Uperio pills 50mg (25.7mg+24.3mg), 56pcs

Composition

1 film-coated tablet,50 mg (25.7 mg + 24.3 mg) contains:

Active ingredient:

sacubitril and valsartan hydrate complex of sodium salts -56.551 mg (in terms of the acidic form anhydrous 50 mg, which is equivalent to the content of 24.3 mg of sacubitril and 25.7 mg of valsartan);

excipients:  microcrystalline cellulose-91.449 mg, giprolose-25,000 mg, crospovidone-18,000 mg, magnesium stearate-6,000 mg, talc-2,000 mg, colloidal silicon dioxide-1,000 mg;

shell:  white shell premix – 7,957 mg (hypromellose – 5,681 mg, titanium dioxide – 1,138 mg, macrogol 4000 – 0.569 mg, talc – 0.569 mg), red shell premix – 0.019 mg (hypromellose – 0.014 mg, iron oxide red dye – 0.003 mg, macrogol 4000 -0.001 mg, talc – 0.001 mg), black shell premix – 0.024 mg (hypromellose – 0.017 mg, iron oxide black dye – 0.003 mg, macrogol 4000 – 0.002 mg, talc – 0.002 mg).

Pharmacological action

The effect of the drug Uperio is mediated by a new mechanism, namely, simultaneous suppression of the activity of neprilysin (neutral endopeptidase, NEP) substance LBQ657 (active metabolite of sacubitril) and angiotensin II receptor blocker type 1 (AT1) valsartan, which is an angiotensin II receptor antagonist (ARA II).

The complementary beneficial effects of sacubitril and valsartan on the cardiovascular system and kidneys in patients with heart failure are due to an increase in the number of peptides cleaved by neprilysin (such as natriuretic peptides (NP)), which is mediated by the action of LBQ657, while valsartan simultaneously suppresses the negative effects of angiotensin II.

NP activates 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 AT1 receptor, 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 restructuring of the cardiovascular system, which exacerbates disorders in its functioning.

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 suppression of neprilysin and blockade of RAAS.

In a seven-day study in patients with reduced left ventricular ejection fraction (LVEF), in which valsartan was used as a control, the use of sacubitril and valsartan 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 atrial natriuretic peptide (MR-proANP) and the N-terminal fragment of the brain natriuretic peptide precursor (NT-proBNP) in the 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 sacubitril and valsartan blocks the AT1 receptor, 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-p (Ar) in the brain and cerebrospinal fluid (CSF). Against the background of the use of the sacubitril and valsartan complex at a dose of 400 mg once a day for 2 weeks in healthy volunteers, the concentration of Ap 1-38 in CSF increased; at the same time, the concentrations of AP 1-40 and 1-42 in 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 acute 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 acute heart failure was 4.7% o (3.1%o for the risk of death due to cardiovascular pathology and 2.8% o for primary hospitalization due to acute 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 (hazard rAT1o, 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-valsartan complex breaks down into sacubitril, which is then metabolized to form the LBQ657 metabolite, and valsartan; plasma concentrations of these substances peak 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. In the case of taking the sacubitril and valsartan complex twice a day, the equilibrium concentrations of sacubitril, LBQ657 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 LBQ657 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, LBQ657, 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 LBQ657 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

Sacubitril under the action of enzymes is rapidly converted to the metabolite LBQ657, which is not significantly metabolized further. Valsartan is metabolized to a small extent, only about 20% of the administered dose is detected in the form of 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 as LBQ657) and -13% of valsartan and its metabolites are excreted by the kidneys; 37-48% of sacubitril (mainly as LBQ657) and 86% of valsartan and its metabolites are excreted through the intestine. Sacubitril, LBQ657, and valsartan are eliminated from 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, LBQ657 and valsartan change proportionally to the dose.

Pharmacokinetics in special clinical cases

Patients over 65 years of age

Exposures to LBQ657 and valsartan in 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 LBQ657, 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 to moderate renal impairment (estimated glomerular filtration rate (eGFR) >30 ml / min/1.73 m > 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 LBQ657 and valsartan are highly 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. LBQ657 exposure increased by 1.5 and 1.9 times, and valsartan exposure increased by 1.2 and 2.1 times (compared to 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 in patients of different racial and ethnic groups did not differ significantly.

Gender

Pharmacokinetics of sacubitril and valsartan complex (sacubitril, LBQ657 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.

Use during pregnancy and lactation

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.

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. Since preclinical studies have noted the isolation of sacubitril and valsartan in the milk of lactating animals, it is not recommended to use the drug Juperio during breastfeeding. The decision to stop breastfeeding or to discontinue Uperio and continue breastfeeding should be made taking into account the importance of its use for the mother. 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 discontinuation of ACE inhibitors.
• The presence of angioedema in the anamnesis against the background of previous therapy with ACE inhibitors or ARA II.
• Concomitant use with aliskiren in patients with diabetes mellitus or in patients with moderate or severe renal impairment (eGFR
• Severe hepatic impairment (Child Pugh Class C), biliary cirrhosis, and cholestasis.
• Intresto 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

Caution should be exercised when using Uperio in patients with severe renal impairment (eGFR <30 ml / min/1.73 m2 of body surface area), including patients undergoing hemodialysis or undergoing hemodialysis (eGFR

Caution should be exercised when using the drug concomitantly with statins, phosphodiesterase type 5 inhibitors.

