Instructions for Vanatex film-coated tablets 80 mg No. 28
Composition
active ingredient: valsartan;
1 film-coated tablet contains 80 or 160 mg of valsartan;
excipients:
core: lactose monohydrate, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate;
tablet coating 80 mg (Mixture for coating the tablets - Type 2): hypromellose, polyethylene glycol, titanium dioxide (E 171), iron oxide red (E 172);
Tablet coating 160 mg (Mixture for coating the tablets - Type 1): hypromellose, polyethylene glycol, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172), black iron oxide (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties: 80 mg tablets: pink, round, biconvex tablets with a score, film-coated;
160 mg tablets: light brown, oblong, biconvex tablets with a score, film-coated.
Pharmacotherapeutic group
Simple angiotensin II antagonists. ATC code C09C A03.
Pharmacological properties
Pharmacodynamics.
Valsartan is an orally active, potent and specific angiotensin II (Ang II) receptor antagonist. It acts selectively on the AT1 receptor subtype, which is responsible for the action of angiotensin II. Increased plasma Ang II levels after blockade of the AT1 receptor with valsartan may stimulate the unblocked AT2 receptor, which is likely to counteract the action of the AT1 receptor. Valsartan does not exhibit partial agonist activity at the AT1 receptor and has a much higher (approximately 20,000-fold) affinity for the AT1 receptor than for the AT2 receptor.
It is not known whether valsartan binds to or blocks other hormone receptors or ion channels known to play an important role in cardiovascular regulation.
Valsartan does not inhibit ACE (also known as kinase II), which converts Ang I to Ang II and destroys bradykinin. Since there is no effect on ACE and no potentiation of bradykinin or protein, angiotensin II antagonists are unlikely to be associated with cough.
Arterial hypertension
Administration of valsartan to patients with arterial hypertension results in a decrease in blood pressure without affecting the pulse rate.
In most patients, after a single oral dose, antihypertensive activity is observed within 2 hours, and the maximum reduction in blood pressure is achieved within 4-6 hours. The hypotensive (antihypertensive) effect is maintained for 24 hours after taking the drug. With repeated doses of the drug, the hypotensive effect is generally maintained for 2 weeks, and the maximum effect is achieved within 4 weeks and is maintained during long-term treatment. In combination with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.
Rapid withdrawal of valsartan is not associated with rebound hypertension or other adverse clinical events.
Recent myocardial infarction
The results of the study demonstrated the efficacy of valsartan, as well as captopril, in reducing overall mortality after myocardial infarction. Valsartan was also effective in reducing cardiovascular mortality, hospitalization for heart failure, and recurrent myocardial infarction. The safety profile of valsartan was consistent with the course of the disease in patients treated after established myocardial infarction.
Heart failure
Patients treated with valsartan demonstrated significant improvement in signs and symptoms of heart failure, including dyspnea, fatigue, edema, and wheezing, compared with those treated with placebo. Patients with chronic heart failure treated with valsartan had better quality of life from baseline to endpoint compared with patients treated with placebo. Ejection fraction was significantly higher in patients treated with valsartan, and left ventricular end-diastolic diameter was significantly reduced from baseline to endpoint compared with patients treated with placebo.
Children
The antihypertensive effect of valsartan was evaluated in 4 randomized, double-blind clinical trials in 561 children aged 6 to 18 years and in 165 children aged 1 to 6 years. Renal and urinary disorders and obesity were the most common underlying medical conditions causing hypertension in the children included in these trials.
Clinical experience in children aged 6 years and over
In a clinical study involving 261 children with hypertension aged 6 to 16 years, patients weighing < 35 kg received 10, 40 or 80 mg of valsartan per day (low, medium and high doses), patients weighing ≥ 35 kg received 20, 80 and 160 mg of valsartan per day (low, medium and high doses). At the end of 2 weeks, valsartan reduced systolic and diastolic blood pressure in a dose-dependent manner. In total, the three valsartan dose levels (low, medium and high) significantly reduced systolic blood pressure by 8, 10, 12 mm Hg from baseline, respectively.
