roots Valerian Sakubytryl | Uperio tablets cover. captivity. obl. 50 mg (25.7 mg + 24.3 mg) 28 pcs.
Special Price
$59.17
Regular Price
$68.00
In stock
SKU
BID702251
Release form
Tablets 50 mg (25.7 mg + 24.3 mg)
Oval biconvex tablets, film-coated, white with a purple tint, beveled, without risks. On one side is engraved “LZ”, on the other - “NVR”. In a cross section, the core is white or almost white.
Tablets 50 mg (25.7 mg + 24.3 mg)
Oval biconvex tablets, film-coated, white with a purple tint, beveled, without risks. On one side is engraved “LZ”, on the other - “NVR”. In a cross section, the core is white or almost white.
Release form
Tablets 50 mg (25.7 mg + 24.3 mg)
Oval biconvex tablets, film-coated, white with a purple tint, beveled, without risks. On one side is engraved “LZ”, on the other - “NVR”. In a cross section, the core is white or almost white.
Pharmacological action of
The action of the drug Uperio is mediated by a new mechanism, namely, the simultaneous suppression of the activity of neprilysin (neutral endopeptidase, NEP)) substance LBQ657 (an active metabolite of sacubitrile) and blockade of receptors for angiotensin II type 1 (AT1) valsartan, which is an antagonist of angiotensin II receptors (APA II). The complementary beneficial effects of sacubitrile and valsartan on the state of 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 (NPs)), which is mediated by the action of LBQ657, while valsartan is suppressed by the negative effects of angiotensin II. NPs activate membrane-bound receptors coupled 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 the release of renin and aldosterone, a decrease in sympathetic activity, as well as antihypertrophic and antifibrotic effects. Valsartan, selectively blocking the AT1 receptor, inhibits 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, activation of cell growth and proliferation, as well as subsequent restructuring of the cardiovascular system, exacerbating disturbances in its functioning.
Indications
Chronic heart failure (NYHA Class II-IV) for patients with systolic dysfunction in order to reduce the risk of cardiovascular mortality and hospitalization for heart failure.
Contraindications
Hypersensitivity to sakubitril or to 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 withdrawal of ACE inhibitors.
The presence of angioedema in the anamnesis against the background of previous therapy with ACE or ARA II inhibitors.
Concomitant use with aliskiren in patients with diabetes mellitus or in patients with moderate or severe impaired renal function (rSCF
Impaired liver function (Child Pu class C), biliary cirrhosis and cholestasis
Intresto is not recommended for use in children under the age of 18 due to a lack of data on efficacy and safety
Pregnancy, pregnancy planning, and the period of breastfeeding
Concomitant use with other drugs containing ARA and II, since the drug enters valsartan.
Caution
Caution should be exercised when using Uperio in patients with severe impaired renal function (rSCF
Caution should be exercised while using the drug with statins, type 5 phosphodiesterase inhibitors.
Caution should be exercised when using the drug in patients with angioedema history due to the lack of data on the use of the drug in patients of this category Patients of the Negroid race may be more at risk for angioedema someone edema.
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 treatment with the drug and within a week after its last dose.
Like other drugs that directly affect RAAS, Uperio should not be used during pregnancy. The action of the drug Uperio is mediated by the blockade of angiotensin II receptors, so the risk to the fetus cannot be ruled out.In pregnant women taking valsartan, there were cases of spontaneous abortion, oligohydramnios and impaired renal function in newborns.
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 release of sacubitrile and valsartan with milk from lactating animals, it is not recommended to use the drug Uperio during breastfeeding. The decision to refuse breastfeeding or to discontinue Uperioi's drug to continue 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, a decrease in fertility was not noted.
Special instructions
Pronounced decrease in blood pressure
In patients receiving the drug Uperio, there were cases of clinically pronounced arterial hypotension. If a pronounced decrease in blood pressure occurs, consideration should be given to adjusting the dose of diuretics, concomitant antihypertensive drugs, as well as addressing 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 Huperio should be reduced or the drug should be temporarily withdrawn. 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 should correct the sodium content in the body and / or replenish the bcc.
