Uperio tabs 50mg (25.7mg + 24.3mg) #28

Uperio instruction

You can buy Uperio here

Release form

Tablets 50 mg (25.7 mg + 24.3 mg)
Oval biconvex tablets, film-coated white with a violet shade of color with a facet, without risks. “LZ” engraved on one side, “NVR” on the other. In cross section, the core is white or almost white.

Tablets 100mg (51.4mg + 48.6mg)
Oval biconvex tablets, film-coated pale yellow with a chamfer, without risks. “L1” engraved on one side and “NVR” on the other. In cross section, the core is white or almost white.

Tablets 200 mg (102.8 mg + 97.2 mg)
Oval biconvex tablets, film coated light pink color with a facet, without risks. “L11” engraved on one side and “NVR” on the other. In cross section, the core is white or almost white.

Composition

1 tablet, film coated, 50 mg (25.7 mg + 24.3 mg) contains:
Active ingredient: sacubitrile and valsartan hydrate complex of sodium salts -56.551 mg (in terms of anhydrous acid form 50 mg, equivalent to 24.3 mg of sacubitrile and 25.7 mg of valsartan);
excipients: microcrystalline cellulose - 91,449 mg, hyprolosis - 25,000 mg, crospovidone - 18,000 mg, magnesium stearate - 6,000 mg, talc - 2,000 mg, colloidal silicon dioxide - 1,000 mg;
shell: white premix premix - 7.957 mg (hypromellose - 5.681 mg, titanium dioxide - 1.138 mg, macrogol 4000 - 0.569 mg, talc - 0.569 mg), red premix shell - 0.019 mg (hypromellose - 0.014 mg, iron red dye - 0.003 mg, macrogol 4000 -0.001 mg, talc - 0.001 mg), shell premix black - 0.024 mg (hypromellose - 0.017 mg, iron dye black oxide - 0.003 mg, macrogol 4000 - 0.002 mg, talc - 0.002 mg).

pharmachologic effect

The action of the drug Uperio is mediated by a new mechanism, namely, the simultaneous suppression of the activity of neprilysin (neutral endopeptidase (neutral endopeptidase, NEP)) with LBQ657 (the active metabolite of sacubitrile) and blockade of receptors for angiotensin II of the 1st type (AT1) valsartan of the applicant, who is an actor of anakubitrile, who is an antiviral receptor blockade. II (APA II). The complementary beneficial effects of sacubitrile 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 neprilisin (such as natriuretic peptides (NP)), which is mediated by LBQ657, while the negative effects of angiotensin are suppressed by valsartan Ii. 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 natririesis and diuresis, an increase in glomerular filtration rate and renal blood flow, inhibition of renin and aldosterone, and in addition, and a decrease in the development of the renal and aldosterone, in addition, in addition to the development of the renal and aldosterone, and in the course of the development of the symptoms of the and antifibrotic action. Valsartan, selectively blocking the AT1 receptor, suppresses the negative effects of angiotensin II on the cardiovascular system and kidneys, and also blocks angiotensin II-dependent release of aldosterone. This prevents the persistent activation of the renin-angiotensin-aldosterone system (RAAS), which causes vasoconstriction, sodium and water retention by the kidneys, growth activation and cell proliferation, as well as the subsequent rearrangement of the cardiovascular system, which aggravates impairments in its functioning.

Uperio, indications for use

Chronic heart failure (NYHA Class II-IV class) in patients with systolic dysfunction to reduce the risk of cardiovascular mortality and hospitalization for heart failure.

Contraindications

    Hypersensitivity to sacubitril or to valsartan, as well as to other auxiliary components of the drug.
    Simultaneous use with inhibitors of angiotensin-converting enzyme (ACE), as well as a period of 36 hours after discontinuation of ACE inhibitors.
    The presence of angioedema in history against the background of previous therapy with ACE or APA II inhibitors.
    Simultaneous use with aliskiren in patients with diabetes mellitus or in patients with moderate or severe renal impairment (eGFR
    Severe liver function impairment (Child Pugh class C), biliary cirrhosis and cholestasis.
    The drug Intresto is not recommended for use in children under the age of 18 years due to the lack of data on efficacy and safety.
    Pregnancy, pregnancy planning and breastfeeding period.
    Simultaneous use with other drugs containing ARA II, because The drug contains valsartan.

