Expiration date: 08/2025
Active substance: Valsartan + Sakubita
Dosage form:
Tablets, film-coated
Composition:
1 film coated tablet, 50 mg (25.7 mg + 24.3 mg) contains:
Active substance: valsartan securitie and hydrated complex sodium salts - 56,551 mg (calculated as anhydrous acid in the form of 50 mg, which is equivalent to the content of 24.3 mg securitie and 25.7 mg of valsartan); excipients: cellulose microcrystalline - 91,449 mg hyprolose - 25,000 mg crospovidon - 18,000 mg, magnesium stearate - 6,000 mg, talc - 2,000 mg, silicon dioxide colloidal - 1,000 mg; shell: the shell premix white - 7,957 mg (polymer - 5,681 mg, titanium dioxide - 1,138 mg, macrogol 4000 - 0,569 mg, talc - 0,569 mg), premix shell red - 0,019 mg (polymer - 0,014 mg, dye iron oxide red - 0,003 mg, macrogol 4000 - 0.001 mg, talc - 0.001 mg), premix sheath black - 0,024 mg (polymer - 0,017 mg, dye iron oxide black - 0,003 mg, macrogol 4000 - 0.002 mg, talc - 0,002 mg).
Description:
Tablets 50 mg (25.7 mg + 24.3 mg)
Oval biconvex tablets coated with a white film shell with a purple tint of color with a chamfer, without risks. On one side is engraved "LZ", on the other "NVR". On the cross section the core is white or almost white.
Composition:
1 film coated tablet, 100 mg (51.4 mg + 48.6 mg) contains:
Active substance: securitie and valsartan hydration complex sodium salts - 113,103 mg (calculated as acid form anhydrous 100 mg, which is equivalent to the content of 48.6 mg securitie and 51.4 mg of valsartan); excipients: cellulose microcrystalline - 34,897 mg hyprolose - 25,000 mg crospovidon - 18,000 mg, magnesium stearate - 6,000 mg, talc - 2,000 mg, silicon dioxide colloidal - 1,000 mg; shell: premix shell white-7,732 mg (hypromellose-5,521 mg, titanium dioxide-1,106 mg, macrogol 4000-0,553 mg, talc-0,553 mg), premix shell yellow-0,256 mg (hypromellose-0,183 mg, iron oxide yellow - 0,037 mg, macrogol 4000 - 0,018 mg, talc - 0,018 mg), premix shell red - 0,012 mg (hypromellose - 0,012 mg) 0.009 mg, iron oxide red dye-0.002 mg, macrogol 4000-0.001 mg, talc-0.001 mg).
Description:
Tablets 100 mg (51.4 mg + 48.6 mg)
Oval biconvex tablets, film-coated pale yellow with chamfer, without risks. On one side is engraved "Ll", on the other - "NVR". On the cross section the core is white or almost white.
Composition:
1 film coated tablet, 200 mg (102.8 mg + 97.2 mg) contains:
Active substance: securitie and valsartan hydration complex sodium salts - 226,206 mg (calculated as acid form anhydrous 200 mg, equivalent to the contents 102,8 97,2 securitie and valsartan mg; excipients: cellulose microcrystalline - 69,794 mg hyprolose - 50,000 mg crospovidon - 36,000 mg, magnesium stearate - 12,000 mg, talc - 4,000 mg; silicon dioxide colloidal - 2,000 mg; shell: the shell premix white - 11,796 mg (polymer - 8,422 mg, titanium dioxide - 1,687 mg, macrogol 4000 - 0,843 mg, talc - 0,843 mg), premix shell red - 0,168 mg (polymer - 0,120 mg, dye iron oxide red - 0,024 mg, macrogol 4000 - 0,012 mg 0,012 mg talc), premix sheath black - 0,036 mg (polymer - 0,026 mg, dye iron oxide black 0.005 mg, macrogol 4000 - 0,003 mg, talc - 0,003 mg).
Description:
Tablets 200 mg (102.8 mg + 97.2 mg)
Oval biconvex tablets coated with a film shell of light pink color with a chamfer, without risks. On one side is engraved "Lll" on the other "NVR". On the cross section the core is white or almost white.