Impaired renal function
Like any other drug acting on the RAAS, Huperio may cause impaired renal function. In a comparative study of safety and efficacy 14/17 (compared with enalapril), clinically significant renal impairment was rare, and Huperio was less likely to be canceled due to such impairment (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 Uperio. When using the drug Uperio in patients with severe impaired renal function, caution should be exercised.
Hyperkalemia
Like any other drug acting on the RAAS, Uperio may increase the risk of hyperkalemia. In a comparative study of safety and efficacy (compared with enalapril), clinically significant hyperkalemia was rarely observed with Huperio due to hyperkalemia was canceled in 0.26% of patients, and enalapril in 0.35% of patients. Drugs that can increase serum potassium (for example, potassium-sparing diuretics, potassium preparations) at the same time as Uperio should be used with caution. In the event of clinically significant hyperkalemia, measures such as reducing potassium intake with food or adjusting the dose of concomitant medications should be considered. It is recommended to regularly monitor the serum potassium content, especially in patients with risk factors such as severe renal impairment, diabetes mellitus, hypoaldosteronism or a diet high in potassium.
Angioneurotic edema
Cases of the development of angioneurotic edema have been noted with the use of Uperio. If angioedema occurs, Uperio should be immediately canceled and appropriate treatment and monitoring of the patient should be prescribed until all symptoms that have arisen are resolved. Repeatedly prescribe the drug Uperio should not be. In cases of confirmed angioedema, in which the swelling spread only to the face and lips, this condition was usually resolved without intervention, although the use of antihistamines helped to alleviate the symptoms.
Angioneurotic edema, accompanied by laryngeal edema, can be fatal. In cases where the swelling extends to the tongue, vocal folds or larynx, which can lead to airway obstruction, it is necessary to immediately begin appropriate treatment, for example, subcutaneous injection of a solution of epinephrine (adrenaline) 1: 1000 (0.3-0.5 ml), and / or take appropriate measures to ensure patency respiratory tract.
In patients with a history of angioedema caused by an ACE inhibitor or ARA II, Uperio should not be used. Negroid patients may be more at risk for angioedema.
Patients with Renal Artery Stenosis
Like other drugs that work on RAAS, Uperio may cause an increase in serum urea and creatinine 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.
Effects on ability to drive vehicles and / or mechanisms
No data are available on the effect of the drug on 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.
Composition
1 film-coated tablet, 50 mg (25.7 mg + 24.3 mg) contains:
Active ingredient: sacubitrile and valsartan hydrated complex of sodium salts -56.551 mg (calculated on the anhydrous form 50 mg, which is equivalent to 24.3 mg of sacubitrile and 25.7 mg of valsartan)
excipients: microcrystalline cellulose - 91.449 mg, hyprolose - 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 shell - 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 dye red oxide - 0.003 mg, macrogol 4000 -0.001 mg, talc - 0.001 mg), black shell premix - 0.024 mg (hypromellose - 0.017 mg, black iron dye - 0.003 mg, macrogol 4000 - 0.002 mg, talc - 0.002 mg).
Dosage and administration
The time of administration of the drug Uperio does not depend on the time of meal.
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 ARA II inhibitors, or who have received these drugs in low doses, Uperio therapy should be started at a dose of 50 mg (25.7 mg + 24.3 mg) 2 times a day with a slow increase in dose (doubling the daily dose once every 3-4 weeks). Depending on tolerability, the dose of Intresto should be doubled every 2-4 weeks until the target (maximum daily) dose is 200 mg (102.8 mg + 97.2 mg) 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, the development of angioedema is possible. Since the composition of the drug Uperio includes ARA II valsartan, it should not be used simultaneously with another drug, which includes ARA II.
With the development of signs of impaired tolerance of the drug Uperio (clinically pronounced decrease in blood pressure, hyperkalemia, impaired renal function), consideration should be given to temporarily reducing the dose or adjusting the dose of the drugs used simultaneously.
Patients of special categories
Patients with impaired renal function
In patients with impaired renal function, mild (rSCF 60-90 ml / min / 1.73 m2) or moderate severity (rSCF 30-60 ml / min / 1, 73 m2) dose adjustment is not required. In patients with severe impaired renal function (rSCF2), the recommended initial dose of the drug is 50 mg twice a day. When using the drug Uperiou patients in this category, caution is recommended due to the limited data.