Carefully

It is necessary to observe caution when using the drug Uperio in patients with severe impaired renal function (eGFR
Caution should be exercised with the simultaneous use of the drug with statins, inhibitors of phosphodiesterase type 5.
Caution should be exercised when using the drug in patients with angioedema in the history of the lack of data on the use of the drug in patients in this category. Patients of the Negroid race may be more at risk for angioedema.

Dosage and administration

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

The target (maximum daily) dose of Uperio is 200 mg (102.8 mg + 97.2 mg) 2 times a day. The recommended initial 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 or APA II inhibitors, or who have received these drugs in low doses, the patient should be given 50 mg (25.7 mg + 24.3 mg) 2 times a day with a slow dose increase ( doubling the daily dose 1 time in 3-4 weeks). Depending on the tolerability, the dose of the drug 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.

Use of the drug Uperio is possible not earlier than 36 hours after discontinuation of the ACE inhibitor, since in the case of simultaneous use, angioedema may develop. Since ARP II valsartan is part of the drug, it should not be used simultaneously with another drug that contains ARA II.

With the development of signs of impaired tolerability of the drug Uperio (clinically pronounced decrease in blood pressure, hyperkalemia, renal dysfunction), it is necessary to consider the issue of temporary dose reduction or dose adjustment of simultaneously used drugs.

Special Category Patients

Patients with impaired renal function

In patients with impaired renal mild (eGFR 60–90 ml / min / 1.73 m2) or moderate severity (eGFR 30–60 ml / min / 1.73 m2), dose adjustment is not required. In patients with severe impaired renal function (eGFR <30 ml / min / 1.73 m2), the recommended initial dose of the drug is 50 mg twice a day. When using the drug Uperio patients in this category it is recommended to be careful due to the limited data.

Patients with impaired liver function

In patients with impaired mild liver function (Child-Pugh class A), the dose adjustment of the drug Uperio is not required. In patients with impaired moderate liver function (Child-Pugh class B), the recommended initial dose of the drug is 50 mg twice a day. The drug Uperio is not recommended for use in patients with severely impaired liver function (class C according to the Child-Pugh classification).

Use in children and adolescents under the age of 18

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

Use for patients older than 65 years

Patients over 65 years of age do not require dose adjustment.

Use during pregnancy and lactation

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

Like other drugs directly acting on the RAAS, drug Uperio should not be used during pregnancy. The effect of the drug Yuprio is mediated by blockade of angiotensin II receptors, so the risk to the fetus cannot be excluded. In pregnant women who took valsartan, there have been cases of spontaneous abortion, low flow and impaired renal function in the newborn.

If pregnancy occurs during drug treatment, the patient should stop taking the drug and inform your doctor. Since preclinical studies have noted the release of sacubitrile and valsartan with the milk of lactating animals, it is not recommended to use the drug Uperio during breastfeeding. The decision to refuse breastfeeding or to discontinue the drug Uperio and the continuation of breastfeeding should be made taking into account the importance of its use for the mother. There is no data on the effect of Uperio on the fertility of men and women. In studies of the drug Uperio in animals, no decrease in fertility was noted.