Clinical experience in children under 6 years of age
Valsartan is not recommended for use in this age group.
Pharmacokinetics.
After oral administration of a single dose of valsartan, peak plasma concentrations of valsartan are reached within 2 to 4 hours. The mean absolute bioavailability is 23%. Food reduces the exposure to valsartan (as measured by mean urinary concentration/AUC) by approximately 40% and the maximum plasma concentration (Cmax) by approximately 50%, although plasma concentrations of valsartan are similar in the fed and fasted groups by approximately 8 hours after dosing. However, this reduction in mean urinary concentration is not associated with a clinically significant reduction in therapeutic effect, and valsartan can therefore be administered with or without food.
Distribution
The steady-state volume of distribution of valsartan after intravenous administration is approximately 17 liters, indicating that valsartan is not extensively distributed into tissues. Valsartan is highly bound to serum proteins (94-97%), mainly to serum albumin.
Biotransformation
Valsartan is not completely biotransformed, as only about 20% of the dose is recovered as metabolites. The hydroxymetabolite has been detected in plasma at low concentrations (less than 10% of the mean urinary valsartan concentration). This metabolite is pharmacologically inactive.
Selection
Valsartan exhibits multiexponential decay kinetics (t½α < 1 h and t½β about 9 h). Valsartan is excreted mainly via the biliary tract in the feces (approximately 83% of the dose) and via the kidneys in the urine (approximately 13% of the dose), mainly unchanged. 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 the total clearance). The half-life of valsartan is 6 h.
Patients with heart failure
The mean time to maximum concentration and half-life of valsartan in patients with heart failure are similar to those observed in healthy volunteers. The AUC and Cmax of valsartan are almost dose proportional (the same) over the clinical dose range (40 to 160 mg twice daily). The average accumulation ratio is approximately 1.7. The apparent clearance of valsartan after oral administration is approximately 4.5 l/h. Age does not affect the apparent clearance in patients with heart failure.
Special patient groups
Elderly patients
A somewhat greater systemic exposure to valsartan was observed in some elderly patients than in younger subjects; however, this was not of any clinical significance.
Kidney dysfunction
As expected for a substance whose renal clearance accounts for only 30% of total plasma clearance, no relationship was observed between renal function and systemic exposure to valsartan. Therefore, dose adjustment is not necessary in patients with renal impairment (creatinine clearance > 10 ml/min). There is currently no experience of safe use in patients with creatinine clearance < 10 ml/min or in patients undergoing dialysis, therefore valsartan should be used with great caution in such patients. Valsartan is highly bound to plasma proteins and is unlikely to be removed by dialysis.
Liver failure
Approximately 70% of the absorbed dose is excreted in the bile, mainly unchanged. Valsartan does not undergo any significant biotransformation. A doubling of exposure (AUC) was observed in patients with mild to moderate hepatic impairment compared to healthy volunteers.
However, no relationship was observed between plasma valsartan concentrations and the degree of hepatic dysfunction. Valsartan has not been studied in patients with severe hepatic dysfunction.
Indication
Arterial hypertension
Treatment of arterial hypertension in adults and children aged 6 years and older.
Post-infarction state
Treatment of clinically stable adult patients with symptomatic heart failure or asymptomatic left ventricular systolic dysfunction following a recent (12 hours-10 days) myocardial infarction.
Heart failure
Treatment of symptomatic heart failure in adult patients when angiotensin-converting enzyme (ACE) inhibitors cannot be used, or as adjunctive therapy to ACE inhibitors when beta-blockers cannot be used.
Contraindication
Hypersensitivity to the active substance or to any of the excipients.
Severe liver failure, biliary cirrhosis and cholestasis.
Pregnancy or planning to become pregnant (see section “Use during pregnancy or breastfeeding”).
Concomitant use of angiotensin receptor antagonists or angiotensin-converting enzyme inhibitors with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2).
