Instructions for use Kombisart tablets 10 mg / 160 mg No. 30
Composition
active ingredients: amlodipine, valsartan;
1 tablet of 5 mg/160 mg contains: amlodipine besylate 6.94 mg, corresponding to 5 mg of amlodipine, valsartan 160 mg;
excipients: microcrystalline cellulose, crospovidone, colloidal anhydrous silicon dioxide, magnesium stearate;
shell: Opadry II Yellow film coating mixture (hypromellose (hydroxypropylmethylcellulose), lactose monohydrate, titanium dioxide (E 171), polyethylene glycol (macrogol), iron oxide yellow (E 172));
active ingredients: amlodipine, valsartan;
1 tablet of 10 mg/160 mg contains: amlodipine besylate 13.87 mg, corresponding to 10 mg of amlodipine, valsartan 160 mg;
excipients: microcrystalline cellulose, crospovidone, colloidal anhydrous silicon dioxide, magnesium stearate;
shell: Opadry II Pink film-coating mixture (hypromellose (hydroxypropylmethylcellulose), lactose monohydrate, titanium dioxide (E 171), polyethylene glycol (macrogol), red iron oxide (E 172)).
Dosage form
Film-coated tablets.
Main physicochemical properties:
5 mg/160 mg tablets: oval-shaped tablets with a flat surface with beveled edges, film-coated, light brownish-yellow in color;
10 mg/160 mg tablets: oval-shaped tablets with a flat surface with beveled edges, film-coated, light pink in color.
Pharmacotherapeutic group
Combination drugs of angiotensin II inhibitors.
ATX code C09DB01.
Pharmacological properties
Pharmacodynamics.
Combisart contains two antihypertensive components with additional mechanisms of blood pressure control in patients with essential hypertension: amlodipine belongs to the class of calcium antagonists, and valsartan belongs to the class of angiotensin II antagonists. The combination of these ingredients has an additive antihypertensive effect and reduces blood pressure to a greater extent than either component alone.
Amlodipine
Amlodipine inhibits the transmembrane penetration of calcium ions into the smooth muscles of the heart and blood vessels. The mechanism of antihypertensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle, which causes a decrease in peripheral vascular resistance and leads to a decrease in blood pressure. Experimental data confirm that amlodipine binds to dihydropyridine and nonhydropyridine binding sites. Contractile processes of the heart muscle and vascular smooth muscle depend on the passage of extracellular calcium into these cells through specific ion channels.
After administration of therapeutic doses to patients with hypertension, amlodipine causes vasodilation, resulting in a decrease in blood pressure in the supine and standing positions. This decrease in blood pressure is not accompanied by a significant change in heart rate or plasma catecholamine levels with prolonged use.
The effect correlates with plasma concentrations in young and elderly patients.
In patients with arterial hypertension and normal renal function, therapeutic doses of amlodipine lead to a decrease in renal vascular resistance and an increase in glomerular filtration rate, as well as effective renal plasma flow without changes in the filtered fraction or proteinuria.
As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or walking) in patients with normal ventricular function treated with amlodipine generally showed a small increase in cardiac index without a significant effect on dP/dt or on end-diastolic pressure or left ventricular volume. In hemodynamic studies, amlodipine did not show a negative inotropic effect at therapeutic doses, even when co-administered with beta-blockers.
Amlodipine does not alter the function of the sinoatrial node or atrioventricular conduction. When amlodipine is used in combination with beta-blockers in patients with essential hypertension or angina pectoris, no changes in electrocardiogram parameters are observed.
Positive clinical effects of amlodipine have been observed in patients with chronic stable angina, vasospastic angina, and angiographically confirmed coronary artery disease.
Valsartan
Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Based on the lack of effect on ACE and potentiation of bradykinin or substance P activity, the use of angiotensin II receptor antagonists is usually not accompanied by cough. Valsartan does not interact with or block receptors for other hormones or ion channels known to play an important role in the regulation of cardiovascular function.
Prescribing the drug to patients with arterial hypertension leads to a decrease in blood pressure without affecting the pulse rate.