Side effects

    Identified adverse events (AEs) corresponded to the pharmacological characteristics of the drug Uperio and associated diseases that are present in patients. The most common AEs were a marked reduction in blood pressure, hyperkalemia, and renal dysfunction caused by dose adjustment of the drug Uperio or discontinuation of therapy. The frequency of AE is not dependent on the gender, age, or race of the patients. AEs are listed in accordance with the system-organ class of the medical dictionary for MedDRA regulatory activities. Within each system-organ class, NAs are distributed by frequency of occurrence in order of decreasing importance. The following criteria were used to estimate the frequency: very often (? 1/10); often (from? 1/100 to Violations from the side of metabolism and nutrition: very often - hyperkalemia; often - hypokalemia.
    Nervous system disorders: often - dizziness, headache; infrequently - orthostatic dizziness.
    Disturbances from an organ of hearing and labyrinth disturbances: often - vertigo.
    Violations of the blood vessels: very often - a pronounced decrease in blood pressure; often - a syncope, orthostatic hypotension.
    Disturbances from the respiratory system, chest and mediastinal organs: often - cough.
    Disorders of the gastrointestinal tract: often - diarrhea, nausea.
    Violations of the skin and subcutaneous tissues: infrequently - angioedema.
    Disturbances from the kidneys and urinary tract: very often - impaired renal function; often - renal failure (including acute renal failure).
    General disorders and disorders at the injection site: often - fatigue, asthenia.
    If any of the side effects indicated in the instruction are aggravated, or you have noticed any other side effects that are not indicated in the instruction, inform your doctor.

special instructions

A pronounced decrease in blood pressure

In patients treated with the drug Uperio, there have been cases of clinically severe arterial hypotension. If a pronounced decrease in blood pressure occurs, the question of dose adjustment of diuretics, concomitant antihypertensive drugs should be considered, as well as the elimination of the causes of the pronounced decrease in blood pressure (for example, hypovolemia). If, despite these measures, a pronounced decrease in blood pressure is maintained, the dose of the drug Uperio should be reduced or the drug should be discontinued for a while. Final drug withdrawal is usually not required. The likelihood of a pronounced decrease in blood pressure is usually higher in patients with hypovolemia, which can be caused by diuretic therapy, a low-salt diet, diarrhea, or vomiting.

Before starting the use of the drug Uperio, a correction should be made to the sodium content in the body and / or replenish the BCC.

Renal dysfunction

Like any other drug that acts on the RAAS, drug Uperio can cause kidney function deterioration. In a comparative study of the safety and efficacy of 14/17 (compared with enalapril), clinically significant impairment of renal function was rarely observed, and Uperio was less frequently canceled due to similar disorders (0.65%) than enalapril (1.28%). In the case of clinically significant impairment of renal function, consideration should be given to reducing the dose of the drug Uperio. When using the drug Uperio in patients with severely impaired renal function, caution should be exercised.

Hyperkalemia

Like any other drug that is acting on the RAAS, drug Uperio may increase the risk of developing hyperkalemia. In a comparative study of safety and efficacy (compared with enalapril), clinically significant hyperkalemia was rarely observed; Due to hyperkalemia, the drug Uperio was canceled in 0.26% of patients and enalapril in 0.35% of patients. Drugs that can increase the content of potassium in the blood serum (for example, potassium-saving diuretics, potassium preparations) should be used with caution at the same time as the drug Uperio. In the event of a clinically significant hyperkalemia, measures such as reducing food intake of potassium or adjusting the dose of related drugs should be considered. It is recommended to regularly monitor the content of potassium in the blood serum, especially in patients with such risk factors as severe renal dysfunction, diabetes mellitus, hypoaldosteronism, or a diet high in potassium.

Angioedema

Against the background of the use of the drug Uperio, cases of angioedema were noted. In the event of angioedema, drug Yupiro should be immediately canceled and appropriate treatment and monitoring of the patient should be prescribed until all symptoms have been resolved. Reappoint the drug Uperio should not be. In cases of confirmed angioedema, in which the edema spreads only to the face and lips, this condition was usually resolved without intervention, although the use of antihistamines helped alleviate the symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. In cases where edema spreads to the tongue, vocal folds or larynx, which can lead to obstruction of the respiratory tract, proper treatment should be started immediately, for example, subcutaneous administration of epinephrine (adrenaline) solution 1: 1000 (0.3-0.5 ml) and / or take appropriate measures to ensure airway obstruction.

Patients with a history of angioedema caused by the use of an ACE inhibitor or ARA II should not be used. Patients of the Negroid race may be more at risk for angionsvrotic edema.

Patients with renal artery stenosis

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

Impact on 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. In connection with the possible occurrence of dizziness or increased fatigue, caution should be exercised when driving vehicles or working with mechanisms.

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 developing angioedema.

