Vipidiya pills coated 25mg N28
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Active ingredients
Alogliptin
Release form
Pills
Composition
1 tablet contains: Alogliptin benzoate 34 mg, which corresponds to the content of alogliptin 25 mg. Supplementary substances: mannitol - 79.7 mg, microcrystalline cellulose - 22.5 mg, hyprolosis - 4.5 mg, croscarmellose sodium - 7.5 mg. Composition of the film coating: hypromellose 2910 - 5.34 mg, titanium dioxide - 0.6 mg, iron dye red oxide - 0.06 mg, macrogol 8000 - trace amounts, gray ink F1 (shellac - 26%, iron dye black oxide - 10%, ethanol - 26%, butanol - 38%) - trace amounts.
Pharmacological effect
Hypoglycemic drug, potent and highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4). Its selectivity for DPP-4 is more than 10,000 times greater than its effect for other related enzymes, including DPP-8 and DPP-9. DPP-4 is the main enzyme involved in the rapid destruction of hormones of the incretin family: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (HIP). Hormones of the incretin family are secreted in the intestine, their concentration increases in response to food intake. GLP-1 and HIP increase insulin synthesis and its secretion by pancreatic β-cells. GLP-1 also inhibits glucagon secretion and reduces the production of glucose by the liver. Therefore, by increasing the concentration of incretins, alogliptin increases glucose-dependent insulin secretion and decreases glucagon secretion at elevated blood glucose concentrations. In patients with type 2 diabetes mellitus with hyperglycemia, these changes in insulin and glucagon secretion lead to a decrease in the concentration of glycated hemoglobin HbA1C and a decrease in plasma glucose concentration in both fasting and postprandial glucose.
Pharmacokinetics
The pharmacokinetics of alogliptin has a similar character in healthy individuals and in patients with type 2 diabetes. Absorption Absolute bioavailability of alogliptin is approximately 100%. Simultaneous intake with a high-fat diet did not affect the AUC of alogliptin, so it can be taken regardless of the intake. In healthy individuals, after a single oral dose of up to 800 mg of alogliptin, rapid absorption of the drug is observed, reaching an average Tmax in the range of 1 to 2 hours from the time of administration. AUCl of alogliptin increases proportionally with a single dose in the therapeutic dose range from 6.25 mg to 100 mg.The variability of AUC of alogliptin among patients is small (17%). The AUC (0-inf) alogliptin after a single dose was similar to the AUC (0-24) after taking the same dose 1 time / day for 6 days. This indicates the absence of a time dependence in the kinetics of alogliptin after repeated administration. Distribution Binding to plasma proteins is approximately 20-30%. After a single IV administration of alogliptin at a dose of 12.5 mg in healthy volunteers, Vd in the terminal phase was 417 liters, which indicates that alogliptin is well distributed in the tissues. Neither healthy volunteers nor patients with type 2 diabetes did not clinically see Significant cumulation of alogliptin after repeated administration. MetabolismAllogliptin is not subjected to intensive metabolism, from 60 to 70% of alogliptin is excreted unchanged by the kidneys. After administration of 14C-labeled alogliptin, two main m metabolite: N-desmethyl alogliptin, M-I (<1% starting material) and N-acetylated alogliptin, M-II (<6% starting material). MI is an active metabolite and a highly selective inhibitor of DPP-4, similar in action to alogliptin itself; M-II does not exhibit inhibitory activity against DPP-4 or other DPP enzymes. In in vivo studies, it was found that CYP2D6 and CYP3A4 are involved in the limited metabolism of alogliptin. Also, in vitro studies show that alogliptin does not induce CYP1A2, CYP2C9, CYP2B6 and does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 in concentrations achievable with the recommended dose of alogliptin 25 mg. In vitro, alogliptin can induce CYP3A4 to a small extent; however, in vivo, alogliptin does not induce CYP3A4. Alogliptin does not inhibit the renal transporters of organic human anions of the first (OAT1), third (OAT3) types and renal transporters of organic cations of the second human (OCT2) Type. Allogliptin exists predominantly