Januvia pills 100mg №28

Packaging

In the blister 14 tablets. In packing 2 blisters.

Mechanism of action

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 analogues of glucagon-like peptide-1 (GLP-1), insulin, sulfonylurea derivatives, biguanides, γ-peroxisome-activated proliferator-receptor agonists, alpha glycosidase inhibitors, amylin analogues. Inhibiting DPP-4, sitagliptin increases the concentration of 2 known hormones of the incretin family: GLP-1 and the glucose-dependent insulinotropic peptide (HIP). Hormones of the family of incretins are secreted in the intestine during the day, their level rises in response to food intake. Incretins are part of the internal physiological system for regulating glucose homeostasis. At normal or elevated blood glucose levels, hormones of the incretin family contribute to an increase in insulin synthesis, as well as its secretion by β-cells of the pancreas due to signaling intracellular mechanisms associated with cyclic AMP.
GLP-1 also contributes to the suppression of increased glucagon secretion by pancreatic α-cells. A decrease in glucagon concentration on the background of an increase in insulin levels 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 HIP do not affect the release of glucagon in response to hypoglycemia. Under physiological conditions, the activity of incretins is limited by the enzyme DPP-4, which quickly hydrolyzes the incretins to form inactive products.
Sitagliptin prevents hydrolysis of incretins by the enzyme DPP-4, thereby increasing the plasma concentrations of the active forms of GLP-1 and HIP. By increasing the level of incretins, sitagliptin increases glucose-dependent insulin release and contributes to a decrease in glucagon secretion. In patients with type 2 diabetes mellitus with hyperglycemia, these changes in insulin and glucagon secretion lead to a decrease in glycated hemoglobin НbА1С and a decrease in plasma glucose concentration, determined on an empty stomach and after a stress test.
In patients with type 2 diabetes, taking a single dose of Januvia drug leads to inhibition of the activity of the enzyme DPP-4 for 24 hours, which leads to an increase in the level of circulating GLP-1 and HIP incretin by a factor of 2–3 peptide, reducing the concentration of glucagon in the blood plasma, reducing fasting glucose, as well as reducing glycemia after loading glucose or food load.

Indications and usage

- Monotherapy: as a supplement to diet and physical exertion 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 the above agents do not lead to adequate glycemic control.

Contraindications

- Type 1 diabetes.

- Diabetic ketoacidosis.

- Pregnancy.

- Lactation period (breastfeeding).

- Hypersensitivity to the drug. It is not recommended to prescribe the drug Januvia to children and adolescents under the age of 18 years (data on the use of the drug in pediatric practice is not available). Use with caution in patients with renal insufficiency. In case of moderate and severe renal failure, as well as in patients with end-stage renal failure requiring hemodialysis, correction of the dosing regimen is required.

Pregnancy and Breastfeeding

Adequate and strictly controlled clinical studies of the safety of the drug Januvia in pregnant women was not conducted. The use of the drug during pregnancy is contraindicated. It is not known whether sitagliptin is excreted in human breast milk. If necessary, the use of the drug during lactation should decide on the termination of breastfeeding.

Dosage and administration

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.
Yanuvia can be taken regardless of the meal. If the patient missed taking Januvia, the drug should be taken as soon as possible. Do not take a double dose of the drug Januvia.
In case of mild renal failure (CC ≥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 (CC ≥30 ml / min, but <50 ml / min, approximately corresponding to serum creatinine> 1.7 mg / dL, but ≤ 3 mg / dL in men,> 1.5 mg / dL, but ≤ 2.5 mg / dl in women) dose of Januvia is 50 mg 1 time / day.
In severe renal failure (CC <30 ml / min, approximately corresponding to serum creatinine> 3 mg / dL for men,> 2.5 mg / dL for women), for patients with end-stage renal failure and the need for hemodialysis, the dose of Januvia is 25 mg 1 time / day Yanuviyu can be used regardless of the schedule of hemodialysis.