Patients with impaired hepatic function
In patients with impaired hepatic function impairment (class A according to the Child-Pugh classification), dose adjustment of Huperio is not required. In patients with moderate liver dysfunction (class B according to the Child-Pugh classification), the recommended initial dose of the drug is 50 mg twice a day. Uperio is not recommended for use in patients with severely impaired liver function (Child-Pugh class C).
Use in children and adolescents under the age of 18
There are no data on the safety and effectiveness of the use of Huperio in children and adolescents.
Use in patients over 65 years of age
In patients older than 65 years, dose adjustment is not required.
Side effects
Identified adverse events (AEs) were consistent with the pharmacological characteristics of the drug Uperio and concomitant diseases present in patients. The most common AEs were a pronounced decrease in blood pressure, hyperkalemia and impaired renal function caused by dose adjustment of the drug Uperio or discontinuation of therapy. The incidence of AE was independent of the gender, age, or race of the patients. AEs are listed according to the system organ class of the medical vocabulary for regulatory activity of MedDRA. Within each system-organ class, AEs 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) Metabolic and nutritional disorders: very often - hyperkalemia often - hypokalemia. Disorders of the nervous system: often - dizziness, headache infrequently - orthostatic dizziness.
Violations on the part of the hearing organ and labyrinth disorders: often - vertigo.
Disorders from the vessels: very often - marked decrease in blood pressure often - fainting, orthostatic hypotension.
Disorders from the respiratory system, chest and mediastinal organs: often - cough .
Disorders of the gastrointestinal tract: often - diarrhea, nausea
Disorders of the skin and subcutaneous tissue side: infrequently - angioedema
Disorders kidney side and the urinary tract.:. 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 indicated in the instructions are aggravated, or you notice any other side effects not listed in the instructions, inform your doctor.
Drug Interactions
Contraindicated Drug Interactions ACE Inhibitors The drug Uperio is contraindicated for use simultaneously with ACE inhibitors, since suppression of neprilysin with the use of an ACE inhibitor may increase the risk of angioedema.
The use of the drug Uperio is possible no earlier than 36 hours after the withdrawal of an ACE inhibitor. The use of an ACE inhibitor is possible no earlier than 36 hours after the last dose of Uperio.
Aliskiren
In patients with diabetes mellitus and in patients with impaired renal function (rSCF
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)
Studies show that sacubitrile inhibits the activity of OATP1B1 and OATP1VZ carriers. Uperio may increase the systemic exposure of OATP1B1 and OATP1B3 substrates such as statins. In patients receiving 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 marked increase in blood pressure receiving the drug Uperio (until equilibrium concentration is reached), a single use of sildenafil increased the antihypertensive effect compared with the use of the drug Uperio in monotherapy. For this reason, in patients receiving Uperio, sildenafil or another type 5 phosphodiesterase inhibitor should be used with caution.
Presumptive drug interactions to consider
Potassium
The simultaneous use of potassium-sparing diuretics (e.g. triamteren and amiloride), antagonists of mineralocorticoids (e.g. spironolactone and eplerenone), potassium preparations, or potassium-containing substitutes for sodium chloride can cause an increase in serum potassium and potassium concentration blood. In patients receiving the drug Uperio simultaneously with these drugs, it is recommended to regularly monitor the potassium content in the blood serum.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors)
Use of Uperio concomitantly with NSAIDs in patients over the age of 65, 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, it is recommended to monitor renal function when prescribing a similar treatment regimen and if it changes.
Lithium preparations
The possibility of drug interaction between Uperio and lithium preparations has not been studied. With the simultaneous use of lithium preparations with ACE inhibitors and ARA II, a reversible increase in the concentration of lithium in the blood serum was observed and an increase, in connection with this, toxic manifestations. In patients receiving Uperio along with lithium, it is recommended that you carefully monitor the serum lithium content. In the case of additional use of a diuretic drug, the risk of toxic effects of lithium may increase.
