Uperio pills 100mg (51.4mg+48.6mg), 56pcs

Composition

1 film-coated tablet,100 mg (51.4 mg + 48.6 mg) contains:

Active ingredient:

sacubitril and valsartan hydrate complex of sodium salts-113.103 mg (in terms of the acidic form anhydrous 100 mg, which is equivalent to the content of sacubitril 48.6 mg and valsartan 51.4 mg);

Excipients: cellulose microcrystalline, hyprolose, crospovidone, magnesium stearate, talc, silica colloidal anhydrous; shell: premix shell white (hypromellose, titanium dioxide (E171), macrogol 4000, talc), premix shell yellow (hypromellose, dye iron oxide yellow (E172), macrogol 4000, talc), premix red shell (hypromellose, dye iron oxide red (E172), macrogol 4000, talc).

Pharmacological action

Pharmacotherapy group: not assigned.

ATX code: C09DX04.

Pharmacological properties

Mechanism of action

The effect of the drug Uperio is mediated by a new mechanism, namely, simultaneous suppression of the activity of neprilysin (neutral endopeptidase, NEP) sacubitrilate (an active metabolite of sacubitril) and angiotensin II receptor blocker type 1 (AT₁) valsartan, which is an angiotensin II receptor antagonist (ARA II).

Under the influence of sacubitrilate, an increase in the number of peptides destroyed by neprilysin (such as natriuretic peptides (NUP)) occurs, which, while simultaneously suppressing the negative effects of angiotensin II by valsartan, causes complementary beneficial effects of sacubitril and valsartan on the cardiovascular system and kidneys in patients with heart failure. NPS activate membrane-bound receptors associated with guanylyl cyclase, which leads to an increase in the concentration of cyclic guanosine monophosphate (cGMP), which causes symptoms of vasodilation, an increase in natriuresis and diuresis, an increase in glomerular filtration rate and renal blood flow, suppression of renin and aldosterone release, a decrease in sympathetic activity, as well as antihypertrophic and antifibrotic effects.

Valsartan selectively blocks the AT₁receptor, suppresses the negative effects of angiotensin II on the cardiovascular system and kidneys, and also blocks the angiotensin II-dependent release of aldosterone. This prevents persistent activation of the renin-angiotensin-aldosterone system (RAAS), which causes vasoconstriction, sodium and water retention by the kidneys, activation of cell growth and proliferation, and subsequent maladaptive remodeling of the cardiovascular system.

Pharmacodynamics

The pharmacodynamic effects of sacubitril and valsartan, which are part of the drug, were evaluated after its single and repeated use in healthy volunteers, as well as in patients with chronic heart failure. The observed effects corresponded to the mechanism of action of the complex of active substances, which consists in simultaneous inhibition of neprilysin and blockade of RAAS.

In a 7-day study in patients with reduced left ventricular ejection fraction (LVEF), in which valsartan was used as a control, the use of the sacubitril and valsartan complex resulted in a statistically significant short-term increase in natriuresis, an increase in the concentration of cGMP in the urine, and a decrease in the concentration of the mid-regional atrial natriuretic peptide precursor (MR-proANP) and the N-terminal fragment of the brain natriuretic peptide precursor (NT-proBNP) in blood plasma (compared to valsartan). In a 21-day study in patients with reduced left ventricular EF, the use of sacubitril and valsartan caused a statistically significant increase in the concentration of atrial natriuretic peptide (ANP) and cGMP in the urine and the concentration of cGMP in the blood plasma, as well as a decrease in the plasma concentrations of NT-proBNP, aldosterone and endothelin-1 (compared to baseline).

In addition, the use of the sacubitril-valsartan complex blocks the AT₁receptor, which is indicated by an increase in the activity and concentration of renin in blood plasma. In another study, the sacubitril-valsartan complex caused a more pronounced decrease in the concentration of NT-proBNP in blood plasma and a more significant increase in the concentration of brain natriuretic peptide (BNP) and cGMP in urine than enalapril. While BNP is a neprilysin substrate, NT-proBNP is not, and therefore NT-proBNP, unlike BNP, can be used as a biomarker in monitoring patients with heart failure receiving the sacubitril-valsartan complex.

In a study with a detailed study of the QTc interval in healthy male volunteers, the use of the sacubitril and valsartan complex once at doses of 400 mg and 1200 mg did not affect myocardial repolarization.

