Onglyza, pills 5mg, 30pcs

Composition

Active ingredient:

saxagliptin in the form of saxagliptin hydrochloride; 

Auxiliary substances:

lactose monohydrate,

microcrystalline cellulose,

croscarmellose sodium,

magnesium stearate,

1 M hydrochloric acid solution or 1 M sodium hydroxide solution,

Opadray II white [polyvinyl alcohol, titanium dioxide, macrogol (PEG 3350), talc],

Opadray II yellow [polyvinyl alcohol, titanium dioxide, macrogol (PEG 3350), talc, dye iron oxide yellow (E 172)] (for a dosage of 2.5 mg),

Opadray II pink [polyvinyl alcohol, titanium dioxide, macrogol (PEG 3350), talc, dye iron oxide red (E 172)] (for a dosage of 5.0 mg), Opacode blue ink

Pharmacological action

Onglyza has a hypoglycemic effect.

Pharmacodynamics

Saxagliptin is a powerful selective reversible competitive inhibitor of dipeptidyl peptidase-4 (DPP-4). In patients with type 2 diabetes mellitus (DM2), taking saxagliptin leads to suppression of the activity of the DPP-4 enzyme for 24 hours. After ingestion of glucose, inhibition of DPP-4 leads to a 2-3-fold increase in the concentration of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), a decrease in the concentration of glucagon and an increase in the glucose-dependent response of beta cells, which leads to an increase in the concentration of insulin and C-peptide. The release of insulin by beta cells of the pancreas and a decrease in the release of glucagon from pancreatic alpha cells leads to a decrease in fasting glycemia and postprandial glycemia. The efficacy and safety of saxagliptin at doses of 2.5 mg,5 mg, and 10 mg once daily were studied in six double-blind, placebo-controlled trials involving 4,148 patients with DM2. Taking the drug was accompanied by a statistically significant improvement in the parameters of glycosylated hemoglobin( HbAlc), fasting plasma glucose (HDL) and postprandial glucose (PPG) of blood plasma compared to the control.

Metformin, glibenclamide, or thiazolidinediones were additionally prescribed to patients who failed to achieve the target glycemic level when taking saxagliptin as monotherapy. When taking saxagliptin at a dose of 5 mg, a decrease in HbAlc was noted after 4 weeks and GPN-after 2 weeks.

In the group of patients treated with saxagliptin in combination with metformin, glibenclamide or thiazolidinediones, a decrease in HbAlc was also observed after 4 weeks and HDN-after 2 weeks.

The effect of saxagliptin on the lipid profile is similar to that of placebo. No weight gain was observed during saxagliptin therapy.

Pharmacokinetics

The pharmacokinetics of saxagliptin and its main metabolite were similar in patients with DM2 and healthy volunteers. Saxagliptin is rapidly absorbed after oral use on an empty stomach, reaching the maximum concentration of saxagliptin and the main metabolite in plasma (Cmax) within 2 hours and 4 hours, respectively. When the dose of saxagliptin was increased, there was a proportional increase in the Cmax and the area under the concentration-time curve (AUC) of saxagliptin and its main metabolite. After a single oral use of saxagliptin at a dose of 5 mg in healthy volunteers, the mean AUC values of saxagliptin and its main metabolite were 78 ngh / ml and 214 ngh/ml, and the plasma Cmax values were 24 ng / ml and 47 ng/ml, respectively.

The mean end-life (half-life) of saxagliptin and its main metabolite was 2.5 hours and 3.1 hours, respectively, and the mean plasma DPP-4 inhibition half-life was 26.9 hours. Inhibition of DPP-4 activity in plasma for at least 24 hours after use of saxagliptin is due to its high affinity for DPP-4 and long-term binding to it. No significant accumulation of saxagliptin and its main metabolite was observed during long-term use of the drug 1 time a day. The clearance of saxagliptin and its main metabolite was not found to depend on the dose of the drug and the duration of therapy when taking saxagliptin once a day in doses from 2.5 mg to 400 mg for 14 days.

Suction

After oral use, at least 75% of the saxagliptin dose is absorbed. Food intake did not significantly affect the pharmacokinetics of saxagliptin in healthy volunteers. High-fat food intake did not affect the Cmax of saxagliptin, while AUC increased by 27% compared to fasting. The time to reach Cmax (Tmax) for saxagliptin increased by approximately 0.5 hours when taking the drug with food compared to taking it on an empty stomach. However, these changes are not clinically significant.

Distribution

The binding of saxagliptin and its main metabolite to serum proteins is insignificant, so it can be assumed that the distribution of saxagliptin with changes in the protein composition of blood serum, observed in hepatic or renal insufficiency, will not be significantly affected.

Metabolism

Saxagliptin is mainly metabolized with the participation of cytochrome P450 4/5 isoenzymes (CYP3A4 / 5) to form the active main metabolite, whose inhibitory effect on DPP-4 is 2 times weaker than that of saxagliptin.

Deduction

Saxagliptin is excreted in the urine and bile. After a single dose of 50 mg of 14C-labeled saxagliptin,24% of the dose was excreted by the kidneys as unchanged saxagliptin and 36% as the main metabolite of saxagliptin. The total radioactivity detected in the urine corresponded to 75% of the drug dose taken. The mean renal clearance of saxagliptin was approximately 230 ml / min, and the mean glomerular filtration rate was approximately 120 ml/min.