Carrier Proteins The active sacubitrile metabolite (LBQ657) and valsartan are substrates of the 0ATP1B1, 0ATP1B3 and OATZ carrier proteins, valsartan is also a substrate of the MRP2 carrier protein. In patients receiving Uperio concomitantly with OATP1B1, OATP1BZ, OATZ inhibitors (e.g., rifampicin and cyclosporin) or MRP2 (e.g., ritonavir), systemic exposure of LBQ657 or valsartan may increase, respectively. At the beginning and at the time of completion of the joint use of the drug Uperio and this group of drugs, caution is required.
Lack of 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 a combination of clinically revealed etiology and levonestravell neestreol eterel.
Interactions with atenolol, indomethacin, gly There were no clinically significant interactions with nitroglycerin intravenously (iv) or with the combined preparation of levonorgestrel and ethinyl estradiol.
Interactions with atenolol, indomethacin, gly There were no clinically significant interactions with nitroglycerin intravenously (iv) or with the combined preparation of levonorgestrel and ethinyl estradiol.
Interactions with atenolol, indomethacin, glybenclamide (glyburide) or cimetidine when combined with the drug Uperio is not expected.
Interactions with isoenzymes of the cytochrome P450 system
Available studies demonstrate that the probability of drug interactions mediated by cytochrome CYP450 isoenzymes is small, since the complex of active substances is slightly metabolized with the participation of CYP450 isoenzymes. The complex of active substances of the drug Uperio is not an inhibitor or inducer of CYP450 isoenzymes.
Overdose of
There is insufficient evidence of an overdose of Huperio in humans. A single use of the drug at a dose of 1200 mg and a multiple dose of 900 mg in healthy volunteers was accompanied by good tolerance.
The most likely symptom of an overdose is a pronounced decrease in blood pressure, due to the antihypertensive effect of active substances. In this case, symptomatic treatment is recommended.
In case of accidental overdose, induce vomiting (if the drug was taken recently) or gastric lavage. In the case of a pronounced decrease in blood pressure as a therapy, intravenous administration of a 0.9% sodium chloride solution is necessary, the patient should be laid with his legs raised for the period of time necessary for therapy, and active measures should be taken to maintain the cardiovascular system, including regular monitoring of the heart and the respiratory system, circulating blood volume (BCC) and the amount of urine excreted. Removal of active substances during hemodialysis is unlikely, since a significant part of them binds to blood plasma proteins.
Storage conditions
At a temperature not exceeding 25 РC. Keep out of the reach and sight of children.
30 months.
The drug should not be used after the expiry date.
Conditions granted through pharmacies
In retseptu
Tablets 50 mg (25.7 mg + 24.3 mg)
Oval biconvex tablets, film-coated, white with a purple tint, beveled, without risks. On one side is engraved “LZ”, on the other - “NVR”. In a cross section, the core is white or almost white.
Pharmacological action of
The action of the drug Uperio is mediated by a new mechanism, namely, the simultaneous suppression of the activity of neprilysin (neutral endopeptidase, NEP)) substance LBQ657 (an active metabolite of sacubitrile) and blockade of receptors for angiotensin II type 1 (AT1) valsartan, which is an antagonist of angiotensin II receptors (APA II). The complementary beneficial effects of sacubitrile and valsartan on the state of 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 (NPs)), which is mediated by the action of LBQ657, while valsartan is suppressed by the negative effects of angiotensin II. NPs activate membrane-bound receptors coupled 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 the release of renin and aldosterone, a decrease in sympathetic activity, as well as antihypertrophic and antifibrotic effects. Valsartan, selectively blocking the AT1 receptor, inhibits 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, activation of cell growth and proliferation, as well as subsequent restructuring of the cardiovascular system, exacerbating disturbances in its functioning.
Indications
Chronic heart failure (NYHA Class II-IV) for patients with systolic dysfunction in order to reduce the risk of cardiovascular mortality and hospitalization for heart failure.
Contraindications
Hypersensitivity to sakubitril or to 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 withdrawal of ACE inhibitors.
The presence of angioedema in the anamnesis against the background of previous therapy with ACE or ARA II inhibitors.