In most patients, after a single oral dose of the drug, the onset of antihypertensive activity is noted within 2 hours, and the maximum reduction in blood pressure is achieved within 4-6 hours.
The antihypertensive effect persists for more than 24 hours after a single dose. With regular use of the drug, the maximum therapeutic effect is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy. Abrupt withdrawal of valsartan does not lead to the resumption of arterial hypertension or other adverse clinical events.
Valsartan has been shown to significantly reduce hospitalization rates in patients with chronic heart failure (NYHA class II-IY). A more significant effect was achieved in patients not receiving ACE inhibitors or beta-blockers. Valsartan has also been shown to reduce cardiovascular mortality in clinically stable patients with left ventricular disease or left ventricular dysfunction after myocardial infarction.
Valsartan/amlodipine
The combination of amlodipine and valsartan provides a dose-dependent additive reduction in blood pressure across the therapeutic dose range. The hypotensive effect after a single dose of the combination is maintained for 24 hours.
Pharmacokinetics.
Linearity.
Valsartan and amlodipine exhibit linear pharmacokinetics.
Amlodipine
Absorption. After oral administration of therapeutic doses of amlodipine alone, peak plasma concentrations (Cmax) are reached within 6-12 hours. The estimated absolute bioavailability is 64% to 80%. Food intake does not affect the bioavailability of amlodipine.
Distribution: The volume of distribution is approximately 21 L/kg. In patients with essential hypertension, approximately 97.5% of the circulating drug is bound to plasma proteins.
Biotransformation: Amlodipine is extensively (approximately 90%) metabolized in the liver to inactive metabolites.
Elimination: Elimination of amlodipine from plasma is biphasic, with a half-life of approximately 30-50 hours. Steady-state plasma levels are reached after continuous administration for 7-8 days. 10% of the parent amlodipine and 60% of the amlodipine metabolites are excreted in the urine.
Valsartan
Absorption. After oral administration of the drug, Cmax of valsartan in plasma is reached within 2-4 hours. The average absolute bioavailability of the drug is 23%. Food reduces the exposure of valsartan, as shown by AUC (plasma concentration - time), by approximately 40%, and Cmax - by 50%, although 8 hours after administration, the concentration of valsartan in plasma is the same for the group that took the drug on an empty stomach and the group of patients that took the drug after a meal. The decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be taken regardless of food intake.
Distribution: The steady-state volume of distribution of valsartan after intravenous administration is approximately 17 L, indicating that valsartan is not extensively distributed into tissues. Valsartan is highly bound to plasma proteins (94-97%), mainly to serum albumin.
Biotransformation: Valsartan is not significantly transformed, with only 20% of the dose converted to metabolites. A hydroxymetabolite, which is pharmacologically inactive, has been identified in plasma at low concentrations (less than 10% of the AUC of valsartan).
Elimination: Valsartan exhibits multi-exponential elimination kinetics (half-life T1/2a < 1 hour and T1/2b approximately 9 hours). Valsartan is excreted mainly unchanged in the feces (approximately 83% of the dose) and urine (approximately 13% of the dose). After intravenous administration, the plasma clearance of valsartan is approximately 2 l/h, and its renal clearance is approximately 0.62 l/h (approximately 30% of the total clearance). The elimination half-life of valsartan is 6 hours.
Valsartan/amlodipine
After oral administration of the drug Combisart Cmax of valsartan and amlodipine in blood plasma is achieved in 3 and 6-8 hours, respectively. The rate and extent of absorption of the drug are equivalent to the bioavailability of valsartan and amlodipine when administered as separate tablets.
Special populations
Children
There are no data on the pharmacokinetics of the drug in children.
Elderly patients (over 65 years of age)
The time to reach Cmax of amlodipine in plasma is approximately the same in young and elderly patients. In elderly patients, the clearance of amlodipine tends to decrease, which leads to an increase in AUC and a prolongation of the half-life. The average systemic AUC of valsartan in elderly patients is 70% higher than in younger patients, so caution should be exercised when increasing the dose.
Renal impairment does not significantly affect the pharmacokinetics of amlodipine. For a compound whose renal clearance accounts for only 30% of total plasma clearance, there was no correlation between renal function status and systemic exposure to valsartan.