Neprilysin is one of several enzymes involved in the metabolism of amyloid-β (Aß) in the brain and cerebrospinal fluid (CSF). When using the sacubitril and valsartan complex at a dose of 400 mg once a day for 2 weeks in healthy volunteers, the concentration of Aß 1-38 in the CSF increased; at the same time, the concentrations of Aß 1-40 and 1-42 in the CSF did not change. The clinical significance of this fact is unknown.

In a clinical study, the use of sacubitril and valsartan in patients with chronic heart failure significantly reduced the risk of death due to cardiovascular pathology or hospitalization due to heart failure (21.8% in the study drug group versus 26.5% in the enalapril group). The absolute reduction in the risk of death due to cardiovascular pathology or hospitalization due to heart failure was 4.7% (3.1% for the risk of death due to cardiovascular pathology and 2.8% for primary hospitalization due to heart failure).

The relative risk reduction compared to enalapril was 20%. The effect was noted at the early stages of drug use and persisted throughout the entire study period. Both active components of the drug contributed to the development of the effect. The incidence of sudden death, which accounted for 45% of all deaths due to cardiovascular pathology, in the study drug group decreased by 20% compared to the enalapril group (hazard ratio (HR) 0.80, p=0.0082).

The incidence of myocardial contractile insufficiency, which was the cause of death in 26% of cases due to cardiovascular pathology, in the study drug group decreased by 21% compared to that in the enalapril group (HR 0.79, p=0.0338).

Pharmacokinetics

Suction

After oral use, the sacubitril and valsartan complex breaks down into sacubitril, which is then metabolized to form the metabolite sacubitrilate, and valsartan; the concentrations of these substances in blood plasma reach a maximum after 0.5 h,2 h, and 1.5 h, respectively. The absolute bioavailability of sacubitril and valsartan after oral use is ≥60% and 23%, respectively. Valsartan in the composition of the drug Uperio has a higher bioavailability compared to other tablet forms.

In the case of taking a complex of sacubitril and valsartan twice a day, the equilibrium concentrations of sacubitril, sacubitrilate and valsartan are reached after 3 days. There is no statistically significant accumulation of sacubitril and valsartan at steady state; at the same time, the accumulation of sacubitrilate exceeds the concentration with a single application by 1.6 times. Concomitant use of sacubitril and valsartan did not have a clinically significant effect on the systemic effects of sacubitril, sacubitrilate, and valsartan. Reduction of valsartan exposure in the case of taking the sacubitril and valsartan complex simultaneously with food intake is not accompanied by a clinically significant decrease in the therapeutic effect. The time of taking the sacubitril and valsartan complex does not depend on the time of food intake.

Distribution

The sacubitril-valsartan complex is largely bound to plasma proteins (94% – 97%). Comparison of exposures in blood plasma and CSF shows that sacubitrilate penetrates the blood-brain barrier to a small extent (0.28%). The apparent volume of distribution of the complex is from 75 to 103 liters.

Metabolism

Sacubitrile is rapidly converted to sacubitrilate under the action of enzymes, which is not significantly metabolized further. Valsartan is only slightly metabolized, and only about 20% of the administered dose is detected as metabolites. In blood plasma in insignificant concentrations ( Since both sacubitril and valsartan are minimally metabolized with the participation of cytochrome CYP450 isoenzymes, a change in their pharmacokinetics in the case of simultaneous use of drugs that affect CYP450 isoenzymes seems unlikely.

Deduction

After oral use,52-68% of sacubitril (mainly in the form of sacubitrilate) and ~13% of valsartan and its metabolites are excreted by the kidneys; 37-48% of sacubitril (mainly in the form of sacubitrilate) and 86% of valsartan and its metabolites are excreted through the intestine.

Sacubitril, sacubitrilate, and valsartan are eliminated from blood plasma with mean half-lives (T_1/2) of approximately 1.43 hours,11.48 hours, and 9.90 hours, respectively.

Linearity / non-linearity

In the studied dose range of sacubitril and valsartan complex (50-400 mg), the pharmacokinetic parameters of sacubitril, sacubitrilate and valsartan change in proportion to the dose.

Pharmacokinetics in special clinical cases

Patients over 65 years of age

Exposures to sacubitrilate and valsartan in patients of this category are 42% and 30% higher, respectively, than in younger patients. Such differences are not associated with clinically significant effects, so no dose adjustment is required.

Patients under 18 years of age

The use of the drug in patients of this category has not been studied.

