Januvia, pills 100mg, 28pcs

Composition

One film-coated tablet contains:

Active ingredient:

Sitagliptin (in the form of phosphate monohydrate) 100 mg.

Auxiliary substances:

Microcrystalline cellulose;

Calcium hydrophosphate;

Croscarmellose sodium;

Magnesium stearate;

Sodium stearyl fumarate.

Shell composition:

Opadry II beige 85 F17438;

Polyvinyl alcohol;

Titanium dioxide;

Macrogol (polyethylene glycol) 3350;

Talc;

Iron oxide yellow;

Iron oxide red.

Pharmacological action

Januvia is an oral hypoglycemic drug, a highly selective dipeptidyl peptidase 4 (DPP-4) inhibitor.

Sitagliptin differs in its chemical structure and pharmacological action from analogs of glucagon-like peptide-1( GLP-1), insulin, sulfonylureas, biguanides, agonists of gamma-receptors activated by the peroxisome proliferator (PPAR-y), alpha-glycosidase inhibitors, and amylin analogues. By inhibiting DPP-4, sitagliptin increases the concentration of 2 known incretin family hormones: GLP-1 and glucose-dependent insulinotropic peptide (GIP).

Hormones of the incretin family are secreted in the intestines during the day, their level increases in response to food intake. Incretins are part of the internal physiological system for regulating glucose homeostasis. At normal or elevated blood glucose levels, incretin family hormones promote increased insulin synthesis and secretion by pancreatic beta cells due to intracellular signaling mechanisms associated with cyclic AMP.

GLP-1 also helps to suppress increased glucagon secretion by pancreatic alpha cells. A decrease in the concentration of glucagon against the background of an increase in the level of insulin contributes to a decrease in glucose production by the liver, which ultimately leads to a decrease in glycemia. At low blood glucose concentrations, the listed effects of incretins on insulin release and a decrease in glucagon secretion are not observed. GLP-1 and GIP do not affect the release of glucagon in response to hypoglycemia. Under physiological conditions, incretin activity is limited by the enzyme DPP-4, which rapidly hydrolyzes incretins to form inactive products.

Sitagliptin prevents incretin hydrolysis by the DPP-4 enzyme, thereby increasing plasma concentrations of GLP-1 and GIP active forms. By increasing incretin levels, sitagliptin increases glucose-dependent insulin release and helps reduce glucagon secretion. In patients with type 2 diabetes mellitus with hyperglycemia, these changes in insulin and glucagon secretion lead to a decrease in the level of glycated hemoglobin HbA1c and a decrease in the plasma glucose concentration determined on an empty stomach and after a load test.

In patients with type 2 diabetes mellitus, taking a single dose of Januvia leads to inhibition of the activity of the DPP-4 enzyme for 24 hours, which leads to an increase in the level of circulating incretins GLP-1 and GIP by 2-3 times, an increase in the plasma concentration of insulin and C-peptide, a decrease in the concentration of glucagon in blood plasma, a decrease in fasting glycemia, and

Indications

• Monotherapy: as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes.

• Combination therapy: type 2 diabetes mellitus to improve glycemic control in combination with metformin or PPAR agonists (for example, thiazolidinedione), when diet and exercise combined with monotherapy with these drugs do not lead to adequate glycemic control.

Use during pregnancy and lactation

Adequate and strictly controlled clinical studies of the safety of Januvia in pregnant women have not been conducted.

The use of the drug during pregnancy is contraindicated.

It is not known whether sitagliptin is excreted in human breast milk.

If it is necessary to use the drug during lactation, the question of stopping breastfeeding should be decided.

Contraindications

• Type 1 diabetes mellitus.

• Diabetic ketoacidosis.

• Pregnancy.

• The period of lactation (breastfeeding).

• Hypersensitivity to the components of the drug.

It is not recommended to prescribe the drug Januvia to children and adolescents under the age of 18 (there are no data on the use of the drug in pediatric practice).

Use with caution in patients with renal insufficiency.

In patients with moderate and severe renal insufficiency, as well as in patients with end-stage renal insufficiency requiring hemodialysis, dosage adjustment is required.

Side effects

From the digestive system: abdominal pain, nausea, vomiting, diarrhea. Laboratory parameters: hyperuricemia, decreased activity of the total and partial bone fraction of alkaline phosphatase, leukocytosis due to an increase in the number of neutrophils.