Liver dysfunction.
In patients with hepatic impairment, the clearance of amlodipine is reduced, resulting in an increase in AUC by approximately 40-60%. In patients with mild to moderate chronic liver disease, valsartan exposure (determined by AUC values) is on average twice that of healthy volunteers (selected for age, sex and body weight). Patients with liver disease should be careful when using the drug.
Indication
Essential hypertension in adult patients whose blood pressure is not controlled with amlodipine or valsartan monotherapy.
Contraindication
· Hypersensitivity to the active substance, dihydropyridine derivatives or to any of the excipients of the drug.
Severe liver dysfunction, biliary cirrhosis or cholestasis.
Severe renal impairment (glomerular filtration rate (GFR) < 30 mg/min/1.73 m2); the drug is also contraindicated in patients on dialysis.
Concomitant use of angiotensin receptor antagonists (ARBs), including valsartan, or angiotensin-converting enzyme (ACE) inhibitors with aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 mg/min/1.73 m2).
Pregnancy or planning pregnancy (see section "Use during pregnancy or breastfeeding").
Severe hypotension.
· Shock (including cardiogenic shock).
· Obstruction of the left ventricular outflow tract (e.g. hypertrophic obstructive cardiomyopathy and severe aortic stenosis).
· Hemodynamically unstable heart failure after acute myocardial infarction.
Interaction with other medicinal products and other types of interactions
Inter-physician interactions
Drug-drug interactions of Combisart with other drugs have not been studied.
Medicines that require caution when used concomitantly
Other antihypertensive drugs
Commonly used antihypertensive drugs (e.g. alpha-blockers, diuretics) and other drugs that can cause hypotensive adverse events (e.g. tricyclic antidepressants, alpha-blockers used to treat benign prostatic hyperplasia) may enhance the hypotensive effect of the combination.
Interactions related to amlodipine
Concomitant use not recommended
Grapefruit or grapefruit juice
The use of amlodipine with grapefruit juice or grapefruit is not recommended, as in some patients the bioavailability of the drug may be increased, leading to an increase in the hypotensive effect.
Medicines that require caution when used concomitantly
CYP3A4 inhibitors
Concomitant use of amlodipine with more or less potent CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may lead to a significant increase in systemic exposure to amlodipine. The clinical manifestations of such pharmacokinetic changes may be enhanced in elderly patients. Clinical monitoring and dose adjustment may be necessary.
CYP3A4 inducers (anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, St. John's wort (Hypericum perforatum)
There are no studies on the effects of CYP3A4 inducers on amlodipine. Concomitant use of CYP3A4 inducers (e.g. rifampicin, Hypericum perforatum) may result in decreased plasma concentrations of amlodipine. Caution is recommended when amlodipine is used with CYP3A4 inducers.
Simvastatin
Multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in simvastatin exposure compared to simvastatin alone. It is recommended that the daily dose of simvastatin be reduced to 20 mg for patients taking amlodipine.
Dantrolene (infusion)
Due to the risk of hyperkalemia, it is recommended to avoid concomitant use of calcium channel blockers such as amlodipine in patients predisposed to the development of malignant hyperthermia and in the treatment of malignant hyperthermia.
Medicines that require caution when used concomitantly
Others
Amlodipine did not affect the pharmacokinetics of atorvastatin, dioxin, warfarin, or cyclosporine.
Interactions related to valsartan
Concomitant use not recommended
Lithium
Reversible increases in serum lithium concentrations and toxicity have been reported with concomitant use of lithium with ACE inhibitors or angiotensin II receptor antagonists, including valsartan. Concomitant use of valsartan and lithium is not recommended. If the combination proves necessary, serum lithium levels should be closely monitored. The risk of lithium toxicity may be further increased by concomitant use of Combisart and diuretics.
If drugs that affect potassium channels are prescribed in combination with valsartan, frequent monitoring of plasma potassium should be considered.