For the main metabolite, renal clearance was comparable to the mean glomerular filtration rate. About 22% of the total radioactivity was detected in feces.

Indications

Type 2 diabetes mellitus in addition to diet and exercise to improve glycemic control as:

• monotherapy;
• starting combination therapy with metformin;
• addition to monotherapy with metformin, thiazolidinediones, sulfonylurea derivatives, in the absence of adequate glycemic control on this therapy.

Use during pregnancy and lactation

Due to the fact that the use of saxagliptin during pregnancy has not been studied, the drug should not be prescribed during this period.

It is not known whether saxagliptin penetrates into breast milk.

Due to the fact that the possibility of penetration of saxagliptin into breast milk is not excluded, breastfeeding should be discontinued for the duration of treatment with saxagliptin or therapy should be discontinued, taking into account the ratio of risk to the child and benefit to the mother.

Contraindications

• Increased individual sensitivity to any component of the drug;
• Type 1 diabetes mellitus (its use has not been studied);
• Use together with insulin (not studied);
• Diabetic ketoacidosis;
• Congenital galactose intolerance, lactase deficiency and glucose-galactose malabsorption;
• Pregnancy and lactation.
• Age up to 18 years (safety and efficacy have not been studied).

With caution: moderate and severe renal insufficiency; elderly patients; co-use with sulfonylurea derivatives.

Interaction

Analysis of the data from clinical studies suggests that the risk of clinically significant interactions of saxagliptin with other drugs when they are used together is low.

The metabolism of saxagliptin is mainly mediated by the cytochrome P450 3A 4/5 isoenzyme system (CYP3A4 / 5). In vitro studies have shown that saxagliptin and its main metabolite do not inhibit the isoenzymes CYP 1A2,2A6,2B6,2C9,2C19,2D6,2E1AND 3A4 and do not induce the isoenzymes CYP 1A2,2B6,2C9, and ZA4. In studies involving healthy volunteers, the pharmacokinetic parameters of saxagliptin and its main metabolite did not significantly change under the influence of metformin, glibenclamide, pioglitazone, digoxin, simvastatin, diltiazem, ketoconazole, omeprazole, a combination of aluminum hydroxide, magnesium hydroxide and simethicone, as well as famotidine. Saxagliptin did not significantly alter the pharmacokinetic parameters of metformin, glibenclamide, pioglitazone, digoxin, simvastatin, diltiazem, or ketoconazole.

The effect of inducers of CYP 3A4 / 5 isoenzymes on the pharmacokinetics of saxagliptin has not been studied. However, co-use of saxagliptin and inducers of CYP 3A4 / 5 isoenzymes, such as carbamazepine, dexamethasone, phenobarbital, phenytoin, and rifampicin, may lead to a decrease in the plasma concentration of saxagliptin and an increase in the concentration of its main metabolite. The effects of smoking, dietary intake, herbal preparations, and alcohol consumption on saxagliptin therapy have not been studied.

How to take it, course of use and dosage

The recommended dose of Onglyza is 5 mg once a day as part of combination therapy

Overdose

Symptoms of intoxication are not described with prolonged use of the drug in doses up to 80 times higher than recommended.

Treatment:

in case of overdose, symptomatic therapy should be used. Saxagliptin and its main metabolite are eliminated from the body by hemodialysis (elimination rate: 23% of the dose in 4 hours).

Special instructions

The use of Onglyza® in combination with insulin, as well as in triple therapy with metformin and thiazolidinediones or metformin and sulfonylurea derivatives, has not been studied.

Patients with impaired renal function.

Dose adjustment is recommended for patients with moderate to severe renal insufficiency, as well as for patients undergoing hemodialysis. Before starting therapy and periodically during treatment with the drug, it is recommended to evaluate renal function.

Use in combination with drugs that may cause hypoglycemia.

Sulfonylurea derivatives can cause hypoglycemia, so reducing the dose of sulfonylurea derivatives may be necessary to reduce the risk of hypoglycemia when used concomitantly with Onglyza®.

Hypersensitivity reactions.

The drug should not be prescribed to patients who have experienced serious hypersensitivity reactions with the use of other DPP-4 inhibitors.

Elderly patients.

According to clinical studies, the efficacy and safety indicators in patients aged 65 years and older did not differ from those in younger patients. However, an increased individual sensitivity to saxagliptin cannot be excluded in some elderly patients.

Saxagliptin and its main metabolite are partially excreted by the kidneys, so it should be taken into account that elderly patients are more likely to have decreased renal function. Onglyza ® contains lactose. Patients with congenital galactose intolerance, lactase deficiency, and glucose-galactose malabsorption should not take this medication.

Influence on the ability to drive motor vehicles and manage mechanisms.

Studies on the effect of saxagliptin on the ability to drive vehicles and manage mechanisms have not been conducted. Keep in mind that saxagliptin can cause dizziness.

Composition

Tablet Form of production

Storage conditions

At a temperature not exceeding 30 °C.

Shelf life

2 years

Active ingredient

Saxagliptin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Type 2 Diabetes