Huperio, 100 mg 28 pcs.

The action of the drug Juperio 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 antagonist of angiotensin II receptors (APA II).

Indications

Active ingredient

Composition

1 film-coated tablet, 100 mg (51.4 mg + 48.6 mg) contains:

The active ingredient:

Sacubitril and valsartan sodium salt hydrate complex -113.103 mg (converted to 100 mg anhydrous acid form, which is equivalent to containing 48.6 mg of sacubitril and 51.4 mg of valsartan);

excipients:

Microcrystalline cellulose – 34.897 mg,

Hyprolose – 25.000 mg,

Crospovidone – 18.000 mg,

Magnesium stearate – 6,000 mg,

talc – 2,000 mg,

colloidal silica – 1,000 mg;

coating:

white shell premix – 7.732 mg (hypromellose – 5.521 mg, titanium dioxide-1.106 mg, macrogol 4000 – 0.553 mg, talc – 0.553 mg), yellow shell premix – 0.256 mg (hypromellose – 0.183 mg, iron oxide yellow dye – 0,0.037 mg, macrogol 4000 – 0.018 mg, talc – 0.018 mg), film coating premix red – 0.012 mg (hypromellose – 0.009 mg, iron oxide dye red – 0.002 mg, macrogol 4000 – 0.001 mg, talc – 0.001 mg).

How to take, the dosage

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

Uperio should not be used concomitantly with aliskiren in patients with diabetes mellitus and in patients with impaired renal function (rSFR <60 ml/min/1.73 m2 body surface area).

Not recommended drug interactions

Angiotensin receptor antagonists

As 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.

Contraindications

Side effects

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 (if the drug has been taken recently) or gastric lavage should be induced.

In case of marked BP decrease, intravenous infusion of 0.9% sodium chloride solution is necessary as therapy, the patient should be laid with his legs elevated for as long as necessary for therapy, active measures to maintain cardiovascular activity, including regular monitoring of heart and respiratory system activity, circulating blood volume (CBC) and amount of urine excreted should be taken.

The removal of active ingredients during hemodialysis is unlikely because much of it is bound to plasma proteins.

Pregnancy use