Pharmacodynamics:
Mechanism of action
The action of the drug, Perio mediated by a new mechanism, namely, simultaneous suppression of the activity between (neutral endopeptidazy (neutral endopeptidase, NEP)) substance LBQ657 (active metabolite securitree) and receptor blockade by the angiotensin II 1 type (AT1) valsartan, which is a receptor antagonist of angiotensin II (APA II). Complementary beneficial effects securitie and valsartan on cardiovascular system and kidneys in patients with heart failure due to the increase in the number of peptides split by neprilysin (such as natriuretic peptides (NP)), which is mediated by the action LBQ657, at the same time is suppressed by valsartan negative effects of angiotensin II. NP activate membrane-bound receptors, associated with guanylyl cyclase, which leads to an increase in the concentration of cyclic guanosine monophosphate (cGMP), causing symptoms of vasodilation, increased natriuresis and diuresis, increased glomerular filtration rate and renal blood flow, suppression of the release of renin and aldosterone, decrease in sympathetic activity, as well as antihypertrophic and antifibrotic action. Valsartan, selectively blocking the AT1 receptor, suppresses the negative effects of angiotensin II on the cardiovascular system and kidneys, and blocks angiotensin II-dependent release of aldosterone. This prevents the persistent activation of the renin-angiotensin-aldosterone system (RAAS), which causes vasoconstriction, retention of sodium and water by the kidneys, activation of growth and proliferation of cells, as well as subsequent restructuring of the cardiovascular system, aggravating disorders in its functioning.
Pharmacodynamics
Pharmacodynamic effects securitie and valsartan included in the composition of the drug, were evaluated after single and multiple dosing in healthy volunteers and in patients with chronic heart failure. The observed effects were consistent with the mechanism of action of the complex of active substances containing the between suppression and blockade in the RAAS. In a seven-day study in patients with reduced left ventricular ejection fraction (LV), in which valsartan was used as a control, the use of sacubitrile and valsartan led to a statistically significant short-term increase in natriuresis, an increase in the concentration of cGMP in urine and a decrease in the concentration of atrial natriuretic peptide (MR-proANP) and N-terminal fragment of brain natriuretic peptide precursor (NT-proBNP) in plasma (compared with valsartan). In a 21-day study in patients with reduced left ventricular PV, the use of sacubitrile and valsartan caused a statistically significant increase in the concentration of atrial natriuretic peptide (ANP) and cGMP in urine and the concentration of cGMP in blood plasma, as well as a decrease in plasma concentrations of NT-proBNP, aldosterone and endothelin-1 (compared to the initial state). In addition, the use securitree and valsartan blocks the AT1 receptor, as indicated by the increase of activity and concentration of renin in blood plasma. In another study, the sacubitril and valsartan complex caused a more pronounced decrease in plasma NT-proBNP concentrations and a more significant increase in brain natriuretic peptide (BNP) and cGMP concentrations in urine than enalapril. While BNP is a non-lysine substrate, NT-proBNP is not. Therefore, NT-proBNP, in contrast to the BNP, can be used as a biomarker for monitoring patients with heart failure receiving complex securitie and valsartan.
In a study with a detailed study of the QTc interval in healthy male volunteers, the use of the sacubitril and valsartan complex once in doses of 400 mg and 1200 mg had no effect on heart repolarization.
Neprilysin is one of several enzymes involved in the metabolism of amyloid-? (? amyloid) in the brain and cerebrospinal fluid (CSF). Against the background of the use of a complex of sacubitrile and valsartan at a dose of 400 mg once a day for 2 weeks in healthy volunteers, the concentration of Aß l-38 in the CSF increased; the concentrations of Aß 1-40 and 1-42 in the CSF did not change. The clinical significance of this fact is unknown.
