Treatment of chronic heart failure in adult patients with reduced left ventricular ejection fraction.ф
Uperio (Entresto) Composition
1 film-coated tablet, 50 mg (25.7 mg + 24.3 mg) contains:
Active ingredient: sacubitril and valsartan hydrated complex of sodium salts -56.551 mg (in terms of the anhydrous acid form 50 mg, which is equivalent to the content of 24.3 mg sacubitril and 25.7 mg 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 shell premix – 7.957 mg (hypromellose – 5.681 mg, titanium dioxide – 1.138 mg, macrogol 4000 – 0.569 mg, talc – 0.569 mg), red shell premix – 0.019 mg (hypromellose – 0.014 mg, iron 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, iron dye black oxide – 0.003 mg, macrogol 4000 – 0.002 mg, talc – 0.002 mg).
Combined drug. The action is mediated by the simultaneous suppression of the activity of neprilysin (neutral endopeptidase, NEP) by the substance LBQ657 (an active metabolite of sacubitrile) and blockade of angiotensin II type 1 (AT1) receptors by valsartan, which is an antagonist of angiotensin II receptors (ARA II). The complementary beneficial effects of sacubitril and valsartan on the state of the cardiovascular system and kidneys in patients with heart failure are due to an increase in the amount of peptides cleaved by neprilysin (such as natriuretic peptides, NP), which is mediated by the action of LBQ657, while valsartan suppresses the negative effects of angiotensin II. NP 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 urine output, an increase in the glomerular filtration rate and renal blood flow, suppression of the release of renin and sympathetic activity, and a decrease in antibacterial and anti-fibrotic action. Valsartan, selectively blocking 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 the persistent activation of the RAAS, which causes vasoconstriction, sodium and water retention by the kidneys, activation of cell growth and proliferation, as well as the subsequent restructuring of the cardiovascular system, which aggravates the disruption of its functioning.
In a clinical study, when using a combination of valsartan / sicubitrile in patients with chronic heart failure, the risk of death due to cardiovascular disease or hospitalization due to acute heart failure was significantly reduced. The absolute reduction in the risk of death due to cardiovascular disease or hospitalization due to acute heart failure was 4.7%.
Uperio, indications for use
Chronic heart failure (NYHA class II-IV) in patients with systolic dysfunction to reduce the risk of cardiovascular mortality and hospitalization for heart failure.
• Hypersensitivity to sacubitril or valsartan, as well as to other auxiliary components of the drug.
• Simultaneous use with angiotensin-converting enzyme (ACE) inhibitors, as well as a period of 36 hours after the withdrawal of ACE inhibitors.
• A history of angioedema in the presence of previous therapy with ACE inhibitors or ARA II.
• Simultaneous use with aliskiren in patients with diabetes mellitus or in patients with moderate or severe renal impairment (eGFR
• Severe liver dysfunction (Child Pugh class C), biliary cirrhosis and cholestasis.
• Intresto is not recommended for use in children under the age of 18 due to the lack of data on efficacy and safety.
• Pregnancy, planning of pregnancy and breastfeeding period.
• Simultaneous use with other preparations containing ARA II, because the drug contains valsartan.
The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. The compliance of the used dosage form of a particular drug with indications for use and dosage regimen should be strictly observed.
For oral administration.
The target (maximum daily) dose of the complex is 200 mg 2 times / day. The recommended starting dose is 100 mg 2 times / day.
In patients who have not previously received therapy with ACE inhibitors or ARA II, or who received these drugs in low doses, therapy with the complex should be started at a dose of 50 mg 2 times / day with a slow increase in the dose (doubling the daily dose once every 3-4 weeks).
Depending on tolerance, the dose should be doubled every 2-4 weeks until the target (maximum daily) dose of 200 mg is reached 2 times / day.
The use of this complex is possible not earlier than 36 hours after the withdrawal of the ACE inhibitor, because in the case of simultaneous use, angioedema may occur.
Since the complex includes ARA II valsartan, it should not be used simultaneously with another drug, which includes ARA II.
Application 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 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 act on the RAAS, the drug Uperio should not be used during pregnancy. The effect of the drug Uperio is mediated by the blockade of angiotensin II receptors, therefore, the risk to the fetus cannot be excluded. In pregnant women taking valsartan, there have been cases of spontaneous abortion, oligohydramnios and renal dysfunction in newborns.
If pregnancy occurs during drug treatment, the patient should stop taking the drug and inform her attending physician. Since preclinical studies have noted the release of sacubitril and valsartan in the milk of lactating animals, it is not recommended to use the drug Uperio during breastfeeding. The decision to discontinue breastfeeding or to discontinue Uperia 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 the drug Uperio on the fertility of men and women. In studies of the drug Uperio in animals, there was no decrease in fertility.
• Disturbances from the nervous system: 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.
• Violations of the respiratory system, chest and mediastinal organs: often – cough.
• Disturbances from the gastrointestinal tract: often – diarrhea, nausea.
• Violations of the skin and subcutaneous tissues: infrequently – angioedema.
• Disorders of 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 – increased fatigue, asthenia.
• If any of the side effects indicated in the instructions get worse, or you notice any other side effects not listed in the instructions, inform your doctor.
There are insufficient data on human overdose with Uperio. A 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 tolerance.
The most likely symptom of an overdose is a pronounced decrease in blood pressure due to the antihypertensive effect of the active ingredients. In this case, symptomatic treatment is recommended.
In case of accidental overdose, induce vomiting (if the drug has been recently taken) or gastric lavage. In the event of a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution is necessary as therapy, the patient should be laid down, raising his legs, for a period of time necessary for therapy, take active measures to maintain the activity of the cardiovascular system, including regular monitoring of heart activity and the respiratory system, the volume of circulating blood (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.
The drug should not be used after the expiration date.
At a temperature not exceeding 25 ° C. Keep out of the reach of children.