in the form of (R) -enantiomer (> 99%) and in in vivo or in small quantities, or not at all subjected to chiral transformation into the (S) -enantiomer. (S) -enantiomer is not detected when taking alogliptin in therapeutic doses. Introduction After oral administration of 14C-labeled alogliptin, 76% of the total radioactivity was excreted by the kidneys and 13% through the intestines. The average renal clearance of alogliptin (170 ml / min) is greater than the average glomerular filtration rate (about 120 ml / min), which suggests that alogliptin is partially excreted due to active renal excretion.The average terminal T1 / 2 is approximately 21 hours. Pharmacokinetics in selected groups of patients. Patients with renal failure. The study of alogliptin at a dose of 50 mg / day was conducted in patients with varying degrees of severity of chronic renal failure. The patients included in the study were divided into 4 groups according to the Cockroft-Gault formula: patients with mild (CK from 50 to 80 ml / min), moderate severity (CK from 30 to 50 ml / min) and severe (CK less 30 ml / min), as well as patients with end-stage chronic renal failure, who need hemodialysis. AUGliptin in patients with mild severity of renal failure increased approximately 1.7 times compared with the control group. However, this increase in AUC was within the tolerance for the control group, therefore, dose adjustment in these patients is not required. An increase in the AUC of alogliptin by about 2 times compared with the control group was observed in patients with moderate renal insufficiency. Approximately fourfold increase in AUC was observed in patients with severe renal insufficiency, as well as in patients with end-stage chronic renal failure compared with the control group. Patients with end-stage renal disease were given hemodialysis immediately after ingesting alogliptin. About 7% of the dose was removed from the body during the 3-hour dialysis session. Thus, to achieve a therapeutic concentration of alogliptin in blood plasma similar to that in patients with normal renal function, dose adjustment in patients with moderately severe renal failure is necessary. Alogliptin is not recommended for patients with severe renal insufficiency, as well as with end-stage renal disease requiring hemodialysis. Patients with hepatic insufficiency. In patients with moderately severe liver failure, the AUC and Cmax of alogliptin are reduced by approximately 10% and 8%, respectively, compared with patients with normal liver function. These values are not clinically significant.Thus, dosage adjustment for mild to moderate liver failure (5 to 9 points on the Child-Pugh scale) is not required. There are no clinical data on the use of alogliptin in patients with severe liver failure (more than 9 points on the Child-Pugh scale). Other groups of patients. Age (65-81 years), gender, race, body weight of patients did not have a clinically significant effect on the pharmacokinetic parameters of alogliptin. Dose adjustment of the drug is not required. The pharmacokinetics in children and adolescents under the age of 18 years have not been studied.
Indications
Diabetes mellitus type 2 in adults to improve glycemic control with the ineffectiveness of diet and exercise: - as monotherapy; - in combination with other oral hypoglycemic agents or insulin.
Contraindications
- hypersensitivity to alogliptin or to any excipient, or serious hypersensitivity reactions to any DPP-4 inhibitor in history, including anaphylactic reactions, anaphylactic shock and angioedema; - diabetes mellitus type 1; - diabetic ketoacidosis; chronic heart failure (FC NYHA class III-IV); - severe liver failure (more than 9 points on the Child-Pugh scale) due to the lack of clinical data on the use; - severe renal failure; - pregnancy (due to lack of clinical data on the application); - breastfeeding period (due to the lack of clinical data on the application); - children and adolescents under 18 years of age (due to the lack of clinical data on the application).
Precautionary measures
Precautions: - history of acute pancreatitis; - in patients with moderate renal insufficiency; - in combination with a sulfonylurea derivative or insulin; - taking a three-component combination of Vipidium with metformin and thiazolidinedione.