Medicines that require caution when used concomitantly
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day), and nonselective NSAIDs
Concomitant use of angiotensin II antagonists and NSAIDs may result in attenuation of the hypotensive effect. Concomitant use of angiotensin II antagonists and NSAIDs may also increase the risk of worsening of renal function and an increase in serum potassium. Therefore, at the beginning of treatment, it is recommended to monitor renal function and ensure adequate fluid intake.
Inhibitors of the accumulation transporter (rifampicin, cyclosporine) or efflux transporter (ritonavir)
Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and the hepatic efflux transporter MRP2. Concomitant use of inhibitors of the uptake transporter (rifampicin, cyclosporine) or efflux transporter (ritonavir) may increase systemic exposure to valsartan.
Dual blockade of the RAAS with ARBs, ACE inhibitors, or aliskiren
Dual blockade of the RAAS with the combined use of ACE inhibitors, ARBs or aliskiren leads to an increased incidence of adverse events such as hypotension, hyperkalemia and decreased renal function (including acute renal failure) compared with treatment with a single drug that affects the RAAS. Therefore, the concomitant use of ARBs, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR < 60 mg/min/1.73 m2).
Others
With valsartan monotherapy, no clinically significant drug interactions have been established with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
Application features
Patients with a deficiency in the body of sodium and/or circulating blood volume.
Excessive hypotension has been observed in patients with uncomplicated hypertension (0.4%). Symptomatic hypotension may occur in patients with an activated renin-angiotensin system (sodium and/or volume depletion and high doses of diuretics) receiving angiotensin receptor blockers. Correction of this condition before the use of Combisart or close medical supervision at the beginning of therapy is recommended.
If hypotension occurs during the use of the drug Kombisart, the patient should be placed on his back and, if necessary, an intravenous infusion of saline should be performed. After stabilization of blood pressure, treatment can be continued.
Hyperkalemia.
Concomitant treatment with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that may increase potassium levels (heparin, etc.) should be carried out with caution, and frequent monitoring of potassium levels should be planned.
Renal artery stenosis.
The drug Combisart should be used with caution for the treatment of hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, as serum urea and creatinine levels may increase.
Kidney transplantation.
There is no experience of the safe use of the drug Kombisart in patients with a recent kidney transplant.
Liver dysfunction.
Valsartan is excreted mainly unchanged in the bile. The half-life of amlodipine is prolonged and the AUC (plasma concentration - time) is higher in patients with impaired liver function; dosage recommendations have not been established. Special caution is required when using the drug Kombisart in patients with mild to moderate liver function impairment or obstructive gallbladder disease.
Kidney dysfunction.
No dose adjustment is required in patients with mild or moderate renal impairment (GFR > 30 ml/min/1.73 m2). In patients with moderate renal impairment, monitoring of potassium and creatinine levels in the blood is recommended.
Concomitant use of angiotensin receptor antagonists, including valsartan, or angiotensin-converting enzyme inhibitors with aliskiren is contraindicated in patients with renal impairment (GFR < 60 mg/min/1.73 m2).
Primary hyperaldosteronism.
Patients with primary hyperaldosteronism should not take the angiotensin II antagonist valsartan because their renin-angiotensin system is impaired due to the underlying disease.
Angioedema.
Angioedema, including swelling of the larynx and glottis, which may lead to airway obstruction, and/or swelling of the face, lips, pharynx and/or tongue, has been reported in patients taking valsartan. Some of these patients had a history of angioedema while taking other drugs, including angiotensin-converting enzyme (ACE) inhibitors. The use of the drug Kombisart should be discontinued immediately if angioedema occurs; repeated use is not recommended.
Due to inhibition of the renin-angiotensin-aldosterone system, renal function may be impaired in susceptible patients. In patients with severe heart failure, in whom renal function may depend on the activity of the renin-angiotensin-aldosterone system, the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with the development of oliguria and/or progressive azotemia, and (in rare cases) acute renal failure and/or death. Similar results have been observed with valsartan. Patients with heart failure or after myocardial infarction should have their renal function assessed.
Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure as they may increase the risk of cardiovascular events and mortality.
Aortic and mitral valve stenosis.
As with other vasodilators, particular caution should be exercised in patients with known mitral valve stenosis or severe low-grade aortic stenosis.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS).