In a clinical study, the use of complex securitie and valsartan in patients with chronic heart failure significantly reduced the risk of death because of cardiovascular disease or hospitalization due to acute heart failure (21.8% in the study drug group versus 26.5% in the enalapril group). The absolute reduction in the risk of death due to cardiovascular disease or hospitalization due to acute heart failure was 4.7% (3.1% for the risk of death due to cardiovascular disease and 2.8% for primary hospitalization due to acute heart failure). The relative risk reduction compared to enalapril was 20%. The effect was noted in the early stages of the drug and remained throughout the study period. Both active components of the drug contributed to the development of the effect. The incidence of sudden death, which accounted for 45% of all deaths due to cardiovascular disease, in the study drug group decreased by 20% compared to the enalapril group (hazard ratio (hazard ratio, HR) 0.80, p=0.0082). The frequency of cases of failure of the contractile function of the heart, which was the cause of death in 26% of cases the cause of cardiovascular pathology, in the group of study drug was reduced by 21% compared with that rate in the enalapril group (HR of 0.79, p=0,0338).
Pharmacokinetics:
Suction
Once inside the complex securitie and valsartan splits into securitel, which is then metabolized to form metabolite LBQ657, and valsartan; the concentration of these compounds in the blood plasma reaches a maximum after 0.5 h, 3 h and 1.5 h, respectively. The absolute bioavailability securitie and valsartan after oral administration is ?60% and 23% respectively.
In case of receiving complex securitie and valsartan twice a day equilibrium concentration alcubilla, LBQ657 and valsartan are reached in 3 days. Statistically significant accumulation securitie and valsartan in the equilibrium state is not observed; at the same time, the accumulation of LBQ657 exceeds the concentration after a single application of 1.6 times. The use of complex securitie and valsartan at the same time with food intake had no clinically significant effect on the performance of systemic exposure alcubilla, LBQ657 and valsartan. The reduction in valsartan exposure in the case of complex securitie and valsartan at the same time with food intake is not accompanied by a clinically significant decrease in therapeutic effect. The use of complex securitie and valsartan does not depend on time of meals.
Distribution
Complex securitie and valsartan is largely associated with blood plasma proteins (94% to 97%). Comparison of exposures in blood plasma and CSF shows that LBQ657 to a small extent penetrates the blood-brain barrier (0.28%). The apparent volume of distribution of valsartan and complex securitree is from 107,8 to 157.4 L.
Metabolism
Sakubita under the action of enzymes rapidly converted into a metabolite LBQ657, which is not significantly metabolized. Valsartan is metabolized to a small extent, in the form of metabolites found only about 20% of the administered dose. In blood plasma at low concentrations (<10%) cyp450="" br="">
Breeding
Once inside 52-68% securitie (mainly in the form of LBQ657) and ~13% of the valsartan and its metabolites are excreted by the kidneys; 37-48% securitie (mainly in the form of LBQ657) and 86% of the valsartan and its metabolites are excreted through the intestines.
Sakubita, LBQ657 and valsartan are excreted from blood plasma with an average half-lives (T½) that make up approximately 1,43 h of 11.48 9,90 h and h, respectively.
Linearity / non-linearity
In the studied dose range of complex securitie and valsartan (50-400 mg) pharmacokinetic parameters alcubilla, LBQ657 valsartan and change proportionally to the dose.
Pharmacokinetics in special clinical cases
Patients older than 65 years
LBQ657 and valsartan exposures in this category of patients are higher by 42% and 30%, respectively, than in younger patients. Such differences are not associated with clinically significant effects, so adjust the dose is not required.
Patients under the age of 18
Complex securitie and valsartan in these patients was not studied.
Patients with impaired renal function
For LBQ657, there was a correlation between renal function and the area under the concentration-time curve (AUC), but no such correlation was observed for valsartan. In patients with renal impairment of mild to moderate severity (estimated glomerular filtration rate (eGFR) >30 ml / min / 1.73 m2 body surface area up to <60 1="" 73="" span= "" >2 body surface areas) AUC for LBQ657 was 2 times higher than in patients with normal renal function. In patients with renal dysfunction severe severity (eGFR <30 1="" 73="" span="">2 of the body surface area) for LBQ657 AUC was increased 2.7 times. In patients with impaired renal function mild to moderate severity adjust the dose is not required. Data on the use in patients with impaired renal function of severe severity is not enough, when using the complex of sacubitrile and valsartan in this category of patients, caution is recommended.
