Januvia, 100 mg 28 pcs.

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

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

The hormones of the incretin family are secreted in the intestine throughout the day and their levels increase in response to food intake. The incretins are part of the internal physiological system of glucose homeostasis regulation. At normal or elevated blood glucose levels hormones of the hormone family of insectins increase insulin synthesis as well as its secretion by pancreatic β-cells through signaling intracellular mechanisms associated with cyclic AMP.

PPP-1 also contributes to the suppression of increased glucagon secretion by pancreatic α-cells. Decrease of glucagon concentration against the background of increase of insulin level promotes decrease of glucose production by liver that results in decrease of glycemia.
When blood glucose concentration is low, the listed effects of incretins on insulin release and decrease in glucagon secretion are not observed. GFP-1 and GIP have no effect on glucagon release in response to hypoglycemia. Under physiological conditions, the activity of the insectins is limited by the enzyme DPP-4, which rapidly hydrolyzes the insectins to form inactive products.

Sitagliptin prevents hydrolysis of incretins by DPP-4 enzyme, thereby increasing plasma concentrations of active forms of GFP-1 and GIP. By increasing the level of incretins, sitagliptin increases glucose-dependent insulin release and helps to decrease glucagon secretion. In patients with type 2 diabetes with hyperglycemia these changes in insulin and glucagon secretion lead to a decrease in glycated hemoglobin HbA1C and a decrease in plasma glucose concentration determined on an empty stomach and after a loading test.

. In patients with type 2 diabetes a single dose of Januvia leads to inhibition of DPP-4 enzyme activity for 24 hours, which leads to increase of circulating insulin GFP-1 and GIP by 2-3 times, increase of plasma concentration of insulin and C-peptide, decrease of plasma glucagon concentration, decrease of fasting glucose, and decrease of glucose after glucose load or food load.

Indications

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

Combination therapy: Type 2 diabetes to improve glycemic control in combination with metformin or PPAR agonists (e.g., thiazolidinedione) when diet and exercise in combination with monotherapy of the listed agents do not result in adequate glycemic control.

Active ingredient

Composition

One film-coated tablet contains:

Active substance:

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

Auxiliary substances:

Cellulose microcrystalline;

Calcium hydrophosphate;

Sodium croscarmellose;

Magnesium stearate;

Sodium stearyl fumarate.

Composition of the shell:

Opadry II beige 85 F17438;

Polyvinyl alcohol;

Titanium dioxide;

Macrogol (polyethylene glycol) 3350;

Talc;

Iron oxide yellow;

Iron oxide red.

How to take, the dosage

When used as monotherapy or in combination with metformin or a PPAR-γ agonist (e.g., thiazolidinedione), the recommended dose of Januvia is 100 mg once daily.

Yanuvia can be taken regardless of meals. If a patient misses Januvia, the drug should be taken as soon as possible. Double doses of Januvia should not be taken.

In mild renal failure (CKR ≥50 ml/min, approximately corresponding to serum creatinine ≤1.7 mg/dL in men, ≤1.5 mg/dL in women) no dose adjustment is required.

In moderate renal failure (CKD ≥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 once daily.

In severe renal failure (CK3 mg/dL in men, >2.5 mg/dL in women), for patients with end-stage renal failure and the need for hemodialysis, the dose of Januvia is 25 mg once daily Januvia can be used regardless of the hemodialysis procedure schedule.

Interaction

In studies of interactions with other medicinal products, sitagliptin had no 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 the 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. A slight increase in the AUC (11%) as well as in the mean C max (18%) of digoxin was observed when coadministered with sitagliptin. This increase is not considered clinically significant. It is not recommended to change the dose of either digoxin or Januvia when used concomitantly.

A 29% and 68% increase in AUC and C max of sitagliptin have been observed, respectively, in patients when co-administering Januvia at a single dose of 100 mg and cyclosporine (a potent p-glycoprotein inhibitor) at a single dose of 600 mg. These changes in sitagliptin pharmacokinetic parameters are not considered clinically significant. It is not recommended to change the dose of Januvia when co-administered with cyclosporine and other p-glycoprotein inhibitors (e.g., ketoconazole).

Population pharmacokinetic analysis in patients and healthy volunteers (n=858) receiving a wide range of concomitant drugs (n=83, approximately half of which are excreted by the kidneys) showed no clinically significant effects of drugs on sitagliptin pharmacokinetics.

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.

The co-administration of Januvia in combination with drugs that may cause hypoglycemia, such as insulin and sulfonylurea derivatives, has not been studied.

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

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

Contraindications

Diabetes mellitus type 1.

Diabetic ketoacidosis.

Pregnancy.

The period of lactation (breastfeeding).

High sensitivity to the ingredients of the drug.

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

Prescribe with caution in patients with renal insufficiency.

In moderate to severe renal failure as well as in patients with terminal renal failure requiring hemodialysis, correction of the dosage regimen is required.

Side effects

Digestive system disorders: abdominal pain, nausea, vomiting, diarrhea. Laboratory parameters: hyperuricemia, decreased activity of total and partially bone fraction of ALP, leukocytosis due to increased number of neutrophils.

Others (causal relationship with drug administration has not been established:) Infections of the upper respiratory tract, nasopharyngitis, headache, arthralgia. The incidence of hypoglycemia is similar to that when taking placebo.

Overdose

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

Minimal QTc interval changes not considered clinically significant were noted in one study of the drug at the indicated dose. There have been no clinical studies of the drug in doses greater than 800 mg/day.

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

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

Pregnancy use

There are no adequate and strictly controlled clinical safety studies of the drug Januvia in pregnant women.

The use of the drug is contraindicated in pregnancy.

It is unknown whether sitagliptin is excreted with breast milk in humans.

If it is necessary to use the drug during lactation, discontinuation of breastfeeding should be considered.

Similarities