There is evidence that the combined use of ACE inhibitors, ARBs or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by the combined use of ACE inhibitors, ARBs or aliskiren is not recommended.
If dual blockade is absolutely necessary, it should only be carried out under specialist supervision with frequent close monitoring of renal function, electrolyte concentrations and blood pressure. ACE inhibitors and ARBs should not be used concomitantly in patients with diabetic nephropathy.
The use of the drug Kombisart has not been studied in patients with diseases other than arterial hypertension.
Use during pregnancy or breastfeeding
Pregnancy
The drug is contraindicated for use in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with this drug, its use should be immediately discontinued and replaced with another drug approved for use in pregnant women.
Epidemiological data on the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy have not been conclusive; however, a small increased risk cannot be excluded. Although there are no data from controlled epidemiological studies with angiotensin II receptor antagonists (ARBs), a similar risk may exist with this class of drugs.
The use of ARAII in the second and third trimesters is known to lead to toxic effects on the human fetus (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the newborn (renal failure, arterial hypotension, hyperkalemia).
If AIIRAs have been used from the second trimester of pregnancy, ultrasound check of renal function and fetal skull is recommended.
Infants whose mothers have taken ARAII should be closely observed for the development of arterial hypotension.
Breastfeeding period
Since no information is available on the use of Combisart during breastfeeding, the drug is not recommended for use during breastfeeding; alternative drugs with better established safety profiles are preferable, especially while breastfeeding a newborn or premature infant.
Fertility
Clinical studies on the effect on fertility have not been conducted.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients using the drug Kombisart may experience dizziness or a feeling of weakness after taking the drug, so they should take this into account when driving vehicles and working with potentially dangerous mechanisms.
Amlodipine may have minor or moderate influence on the ability to drive or use machines. If patients experience dizziness, headache, fatigue or nausea while taking amlodipine, their reactions may be impaired.
Method of administration and doses
Patients whose blood pressure is inadequately controlled with amlodipine or valsartan monotherapy may be switched to combination therapy with the drug Combisart. The recommended dose is 1 tablet per day. Combisart tablets can be taken regardless of meals. It is recommended to take Combisart with a small amount of water.
Patients taking valsartan and amlodipine separately can be switched to Combisart, which contains the same doses of the components.
Individual dose titration of the components (i.e. amlodipine and valsartan) is recommended before switching to a fixed-dose combination. If clinically indicated, direct conversion from monotherapy to a fixed-dose combination may be considered.
The maximum daily dose of the drug Combisart is 2 tablets of 5 mg/160 mg or 1 tablet of 10 mg/160 mg (the maximum permissible doses of the drug components are 10 mg of amlodipine content, 320 mg of valsartan content).
Kidney dysfunction
The drug Combisart is contraindicated in patients with severe renal impairment.
No dose adjustment is required in patients with mild or moderate renal impairment. In patients with moderate renal impairment, it is recommended to monitor potassium and creatinine levels in the blood.
Concomitant use of Combisart with aliskiren is contraindicated in patients with renal impairment (GFR < 60 mg/min/1.73 m2).
Diabetes mellitus
Concomitant use of Combisart with aliskiren is contraindicated in patients with diabetes mellitus.
Liver dysfunction
The drug Combisart is contraindicated in patients with severe liver dysfunction.
Combisart should be used with caution in patients with impaired liver function or obstructive biliary tract diseases. Dosage recommendations for amlodipine in patients with mild or moderate hepatic impairment have not been developed.
Elderly patients (over 65 years of age)
For elderly patients, usual doses of the drug are recommended.
Caution should be exercised when increasing the dose of the drug in elderly patients.
Pediatric populations
The safety and efficacy of the drug Kombisart in children (under 18 years of age) have not been studied. Data are lacking.
Children.
This medicine has not been studied in children (under 18 years of age). Therefore, until more information is available, Kombisart is not recommended for use in children.
Overdose
Symptoms.