Patients with impaired renal function

For sacubitrilate, there was a correlation between renal function and the area under the concentration-time curve (AUC), but no such correlation was observed for valsartan. In patients with mild (estimated glomerular filtration rate (eGFR) 89-60 ml/min/1.73 m2) and moderate (59-30 ml/min/1.73 m2) renal impairment.

The AUC of sacubitrilate was 2 times higher than in patients with normal renal function. No dose adjustment is required in patients with mild to moderate renal impairment.

In patients with severe renal impairment (eGFR Caution should be exercised when using the drug in patients with severe renal impairment due to limited relevant data.

There are no data on the use of the drug in patients undergoing hemodialysis. However, both sacubitrilate and valsartan are largely bound to plasma proteins, so their effective removal from the blood during hemodialysis is unlikely.

Patients with impaired liver function

In patients with mild and moderate hepatic impairment, sacubitril exposure increased 1.5 and 3.4 times, respectively. Exposure to sacubitrilate increased by 1.5 and 1.9 times, valsartan – by 1.2 and 2.1 times (in comparison with healthy volunteers). In patients with mild hepatic impairment (Child-Pugh Class A), including patients with biliary tract obstruction, no dose adjustment is required.

In patients with moderate hepatic impairment (Child-Pugh Class B), the recommended starting dose is 50 mg twice daily.

Due to the lack of data, use in patients with severe hepatic impairment is not recommended.

The pharmacokinetics of the sacubitril-valsartan complex (sacubitril, sacubitrilate, and valsartan) in patients of different racial and ethnic groups did not differ significantly.

Gender

Pharmacokinetics of sacubitril and valsartan complex (sacubitril, sacubitrilate and valsartan) it does not differ significantly between men and women.

Indications

Chronic heart failure (NYHA class II-IV) in patients with systolic dysfunction in order to reduce the risk of cardiovascular mortality and hospitalization for heart failure. The drug is used in combination therapy with other drugs for the treatment of chronic heart failure as a substitute for angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists (ARA II).

Use during pregnancy and lactation

Patients and patients with preserved reproductive potential, contraception (if applicable)

Patients with preserved reproductive potential should be informed about the possible consequences of using the drug during pregnancy, as well as about the need to use reliable methods of contraception during treatment with the drug and within a week after its last intake.

Pregnancy

Like other drugs that directly affect the RAAS, Juperio should not be used during pregnancy. The effect of Uperio is mediated by angiotensin II receptor blockade, so the risk to the fetus cannot be excluded. In pregnant women taking valsartan, cases of spontaneous termination of pregnancy, lack of water and impaired renal function in newborns have been reported. If pregnancy occurs during treatment with the drug, the patient should stop taking the drug and inform her doctor.

Breast-feeding

It is not known whether the drug Juperio penetrates into human breast milk. Since preclinical studies have noted the isolation of sacubitril and valsartan in the milk of lactating rats, it is not recommended to use the drug Juperio during breastfeeding. The decision to stop breastfeeding or to discontinue treatment with Uperio and continue breastfeeding should be made taking into account the importance of its use for the mother.

Fertility

There are no data on the effect of Uperio on male and female fertility. In animal studies of the drug Uperio, there was no decrease in fertility.

Contraindications

• Hypersensitivity to sacubitril or valsartan, as well as to other auxiliary components of the drug.
• Concomitant use with angiotensin converting enzyme (ACE) inhibitors, as well as a period of 36 hours after ACE inhibitor withdrawal.
• The presence of angioedema in the anamnesis against the background of previous therapy with ACE inhibitors or ARA II.
• Hereditary angioedema.
• Concomitant use with drugs containing aliskiren in patients with diabetes mellitus or with moderate or severe renal impairment (eGFR <60 ml / min/1.73 m2.
• Severe hepatic impairment (Child Pugh Class C), biliary cirrhosis, and cholestasis.
• Uperio is not recommended for use in children under 18 years of age due to the lack of efficacy and safety data.
• Pregnancy, pregnancy planning, and the period of breastfeeding.
• Simultaneous use with other drugs containing ARA II, because the drug contains valsartan.

With caution

• Severe violations of kidney function (eGFR <30 ml/min/1.73 m 2), including patients on hemodialysis or undergoing hemodialysis (eGFR <15 ml/min/1.73 m 2) in the absence of safety data in patients of this category;
• bilateral renal artery stenosis;
• hypovolemia, which may be caused by diuretic therapy, nikoalev diet, diarrhoea, or vomiting;
• concurrent use with drugs that can increase potassium in the blood serum (e. g., potassium-sparing diuretics, potassium supplements);
• the simultaneous use with statins, inhibitors of phosphodiesterase 5 type;
• a history of angioedema in the absence of data on the drug in patients of this category; patients of the Negroid race may be at increased risk of angioedema.

