Huperio, 50 mg 28 pcs.

The action of Huperio is mediated by a new mechanism, namely, the simultaneous inhibition of neprilysin activity (neutral endopeptidase, NEP) by the substance LBQ657 (active metabolite of sacubitril) and blockade of angiotensin II type 1 receptors (AT1) by valsartan, which is an angiotensin II receptor antagonist (APA II).

Indications

• Cronic heart failure (NYHA class II-IV) in patients with systolic dysfunction to reduce the risk of cardiovascular mortality and hospitalization for heart failure.
• The drug is used in combination therapy with other drugs to treat chronic heart failure as a substitute for angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARA II).
• Essential arterial hypertension.
  

Active ingredient

Valsartan, Sacubitril

Composition

1 film-coated tablet, 50 mg (25.7 mg + 24.3 mg) contains:

The active ingredient:

Sacubitril and valsartan sodium salt hydrate complex -56.551 mg (converted to 50 mg anhydrous acid form, which is equivalent to containing 24.3 mg of sacubitril and 25.7 mg of valsartan);

auxiliary substances:

Microcrystalline cellulose, 91.449 mg,

Hyprolose, 25.000 mg,

Crospovidone, 18.000 mg,

/p>

magnesium stearate – 6,000 mg,

talc – 2,000 mg,

colloidal silica – 1,000 mg;

coating:

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 oxide red dye – 0,003 mg, macrogol 4000 – 0.001 mg, talc – 0.001 mg), film coating premix black – 0.024 mg (hypromellose – 0.017 mg, iron oxide black dye – 0.003 mg, macrogol 4000 – 0.002 mg, talc – 0.002 mg).

How to take, the dosage

The timing of taking Juperio is independent of the time of eating.

The target (maximum daily) dose of Huperio is 200 mg (102.8 mg + 97.2 mg) 2 times daily. The recommended starting dose of Huperio is 100 mg (51.4 mg + 48.6 mg) 2 times daily.

In patients who have not previously received ACE inhibitors or ARA II therapy, or who received these drugs in low doses, therapy with Huperio should be started in a dose of 50 mg (25.7 mg + 24.3 mg) 2 times daily with a slow increase of the dose (doubling the daily dose once every 3 to 4 weeks). Depending on tolerability the dose of Intresto should be doubled every 2-4 weeks up to the target (maximum daily) dose of 200 mg (102.8 mg + 97.2 mg) 2 times per day.

The use of Juperio is possible not earlier than 36 hours after ACE inhibitor withdrawal because development of angioedema is possible in case of concomitant use. Because Imperio contains ARA II valsartan, it should not be used concomitantly with another drug containing ARA II.

If signs of impaired tolerability of Imperio develop (clinically significant decrease in BP, hyperkalemia, impaired renal function), a temporary dose reduction or dose adjustment of concomitant medications should be considered.

Patients with special categories

Patients with impaired renal function

In patients with mild (rCF 60-90 ml/min/1.73 m2) or moderate (rCF 30-60 ml/min/1.73 m2) renal dosage adjustment is not required. In patients with severe renal impairment (rSKF2), the recommended starting dose is 50 mg twice daily. Caution is recommended when using Imperio in this category of patients due to the limited data available.

Patients with hepatic impairment

In patients with mild hepatic impairment (class A according to the Child-Pugh classification), no adjustment of the dose of Imperio is required. In patients with moderate hepatic impairment (Child-Pugh class B), the recommended starting dose is 50 mg twice daily. Huperio is not recommended for use in patients with severe hepatic impairment (Child-Pugh class C).

The use in children and adolescents under 18 years of age

There are no data on the safety and effectiveness of Huperio in children and adolescents.

Uperio use in patients over 65 years of age

There is no need for dose adjustment in patients over 65 years of age.

Interaction

Contraindicated drug interactions ACE inhibitors Imperio is contraindicated for use concomitantly with ACE inhibitors because suppression of nepralysin concomitantly with ACE inhibitor use may increase the risk of angioedema.

Uperio may be used no sooner than 36 hours after ACE inhibitor withdrawal. Use of an ACE inhibitor is possible no sooner than 36 hours after the last dose of Huperio.

Aliskiren

In patients with diabetes mellitus and in patients with impaired renal function (rCF)

Not recommended drug interactions

Angiotensin receptor antagonists

Because one of the active substances of the drug is an angiotensin II receptor antagonist, concomitant use with another drug containing ARA II is not recommended.