Interaction with other medicinal products and other types of interactions
Caution should be exercised when using ARBs with other RAAS-blocking drugs, such as ACE inhibitors or aliskiren, due to the potential risk of increased adverse reactions such as hypotension, hyperkalemia and renal dysfunction (including acute renal failure) (see sections "Contraindications" and "Special warnings and precautions for use").
The concomitant use of angiotensin receptor antagonists, including valsartan, or angiotensin-converting enzyme inhibitors with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 ml/min/1.73 m2) (see section 4.3).
Concomitant use is not recommended.
Lithium
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant use of ACE inhibitors. Due to the lack of experience with the concomitant use of valsartan and lithium, this combination is not recommended. If the combination is considered necessary, careful monitoring of serum lithium levels is recommended.
Potassium
Potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium and other medicinal products that may increase potassium levels (heparin) may lead to increases in serum potassium and, in patients with heart failure, to increases in creatinine levels.
If the use of a medicinal product that affects potassium levels in combination with valsartan is considered necessary, monitoring of potassium levels in the blood plasma is recommended.
Caution is required during concomitant use
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid > 3 g/day, and nonselective NSAIDs
When angiotensin II antagonists are used concomitantly with NSAIDs, attenuation of the antihypertensive effect may occur. In addition, concomitant use of angiotensin II antagonists and NSAIDs may lead to deterioration of renal function and an increase in serum potassium. Therefore, monitoring of renal function is recommended at the beginning of treatment, as well as adequate hydration of the patient.
Conveyors
In vitro studies have shown that valsartan is a substrate for the hepatic uptake transporter OATP1B1/OATP1B3 and the hepatic efflux transporter MRP2. The clinical significance of these findings is unknown. Concomitant use of inhibitors of the uptake transporter (e.g. rifampicin, cyclosporine) or efflux transporter (e.g. ritonavir) may increase systemic exposure to valsartan. Appropriate precautions should be taken when initiating or discontinuing concomitant use of these medicinal products.
Others
In drug interaction studies with valsartan, no clinically significant interactions were observed with valsartan or any of the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
Children
Caution is advised when valsartan is co-administered with other agents that inhibit the renin-angiotensin-aldosterone system, which may increase serum potassium levels, in children and adolescents with arterial hypertension. Renal function and serum potassium levels should be closely monitored.
Application features
Hyperkalemia
Concomitant use of potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other agents that may increase potassium levels (heparin) is not recommended. Potassium levels should be monitored if necessary.
Renal impairment. There are currently no data on the safety of the drug in patients with creatinine clearance < 10 ml/min and patients undergoing dialysis, therefore valsartan should be used with caution in such patients. No dose adjustment is required for adult patients with creatinine clearance > 10 ml/min.
The concomitant use of angiotensin receptor antagonists or angiotensin-converting enzyme inhibitors with aliskiren is contraindicated in patients with renal impairment (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2).
Hepatic impairment: Valsartan should be used with caution in patients with mild to moderate hepatic impairment without cholestasis.
Renal artery stenosis. The safety of angiotensin receptor antagonists has not been established in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Short-term administration of valsartan to 12 patients with vasorenal hypertension secondary to unilateral renal artery stenosis did not cause any significant changes in renal haemodynamic parameters, serum creatinine or blood urea nitrogen. Since other medicinal products that affect the renin-angiotensin-aldosterone system (RAAS) may increase blood urea and serum creatinine in patients with unilateral renal artery stenosis, monitoring of renal function is recommended as a precautionary measure during treatment with valsartan.
Kidney transplantation
There are currently no data on the safety of valsartan in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism should not use valsartan because they do not have an activated renin-angiotensin system.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, the drug should be administered with extreme caution to patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.
Pregnancy
Angiotensin II receptor antagonists should not be used during pregnancy. Unless continued therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment should be stopped immediately, and, if appropriate, alternative therapy should be started.
Recent myocardial infarction
The combination of captopril and valsartan did not show any additional clinical benefit, but the risk of adverse reactions was increased compared with that of the respective drugs. Therefore, the combination of valsartan with an ACE inhibitor is not recommended.
Caution should be exercised in patients after myocardial infarction. Evaluation of patients after myocardial infarction should always include assessment of renal function.