Data on the use of complex securitie and valsartan in patients undergoing hemodialysis, no. However, both LBQ657 and valsartan are largely bound to plasma proteins, so their effective removal from the blood during hemodialysis is unlikely.
Patients with impaired liver function
In patients with impaired hepatic function mild to moderate severity exposure securitie increased by 1.5 and 3.4 times, respectively. Exposure LBQ657-1.5 and 1.9 times, and valsartan-1.2 and 2.1 times (compared with healthy volunteers). In patients with impaired hepatic function mild or moderate severity (class a and b according to the classification of child-Pugh), including patients with obstruction of the biliary tract, the dose of the complex securitie and valsartan does need to be adjusted. There has been no study of the application of complex securitie and valsartan in patients with impaired liver function severe degrees of severity, the drug is not recommended for these patients.
Ethnicity
Pharmacokinetics of the complex securitie and valsartan in patients from different racial and ethnic groups were not significantly different.
Floor
Pharmacokinetics of the complex securitie and valsartan (securitel, LBQ657 and valsartan) in men and women were not significantly different.
Indications:
Chronic heart failure (II-IV class classification NYHA) in patients with systolic dysfunction to reduce risk of cardiovascular mortality and hospitalization for heart failure reason.
Contraindications:
Hypersensitivity to sakubita or valsartan, as well as other auxiliary components of the drug.
Concomitant use with angiotensin converting enzyme inhibitors (ACE), and a period of 36 hours after the withdrawal of ACE inhibitors.
The presence of angioedema in the anamnesis on the background of previous therapy with ACE inhibitors or ARA II.
Concomitant use with aliskiren in patients with diabetes or in patients with moderate or severe renal impairment (eGFR <60 1="" 73="" span= "" >2 body surface areas).
Severe hepatic impairment (class C, child Pugh classification), biliary cirrhosis and cholestasis.
Intrest the drug is not recommended for use in children under the age of 18 years due to a lack of data on efficacy and safety.
Pregnancy, pregnancy planning and breastfeeding.
Simultaneous use with other drugs containing ARA II, as part of the drug is valsartan.With caution:
Care should be taken when using the drug, Perio in patients with severe renal impairment (eGFR <30 1="" 73="" span="">2 of the body surface area), including patients undergoing hemodialysis or hemodialysis (eGFR <15 1="" 73="" span="">2 body surface areas) due to the lack of safety data in this category of patients, patients with bilateral renal artery stenosis, hypovolemia, which may be caused by diuretic therapy, low-salt diet, diarrhea or vomiting, as well as in patients taking drugs that can increase the potassium content in the blood serum (for example, potassium-sparing diuretics, potassium preparations).
Caution should be exercised while using the drug with statins, phosphodiesterase inhibitors type 5.
Caution should be exercised when using the drug in patients with angioedema in 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.
If You have one of these diseases, before taking the drug, be sure to consult your doctor.Pregnancy and lactation:
Women with saved reproductive function during drug treatment, Perio and during the week after the latest treatment must use reliable methods of contraception.
As with other drugs, directly acting on the RAAS, drug Perio should not be used during pregnancy. The action of the drug, Perio mediated by blockade of the angiotensin II receptor, therefore, we cannot exclude a risk to the fetus. In pregnant women taking valsartan, there were cases of spontaneous abortion, lack of water and impaired renal function in newborns. If the background of the drug, Perio a pregnancy, the drug should be discontinued as soon as possible.
Since the pilot studies have noted the allocation of securitel and valsartan milk of lactating animals, it is not recommended to use the drug, Perio in the period of breastfeeding. The decision to abandon breastfeeding or the cancellation of the drug, Perio and continued breastfeeding should be taken, given the importance of its application for mother.
Data on the impact of drug Aperio on fertility of men and women there. In studies of the drug, Perio in animals, fertility was not observed.
Method of application and doses:
The drug, Perio does not depend on time of meals.
The target (maximum daily) dose of Aperio is 200 milligrams (mg 102,8 + 97,2 mg) 2 times a day. The recommended initial dose of the drug, Perio is 100 mg (51,4 mg + 48,6 mg) 2 times a day.