Concomitant use with aliskiren in patients with diabetes mellitus or in patients with moderate or severe impaired renal function (rSCF
Impaired liver function (Child Pu class C), biliary cirrhosis and cholestasis
Intresto is not recommended for use in children under the age of 18 due to a lack of data on efficacy and safety
Pregnancy, pregnancy planning, and the period of breastfeeding
Concomitant use with other drugs containing ARA and II, since the drug enters valsartan.
Caution
Caution should be exercised when using Uperio in patients with severe impaired renal function (rSCF
Caution should be exercised while using the drug with statins, type 5 phosphodiesterase inhibitors.
Caution should be exercised when using the drug in patients with angioedema history due to the lack of data on the use of the drug in patients of this category Patients of the Negroid race may be more at risk for angioedema someone edema.
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 treatment with the drug and within a week after its last dose.
Like other drugs that directly affect RAAS, Uperio should not be used during pregnancy. The action of the drug Uperio is mediated by the blockade of angiotensin II receptors, so the risk to the fetus cannot be ruled out.In pregnant women taking valsartan, there were cases of spontaneous abortion, oligohydramnios and impaired renal function in newborns.
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 release of sacubitrile and valsartan with milk from lactating animals, it is not recommended to use the drug Uperio during breastfeeding. The decision to refuse breastfeeding or to discontinue Uperioi's drug to continue 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, a decrease in fertility was not noted.
Special instructions
Pronounced decrease in blood pressure
In patients receiving the drug Uperio, there were cases of clinically pronounced arterial hypotension. If a pronounced decrease in blood pressure occurs, consideration should be given to adjusting the dose of diuretics, concomitant antihypertensive drugs, as well as addressing 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 Huperio should be reduced or the drug should be temporarily withdrawn. 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 should correct the sodium content in the body and / or replenish the bcc.
Impaired renal function
Like any other drug acting on the RAAS, Huperio may cause impaired renal function. In a comparative study of safety and efficacy 14/17 (compared with enalapril), clinically significant renal impairment was rare, and Huperio was less likely to be canceled due to such impairment (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 Uperio. When using the drug Uperio in patients with severe impaired renal function, caution should be exercised.
Hyperkalemia
Like any other drug acting on the RAAS, Uperio may increase the risk of hyperkalemia. In a comparative study of safety and efficacy (compared with enalapril), clinically significant hyperkalemia was rarely observed with Huperio due to hyperkalemia was canceled in 0.26% of patients, and enalapril in 0.35% of patients. Drugs that can increase serum potassium (for example, potassium-sparing diuretics, potassium preparations) at the same time as Uperio should be used with caution. In the event of clinically significant hyperkalemia, measures such as reducing potassium intake with food or adjusting the dose of concomitant medications should be considered. It is recommended to regularly monitor the serum potassium content, especially in patients with risk factors such as severe renal impairment, diabetes mellitus, hypoaldosteronism or a diet high in potassium.
Angioneurotic edema
Cases of the development of angioneurotic edema have been noted with the use of Uperio. If angioedema occurs, Uperio should be immediately canceled and appropriate treatment and monitoring of the patient should be prescribed until all symptoms that have arisen are resolved. Repeatedly prescribe the drug Uperio should not be. In cases of confirmed angioedema, in which the swelling spread only to the face and lips, this condition was usually resolved without intervention, although the use of antihistamines helped to alleviate the symptoms.
Angioneurotic edema, accompanied by laryngeal edema, can be fatal. In cases where the swelling extends to the tongue, vocal folds or larynx, which can lead to airway obstruction, it is necessary to immediately begin appropriate treatment, for example, subcutaneous injection of a solution of epinephrine (adrenaline) 1: 1000 (0.3-0.5 ml), and / or take appropriate measures to ensure patency respiratory tract.
In patients with a history of angioedema caused by an ACE inhibitor or ARA II, Uperio should not be used. Negroid patients may be more at risk for angioedema.
Patients with Renal Artery Stenosis
Like other drugs that work on RAAS, Uperio may cause an increase in serum urea and creatinine 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.
Effects on ability to drive vehicles and / or mechanisms
No data are available on the effect of the drug on 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.