The use of valsartan in patients after myocardial infarction often results in some reduction in blood pressure, but there is usually no need to discontinue therapy due to ongoing symptomatic hypotension, provided that the dosage instructions are followed.
Heart failure
In patients with heart failure, the triple combination of an ACE inhibitor, a beta-blocker, and an ARB has not shown any clinical benefit. This combination is likely to increase the risk of adverse effects and is therefore not recommended. Caution should be exercised in patients with heart failure and renal function should always be assessed.
The use of angiotensin receptor antagonists in patients with heart failure often results in some reduction in blood pressure, but there is usually no need to discontinue therapy because of ongoing symptomatic hypotension, provided that the dosage instructions are followed.
In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g. patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and, in isolated cases, with acute renal failure and/or fatal outcome. Since valsartan is an angiotensin II antagonist, it cannot be excluded that the use of the drug may be associated with impaired renal function.
History of angioedema
Angioedema, including laryngeal and glottis edema resulting in airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue, has been reported in patients treated with valsartan; some of these patients had previously experienced angioedema while taking other drugs, including ACE inhibitors. The development of angioedema requires immediate discontinuation of Vanatex, and valsartan should not be re-administered.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
Concomitant use of ARA drugs with other drugs that affect the RAAS is associated with an increased incidence of hypotension, hyperkalemia, and changes in renal function compared with monotherapy. Monitoring of blood pressure, renal function, and electrolytes is recommended in patients receiving valsartan and other drugs that affect the RAAS.
Children
Kidney dysfunction
The concomitant use of angiotensin receptor antagonists or angiotensin-converting enzyme inhibitors with aliskiren is contraindicated in patients with renal impairment (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2).
Liver dysfunction
Valsartan is contraindicated in children with severe hepatic impairment, biliary cirrhosis and cholestasis. There is limited clinical experience with valsartan in children with mild to moderate hepatic impairment. The dose of valsartan should not exceed 80 mg in such patients.
The medicinal product contains lactose, therefore patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Use during pregnancy or breastfeeding
The use of angiotensin II receptor antagonists (ARBs) is contraindicated throughout pregnancy.
Epidemiological data on the risk of teratogenic effects following exposure to ACE inhibitors during the first trimester of pregnancy are inconclusive, but a small increase in risk cannot be excluded. Since there are no controlled epidemiological data on the risk with angiotensin II receptor antagonists, a risk of teratogenic effects may also exist for this class of drugs. Unless continued therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.
It is known that the use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy induces human fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
If AIIRAs have been used from the second trimester of pregnancy, ultrasound examination is recommended to check kidney function and the condition of the skull bones.
The condition of newborns whose mothers used ARAII should be carefully monitored for the development of arterial hypotension.
Due to the lack of information on the use of valsartan during breastfeeding, Vanatex is not recommended for use during this period.
Fertility
Valsartan did not cause adverse reproductive effects in rats at doses up to 200 mg/kg/day. This dose of up to 200 mg/kg/day is 6 times the maximum recommended human dose on a mg/m2 basis (calculations were made for an oral dose of 320 mg/day for a 60 kg patient).
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the effects on the ability to drive have been conducted. When driving vehicles or operating other mechanisms, it should be taken into account that dizziness or fatigue may occasionally occur.
Method of administration and doses
Valsartan can be taken regardless of meals, with water.
Arterial hypertension
The recommended initial dose of valsartan is 80 mg (1 tablet of Vanatex 80 mg or ½ tablet of Vanatex 160 mg) once daily. The antihypertensive effect is achieved within the first 2 weeks, and the maximum effect is observed within 4 weeks.
For some patients whose blood pressure is not adequately controlled, the dose may be increased to 160 mg and a maximum of 320 mg.
Valsartan can be taken with other antihypertensive drugs.
Adding a diuretic such as hydrochlorothiazide further lowers blood pressure in such patients.