In patients who had not previously received therapy with ACE inhibitors or ARA II, or treated with these drugs in low doses to initiate therapy with the drug, Perio in the dose of 50 mg (of 25.7 mg + 24,3 mg) 2 times a day with slow increases in dose (doubling the daily dose 1 per 3-4 weeks).
Depending on the tolerance dose of the drug, Perio should be doubled every 2-4 weeks until achieve the target (maximum daily) doses of 200 mg (mg 102,8 + 97,2 mg) 2 times a day.
The application of the product Perio may not be earlier than 36 hours after discontinuation of the ACE inhibitor, as in the case of simultaneous use may occur angioedema.
As part of the drug, Perio included valsartan ARA II, it should not be used simultaneously with other medication, which includes ARA II.
If patients have problems with drug tolerance, Aperio (clinically significant decrease in blood pressure, hyperkalemia, impaired renal function), should consider temporary dose reduction or dose adjustment of concomitant medicines.
Patients of special categories
Patients with renal impairment
In patients with impaired renal function light (eGFR 60-90 ml/min/1.73 m2 body surface area) or moderate severity (eGFR 30-60 ml/min/1.73 m2 body surface area) dose adjustment is not required. Data on the drug, Perio in patients with renal dysfunction severe severity (eGFR <30 1="" 73="" span="">2 of the body surface area) is not enough, so the use of the drug, Perio in this category of patients are advised to exercise caution.
Patients with hepatic impairment
In patients with impaired hepatic function mild or moderate severity (class a and b according to the classification of child-Pugh) dose, Aperio does need to be adjusted. The drug Perio is not recommended in patients with severely impaired liver function (class C classification for child-Pugh).
Use in children and adolescents under the age of 18 years
Data on the safety and efficacy of Perio in children and adolescents no.
Use in patients over 65 years
In patients older than 65 years no dosage adjustment is required.
Side effect:
Identified adverse events (AES) were consistent with the pharmacological characteristics of the drug, Perio and related diseases available to patients. Most frequent AES were marked reduction in blood pressure, hyperkalemia and impaired renal function caused by the correction of the dose, Uperi or termination of therapy.
The frequency of NYA did not depend on the sex, age or race of the patients.
NYA are listed according to the system-organ class of the medical dictionary for the regulatory activities of Meddra. Within each organ-system class, NYA are distributed by frequency of occurrence in order of decreasing their importance. The following criteria are used to estimate the frequency: very often (?1/10); often (?1/100 to <1 10="" 1="" 000="" 100="" 10000="" 1000="" br= "" > metabolic and nutritional Disorders: very often - hyperkalemia; often-hypokalemia.
Disorders of the nervous system: often-dizziness, headache; infrequently-orthostatic dizziness.
Violations of the organ of hearing and labyrinth disorders: common - vertigo.
Vascular disorders: very often - a marked decrease in blood PRESSURE; often-fainting, orthostatic hypotension.
Disorders of the respiratory system, chest and mediastinal organs: often-cough.
Disorders of the gastrointestinal tract: often-diarrhea, nausea.
Disorders of the skin and subcutaneous tissues: infrequent - angioedema.
Disorders of the kidneys and urinary tract: very often - a violation of kidney function; often - renal failure (including acute renal failure).
General disorders and disorders at the injection site: often-fatigue, asthenia.
If any of the side effects listed in the instructions are aggravated, or you notice any other side effects that are not listed in the instructions, tell your doctor.
Overdose:
Data on overdose of the drug, Perio person is not enough. A single use of the drug at a dose of 1200 mg and repeated at a dose of 900 mg in healthy volunteers was accompanied by good tolerability.
The most likely symptom of an overdose is a marked decrease in blood PRESSURE, due to the antihypertensive action of the active substances. In this case, symptomatic treatment is recommended.