Composition
1 film-coated tablet, 50 mg (25.7 mg + 24.3 mg) contains:
Active ingredient: sacubitrile and valsartan hydrated complex of sodium salts -56.551 mg (calculated on the anhydrous form 50 mg, which is equivalent to 24.3 mg of sacubitrile and 25.7 mg of valsartan)
excipients: microcrystalline cellulose - 91.449 mg, hyprolose - 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 shell - 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 dye red oxide - 0.003 mg, macrogol 4000 -0.001 mg, talc - 0.001 mg), black shell premix - 0.024 mg (hypromellose - 0.017 mg, black iron dye - 0.003 mg, macrogol 4000 - 0.002 mg, talc - 0.002 mg).
Dosage and administration
The time of administration of the drug Uperio does not depend on the time of meal.
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 ARA II inhibitors, or who have received these drugs in low doses, Uperio therapy should be started at a dose of 50 mg (25.7 mg + 24.3 mg) 2 times a day with a slow increase in dose (doubling the daily dose once every 3-4 weeks). Depending on tolerability, the dose of Intresto should be doubled every 2-4 weeks until the target (maximum daily) dose is 200 mg (102.8 mg + 97.2 mg) 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, the development of angioedema is possible. Since the composition of the drug Uperio includes ARA II valsartan, it should not be used simultaneously with another drug, which includes ARA II.
With the development of signs of impaired tolerance of the drug Uperio (clinically pronounced decrease in blood pressure, hyperkalemia, impaired renal function), consideration should be given to temporarily reducing the dose or adjusting the dose of the drugs used simultaneously.
Patients of special categories
Patients with impaired renal function
In patients with impaired renal function, mild (rSCF 60-90 ml / min / 1.73 m2) or moderate severity (rSCF 30-60 ml / min / 1, 73 m2) dose adjustment is not required. In patients with severe impaired renal function (rSCF2), the recommended initial dose of the drug is 50 mg twice a day. When using the drug Uperiou patients in this category, caution is recommended due to the limited data.
Patients with impaired hepatic function
In patients with impaired hepatic function impairment (class A according to the Child-Pugh classification), dose adjustment of Huperio is not required. In patients with moderate liver dysfunction (class B according to the Child-Pugh classification), the recommended initial dose of the drug is 50 mg twice a day. Uperio is not recommended for use in patients with severely impaired liver function (Child-Pugh class C).
Use in children and adolescents under the age of 18
There are no data on the safety and effectiveness of the use of Huperio in children and adolescents.
Use in patients over 65 years of age
In patients older than 65 years, dose adjustment is not required.
Side effects
Identified adverse events (AEs) were consistent with the pharmacological characteristics of the drug Uperio and concomitant diseases present in patients. The most common AEs were a pronounced decrease in blood pressure, hyperkalemia and impaired renal function caused by dose adjustment of the drug Uperio or discontinuation of therapy. The incidence of AE was independent of the gender, age, or race of the patients. AEs are listed according to the system organ class of the medical vocabulary for regulatory activity of MedDRA. Within each system-organ class, AEs 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) Metabolic and nutritional disorders: very often - hyperkalemia often - hypokalemia. Disorders of the nervous system: often - dizziness, headache infrequently - orthostatic dizziness.
Violations on the part of the hearing organ and labyrinth disorders: often - vertigo.
Disorders from the vessels: very often - marked decrease in blood pressure often - fainting, orthostatic hypotension.
Disorders from the respiratory system, chest and mediastinal organs: often - cough .
Disorders of the gastrointestinal tract: often - diarrhea, nausea
Disorders of the skin and subcutaneous tissue side: infrequently - angioedema
Disorders kidney side and the urinary tract.:. 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 indicated in the instructions are aggravated, or you notice any other side effects not listed in the instructions, inform your doctor.
Drug Interactions
Contraindicated Drug Interactions ACE Inhibitors The drug Uperio is contraindicated for use simultaneously with ACE inhibitors, since suppression of neprilysin with the use of an ACE inhibitor may increase the risk of angioedema.
The use of the drug Uperio is possible no earlier than 36 hours after the withdrawal of an ACE inhibitor. The use of an ACE inhibitor is possible no earlier than 36 hours after the last dose of Uperio.