Use during pregnancy and lactation
No studies have been conducted on the use of alogliptin in pregnant women. Experimental studies on animals did not show a direct or indirect negative impact of alogliptin on the reproductive system. However, as a precaution, the use of the drug Vipidia during pregnancy is contraindicated. It is not known whether alogliptin is excreted in human breast milk. Experimental studies on animals have shown that alogliptin is excreted in breast milk, so the risk of side effects in infants cannot be excluded.In this regard, the use of the drug during breastfeeding is contraindicated.
Dosage and administration
Vipidiya drug can be taken regardless of the meal. Tablets should be swallowed whole, not chewed, squeezed with water. The recommended dose of Vipidia is 25 mg 1 time / day as monotherapy or in addition to metformin, thiazolidinedione, a sulfonylurea derivative or insulin, or as a three-component combination with a metformin, a tiazolidine. If a patient misses taking Vipidia, he should take the missed dose as soon as possible. Do not take a double dose of Vipidia on the same day. When prescribing Vipidium, in addition to metformin or thiazolidinedione, the dose of the last drugs should be left unchanged. When combining Vipidia with a sulfonylurea derivative or insulin, the last dose should be reduced to reduce the risk of hypoglycemia. In connection with the risk of hypoglycemia, caution should be exercised when prescribing a three-component combination of the drug Vipidium with metformin and thiazolidinedione. In the case of hypoglycemia, it is possible to consider reducing the dose of metformin or thiazolidinedione. The effectiveness and safety of alogliptin when taken in triple combination with metformin and a sulfonylurea derivative have not been studied. Patients with renal insufficiency Patients with mild renal insufficiency (CK from 50 to ≤80 ml / min) dose adjustment drug Vipidiya not required. In patients with moderate renal failure (CC from ≥30 to ≤50 ml / min), the dose of Vipidia is 12.5 mg 1 time / day. Alogliptin should not be used in patients with severe renal failure and in patients with end-stage renal failure needing hemodialysis (CC <30 ml / min). In patients with renal insufficiency, it is recommended to evaluate kidney function before starting treatment with Vipidia and periodically during the course of treatment. Patients with hepatic insufficiency Reactions of the dose of the drug Vipidia in patients with mild to moderate hepatic insufficiency (from 5 to 9 points on the Child-Pugh scale).The drug has not been studied in patients with severe liver failure (more than 9 points on the Child-Pugh scale), so it should not be used in this group of patients. Patients over 65 years old Do not require dose adjustment of Vipidia in patients over 65 years of age. Nevertheless, it is necessary to carefully select the dose of alogliptin in connection with the potential for reducing renal function in this group of patients.
Side effects
From the nervous system: often - headache. From the digestive system: often - pain in the epigastric region, gastroesophageal reflux disease; frequency not established - acute pancreatitis. From the side of the liver and biliary tract: frequency not established - impaired liver function, incl. liver failure. On the side of the skin and subcutaneous tissues: often - itching, rash; frequency not established - exfoliative skin diseases, including Stevens-Johnson syndrome, angioedema, urticaria. On the respiratory system: often - upper respiratory tract infections, nasopharyngitis. On the immune system: frequency not established - hypersensitivity reactions, including anaphylactic reaction.
Overdose
The maximum dose of alogliptin in clinical studies was 800 mg / day in healthy volunteers and 400 mg / day in patients with type 2 diabetes for 14 days. This is 32 and 16 times, respectively, higher than the recommended daily dose of 25 mg alogliptin. There were no serious adverse events when taking the drug in these doses. Treatment: in case of overdose, gastric lavage and symptomatic treatment may be recommended. Aogliptin is poorly dialyzed. In clinical studies, only 7% of the dose was removed from the body during the 3-hour dialysis session. Data on the effectiveness of peritoneal dialysis alogliptin not.