In case of accidental overdose should cause vomiting (if the drug was taken recently) or gastric lavage. In the event of a marked decrease in blood PRESSURE as a therapy, intravenous administration of 0.9% sodium chloride solution is necessary, the patient should be placed, raising his legs, for the necessary period of time for therapy, take active measures to maintain the cardiovascular system, including regular monitoring of the heart and respiratory system, the volume of circulating blood (BCC) and the amount of urine released.
Removal of active substances during hemodialysis is unlikely, since a significant part of them is associated with plasma proteins.
Interaction:
Contraindicated drug interactions
ACE inhibitors
The drug Perio contraindicated concurrently with ACE inhibitors, as suppression between simultaneously with the use of ACE inhibitors may increase the risk of developing angioedema. The application of the product Aperio possible possible not earlier than 36 hours after discontinuation of the ACE inhibitor. The use of ACE inhibitors may not be earlier than 36 hours after the last administration of the drug, Perio.
Aliskiren
In patients with diabetes mellitus and in patients with impaired renal function (eGFR <60 1="" 73="" span="">2 of the body surface area), Operio the drug should not be used in conjunction with aliskiren.
Not recommended drug interactions
Angiotensin receptor antagonists
Since one of the active substances of the drug is an antagonist of angiotensin II receptors, simultaneous use with another drug containing ARA II is not recommended.
Drug interactions to be considered
Inhibitors of HMG-COA reductase inhibitors (statins)
Research shows that sakubita inhibits the activity vectors OATP1B1 and OATP1B3. The drug Perio may increase systemic exposure to such substrates OATP1B1 and OATP1B3 as statins. Patients receiving the drug, Perio concurrently with atorvastatin, maximum concentration in plasma (Cmax) of atorvastatin and its metabolites increased up to 2 times, a AUC up to 1.3 times. For this reason, the drug Perio simultaneously with statins should be used with caution.
Sildenafil.
In patients with a marked increase in blood PRESSURE, receiving the drug Juperio (until equilibrium concentration), a single use of sildenafil increased antihypertensive effect compared with the use of the drug Juperio in monotherapy. For this reason, in patients receiving Perio, apply sildenafil or other phosphodiesterase inhibitor 5-th type should be used with caution.
Suggested drug interactions that need to be considered
Potassium
Concomitant use of potassium-sparing diuretics (e.g., triamterene and amiloride), mineralocorticoid antagonists (e.g., spironolactone and eplerenone), potassium preparations or potassium-containing salt substitutes may cause an increase in potassium content and serum creatinine concentration. In patients receiving the drug, Perio simultaneously with these drugs, it is recommended to regularly monitor the content of potassium in the blood serum.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2 inhibitors)
The use of Juperio concomitantly with NSAIDs in patients over the age of 65 years, 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, Perio simultaneously with NSAIDs, the appointment of such a scheme of treatment and, if changes are recommended to monitor renal function.
Lithium preparations
The possibility of drug interaction between the drug, Perio and lithium drugs not studied. With the simultaneous use of lithium preparations with ACE inhibitors and ARA II, there was a reversible increase in the concentration of lithium in the blood serum and an increase in toxic manifestations in this regard.
In patients receiving the drug, Perio together with the drug lithium, it is recommended to carefully control the lithium content in the blood serum. In the case of additional use of a diuretic drug, the risk of toxic effects of lithium may increase.
Proteins-carriers
Active metabolite securitie (LBQ657) and valsartan are substrates of protein-vectors of OATP1B1, OATP1B3 and OAT3; also, valsartan is a substrate of protein-carrier MRP2. In patients receiving the drug, Perio simultaneously with inhibitors OATP1B1, OATP1B3, OAT3 (for example, rifampicin and cyclosporine) or MRP2 (e.g., ritonavir) may increase systemic exposure LBQ657 or valsartan, respectively. At the beginning and at the end of a joint of the drug, Perio and this group of drugs requires caution.
The lack of significant drug interactions
In the case of using the drug Yuperio in combination with furosemide, digoxin, warfarin, hydrochlorothiazide, amlodipine, Metformin, omeprazole, carvedilol, nitroglycerin intravenously (in/in) or a combined drug levonorgestrel and ethinyl estradiol clinically significant interactions were not revealed. Interactions with atenolol, indomethacin, glibenclamide (glyburide) or cimetidine in a joint application with the drug, Perio not expected.
