JENTIN Tablet

Monotherapy

JENTIN is indicated as adjunct to diet and exercise to Improve glycemic control in patients with type2 diabetes mellitus.

Combination Therapy

JENTIN is indicated in patients with type2 diabetes mellitus to improve glycemic control in combination with metformin or a Peroxisome proliferator activated receptor gamma (PPAR gamma) agonist (e.g., thiazolidinediones) when the single agent alone, with diet and exercise, does not provide adequate glycemic control.

Important Limitations of Use

JENTIN should not be used in patients with type1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

DOSAGE AND ADMINISTRATION

100mg once daily as monotherapy or as combination therapy with metformin or Peroxisome proliferator activated receptor gamma (PPAR gamma) agonist (e.g. thiazolidinediones) JENTIN can be taken with or without food.

Patients with Renal Insufficiency: See the package insert about the details.

In patients with:

- Real disease or renal dysfunction, e.g., as suggested by serum creatinine levels ≥1.5mg/dL[males], ≥1.4mg/dL[females] or abnormal creatinine clearance which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia.

- Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

- History of a serious hypersensitivity reaction to Sitagliptin, such as anaphylaxis or angioedema.

A very serious allergic reaction to this drug is rare. However, medical help is advised against any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

The most common side effect from Sitagliptin can be upper respiratory tract infection, vaso-pharyngitis and headaches. The other side effects which can occur with monotherapy of sitagliptin or combination therapy with metformin are Hypoglycemia, abdominal pain, nausea and diarrhea.

If any meaningful changes in vital signs or in ECG (including in QTc interval) is observed should be clinically correlated. Small WBC count can be observed due to increase in neutrophils but not clinically relevant. Mean increase in serum creatinine can be observed in patients with chronic renal insufficiency.

Sitagliptin does not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin or oral contraceptives, providing in vivo evidence of a low propensity for causing drug interactions with substrates of CYP3A4, CYP2C8, CYP2C9 and organic cationic transporter.

See the package insert about the details below:

- Digoxin

- Metformin

- Sulfonylureas

- Simvastatin

- Thiazolidiones

- Warfarin

- Oral contraceptives

Pregnancy

Pregnancy Category B: Doses of sitagliptin up to 125mg/kg do not impair fertility or harm the fetus. There are however, no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when JENTIN is administered to a nursing woman.

See the package insert about the details below:

- Renal Insufficiency: A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with ESRD requiring hemodialysis or peritoneal dialysis.

- Hepatic Insufficiency, Body Mass Index (BMI), Gender, Geriatric, Race: No dosage adjustment is necessary.

- Pediatric: Studies characterizing the pharmacokinetics of sitagliptin in pediatric patients have not been performed.

Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by Sitagliptin, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4.

The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, Sitagliptin increases insulin release and decreases glucagon levels in the circulation, in a glucose-dependent manner. Sitagliptin demonstrated selectively for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.