There is no experience of overdose with the drug Combisart. The main symptom of valsartan overdose is likely to be severe hypotension with dizziness. Overdose of amlodipine may lead to increasing peripheral vasodilation and, possibly, reflex tachycardia. There is evidence of significant and potentially prolonged systemic hypotension, up to shock and death.
Treatment.
If the drug has been taken recently, vomiting should be induced or the stomach should be lavaged. The absorption of amlodipine is significantly reduced by the use of activated charcoal immediately or within two hours after taking amlodipine.
Clinically significant hypotension caused by an overdose of Combisart requires active support of the cardiovascular system, including frequent monitoring of cardiac and respiratory function, elevation of the patient's lower extremities, attention to the volume of circulating fluid and urination. To restore vascular tone and blood pressure, a vasoconstrictor can be used in the absence of contraindications to its use. In case of persistent decrease in blood pressure, which is a consequence of calcium channel blockade, intravenous administration of calcium gluconate may be appropriate.
Removal of valsartan and amlodipine by hemodialysis is unlikely.
Adverse reactions
The following adverse reactions may occur during use of the drug:
– from the immune system: hypersensitivity;
– on the part of the organs of vision: visual impairment, vision impairment;
– from the psyche: excitement;
– from the nervous system: headache, coordination disorders, dizziness, drowsiness, postural dizziness, paresthesia;
– from the organs of hearing and labyrinth: dizziness, tinnitus;
– on the part of the heart: tachycardia, palpitations, fainting;
– from the vascular system: orthostatic hypotension, arterial hypotension;
– from the respiratory system: cough, sore throat and larynx;
– from the side of nutrition and metabolism: hypokalemia, anorexia, hypercalcemia, hyperlipidemia, hyperuricemia, hyponatremia;
– from the digestive system: abdominal discomfort and pain in the upper abdomen, constipation, diarrhea, nausea, dry mouth;
– on the part of the skin and subcutaneous tissues: rash, erythema, increased sweating, urticaria, exanthema, itching;
– from the musculoskeletal system: joint swelling, back pain, arthralgia, muscle cramps, feeling of heaviness;
– from the kidneys and urinary system: increased urination, increased urine output;
– from the reproductive system: erectile dysfunction;
– general disorders: edema, soft tissue edema, facial edema, peripheral edema, increased fatigue, facial flushing, hot flashes, asthenia, hyperemia;
– infections: nasopharyngitis, flu.
Additional information about the combination
Peripheral edema, a known side effect of amlodipine, was generally reported less frequently in patients taking the amlodipine/valsartan combination than in patients taking amlodipine alone.
Additional information about the components of the drug
Adverse reactions previously observed with one of the components of the drug (amlodipine or valsartan) may also occur with the use of the drug Combisart, even if they were not observed during clinical trials.
Vomiting, nausea, alopecia, dyspepsia, dyspnea, rhinitis, gastritis, abdominal pain, gingival hyperplasia, gynecomastia, hyperglycemia, impotence, urinary disorders, increased urinary frequency, leukopenia, malaise, tinnitus, mood changes (including anxiety), myalgia, muscle cramps, ankle swelling, peripheral neuropathy, pancreatitis, hepatitis, thrombocytopenia, vasculitis, allergic reactions, angioedema, angioedema, erythema multiforme, insomnia, depression, confusion, fainting, dizziness, drowsiness, tremor, dysgeusia, hypoesthesia, visual disturbances (including diplopia), skin discoloration, hyperhidrosis, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity, weight gain or loss, jaundice, urticaria, purpura, exanthema, pruritus; isolated cases of extrapyramidal syndrome, increased liver enzymes (usually associated with cholestasis), chest pain, palpitations, hypertension, arrhythmia, myocardial infarction (including bradycardia, ventricular tachycardia and atrial fibrillation) have been reported.
Adverse reactions specific to valsartan
Decreased hemoglobin, decreased hematocrit, neutropenia, thrombocytopenia, increased serum potassium, increased liver function tests, including serum bilirubin, renal failure and renal dysfunction, increased serum creatinine, angioedema, myalgia, vasculitis, hypersensitivity reactions, including serum sickness.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25°C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyiv Vitamin Plant".
Location of the manufacturer and its business address
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua.