Use of the drug Uperio can be possible not earlier than 36 hours after discontinuation of the ACE inhibitor. The use of an ACE inhibitor is possible no earlier than 36 hours after the last dose of the drug, Uperio.

Aliskiren

In patients with diabetes 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 that need to be considered
HMG-CoA reductase inhibitors (statins)
Research data shows that sacubitrile inhibits the activity of the OATR1B1 and OATR1BZ carriers. The drug Uperio can increase the systemic exposure of such substrates OATP1B1 and OATP1VZ, as statins. In patients who received the drug Uperio simultaneously 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, the drug Uperio simultaneously with statins should be used with caution.

Sildenafil

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

Estimated drug interactions that need to be considered

Potassium

The simultaneous use of potassium-sparing diuretics (for example, triamterene and amiloride), antagonists of mineralocorticoids (for example, spironolactone and eplerenone), potassium preparations or potassium-containing salt substitutes can cause an increase in the content of potassium and serum creatinine concentration. In patients receiving the drug Uperio simultaneously with these drugs, it is recommended to regularly monitor the content of potassium in the blood serum.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors)
The use of drug Uperio simultaneously with NSAIDs in patients over the age of 65 years, in patients with hypovolemia (including patients receiving diuretics) and in patients with impaired renal function may increase the risk of impaired renal function. In patients receiving the drug Uperio simultaneously with NSAIDs, when prescribing such a treatment regimen and in case of its change, it is recommended to monitor renal function.

Lithium preparations

The possibility of drug interactions between the drug and drugs Yuprio lithium has not been studied. With the simultaneous use of lithium preparations with ACE and APA II inhibitors, there was a reversible increase in the concentration of lithium in the blood serum and, in this connection, an increase in toxic manifestations. In patients receiving the drug Uperio along with lithium preparations, it is recommended to carefully control the lithium content in the serum. In the case of additional use of a diuretic drug, the risk of the toxic effect of lithium may increase.

Protein carriers

The active metabolite of sacubitrile (LBQ657) and valsartan are substrates of the carrier proteins 0ATP1B1, 0ATP1B3 and OATZ; valsartan is also a substrate of the protein carrier MRP2. In patients receiving Uperio simultaneously with inhibitors OATP1B1, OATPR1VZ, OATZ (for example, rifampicin and cyclosporine) or MRP2 (for example, ritonavir), systemic exposure to LBQ657 or valsartan, respectively, may increase. At the beginning and at the time of completion of the joint use of the drug Uperio and this group of drugs requires caution.

No significant drug interactions

In the case of the use of the drug Uperio in combination with furosemide, digoxin, warfarin, hydrochlorothiazide, amlodipine, metformin, omeprazole, carvedilol, nitroglycerin intravenously (IV) or the combined drug levonorgestrel and ethinyl estradiol, we found no significant interactions.

No interactions with atenolol, indomethacin, glibenclamide (glyburide) or cimetidine when combined with the drug Uperio is not expected.

Interactions with isoenzymes of cytochrome P450 system

Existing studies demonstrate that the probability of drug interactions mediated by cytochrome CYP450 isoenzymes is low, since the complex of active substances to a small extent is 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.

Overdose

There is not enough data on overdose with Uperio in humans. A single use of the drug at a dose of 1200 mg and multiple doses of 900 mg in healthy volunteers was accompanied by good tolerability.

The most likely symptom of overdose is a pronounced decrease in blood pressure due to the antihypertensive effect of the active substances. In this case, symptomatic treatment is recommended.

In case of accidental overdose, it is necessary to induce vomiting (if the drug has been taken recently) or to perform a gastric lavage. If a pronounced decrease in blood pressure occurs as a therapy, intravenous administration of 0.9% sodium chloride solution is necessary, the patient should be laid, raising his legs for a period of time necessary for therapy, to take active measures to maintain the cardiovascular system, including regular monitoring of the heart and respiratory system, circulating blood volume (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.

Storage conditions

Shelf life - 30 months.
The drug should not be used after the expiration date.
At temperatures not above 25 ° C. Keep out of the reach of children.

Terms of sell

You don't need a prescription to buy Uperio.