Interactions with cytochrome P450 isoenzymes
Existing studies demonstrate that the likelihood of drug interactions mediated by the isoenzymes of cytochrome CYP450 small, as the complex of active substances to a small extent metabolized with the participation of isoenzymes CYP450. The complex of active substances of the drug, Perio is not an inhibitor or inducer of isozymes CYP450.Special instruction:
Marked decrease in blood PRESSURE
Patients receiving the drug, Perio, there have been cases of clinically expressed arterial hypotension. In the event of a marked decrease in blood PRESSURE should consider the correction of the dose of diuretics, concomitant antihypertensive agents, as well as to eliminate the causes of a marked decrease in blood PRESSURE (eg, hypovolemia). If, despite these measures, marked reduction in blood pressure persists, the dose of Perio should be reduced or the drug should be on time to cancel. Final withdrawal of the drug is usually not required. The likelihood of a marked decrease in blood PRESSURE is usually higher in patients with hypovolemia, which can be caused by diuretic therapy, low-salt diet, diarrhea or vomiting. Before beginning use of the drug, Perio should be performed correction of sodium in the body and/or to fill the BCC.
Violations of kidney function
Like any other drug acting on the RAAS, drug Perio can cause deterioration of renal function. In a comparative study of safety and effectiveness (compared with amlodipine) clinically significant abnormalities in renal function have been rare, and the drug Perio in connection with such violations were rarely abolished (0,65%) than enalapril (1,28%). In the case of clinically significant deterioration in renal function should consider dose reduction, Upery. In applying the drug, Perio in patients with severe renal impairment should proceed with caution.
Hyperkalemia
Like any other drug acting on the RAAS, drug Perio may increase the risk of hyperkalemia. In a comparative study of safety and efficacy (compared with enalapril) clinically significant hyperkalemia was rare; drug Juperio due to hyperkalemia was canceled in 0.26% of patients, and enalapril - in 0.35% of patients. Drugs that can increase the potassium content in the blood serum (eg, potassium-sparing diuretics, potassium preparations) at the same time with the drug Juperio should be used with caution. In case of clinically significant hyperkalemia, measures such as reducing potassium intake with food or adjusting the dose of concomitant drugs should be considered. It is recommended to regularly monitor serum potassium levels, especially in patients with risk factors such as severe renal impairment, diabetes, hypoaldosteronism or a high potassium diet.
Angioneurotic edema
On the background of the drug, Perio been cases of development of angioedema. If you experience angioedema Operio the drug should be discontinued immediately and to appoint adequate treatment and monitoring the patient to complete and persistent resolution of all symptoms occurred. Re-assign the drug Perio should not be. In cases of confirmed angioedema, in which the swelling was limited to the face and lips, the condition was generally resolved without intervention, although the use of antihistamines helped to alleviate the symptoms.
Angioedema, accompanied by swelling of the larynx, can lead to death. In cases where swelling spreads to the tongue, vocal folds or larynx, which can lead to airway obstruction, appropriate treatment should be initiated immediately, such as subcutaneous administration of epinephrine solution (epinephrine) 1:1000 (0.3-0.5 ml), and/or appropriate measures to ensure airway patency.
In patients with a history of angioedema caused by the use of ACE inhibitors or ARA II, the drug Perio should not be used. Patients of the Negroid race may be more at risk for angioedema.
Patients with renal artery stenosis
Like other drugs acting on RAAS, the drug Juperio can cause an increase in the concentration of urea and creatinine in the serum of 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.Influence on the ability to drive transp. Ms. and fur.:
There are no data on the effect of the drug on the ability to drive vehicles and/or mechanisms. In connection with the possible occurrence of dizziness or fatigue should be careful when driving or working with machinery.
Product form/dosage:
Tablets, film-coated, 50 mg (of 25.7 mg + 24,3 mg); 100 mg (51,4 mg + 48,6 mg); 200 mg (mg 102,8 + 97,2 mg).
Storage conditions:
At a temperature not exceeding 25° C.
Keep out of reach of children.