Drug interactions to be considered

HMG-CoA reductase inhibitors (statins)

The data from studies show that sacubitril inhibits the activity of OATP1B1 and OATP1BZ transporters. Huperio may increase systemic exposure to OATP1B1 and OATP1BZ substrates such as statins. In patients who received Juperio concomitantly with atorvastatin, maximum plasma concentrations (Cmax) of atorvastatin and its metabolites were increased up to 2 times, and AUC – up to 1.3 times. For this reason, Juperio should be used with caution concomitantly with statins.

Sildenafil

In patients with significant BP elevation receiving Huperio (before reaching equilibrium concentration), single use of sildenafil enhanced the antihypertensive effect compared to use of Huperio in monotherapy. For this reason, sildenafil or another type 5 phosphodiesterase inhibitor should be used with caution in patients receiving Huperio.

Presumed drug interactions to be considered

Potassium

Concomitant use of potassium-saving diuretics (e.g., triamterene and amiloride), mineralocorticoid antagonists (e.g., spironolactone and eplerenone), potassium products or potassium-containing table salt substitutes may cause increased potassium and serum creatinine concentrations. In patients receiving Juperio concomitantly with these drugs, it is recommended to monitor serum potassium levels regularly.

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

Lithium preparations

The possibility of drug interaction between Huperio and lithium preparations has not been studied. Concomitant use of lithium with ACE inhibitors and ARA II has resulted in a reversible increase in serum lithium concentration and, therefore, in an increase in toxic effects. In patients receiving Juperio together with lithium preparations, it is recommended to carefully monitor the lithium content in blood serum. The risk of lithium toxicity may increase if additional diuretic medication is used.

The transporter proteins

The active metabolite of sacubitril (LBQ657) and valsartan are substrates of the transporter proteins 0ATP1B1, 0ATP1BZ and OATZ; valsartan is also a substrate of the transporter protein MRP2. Patients receiving Huperio concomitantly with OATP1B1, OATP1BZ, OATZ inhibitors (e.g., rifampicin and cyclosporine) or MRP2 (e.g., ritonavir) may have increased systemic exposure to LBQ657 or valsartan, respectively. Caution is required at the start and end of coadministration of Huperio and this group of drugs.

There are no significant drug interactions. No clinically significant interactions have been identified when Huperio is used in combination with furosemide, digoxin, warfarin, hydrochlorothiazide, amlodipine, metformin, omeprazole, carvedilol, IV nitroglycerin (IV) or a combination of levonorgestrel and ethinylestradiol.

Interactions with atenolol, indomethacin, glibenclamide (gliburide) or cimetidine are not expected when combined with Huperio.

Interactions with cytochrome P450 isoenzymes

The available studies demonstrate that the likelihood of drug interactions mediated by CYP450 cytochrome isoenzymes is low, because the active substance complex is only slightly metabolized with the participation of CYP450 isoenzymes. The active substance complex of Huperio is not an inhibitor or inducer of CYP450 isoenzymes.

Special Instructions

Significant decrease in BP

In patients treated with Huperio, there have been cases of clinically significant arterial hypotension. If a marked decrease in BP occurs, consideration should be given to adjusting the dose of diuretics, concomitant hypotensive agents, and the cause of the marked decrease in BP (e.g., hypovolemia). If, despite these measures, the pronounced BP decrease persists, the dose of Huperio should be reduced or the drug should be temporarily withdrawn. Definitive withdrawal of the drug is usually not required. The likelihood of significant BP decrease is generally higher in patients with hypovolemia, which may be caused by diuretic therapy, low-salt diet, diarrhea, or vomiting.

Before starting Hyperio, sodium should be corrected and/or the BOD should be replenished.

Kidney function impairment

Like any other drug acting on the RAAS, Huperio may cause impairment of renal function. In a comparative safety and efficacy study of 14/17 (compared with enalapril), clinically significant impairment of renal function was rare, and Huperio was withdrawn less frequently (0.65%) than enalapril (1.28%) for such impairment. In cases of clinically significant impairment of renal function, a reduction in the dose of Huperio should be considered. Caution should be exercised when using Huperio in patients with severe renal dysfunction.

Hyperkalemia

Like any other drug acting on the RAAS, Huperio may increase the risk of hyperkalemia. In a comparative safety and efficacy study (compared with enalapril), clinically significant hyperkalemia was rare; hyperkalemia was withdrawn due to hyperkalemia in 0.26% of patients and enalapril in 0.35% of patients. Drugs that may increase serum potassium levels (e.g., potassium-saving diuretics, potassium preparations) should be used with caution concomitantly with Huperio. In case of clinically significant hyperkalemia, measures such as reducing potassium intake with food or adjusting the dose of concomitant drugs should be considered. Regular monitoring of serum potassium is recommended, especially in patients with risk factors such as severe renal dysfunction, diabetes mellitus, hypoaldosteronism, or a diet high in potassium.