Side effects

In the safety study, the duration of therapy with the drug in patients with chronic heart failure was up to 4.3 years, the average duration of use was 24 months.

Discontinuation of therapy due to the development of adverse events (AES) was required in 10.71% of patients treated with Uperio, and in 12.20% of patients treated with the reference drug. The events most commonly associated with dose adjustment or discontinuation of therapy were: hypotension, hyperkalemia, and impaired renal function. The identified adverse drug reactions (NLR) corresponded to the pharmacological characteristics of the drug Uperio and concomitant diseases present in patients.

The frequency of adverse reactions (RR) did not depend on gender, age, or race.

NLRs are listed in accordance with the system-organ class of the MedDRA Medical Dictionary for regulatory activities. Within each organ-system class, NLRs are distributed by frequency of occurrence in order of decreasing significance. To assess the frequency used the following criteria: very common (≥1/10); often (from ≥1/100 to <1/10); infrequently (≥1/1000 to <1/100); rarely (from ≥1/10000 to <1/1000); very rare (<1/10000), including individual messages; frequency unknown – since the information about the NLR data obtained in the post-marketing period of spontaneous messages in the literature to accurately assess the incidence and causal relationship with the drug is not always possible, for these reactions are given a”frequency unknown”).

Immune system disorders: frequency unknown-hypersensitivity (including skin rash, pruritus, anaphylaxis).

Metabolic and nutritional disorders: very often – hyperkalemia; often-hypokalemia.

Nervous system disorders: often – dizziness, headache; infrequently-orthostatic dizziness.

Hearing disorders and labyrinth disorders: often – vertigo.

Vascular disorders: very often – arterial hypotension; often-syncope, orthostatic hypotension.

Respiratory, thoracic, and mediastinal disorders: cough is common.

Disorders of the gastrointestinal tract: often – diarrhea, nausea.

Skin and subcutaneous tissue disorders: infrequently-angioedema.

Kidney and urinary tract disorders: very often – impaired renal function; often-renal failure (including acute renal failure).

General disorders and disorders at the injection site: often – increased fatigue, asthenia.

If any of the side effects listed in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Contraindicated drug interactions

ACE inhibitors

Juperio is contraindicated for concomitant use with an ACE inhibitor, since inhibition of neprilysin concomitantly with the use of an ACE inhibitor may increase the risk of angioedema. The use of the drug Uperio is possible no earlier than 36 hours after the withdrawal of ACE inhibitors. The use of ACE inhibitors is possible no earlier than 36 hours after the last use of the drug Juperio.

Aliskiren

Concomitant use of Uperio with aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or with impaired renal function (eGFR

Not recommended drug interactions

Angiotensin receptor antagonists

Since one of the active ingredients of the drug is ARA II, simultaneous use with another drug containing ARA II is not recommended.

Drug interactions to consider

HMG-CoA reductase inhibitors (statins)

Research data show that sacubitril inhibits the activity of OATP1B1 and OATP1B3 transporters. Uperio may increase systemic exposure to OATP1B1 and OATP1B3 substrates such as statins. In patients receiving Juperio concomitantly with atorvastatin, the maximum plasma concentration (cmax) of atorvastatin and its metabolites increased up to 2 times, and AUC — up to 1.3 times. Caution should be exercised when statins are co-administered with Uperio. There was no clinically significant drug interaction when Juperio was co-administered with simvastatin.

Sildenafil

In patients with a marked increase in blood pressure, receiving the drug Uperio (before reaching equilibrium concentration), a single use of sildenafil increased the antihypertensive effect compared to the use of the drug Uperio in monotherapy. For this reason, sildenafil or another phosphodiesterase type 5 inhibitor should be used with caution in patients receiving Uperio.

Suspected drug interactions to be considered

Potassium

Concomitant use of potassium-sparing diuretics (for example, triamterene and amiloride), mineralocorticoid antagonists (for example, spironolactone and eplerenone), potassium preparations or potassium-containing salt substitutes may cause an increase in serum potassium and creatinine concentrations. In patients receiving Juperio concomitantly with these medications, it is recommended to regularly monitor the serum potassium content.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors)

Concomitant use of Uperio with NSAIDs in patients over 65 years of age, in patients with hypovolemia (including patients receiving diuretics), and in patients with impaired renal function may increase the risk of deterioration of renal function. In patients receiving Juperio concomitantly with NSAIDs, it is recommended to monitor renal function when using such a treatment regimen and if it changes.