Other (no causal relationship has been established with taking the drug): upper respiratory tract infections, nasopharyngitis, headache, arthralgia. The incidence of hypoglycemia is similar to that of placebo.

Interaction

In interaction studies with other drugs, sitagliptin did not have a clinically significant effect on the pharmacokinetics of the following drugs: metformin, rosiglitazone, glibenclamide, simvastatin, warfarin, oral contraceptives.

Based on these data, sitagliptin does not inhibit CYP3A4,2C8, or 2C9 isoenzymes. Based on in vitro data, sitagliptin also probably does not inhibit CYP2D6,1A2,2C19, or 2B6, nor does it induce CYP3A4. There was a slight increase in the AUC (11%) and mean cmax (18%) of digoxin when co-administered with sitagliptin. This increase is not considered clinically significant. It is not recommended to change the dose of either digoxin or Januvia when they are used simultaneously.

The AUC and cmax of sitagliptin increased by 29% and 68%, respectively, in patients treated with a single 100 mg dose of Januvia and a single 600 mg dose of cyclosporine (a potent p-glycoprotein inhibitor). These changes in the pharmacokinetic parameters of sitagliptin are not considered clinically significant. It is not recommended to change the dose of Januvia in combination with cyclosporine and other p-glycoprotein inhibitors (for example, ketoconazole).

A population pharmacokinetic analysis in patients and healthy volunteers (n=858) treated with a wide range of concomitant medications (n=83, approximately half of which are excreted by the kidneys) did not reveal any clinically significant drug effects on the pharmacokinetics of sitagliptin.

How to take, course of use and dosage

When used as monotherapy or in combination with metformin or a PPAR-γ agonist (for example, thiazolidinedione), the recommended dose of Januvia is 100 mg 1 time/day.

Januvia can be taken regardless of food intake. If the patient missed taking Januvia, the drug should be taken as soon as possible. It is unacceptable to take a double dose of the drug Januvia.

In patients with mild renal insufficiency (creatinine clearance ≥50 ml / min, approximately corresponding to the content of serum creatinine ≤1.7 mg / dl in men, ≤1.5 mg / dl in women), no dose adjustment is required.

In moderate renal insufficiency (creatinine clearance ≥30 ml/min, but 1.7 mg/dl, but ≤3 mg/dl in men, >1.5 mg/dl, but ≤2.5 mg/dl in women), the dose of Januvia is 50 mg 1 time/day. >

In severe renal insufficiency (creatinine clearance 3 mg / dl in men, >2.5 mg / dl in women), for patients with end-stage renal insufficiency and the need for hemodialysis, the dose of Januvia is 25 mg 1 time/day, Januvia can be used regardless of the schedule of the hemodialysis procedure.

Overdose

Symptoms:  during clinical studies in healthy volunteers, good tolerability was observed when taking Januvia in a single dose of 800 mg.

Minimal changes in the QTc interval that are not considered clinically significant were observed in one of the studies of the drug at the specified dose. Clinical studies of the drug at a dose of more than 800 mg / day have not been conducted.

Treatment:  removal of unabsorbed drug from the gastrointestinal tract, monitoring of vital signs, including ECG, if necessary – carrying out symptomatic and maintenance therapy. Sitagliptin is poorly dialyzed.

In clinical trials, only 13.5% of the dose was removed from the body during a 3-4-hour dialysis session. Prolonged dialysis can be prescribed with if clinically necessary. There are no data on the effectiveness of sitagliptin peritoneal dialysis.

Special instructions

In clinical trials of Januvia as monotherapy or as part of combination therapy with metformin or pioglitazone, the incidence of hypoglycemia when using Januvia was similar to the incidence of hypoglycemia when using placebo.

Concomitant use of Januvia in combination with drugs that can cause hypoglycemia, such as insulin, sulfonylureas, has not been studied.

Patients with mild to moderate hepatic insufficiency do not need to adjust the dose of Januvia. In clinical trials, the efficacy and safety of Januvia in elderly patients (≥65 years,409 patients) were comparable to those in patients younger than 65 years. No age-appropriate dose adjustment is required.

Elderly patients are more likely to develop renal failure. Accordingly, as in other age groups, dose adjustment is necessary in patients with severe renal insufficiency.

Storage conditions

At a temperature not exceeding 30 °C.

Shelf

life is 2 years.

Active ingredient

Sitagliptin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Type 2 Diabetes