Post-infarction state
Treatment of clinically stable patients can be started with valsartan as early as 12 hours after myocardial infarction. After an initial dose of 20 mg twice daily, the dose of valsartan should be increased to 40 mg, 80 mg and 160 mg twice daily over the next few weeks. Vanatex should not be prescribed for initial treatment. For lower dosages (20 mg, 40 mg), a different dosage form should be used.
The target maximum dose is 160 mg twice daily. In general, it is recommended that a dosage level of 80 mg twice daily be reached 2 weeks after initiation of treatment and a maximum dose of 160 mg twice daily be reached after 3 months, taking into account the patient's tolerability of the treatment. If symptomatic hypotension or renal dysfunction occurs, a dose reduction should be considered.
Valsartan can be used in patients who have received other treatments after myocardial infarction, such as thrombolytics, acetylsalicylic acid, beta-blockers, statins and diuretics. Combination with ACE inhibitors is not recommended.
Assessment of patients after myocardial infarction should always include renal function testing.
The recommended starting dose of valsartan is 40 mg twice daily. Vanatex should not be used for initial treatment. For lower doses (40 mg), a different dosage form should be used.
Dose increases to 80 mg and 160 mg twice daily should be made at intervals of at least 2 weeks, based on patient tolerability. Consideration should be given to reducing the dose of concomitant diuretics. The maximum daily dose prescribed was 320 mg in divided doses.
Valsartan can be taken with other medications to treat heart failure.
However, the triple combination of an ACE inhibitor, a beta-blocker, and valsartan is not recommended.
Evaluation of patients with heart failure should always include renal function testing.
Application to specific patient groups
Elderly patients
Elderly patients do not require dose adjustment.
Kidney failure
No dose adjustment is required in adult patients with creatinine clearance > 10 ml/min. The concomitant use of angiotensin receptor antagonists with aliskiren is contraindicated in patients with renal impairment (glomerular filtration rate (GFR) < 60 ml/min/1.73 m2).
Diabetes mellitus
The concomitant use of angiotensin receptor antagonists with aliskiren is contraindicated in patients with diabetes mellitus.
Liver failure
Angiotensin receptor antagonists are contraindicated in patients with severe hepatic impairment, biliary cirrhosis and patients with cholestasis. For patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg.
Children.
Valsartan is indicated for the treatment of hypertension in children aged 6 years and older. The safety and efficacy of angiotensin receptor antagonists in children aged 1 to 6 years have not been established. The drug is not recommended for the treatment of heart failure or post-infarction conditions in children due to a lack of data on safety and efficacy.
Arterial hypertension in children
Children from 6 years old
The initial dose is 40 mg once daily for children weighing less than 35 kg and 80 mg once daily for children weighing 35 kg and above. Vanatex should not be used for initial treatment. For lower doses (40 mg), a different dosage form should be used.
The dose should be adjusted based on blood pressure response. The maximum doses studied in clinical trials are listed in the table below.
Doses higher than those indicated have not been studied.
| Body weight | Maximum dose of valsartan studied in clinical trials |
| From ≥ 18 kg to < 35 kg | 80 mg |
| From ≥ 35 kg to < 80 kg | 160 mg |
| From ≥ 80 kg to ≤ 160 kg | 320 mg |
Children under 6 years old
The safety and efficacy of angiotensin receptor antagonists in children aged 1 to 6 years have not been established.
Use in children aged 6 years and older with renal insufficiency
Use in children with creatinine clearance < 30 ml/min and in children undergoing dialysis has not been studied, therefore valsartan is not recommended for use in such patients. No dose adjustment is required for children with creatinine clearance > 30 ml/min. Renal function and serum potassium levels should be closely monitored.
Use in children aged 6 years and older with hepatic insufficiency
Angiotensin receptor antagonists are contraindicated in children with severe hepatic impairment, biliary cirrhosis and patients with cholestasis. Clinical experience with angiotensin receptor antagonists in children with mild to moderate hepatic impairment is limited. The dose of valsartan should not exceed 80 mg in such patients.
Heart failure and recent myocardial infarction in children
Angiotensin receptor antagonists are not recommended for the treatment of heart failure or recent myocardial infarction in children due to a lack of data on safety and efficacy.