Lithium preparations

The possibility of drug interaction between the drug Uperio and lithium preparations has not been studied. With simultaneous use of lithium preparations with ACE inhibitors and ARA II, there was a reversible increase in the content of lithium in the blood serum and an increase in toxic manifestations in this regard.

In patients receiving Uperio together with lithium preparations, it is recommended to carefully monitor the lithium content in the blood serum. In the case of additional use of a diuretic drug, the risk of toxic effects of lithium may increase.

Carrier proteins

The active metabolite of sacubitril (sacubitrilate) and valsartan are substrates of the OATP1B1, OATP1B3, and OAT3 transporter proteins; valsartan is also a substrate of the MRP2 transporter protein. Patients receiving Juperio concomitantly with OATP1B1, OATP1B3, OAT3 inhibitors (e. g. rifampicin and cyclosporine) or MPR2 (e. g. ritonavir) may have increased systemic exposure to sacubitrilate or valsartan, respectively. Caution should be exercised at the beginning and end of concomitant use of Uperio and this group of drugs.

No significant drug interactions

No clinically significant interactions were observed when Juperio was used in combination with furosemide, digoxin, warfarin, hydrochlorothiazide, amlodipine, metformin, omeprazole, carvedilol, nitroglycerin intravenously (iv) or a combination of levonorgestrel and ethinyl estradiol. Interactions with atenolol, Indometacin, glibenclamide (glyburide) or cimetidine are not expected when co-administered with Yuperio.

Interactions with cytochrome P450 isoenzymes

Available studies demonstrate that the probability of drug interactions mediated by cytochrome CYP450 isoenzymes is low, since the complex of active substances is slightly metabolized with the participation of CYP450 isoenzymes. The complex of active ingredients of the drug Uperio is not an inhibitor or inducer of CYP450 isoenzymes.

How to take, course of use and dosage

The time of taking the drug Uperio does not depend on the time of food intake.

The target (maximum daily) dose of Uperio is 200 mg (102.8 mg + 97.2 mg) 2 times a day. The recommended starting dose of Uperio is 100 mg (51.4 mg + 48.6 mg) 2 times a day. Depending on the tolerance, the dose of Uperio should be increased 2 times every 2-4 weeks until the target (maximum daily) dose of 200 mg (102.8 mg + 97.2 mg) is reached 2 times a day.

In patients who have not previously received ACE inhibitor or ARA II therapy, or who have received these drugs in low doses, start therapy with Uperio at a dose of 50 mg (25.7 mg + 24.3 mg) 2 times a day with a slow increase in the dose (doubling the daily dose 1 time in 3-4 weeks).

The use of the drug Uperio is possible no earlier than 36 hours after the withdrawal of ACE inhibitors, since in the case of simultaneous use, angioedema may develop.

Since Juperio contains ARA II valsartan, it should not be used simultaneously with another drug that contains ARA II.

If you develop signs of impaired tolerability of the drug Uperio (clinically pronounced decrease in blood pressure, hyperkalemia, impaired renal function), you should consider temporarily reducing the dose or adjusting the dose of concomitantly used drugs.

Special categories of patients

Patients with impaired renal function

In patients with mild (eGFR 60-90 ml/min/1.73 m2) or moderate (eGFR 30-60 ml/min/1.73 m2) renal impairment, no dose adjustment is required (see section “Pharmacological properties”). ).

In patients with severe renal impairment (eGFR

Caution is recommended when using the drug Uperio in patients of this category due to the limited relevant data.

Patients with impaired liver function

In patients with mild hepatic impairment (Child-Pugh class A), no dose adjustment of Uperio is required.

In patients with moderate hepatic impairment (Child-Pugh Class B), the recommended starting dose is 50 mg twice daily.

Uperio is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C).

Use in children and adolescents under 18 years of age

There are no data on the safety and efficacy of Uperio in children and adolescents.

Use in patients over 65 years of age

No dose adjustment is required in patients over 65 years of age.

Overdose

There are insufficient data on human overdose with Uperio. Single use of the drug at a dose of 1200 mg and multiple use at a dose of 900 mg in healthy volunteers was accompanied by good tolerability.

The most likely symptom of overdose is hypotension due to the antihypertensive effect of the drug. Symptomatic treatment is recommended.

Removal of active substances during hemodialysis is unlikely, since a significant part of them binds to plasma proteins.