Aliskiren
In patients with diabetes mellitus and in patients with impaired renal function (rSCF
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)
Studies show that sacubitrile inhibits the activity of OATP1B1 and OATP1VZ carriers. Uperio may increase the systemic exposure of OATP1B1 and OATP1B3 substrates such as statins. In patients receiving 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 marked increase in blood pressure receiving the drug Uperio (until equilibrium concentration is reached), a single use of sildenafil increased the antihypertensive effect compared with the use of the drug Uperio in monotherapy. For this reason, in patients receiving Uperio, sildenafil or another type 5 phosphodiesterase inhibitor should be used with caution.
Presumptive drug interactions to consider
Potassium
The simultaneous use of potassium-sparing diuretics (e.g. triamteren and amiloride), antagonists of mineralocorticoids (e.g. spironolactone and eplerenone), potassium preparations, or potassium-containing substitutes for sodium chloride can cause an increase in serum potassium and potassium concentration blood. In patients receiving the drug Uperio simultaneously with these drugs, it is recommended to regularly monitor the potassium content in the blood serum.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors)
Use of Uperio concomitantly with NSAIDs in patients over the age of 65, 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, it is recommended to monitor renal function when prescribing a similar treatment regimen and if it changes.
Lithium preparations
The possibility of drug interaction between Uperio and lithium preparations has not been studied. With the simultaneous use of lithium preparations with ACE inhibitors and ARA II, a reversible increase in the concentration of lithium in the blood serum was observed and an increase, in connection with this, toxic manifestations. In patients receiving Uperio along with lithium, it is recommended that you carefully monitor the serum lithium content. In the case of additional use of a diuretic drug, the risk of toxic effects of lithium may increase.
Carrier Proteins The active sacubitrile metabolite (LBQ657) and valsartan are substrates of the 0ATP1B1, 0ATP1B3 and OATZ carrier proteins, valsartan is also a substrate of the MRP2 carrier protein. In patients receiving Uperio concomitantly with OATP1B1, OATP1BZ, OATZ inhibitors (e.g., rifampicin and cyclosporin) or MRP2 (e.g., ritonavir), systemic exposure of LBQ657 or valsartan may increase, respectively. At the beginning and at the time of completion of the joint use of the drug Uperio and this group of drugs, caution is required.
Lack of 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 a combination of clinically revealed etiology and levonestravell neestreol eterel.
Interactions with atenolol, indomethacin, gly There were no clinically significant interactions with nitroglycerin intravenously (iv) or with the combined preparation of levonorgestrel and ethinyl estradiol.
Interactions with atenolol, indomethacin, gly There were no clinically significant interactions with nitroglycerin intravenously (iv) or with the combined preparation of levonorgestrel and ethinyl estradiol.
Interactions with atenolol, indomethacin, glybenclamide (glyburide) or cimetidine when combined with the drug Uperio is not expected.
Interactions with isoenzymes of the cytochrome P450 system
Available studies demonstrate that the probability of drug interactions mediated by cytochrome CYP450 isoenzymes is small, since the complex of active substances is slightly metabolized with the participation of CYP450 isoenzymes. The complex of active substances of the drug Uperio is not an inhibitor or inducer of CYP450 isoenzymes.
Overdose of
There is insufficient evidence of an overdose of Huperio in humans. A single use of the drug at a dose of 1200 mg and a multiple dose of 900 mg in healthy volunteers was accompanied by good tolerance.
The most likely symptom of an overdose is a pronounced decrease in blood pressure, due to the antihypertensive effect of active substances. In this case, symptomatic treatment is recommended.
In case of accidental overdose, induce vomiting (if the drug was taken recently) or gastric lavage. In the case of a pronounced decrease in blood pressure as a therapy, intravenous administration of a 0.9% sodium chloride solution is necessary, the patient should be laid with his legs raised for the period of time necessary for therapy, and active measures should be taken to maintain the cardiovascular system, including regular monitoring of the heart and the respiratory system, circulating blood volume (BCC) and the amount of urine excreted. Removal of active substances during hemodialysis is unlikely, since a significant part of them binds to blood plasma proteins.
Storage conditions
At a temperature not exceeding 25 РC. Keep out of the reach and sight of children.
30 months.
The drug should not be used after the expiry date.
Conditions granted through pharmacies
In retseptu
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