Interaction with other drugs
The effect of other drugs on alogliptinAlgliptin is mainly excreted unchanged by the kidneys, and is slightly metabolized by the cytochrome CYP450 enzyme system. In the studies on the interaction with other drugs on the pharmacokinetics of alogliptin, the following drugs did not have a clinically significant effect: gemfibrozil (an inhibitor of CYP2C8 / 9),fluconazole (CYP2C9 inhibitor), ketoconazole (CYP3A4 inhibitor), cyclosporine (P-glycoprotein inhibitor), α-glycosidase inhibitor, digoxin, metformin, cimetidine, pioglitazone or atorvastatin. and does not induce CYP450 isoenzymes in concentrations achieved when taking alogliptin at the recommended dose of 25 mg. Interactions with CYP450 isoenzymes are not expected and have not been identified. In vitro studies revealed that alogliptin is neither a substrate nor an inhibitor of OAT1, OAT3 and OCT2. In addition, data from clinical studies do not indicate interaction with inhibitors or substrates of P-glycoprotein. In clinical studies on the interaction with other drugs, alogliptin had no clinically significant effect on the pharmacokinetics of the following drugs: caffeine, (R) - and (S) -varfarin , pioglitazone, glibenclamide, tolbutamide, dextromethorphan, atorvastatin, midazolam, oral contraceptives (norethindrone and ethinyl estradiol), digoxin, fexofenadine, metformin or cimetidine. Based on these data, alogliptin does not inhibit isoenzymes of the cytochrome CYP1A2, CYP3A4, CYP2D6, CYP2C9, P-glycoprotein and OCT2 systems. Alogliptin did not affect the prothrombin index or MHO in healthy volunteers while taking it with warfarin. , or pioglitazone (thiazolidinedione), or an α-glycosidase inhibitor, or glibenclamide (a sulfonylurea derivative), no clinically significant pharmacokinetic interaction was observed.
special instructions
Use with other hypoglycemic drugs. In order to reduce the risk of hypoglycemia, it is recommended to reduce the dose of sulfonylurea, insulin, or a combination of pioglitazone (thiazolidinedione) with metformin while being used with Vipidia. analogs of the glucagon-like peptide and in triple combination with metformin and sulfonyl derivatives ocheyny not studied. Renal failureTk.patients with moderate renal failure require dose adjustment of the drug Vipidia, it is recommended to evaluate kidney function before and periodically during treatment. Vipidia should not be used in patients with severe renal failure, as well as in patients with end-stage chronic renal failure requiring hemodialysis. Acute pancreatitis. The use of DPP-4 inhibitors is associated with the potential risk of developing acute pancreatitis. In a generalized analysis of 13 clinical studies of the use of alogliptin at a dose of 25 mg / day, 12.5 mg / day, the comparator drug and placebo, the incidence of acute pancreatitis was 3, 1, 1 or 0 cases per 1000 patient-years in each group, respectively. Patients should be informed about the characteristic symptoms of acute pancreatitis: persistent severe abdominal pain, which may radiate to the back. If you suspect the development of acute pancreatitis, Vipidia is discontinued; when confirming acute pancreatitis, the drug is not resumed. There is no evidence that there is an increased risk of developing pancreatitis while taking the drug Vipidia in patients with a history of pancreatitis. Therefore, when using the drug in patients with a history of pancreatitis, caution should be exercised. Hepatic insufficiencyPost-marketing reports of impaired liver function, including hepatic insufficiency, have been received when taking alogiptin. Their relationship with the use of the drug has not been established. However, patients should be carefully examined for possible abnormalities in liver function. If abnormalities in liver function are found and the alternative etiology of their occurrence has not been established, the possibility of discontinuing drug treatment should be considered. Influence on the ability to drive motor vehicles and control mechanisms Vipidia does not have or has little effect on the ability to drive vehicles and mechanisms. However, the risk of hypoglycemia should be considered when using the drug in combination with other hypoglycemic drugs (sulfonylurea derivatives, insulin or combination therapy with pioglitazone and metformin) and caution should be exercised when driving vehicles and mechanisms.