Uperio pills 100mg (51.4mg+48.6mg), 28pcs

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 anhydrous form of 100 mg, which is equivalent to the content of 48.6 mg of sacubitril and 51.4 mg of valsartan);

excipients:

microcrystalline cellulose-34,897 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:

premix sheath white – 7,732 mg (hypromellose – 5,521 mg, titanium dioxide-1,106 mg, macrogol 4000 – 0,553 mg, talc – 0,553 mg), premix shell yellow – 0,256 mg (hypromellose – 0,183 mg, dye iron oxide yellow – 0,037 mg, macrogol 4000 -0,018 mg, talc – 0,018 mg), premix sheath red – 0.012 mg (hypromellose – 0,009 mg, dye iron oxide red – 0.002 mg, macrogol 4000 – 0.001 mg, talc – 0.001 mg).

Action

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.

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 (APA 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.

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 (from 1/100 to <1/10); infrequent (from 1/1,000 to <1/100); rare (from ?1/10000 to <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 labyrinthine disorders: often-vertigo.
• Vascular disorders: very often – a marked decrease in blood pressure; often-fainting, 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.
• Renal 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 recommended starting dose of the drug is 100 mg (51.4 mg + 48.6 mg) 2 times a day. Depending on tolerability, the dose of Uperio 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 is possible no earlier than 36 hours after the withdrawal of the ACE inhibitor, since in the case of simultaneous use, angioedema may occur. Since Juperio contains ARA II valsartan, it should not be used simultaneously with another drug that contains ARA II. If patients have problems tolerating the drug (clinically significant decrease in blood pressure, hyperkalemia, impaired renal function), you should consider temporarily reducing the dose or adjusting the dose of concomitant medications. 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 (eGFRCaution 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.

Form of production

Oval biconvex tablets, covered with a film-coated pale yellow color with a chamfer, without risk. On one side is engraved “L1”, on the other – “NVR”. On a cross-section, the core is white or almost white in color.

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

By prescription

Purpose

For adults as directed by your doctor

Indications

Heart Failure