Description

Oval biconvex tablets, covered with a film-coated light yellow color with a chamfer, without risk. On one side is engraved “L1”, on the other – “NVR”.

Special instructions

Marked decrease in blood pressure

Cases of clinically significant hypotension have been reported in patients treated with Uperio.If hypotension occurs, consideration should be given to adjusting the dose of diuretics, concomitant antihypertensive agents, and eliminating the causes of hypotension (for example, hypovolemia). If, despite these measures, hypotension persists, the dose of Uperio should be reduced or the drug should be temporarily discontinued. Final withdrawal of the drug is usually not required. Hypotension is generally more likely to occur in patients with hypovolemia, which may be caused by diuretic therapy, a low-salt diet, diarrhea, or vomiting. Before starting the use of the drug Uperio, it is necessary to correct the sodium content in the body and / or replenish the BCC.

Impaired renal function

Like any other drug that acts on the RAAS, Juperio may cause deterioration of renal function. In a comparative safety and efficacy study (compared to enalapril), clinically significant renal dysfunction was rarely observed, and the drug Uperio was discontinued due to such disorders less often (0.65%) than enalapril (1.28%). In case of clinically significant deterioration of renal function, a reduction in the dose of Uperio should be considered. Caution should be exercised when using Uperio in patients with severe renal impairment.

Hyperkalemia

Like any other drug that acts on the RAAS, the drug Uperio may increase the risk of hyperkalemia. In a comparative safety and efficacy study (compared to enalapril), clinically significant hyperkalemia was rarely observed; Huperio was discontinued due to hyperkalemia in 0.26% of patients, and enalapril was discontinued in 0.35% of patients. Drugs that can increase the content of potassium in the blood serum (for example, potassium-sparing diuretics, potassium preparations) should be used with caution simultaneously with the drug Uperio. If clinically significant hyperkalemia occurs, measures such as reducing dietary potassium intake or adjusting the dose of concomitant medications should be considered. Regular monitoring of serum potassium is recommended, especially in patients with risk factors such as severe renal impairment, diabetes mellitus, hypoaldosteronism, or a high-potassium diet.

Angioedema

Against the background of the use of the drug Uperio, there were cases of angioedema. If angioedema occurs, Uperio should be discontinued immediately and appropriate treatment should be initiated under the patient’s supervision until all symptoms are fully and permanently resolved. You should not re-prescribe the drug Uperio. In cases of confirmed angioedema, in which the edema spread only to the face and lips, the condition was usually resolved without intervention, although the use of antihistamines helped to alleviate the symptoms.

Angioedema accompanied by laryngeal edema can be fatal. In cases where edema spreads to the tongue, vocal folds, or larynx, which can lead to airway obstruction, appropriate treatment should be initiated immediately, such as subcutaneous use of epinephrine (epinephrine)solution 1: 1000 (0.3-0.5 ml), and / or take appropriate measures to ensure airway patency.

In patients with angioedema on the background of previous therapy with ACE inhibitors or ARA II in the anamnesis, as well as in patients with hereditary angioedema, the use of the drug is contraindicated

Patients of the black race may be more at risk of angioedema.

Patients with renal artery stenosis

Like other drugs acting on the RAAS, Uperio may cause an increase in serum urea and creatinine concentrations in patients with unilateral or bilateral renal artery stenosis. In patients with renal artery stenosis, the drug should be used with caution, regularly monitoring renal function.

Influence on the ability to drive vehicles and / or mechanisms

There are no data on the effect of the drug on the ability to drive vehicles and / or mechanisms. Due to the possible occurrence of dizziness or increased fatigue, care should be taken when driving vehicles or working with mechanisms.

Form of production

Film-coated tablets,50 mg (25.7 mg + 24.3 mg)

14 tablets in a PVC blister/PVDC and aluminum foil. 2 or 4 blisters together with the instructions for medical use in a cardboard pack.

Film-coated tablets,100 mg (51.4 mg + 48.6 mg)

14 tablets in a PVC blister/PVDC and aluminum foil. 2 or 4 blisters together with the instructions for medical use in a cardboard pack.

Film-coated tablets,200 mg (102.8 mg + 97.2 mg)

14 tablets in a PVC blister/PVDC and aluminum foil. 2 or 4 blisters together with the instructions for medical use in a cardboard pack.

It is allowed to have a primary opening control on the cardboard pack.

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 3 years. The drug should not be used after the expiration date.

Active ingredient

Valsartan, Sacubitril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets