Uperio
Uperio: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Uperio
ATX code: C09DX04
Active ingredient: valsartan + sacubitril (valsartanum + sacubitrilum)
Producer: Novartis Farma, SpA (Italy)
Description and photo update: 2018-27-07
Prices in pharmacies: from 1500 rubles.
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Uperio is a drug used for chronic heart failure.
Release form and composition
Dosage form of Uperio - film-coated tablets:
- dosage of 50 mg (25.7 mg + 24.3 mg): biconvex, oval, white with a violet tinge, without risks, with a chamfer, LZ engraving on one side and NVR on the other side (in blisters of 14 pcs., in a cardboard box 2 blisters);
- dosage of 100 mg (51.4 mg + 48.6 mg): biconvex, oval, pale yellow, without risks, with a chamfer, LI engraving on one side and NVR on the other side (in blisters of 14 pcs., in a cardboard box 2 or 4 blisters);
- dosage of 200 mg (102.8 mg + 97.2 mg): biconvex, oval, light pink, without risks, with a chamfer, LII engraving on one side and NVR on the other side (in blisters of 14 pcs., in a cardboard box 2 or 4 blisters).
Composition of 1 tablet (50/100/200 mg, respectively):
- active substance: valsartan and sacubitril hydrated complex of sodium salts - 56.551 / 113.103 / 226.206 mg (corresponds to the content of the anhydrous acid form - 50/100/200 mg, of which the content of valsartan is 25.7 / 51.4 / 102.8 mg, sacubitril - 24.3 / 48.6 / 97.2 mg);
- auxiliary components: colloidal silicon dioxide - 1/1/2 mg; talc - 2/2/4 mg; magnesium stearate - 6/6/12 mg; crospovidone - 18/18/36 mg; hyprolosis - 25/25/50 mg; microcrystalline cellulose - 91.449 / 34.897 / 69.794 mg;
- shell: red shell premix - 0.019 / 0.012 / 0.168 mg (talc - 0.001 / 0.001 / 0.012 mg; macrogol 4000 - 0.001 / 0.001 / 0.012 mg; iron dye red oxide - 0.003 / 0.002 / 0.024 mg; hypromellose - 0.014 / 0.009 / 0.120 mg); white shell premix - 7.957 / 7.732 / 11.796 mg (talc - 0.569 / 0.553 / 0.843 mg; macrogol 4000 - 0.569 / 0.553 / 0.843 mg; titanium dioxide - 1.138 / 1.106 / 1.687 mg; hypromellose - 5.681 / 5.521 / 8.422 mg); tablets of 50 and 200 mg - black shell premix - 0.024 / 0.036 mg (talc - 0.002 / 0.003 mg; macrogol 4000 - 0.002 / 0.003 mg; iron dye black oxide - 0.003 / 0.005 mg; hypromellose - 0.017 / 0.026 mg); tablets of 100 mg - yellow shell premix - 0.256 mg (talc - 0.018 mg; macrogol 4000 - 0.018 mg; iron dye yellow oxide - 0.037 mg; hypromellose - 0.183 mg).
Pharmacological properties
Pharmacodynamics
The action of Uperio is mediated by a new mechanism: the simultaneous blockade of receptors for angiotensin II type 1 (AT1) by valsartan, which is an antagonist of angiotensin II receptors (APA II), as well as suppression of the activity of neprilisin by the substance LBQ657, which is an active metabolite of sacubitrile. The complementary beneficial effects of the active substances of the drug on the state of the cardiovascular system and kidneys against the background of heart failure are due to an increase in the amount of peptides cleaved by neprilysin (such as natriuretic peptides), which is mediated by the action of LBQ657 with a simultaneous suppression of the negative effects of angiotensin II by valsartan.
Natriuretic peptides activate membrane-bound receptors coupled with guanylyl cyclase, thereby increasing the concentration of cyclic guanosine monophosphate, which causes a decrease in sympathetic activity, suppression of the release of renin and aldosterone, an increase in the rate of glomerular filtration, renal blood flow, diuresis and natriuresis, symptoms of vasfodibrotropathy and anti-phlegm.
Valsartan blocks angiotensin II-dependent aldosterone release and suppresses the negative effects of angiotensin II on the kidneys and cardiovascular system by selectively blocking the AT1 receptor. Thus, it prevents the persistent activation of the renin-angiotensin-aldosterone system, which causes the proliferation and activation of cell growth, water and sodium retention by the kidneys, vasoconstriction, as well as the subsequent restructuring of the cardiovascular system, which aggravates disturbances in its functioning.
Evaluation of the pharmacodynamic effects of the valsartan-sacubitril complex was carried out after its single and multiple use in patients with chronic heart failure and healthy volunteers. The observed effects corresponded to the mechanism of action of the complex of active substances Uperio, consisting in the simultaneous blockade of the renin-angiotensin-aldosterone system and the suppression of neprilisin. During a 7-day study in patients with reduced left ventricular ejection fraction, to whom valsartan was prescribed for control, the use of sacubitril and valsartan served to increase the concentration of cyclic guanosine monophosphate in urine,a statistically significant short-term increase in natriuresis 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 blood plasma (in comparison with valsartan). During a 21-day study in patients with a reduced left ventricular ejection fraction, the use of a combination of sacubitril and valsartan served to reduce plasma concentrations of NT-proBNP, endothelin-1 and aldosterone, a statistically significant increase in the concentration of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate in urine cyclic guanosine monophosphate in blood plasma (in comparison with the initial state). During a 21-day study in patients with a reduced left ventricular ejection fraction, the use of a combination of sacubitril and valsartan served to reduce plasma concentrations of NT-proBNP, endothelin-1 and aldosterone, a statistically significant increase in the concentration of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate in urine cyclic guanosine monophosphate in blood plasma (in comparison with the initial state). During a 21-day study in patients with a reduced left ventricular ejection fraction, the use of a combination of sacubitril and valsartan served to reduce plasma concentrations of NT-proBNP, endothelin-1 and aldosterone, a statistically significant increase in the concentration of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate in urine cyclic guanosine monophosphate in blood plasma (in comparison with the initial state).
In addition, the combined use of valsartan and sacubitril blocks the AT1 receptor, as evidenced by an increase in the concentration and activity of renin in the blood plasma.
Another study of the use of a complex of valsartan and sacubitril showed a more significant increase in the concentrations of cyclic guanosine monophosphate and brain natriuretic peptide (BNP) in the urine and a more pronounced decrease in the concentration of NT-proBNP in blood plasma (compared with the use of enalapril). Since NT-proBNP, unlike BNP, is not a substrate of neprilisin, it can be used as a biomarker in monitoring patients with heart failure receiving a complex of sacubitrile and valsartan.
In a study with a detailed study of the QT interval in healthy men, a single use of a complex of sacubitril and valsartan in doses of 0.4 and 1.2 g on cardiac repolarization had no effect.
Neprilisin is one of several enzymes involved in the metabolism of amyloid-β (Aβ) in the brain and cerebrospinal fluid. During therapy with a complex of sacubitril and valsartan at a dose of 0.4 g once a day for 14 days in healthy volunteers, the concentration of Aβ l-38 in the cerebrospinal fluid increased, and Aβ 1-40 and 1-42 did not change in any way. The clinical significance of this fact is unknown.
When conducting a study of the use of a complex of sacubitril and valsartan in patients with chronic heart failure, a statistically significant reduction in the risk of mortality due to cardiovascular disease or hospitalization due to acute heart failure was noted. The absolute decrease in these indicators was 4.7%, relative (compared with enalapril) - 20%. The effect was noted in the early stages of the study and persisted throughout the entire period of its study. The development of such an action of the drug was facilitated by both active substances of Uperio.
In the study drug group, the incidence of sudden death due to cardiovascular disease, which accounted for 45% of all deaths, decreased by 20% compared with the enalapril group. The incidence of the development of insufficiency of the contractile function of the heart, which is in 26% of cases the cause of death due to cardiovascular pathology, decreased in the group of the study drug by 21% compared with that in the group of enalapril.
Pharmacokinetics
Characteristics of the complex of sacubitril and valsartan:
- absorption: after oral administration, the complex breaks down into valsartan and sacubitril. sacubitrile is further metabolized to form the LBQ657 metabolite, Cmax (maximum concentration) of which in blood plasma is reached after 3 hours; The Cmax of the components of the complex is 0.5 and 1.5 hours, respectively, and their absolute bioavailability is ≥ 60 and 23%; equilibrium concentrations of valsartan, LBQ657 and sacubitril when taken 2 times a day are reached after 3 days; in the equilibrium state, statistically significant accumulation of valsartan and sacubitril is not observed, however, the accumulation of LBQ657 with a single use exceeds the concentration by 1.6 times; simultaneous food intake on the indicators of systemic exposure to valsartan, LBQ657 and sacubitril has no clinically significant effect;when taking the complex simultaneously with food, a decrease in the exposure of valsartan is not accompanied by a clinically significant decrease in the therapeutic effect; the use of the complex does not depend on the time of the meal;
- distribution: the complex has a significant degree of connection with blood plasma proteins - from 94 to 97%; when comparing exposures in cerebrospinal fluid and blood plasma, it was found that LBQ657 penetrates the blood-brain barrier to a small extent (0.28%); the apparent Vd (volume of distribution) of the complex varies from 107.8 to 157.4 liters;
- metabolism: under the action of enzymes, sacubitril is rapidly converted into the metabolite LBQ657, which is not significantly metabolized further; the metabolism of valsartan is insignificant and only 20% of the applied dose is found in the form of metabolites; the hydroxyl metabolite is found in blood plasma in insignificant concentrations (<10%); due to the fact that both substances are minimally metabolized by cytochrome CYP450 isoenzymes, a change in their pharmacokinetics with the combined use of drugs that affect CYP450 isoenzymes is unlikely;
- Excretion: 52 to 68% of sacubitrile (mainly in the form of LBQ657) and approximately 13% of valsartan and its metabolites are excreted by the kidneys after oral administration; 37–48% of sacubitril (mainly in the form of LBQ657) and 86% of valsartan and its metabolites through the intestines; T 1/2 (half-life) of valsartan, LBQ657 and sacubitril averages 9.9; 11.48 and 1.43 hours, respectively.
Pharmacokinetic parameters of sacubitril, LBQ657 and valsartan in the studied range of doses of the complex from 0.05 to 0.4 g vary in proportion to the dose taken.
Exposures of valsartan and LBQ657 in patients aged 65 and over are 30 and 42% higher, respectively, compared with younger patients. This difference is not associated with clinically significant effects, and therefore no dose adjustment of the drug is required.
There was no correlation between renal function and AUC (area under the concentration-time curve) for valsartan, but was observed for LBQ657.
In case of impaired renal function of mild and moderate severity, AUC for LBQ657 was 2 times higher than in patients with normal renal function, and in severe impairment, it increased 2.7 times.
In cases of impaired renal function of mild to moderate severity, dose adjustment of the drug is not required. Since there is not enough data on the use of the drug in severe renal impairment, it is recommended to be careful when prescribing Uperio to patients in this category.
There are no data on the use of the drug in patients on hemodialysis. However, since valsartan and LBQ657 bind to plasma proteins to a large extent, they are unlikely to be effectively cleared from the blood during hemodialysis.
The exposure of sacubitril in patients with mild and moderate liver dysfunctions increased by 1.5 and 3.4 times, respectively; LBQ657 - 1.5 and 1.9 times; valsartan - 1.2 and 2.1 times. In case of mild to moderate hepatic dysfunction, including biliary obstruction, the dose of Uperio is not adjusted. Due to the fact that studies on the use of the drug in patients with severe liver dysfunction have not been conducted, its appointment in such cases is not recommended.
Indications for use
According to the instructions, Uperio is prescribed for the treatment of chronic heart failure (class II-IV according to the NYHA classification) with systolic dysfunction to reduce the risk of cardiovascular mortality and hospitalization for heart failure.
Contraindications
Absolute:
- cholestasis, biliary cirrhosis, severe liver dysfunction;
- a history of angioedema against the background of previous treatment with angiotensin-converting enzyme inhibitors or ARA II;
- a period of 36 hours after the withdrawal of angiotensin-converting enzyme inhibitors;
- combined therapy with aliskiren (for diabetes mellitus, moderate or severe renal dysfunction), angiotensin-converting enzyme inhibitors, and other drugs that include ARA II;
- age under 18;
- pregnancy (planning pregnancy);
- lactation period;
- individual intolerance to the components contained in the preparation.
Relative (diseases / conditions, in the presence of which the appointment of Yuperio requires caution):
- severe renal dysfunction (including in patients on hemodialysis or undergoing hemodialysis);
- bilateral renal artery stenosis;
- a history of angioedema;
- hypovolemia, which can be caused by the use of diuretics, adherence to a low-salt diet, diarrhea or vomiting;
- simultaneous treatment with drugs that can increase the serum potassium content (for example, potassium preparations, potassium-sparing diuretics), phosphodiesterase type 5 inhibitors, statins.
Instructions for use Uperio: method and dosage
The tablets are taken orally, regardless of the diet.
Initial dose - 1 tablet of 100 mg (51.4 + 48.6 mg) 2 times a day; maximum - 1 pc. 200 mg (102.8 + 97.2 mg) 2 times a day.
Patients who have not previously received angiotensin-converting enzyme inhibitors or ARA II, or who have received low doses of these drugs, are prescribed Uperio 50 mg (25.7 + 24.3 mg) 2 times a day with a slow further increase in the dose by 2 times with an interval of 1 time 21-28 days.
Taking into account the patient's tolerance of the drug, the dose of Uperio is doubled every 14–28 days to the maximum daily dose.
After the abolition of the angiotensin-converting enzyme inhibitor, pills should be taken no earlier than after 36 hours, since angioedema may develop due to the combined use of drugs.
Due to the fact that the drug contains valsartan (ARA II), it cannot be used in combination with other drugs that include ARA II.
If the patient develops impaired renal function, hyperkalemia, a clinically pronounced decrease in blood pressure, indicating intolerance to Yuperio, it is recommended to consider a temporary reduction in its dose or dose adjustment of concurrently used drugs.
Side effects
Possible adverse reactions (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare):
- metabolism and nutrition: very often - hyperkalemia; often hypokalemia;
- nervous system: often - headache, dizziness; infrequently - orthostatic dizziness;
- organ of hearing and labyrinthine disorders: often - vertigo;
- vessels: very often - a pronounced decrease in blood pressure; often - orthostatic hypotension, fainting;
- respiratory system, chest and mediastinal organs: often - cough;
- gastrointestinal tract: often - nausea, diarrhea;
- skin and subcutaneous tissues: infrequently - angioedema;
- 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 - asthenia, increased fatigue.
Overdose
The main symptoms: the most likely pronounced decrease in blood pressure.
Symptomatic treatment is recommended; in case of accidental overdose - gastric lavage or vomiting; with a pronounced decrease in blood pressure - intravenous administration of 0.9% sodium chloride solution, ensuring the patient's stay in the supine position with raised legs for the period necessary for treatment, maintaining the activity of the cardiovascular system, including regular monitoring of the amount of urine excreted, the volume of circulating blood, the activity of the respiratory system and heart.
special instructions
There are reports of the development of clinically pronounced arterial hypotension during therapy with Uperio. It is recommended, with a pronounced decrease in blood pressure, to consider adjusting the dose of diuretics and concomitant antihypertensive drugs, as well as to eliminate the causes of the development of the condition (for example, hypovolemia). When, after applying these measures, a pronounced decrease in blood pressure persists, reduce the dose or temporarily stop taking the drug. In most cases, permanent withdrawal of treatment is not required. Patients with hypovolemia due to vomiting, diarrhea, low-salt diet or diuretic use are generally more likely to develop a pronounced decrease in blood pressure. Before starting drug therapy, it is necessary to replenish the circulating blood volume and / or adjust the sodium content in the body.
Like any other drug that has an effect on the renin-angiotensin system, Uperio can cause deterioration of renal function, the development of hyperkalemia and an increase in the concentration of urea and creatinine in the blood serum with unilateral or bilateral stenosis of the renal arteries. In the ongoing comparative study on the safety and efficacy of the drug in comparison with enalapril, clinically significant renal impairment or hyperkalemia were rarely observed, and it was less likely to be canceled due to similar impairments than enalapril.
A dose reduction of Uperio may be required when a patient has a clinical deterioration in renal function.
With the development of clinically significant hyperkalemia, it is recommended to reduce potassium intake with food or adjust the dose of concomitant drugs. Regular monitoring of serum potassium is especially necessary in the presence of such risk factors as adherence to a diet high in potassium, hypoaldosteronism, diabetes mellitus and severe renal impairment.
During treatment, cases of angioedema have been reported. With its development, the immediate cancellation of Uperio and the adoption of appropriate measures are required: symptomatic therapy and medical monitoring of the patient until the complete and stable resolution of all the symptoms that have arisen. Reappointment of the product is not recommended.
Influence on the ability to drive vehicles and complex mechanisms
Patients during the period of therapy should be careful when driving and conducting potentially hazardous activities, since dizziness or increased fatigue may occur while taking Yuperio.
Application during pregnancy and lactation
The drug is contraindicated for use during pregnancy and lactation. If pregnancy occurs during therapy with Yuperio, the appointment is canceled as soon as possible.
Patients with preserved reproductive function during the period of taking the tablets and for 1 week after their last dose should use reliable methods of contraception.
Pediatric use
Uperio is contraindicated in children and adolescents under the age of 18, since the safety and effectiveness of its use in patients of this age group have not been established.
With impaired renal function
With caution, Yuperio is used in patients with bilateral renal artery stenosis, severe renal impairment, including in patients on hemodialysis or undergoing hemodialysis, since there are no data on the safety of using the drug in such cases.
For violations of liver function
Taking pills is contraindicated in cholestasis, biliary cirrhosis and severe liver dysfunction.
Drug interactions
With the combined use of Uperio with some drugs / substances, the following effects may develop:
- statins (inhibitors of HMG-CoA reductase): since the activity of carriers of OATP1B1 and OATP1B3 is suppressed by sacubitrile, taking the complex can increase the systemic exposure of statins (substrates OATP1B1 and OATP1B3);
- atorvastatin: the drug increases the Cmax and AUC of atorvastatin and its metabolites;
- sildenafil: increases the antihypertensive effect of the drug;
- potassium-containing table salt substitutes, potassium preparations, mineralocorticoid antagonists, potassium-sparing diuretics: Uperio may increase serum creatinine and potassium levels;
- lithium preparations: a reversible increase in the concentration of lithium in the blood serum and an increase in its toxic manifestations are possible;
- transport proteins (carrier proteins): an increase in systemic exposure of LBQ657 or valsartan is possible.
In the case of the appointment of Uperio in combination with non-steroidal anti-inflammatory drugs, including selective inhibitors of cyclooxygenase-2, patients over the age of 65, patients with impaired renal function or hypovolemia, including those receiving diuretic therapy, may increase the risk of deteriorating renal function.
Analogs
Uperio's analogs are: Sakubitril and valsartan hydrated complex of sodium salts, Intresto.
Terms and conditions of storage
Store in a place protected from light and moisture at temperatures up to 25 ° C. Keep out of the reach of children.
The shelf life is 2.5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Uperio
Due to the fact that the drug was launched on the market this year, there are practically no reviews of Uperio left by patients. Experts say that this new generation drug reduces the risk of cardiovascular death, as well as hospitalization for heart failure, significantly better than previously used drugs.
Price for Uperio in pharmacies
The approximate price of Yuperio 50 mg (25.7 mg + 24.3 mg, 28 tablets per pack) - 2440 rubles; 100 mg (51.4 mg + 48.6 mg; 28 pcs per package) - 2200 rubles; 200 mg (102.8 mg + 97.2 mg; 28 pcs in a package) - 2218 rubles.
Uperio: prices in online pharmacies
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Drug name Price Pharmacy |
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Uperio 50 mg (25.7 mg + 24.3 mg) film-coated tablets 28 pcs. RUB 1,500 Buy |
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Uperio 200 mg (102.8 mg + 97.2 mg) film-coated tablets 28 pcs. 1698 RUB Buy |
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Uperio 100 mg (51.4 mg + 48.6 mg) film-coated tablets 28 pcs. RUB 2110 Buy |
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Uperio tablets p.p. 200mg 28 pcs. 2409 RUB Buy |
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Uperio tablets p.p. 50mg 28 Pcs. 2421 RUB Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