Anhyoneurotic edema

In cases of angioedema have been reported with the use of Huperio. If angioedema occurs, Imperio should be stopped immediately and the patient should be appropriately treated and monitored until all symptoms have resolved completely and permanently. Reapplication of Huperio should not be repeated. In cases of confirmed angioedema, in which the swelling was limited to the face and lips, the condition usually resolved without intervention, although use of antihistamines did ameliorate the symptoms.

In patients with a history of angioedema caused by the use of an ACE inhibitor or ARA II, Huperio should not be used. Patients who are of non-human race may be at greater risk of angioedema.

Patients with renal artery stenosis

Like other drugs acting on the RAAS, Huperio may cause increased serum urea and creatinine concentrations in patients with unilateral or bilateral renal artery stenosis. In patients with renal artery stenosis, the drug should be used with caution with regular monitoring of renal function.

Influence on driving and/or operating machinery

There are no data on the effect of the drug on driving and/or operating machinery. Due to possible dizziness or increased fatigue, caution should be exercised when driving or operating machinery.

Contraindications

• High sensitivity to sacubitril or valsartan or other excipients.
• Simultaneous use with angiotensin-converting enzyme (ACE) inhibitors and 36 hours after ACE inhibitor withdrawal.
• An history of angioedema on prior therapy with ACE inhibitors or ARA II.
• Simultaneous use with aliskiren in patients with diabetes mellitus or in patients with moderate to severe renal impairment (rCKF
• Severe hepatic impairment (Child Pugh class C), biliary cirrhosis and cholestasis.
• It is not recommended for use in children <18 years of age due to lack of efficacy and safety data
• Pregnancy, pregnancy planning and breastfeeding
• Simultaneous use with other drugs containing ARA II, because
• Combined use with other drugs that contain ARA II because they contain valsartan.

Cautions

Cautions should be taken when using Huperio in patients with severe renal impairment (rCF

Patients with severe renal impairment should be treated with caution.

Pcaution should be exercised when using the drug concomitantly with statins, phosphodiesterase type 5 inhibitors.

Caution should be exercised when using the drug in patients with a history of angioedema due to the lack of data on the use of the drug in this category of patients. Patients of Negro race may be more at risk of angioedema.

Side effects

The observed adverse events (AEs) were consistent with the pharmacological characteristics of Huperio and the comorbidities present in the patients. The most frequent NIs were marked decrease in blood pressure, hyperkalemia, and renal dysfunction caused by adjusting the dose of Huperio or discontinuing therapy. The frequency of NNIs was independent of patient gender, age, or race.

NNIs are listed according to the system-organ class of the MedDRA Regulatory Medical Dictionary. Within each system-organ class, NUIs are categorized by frequency of occurrence in decreasing order of importance. The following criteria were used to estimate the frequency: very common (1/10); common (1/100 to 1/100). Metabolism and nutrition disorders: very common – hyperkalemia; common – hypokalemia.

• Nervous system disorders: common – dizziness, headache; infrequent – orthostatic dizziness.
• Hearing and labyrinth disorders: frequently – vertigo.
• vascular disorders: very frequently – marked BP decrease; frequently – syncope, orthostatic hypotension.
• Respiratory system, thorax and mediastinum disorders: frequently – cough.
• Gastrointestinal tract disorders: frequently – diarrhea, nausea.
• Skin and subcutaneous tissue disorders: infrequently – angioedema.
• Renal and urinary tract disorders: very common – renal dysfunction; common – renal failure (including acute renal failure). acute renal failure).
• General disorders and disorders at the site of administration: often – increased fatigue, asthenia.
• If any of the side effects mentioned in the instructions are aggravated, or if you notice any other side effects not specified in the instructions, inform your doctor.

Overdose

There are insufficient data on overdose with Huperio in humans. A single dose of 1200 mg and multiple doses of 900 mg in healthy volunteers were well tolerated.

The most likely symptom of overdose is a marked decrease in BP due to the antihypertensive effect of the active substances. Symptomatic treatment is recommended in this case.

In case of accidental overdose, vomiting should be induced (if the drug was taken recently) or gastric lavage should be performed. In case of pronounced BP lowering as a therapy intravenous injection of 0.9% sodium chloride solution is necessary, the patient should be laid with his legs elevated for the period required for therapy, active measures on cardiovascular system support, including regular monitoring of heart and respiratory system activity, circulating blood volume (CBC) and amount of urine excreted should be taken. Removal of active ingredients during hemodialysis is unlikely, as much of them are bound to plasma proteins.

Pregnancy use

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