Product Information
Registration Status: ActiveJANUVIA 25MG TABLET is approved to be sold in Singapore with effective from 2007-04-23. It is marketed by MSD PHARMA (SINGAPORE) PTE LTD, with the registration number of SIN13259P.
This product contains Sitagliptin 25mg in the form of TABLET. It is approved for ORAL use.
This product is manufactured by PT. Merck Sharp Dohme Pharma Tbk. (Primary and Secondary Packager) in UNITED KINGDOM, andMerck Sharp & Dohme Ltd. in INDONESIA REP OF.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Sitagliptin is a new oral hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. This enzyme-inhibiting drug is to be used either alone or in combination with metformin or a thiazolidinedione for control of type 2 diabetes mellitus. The drug works to competitively inhibit a protein/enzyme, dipeptidyl peptidase 4 (DPP-4), that results in an increased amount of active incretins (GLP-1 and GIP), reduced amount of release of glucagon (diminishes its release) and increased release of insulin.
Indication
For use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Also for use in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin or a PPARγ agonist (e.g., thiazolidinediones) when the single agent alone, with diet and exercise, does not provide adequate glycemic control.
Mechanism of Action
Sitagliptin is a highly selective DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones, thereby increasing the concentration and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic 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. These changes lead to a decrease in hemoglobin A1c (HbA1c)levels, as well as a lower fasting and postprandial glucose concentration. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.
Pharmacokinetics
- Absorption
- Rapidly absorbed following oral administration, with an absolute bioavailability of 87%.
- Distribution
- * 198 L [healthy subjects]
- Metabolism
- Sitagliptin does not undergo extensive metabolism. In vitro studies indicate that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4 (oxidation), with contribution from CYP2C8.
- Elimination
Clearance
* renal cl=350 mL/min [Healthy subjects receiving 100 mg oral dose]
Active Ingredient/Synonyms
(2R)-4-OXO-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine | MK-0431 | Sitagliptan | Sitagliptin phosphate | Sitagliptina | Sitagliptine | Sitagliptinum | Sitagliptin |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.