Adverse reactions

There are side reactions that occur without a causal relationship with taking the drug Januvia in doses of 100 mg and 200 mg per day, but more often than when taking a placebo.
Respiratory: upper respiratory tract infections (100 mg - 6.8%, 200 mg - 6.1%, placebo - 6.7%), nasopharyngitis (100 mg - 4.5%, 200 mg - 4.4%, placebo - 3.3%).
From the side of the central nervous system: headache (100 mg - 3.6%, 200 mg - 3.9%, placebo - 3.6%).
Gastrointestinal: diarrhea (100 mg - 3%, 200 mg - 2.6%, placebo - 2.3%), abdominal pain (100 mg - 2.3%, 200 mg - 1.3%, placebo - 2.1%), nausea (100 mg - 1.4%, 200 mg - 2.9%, placebo - 0.6%), vomiting (100 mg - 0.8%, 200 mg - 0.7%, placebo - 0.9%), diarrhea (100 mg - 3%, 200 mg - 2.6%, placebo - 2.3% ).
Musculoskeletal system: arthralgia (100 mg - 2.1%, 200 mg - 3.3%, placebo - 1.8%).
On the part of the endocrine system: hypoglycemia (100 mg - 1.2%, 200 mg - 0.9%, placebo - 0.9%).
From the laboratory indicators: at doses of 100 mg / day and 200 mg / day - an increase in uric acid by about 0.2 mg / dl compared with placebo (median level 5-5.5 mg / dl) in patients who received the drug at a dose of 100 mg / day and 200 mg / day Cases of gout is not registered.
A slight decrease in the concentration of total alkaline phosphatase (approximately 5 IU / L compared with placebo, an average level of 56–62 IU / L), partly due to a slight decrease in the bone fraction of alkaline phosphatase.
A slight increase in leukocyte count (approximately 200 / mcl compared to placebo, average 6,600 / mcl), due to an increase in the number of neutrophils. This observation was noted in most, but not all studies.
The listed changes in laboratory parameters are not considered clinically significant.
On the background of the use of the drug Januvia, there were no clinically significant changes in vital signs and ECG (including the QTc interval).
Januvia is generally well tolerated, both as monotherapy and in combination with other hypoglycemic drugs. In clinical studies, the overall incidence of side effects, as well as the frequency of withdrawal of Januvia due to side effects, were similar to those taken with placebo.

Special notes

In clinical studies of the drug Januvia as monotherapy or as part of combination therapy with metformin or pioglitazone, the incidence of hypoglycemia with the use of the drug Januvia was similar to the incidence of hypoglycemia with placebo. The combined use of the drug Januvia in combination with drugs that can cause hypoglycemia, such as insulin, sulfonylurea derivatives, has not been studied.
Patients with mild and moderate hepatic insufficiency do not require dose adjustment of the drug Januvia.
In clinical studies, the efficacy and safety of the drug Januvia in elderly patients (≥65 years, 409 patients) were comparable with these indicators in patients younger than 65 years. Dose adjustment for age is not 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 failure.
 

In studies of the interaction with other drugs, 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 CYP3A4, 2C8 or 2C9 isoenzymes. Based on in vitro data, sitagliptin probably does not inhibit CYP2D6, 1A2, 2C19 or 2B6, nor does it induce CYP3A4. There was a slight increase in AUC (11%), as well as an average C max (18%) of Digoxin when used together with sitagliptin. This increase is not considered clinically significant. It is not recommended to change the dose of either digoxin or Januvia when used simultaneously. An increase in AUC and С max of sitagliptin was noted by 29% and 68%, respectively, in patients with a joint use of Januvia in a single dose of 100 mg and cyclosporine (a p-glycoprotein potent inhibitor) in a single dose of 600 mg. These changes in the pharmacokinetic parameters of sitagliptin are not considered clinically significant. It is not recommended to change the dose of the drug Januvia when used together with cyclosporine and other inhibitors of p-glycoprotein (for example, ketoconazole). A population pharmacokinetic analysis in patients and healthy volunteers (n = 858) who received a wide range of concomitant medications (n ​​= 83, about half of which are excreted by the kidneys), did not reveal any clinically significant effect of drugs on the pharmacokinetics of sitagliptin.

Symptoms: During clinical studies on healthy volunteers, good tolerance was observed when taking Januvia in a single dose of 800 mg. Minimal changes in the QTc interval, not considered clinically significant, were noted in one of the studies of the drug at the indicated dose. Clinical studies of the drug in a dose of more than 800 mg / day was not conducted.

Treatment: removal of an unabsorbed drug from the gastrointestinal tract, monitoring of vital signs, including an ECG, and, 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 the 3-4 hour dialysis session. Prolonged dialysis can be prescribed with in case of clinical need.There is no data on the effectiveness of peritoneal dialysis of sitagliptin.

The drug should be stored at a temperature not higher than 30 ° C.

2 years