Overdose
Symptoms
Overdose with valsartan may lead to severe hypotension, which may lead to depression of consciousness, vascular collapse and/or shock.
Treatment
Therapeutic measures depend on the time of administration and the type and severity of symptoms; stabilization of blood circulation is of paramount importance. In case of arterial hypotension, the patient should be in a supine position, and it is necessary to correct the volume of circulating blood.
Valsartan is unlikely to be removed by hemodialysis.
Side effects
In controlled clinical trials in adult patients with hypertension, the incidence of adverse reactions with placebo was similar to that with valsartan. The incidence of adverse reactions was not related to dose or duration of treatment, and there was no association with gender, age, or race.
The frequency of adverse reactions is estimated as follows, starting with the most frequent: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/100000), including isolated reports. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
All adverse reactions reported during post-marketing and laboratory studies cannot be assigned to any of the above frequencies and are therefore assigned a frequency of “not known”.
Arterial hypertension
Blood and lymphatic system disorders
Not known: decreased hemoglobin, decreased hematocrit, neutropenia, thrombocytopenia.
On the part of the immune system
Not known: hypersensitivity, including serum sickness.
Metabolism and digestion
Not known: increased serum potassium, hyponatremia.
From the side of the organs of hearing and labyrinth
Uncommon: vertigo.
From the vascular side
Not known: vasculitis.
Respiratory, thoracic and mediastinal disorders
Uncommon: cough.
Gastrointestinal tract
Uncommon: abdominal pain.
Liver and biliary tract disorders
Not known: increased liver function tests, including increased serum bilirubin.
Skin and subcutaneous tissue disorders
Uncommon: angioedema, rash, pruritus.
Not known: bullous dermatitis.
Musculoskeletal and connective tissue disorders
Not known: myalgia.
Renal and urinary disorders
Not known: renal failure and renal impairment, increased serum creatinine
General violations
Uncommon: increased fatigue.
Reactions observed during clinical studies in patients with arterial hypertension regardless of causal relationship to the study drug: arthralgia, asthenia, back pain, diarrhea, dizziness, headache, insomnia, decreased libido, nausea, edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infections, viral infections.
Children
Arterial hypertension
The antihypertensive effect of valsartan was evaluated in two randomised, double-blind clinical trials (each with a subsequent extension or study) in 711 children aged 6 to 18 years, 560 of whom received valsartan. With the exception of isolated gastrointestinal disorders (such as abdominal pain, nausea, vomiting) and dizziness, no significant differences in the type, frequency or severity of adverse reactions were identified between the safety profile for children aged 6 to 18 years and the previously reported safety profile for adult patients.
Neurocognitive and developmental assessments of children aged 6 to 16 years revealed no clinically significant overall adverse effect after treatment with valsartan for up to 1 year.
In a double-blind, randomized study in 90 children aged 1 to 6 years, which was extended as an open-label study for one year, two fatalities and isolated cases of marked elevations in hepatic transaminases were reported.
These cases occurred in a population with significant comorbidities. A causal relationship to valsartan has not been established. In a second study, which randomized 75 children aged 1 to 6 years, no significant increases in hepatic transaminases or deaths were observed during treatment with valsartan.
Hyperkalemia was more common in children aged 6 to 18 years with underlying chronic kidney disease.
A pooled analysis was performed of 560 pediatric hypertensive patients (aged 6-17 years) receiving valsartan monotherapy [n=483] or combination antihypertensive therapy including valsartan [n=77]. Of the 560 patients, 85 (15.2%) had chronic renal failure (CKD) (baseline GFR <90 mL/min/1.73 m2). A total of 45 (8.0%) patients discontinued the study due to adverse events. A total of 111 (19.8%) patients experienced adverse drug reactions, the most common of which were headache (5.4%), dizziness (2.3%), and hyperkalemia (2.3%). In patients with CKD, the most common adverse events were hyperkalemia (12.9%), headache (7.1%), increased plasma creatinine (5.9%), and hypotension (4.7%). In patients