Caution should be exercised when using the drug in patients with a history of angioedema due to the lack of data on the use of the drug in patients of this category. Patients of the black race may be more at risk of angioedema.

Side effects

The identified adverse events (AES) corresponded to the pharmacological characteristics of the drug Uperio and concomitant diseases present in patients. The most common AES were a marked decrease in blood pressure, hyperkalemia, and impaired renal function caused by dose adjustment of Uperio or discontinuation of therapy. The incidence of AE did not depend on the gender, age, or race of the patients. AES are listed in accordance with the system-organ class of the MedDRA Medical Dictionary for regulatory activities. Within each organ-system class, AES are distributed by frequency of occurrence in order of decreasing importance.

The following criteria were used to estimate the frequency: very common (>1/10); common (>>1/100 to >><1/10); infrequent (>1/1,000 to <1/10); infrequent (><1/100); rare (>1/10000 to < 1/100); rare (><1/1000); very rare (

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 – a marked decrease in blood pressure: often – fainting, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders: often – cough.

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

Track 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 The drug Uperio is contraindicated for use simultaneously with ACE inhibitors, since the suppression of neprilysin simultaneously with the use of an ACE inhibitor may increase the risk of angioedema.

The use of the drug Uperio can be stopped no earlier than 36 hours after the withdrawal of the ACE inhibitor. The use of an ACE inhibitor is possible no earlier than 36 hours after the last dose of the drug Juperio.

Aliskiren

In patients with diabetes mellitus and in patients with impaired renal function (eGFR

Not recommended drug interactions

Angiotensin receptor antagonists

Since one of the active ingredients of the drug is an angiotensin II receptor antagonist, 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 OATP1-In-1 and OATP1-IN-1 transporters. Uperio may increase the systemic exposure of OATP 1-In-1 and OATP 1-IN-1 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. For this reason, Juperio should be used with caution in combination with statins.

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 prescribing 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. When lithium preparations were co-administered with ACE inhibitors and ARA II inhibitors, a reversible increase in the concentration of lithium in the blood serum and an increase in toxic manifestations were observed. 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 (LBQ657) and valsartan are substrates of the 0 ATP1B1,0 ATP1B1 and OATP1 transporter proteins; valsartan is also a substrate of the MRP2 transporter protein. Systemic exposure to LBQ657 or valsartan may increase in patients receiving Juperio concomitantly with OATP1-In-1, OATP1-IN-1, OATP1-in-1 inhibitors (e. g. rifampicin and cyclosporine) or MRP2 (e. g. ritonavir), respectively. Caution should be exercised at the beginning and at the end of the combined use of the drug 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 (gliburide) or cimetidine are not expected when co-administered with the drug Uperio.

Interactions with cytochrome P 450 isoenzymes

Available studies demonstrate that the probability of drug interactions mediated by cytochrome CYP450 isoenzymes is low, since the complex of active substances is only 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.

In patients who have not previously received therapy with ACE inhibitors or ARA II, or who 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). Depending on the tolerance, the dose of Intresto should be doubled 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.

The use of the drug Uperio is possible no earlier than 36 hours after the withdrawal of the ACE inhibitor, 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 Perio(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. In patients with severe renal impairment (eGFR Caution is recommended when using the drug in patients of this category due to the limited availability of 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 a marked decrease in blood pressure due to the antihypertensive effect of active substances. In this case, symptomatic treatment is recommended.

In case of accidental overdose, you should induce vomiting (if the drug was taken recently) or perform gastric lavage. In case of a marked decrease in blood pressure, intravenous use of 0.9% sodium chloride solution is necessary as therapy, the patient should be placed with his legs raised for the necessary period of time for therapy, take active measures to maintain the activity of the cardiovascular system, including regular monitoring of the activity of the heart and respiratory system, the volume of circulating blood (BCC) and the amount of urine released. 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 white with a purple tinge of color with a chamfer, without risk. On one side is engraved “LZ”, on the other – “NVR”. On a cross-section, the core is white or almost white in color.

Special instructions

Marked decrease in blood pressure

Cases of clinically significant hypotension have been reported in patients treated with Uperio. If a marked decrease in blood pressure occurs, consideration should be given to adjusting the dose of diuretics, concomitant antihypertensive agents, as well as eliminating the causes of a pronounced decrease in blood pressure (for example, hypovolemia). If, despite these measures, a marked decrease in blood pressure persists, the dose of Uperio should be reduced or the drug should be temporarily discontinued. Final withdrawal of the drug is usually not required. Patients with hypovolemia, which may be caused by diuretic therapy, a low-salt diet, diarrhea, or vomiting, are generally more likely to experience a marked decrease in blood pressure.

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 the comparative safety and efficacy study 14/17 (compared with 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 and monitoring should be provided 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 the swelling 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 a history of angioedema caused by the use of an ACE inhibitor or ARA II, the drug Juperio should not be used. 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.

Storage conditions

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

The shelf

life is 30 months. The drug should not be used after the expiration date.

Active ingredient

Valsartan, Sacubitril

Conditions of release from pharmacies

Prescription