Period

In patients with CHF or after myocardial infarction starting treatment with Valz, some decrease in blood pressure is often observed, therefore blood pressure monitoring is recommended at the beginning of therapy. Provided that the dosing regimen recommendations are followed, it is usually not necessary to discontinue Valz due to arterial hypotension. Assessment of patients with CHF should include assessment of renal function.

Due to inhibition of the RAAS, some patients may experience impaired renal function. In patients with CHF functional class III-IV according to the NYHA classification, whose renal function depends on the state of the RAAS, treatment with ACE inhibitors and angiotensin II receptor antagonists may be accompanied by oliguria and/or increased azotemia and, in rare cases, the development of acute renal failure and/or death. Therefore, in these categories of patients, renal function should be assessed before using Valz and periodically during treatment with the drug.

Combination Therapy for Arterial Hypertension

For arterial hypertension, Valz can be used in monotherapy, as well as in combination with other antihypertensive agents, in particular, with diuretics.

Combination Therapy in the Post-Myocardial Infarction Period

Valz can be used in combination with other drugs used after myocardial infarction, namely thrombolytics, acetylsalicylic acid as an antiplatelet agent, beta-blockers and HMG-CoA reductase inhibitors. In this category of patients, it is not recommended to use Valz simultaneously with ACE inhibitors, since this combination therapy does not have advantages over monotherapy with valsartan or an ACE inhibitor in terms of all-cause mortality.

Combination Therapy for CHF

For CHF, Valz can be used both in monotherapy and simultaneously with other agents – diuretics, cardiac glycosides, as well as ACE inhibitors or beta-blockers.

In this category of patients, triple combination therapy with an ACE inhibitor, a beta-blocker and Valz is not recommended.

Angioedema, including Quincke’s Edema

Angioedema, including laryngeal and glottis edema leading to airway obstruction, and/or edema of the face, lips, pharynx and/or tongue, has occurred in patients receiving valsartan; some of these patients had previously experienced angioedema while taking other drugs, including ACE inhibitors. Administration of Valz in case of angioedema development should be immediately discontinued; resumption of Valz is prohibited.

Hepatic Impairment

Valsartan is primarily excreted unchanged via the intestine with bile, while amlodipine is extensively metabolized in the liver. Caution should be exercised when using Valz in patients with liver diseases (especially obstructive biliary tract diseases) accompanied by hepatic impairment.

Patients with Left Ventricular Outflow Tract Obstruction (Mitral Stenosis, Aortic Stenosis, or Hypertrophic Obstructive Cardiomyopathy)

Special caution should be exercised when using Valz in patients suffering from aortic stenosis, mitral stenosis or hypertrophic obstructive cardiomyopathy.

Dual Blockade of the RAAS

Concomitant use with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR <60 ml/min/1.73 m²) and is not recommended in other patients.

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

Dual blockade of the RAAS by simultaneous use of an ACE inhibitor, ARA II, or aliskiren is not recommended in the general population. However, if combination therapy with these drugs is absolutely necessary, such use should be carried out under close medical supervision, with frequent monitoring of blood pressure, renal function, and plasma electrolyte levels.

Effect on Ability to Drive and Operate Machinery

Since adverse reactions such as dizziness or fainting may develop during therapy, patients taking Valz should exercise caution when driving vehicles and engaging in other potentially hazardous activities.

Overdose

Symptoms of Valz overdose are primarily manifested by a pronounced decrease in blood pressure, which can lead to depression of consciousness, collapse and/or shock.

Treatment is symptomatic, the nature of which depends on the time elapsed since drug intake and the severity of symptoms.

In case of accidental overdose, vomiting should be induced (if the drug was taken recently) or gastric lavage should be performed. In case of a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution is necessary as therapy; the patient should be placed in a supine position with legs elevated for the necessary period of therapy, taking active measures to maintain cardiovascular system activity, including regular monitoring of heart and respiratory system activity, circulating blood volume (CBV) and urine output.

Drug Interactions

No clinically significant interactions have been established with valsartan monotherapy with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.

Dual Blockade of the RAAS with Angiotensin II Receptor Antagonists, ACE Inhibitors, or Aliskiren

Concomitant use of angiotensin II receptor antagonists, including Valz, with other agents affecting the RAAS is associated with an increased incidence of arterial hypotension, hyperkalemia, and changes in renal function compared with monotherapy. It is recommended to monitor blood pressure, renal function, and electrolyte levels in patients taking Valz and other drugs affecting the RAAS.

In children and adolescents, arterial hypertension is often associated with renal impairment. It is recommended to use valsartan with caution simultaneously with other drugs affecting the renin-angiotensin-aldosterone system in patients of this category, as this may lead to an increase in serum potassium levels. Regular monitoring of renal function and serum potassium levels should be performed in patients of this group.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

When valsartan is used concomitantly with NSAIDs (including selective COX-2 inhibitors), a reduction in its antihypertensive effect is possible. When angiotensin II receptor antagonists are used concomitantly with NSAIDs, deterioration of renal function and an increase in plasma potassium levels are possible. If concomitant use of valsartan and NSAIDs is necessary, renal function should be assessed and water-electrolyte balance disorders should be corrected before starting treatment.

Transporter Proteins

According to in vitro studies on liver cultures, valsartan is a substrate for the transporter proteins OATP1B1 and MRP2. When valsartan is used concomitantly with inhibitors of the OATP1B1 transporter protein (rifampicin, cyclosporine) and with an inhibitor of the MRP2 transporter protein (ritonavir), the systemic exposure to valsartan (C_max and AUC) may increase.

Lithium Preparations

When lithium preparations are used concomitantly with ACE inhibitors and ARAs, a reversible increase in serum lithium levels and, consequently, an increase in toxic manifestations have been observed, therefore monitoring of serum lithium levels is recommended. The risk of toxic manifestations associated with the use of lithium preparations may be further increased with concomitant use of Valz and diuretics.

Drugs That May Lead to an Increase in Plasma Potassium Levels

Concomitant use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salts containing potassium, as well as other drugs that can increase potassium levels (e.g., heparin, etc.), may lead to an increase in serum potassium levels and in patients with heart failure to an increase in serum creatinine concentration. If such combined treatment is deemed necessary, caution should be exercised.

Storage Conditions

The drug should be stored at a temperature not exceeding 30°C (86°F).

Keep out of reach of children!

Shelf Life

Shelf life – 3 years. Do not use after the expiration date stated on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.