Product Information
Registration Status: ActiveSTEGLUJAN FILM-COATED TABLETS 5MG/100MG is approved to be sold in Singapore with effective from 2020-03-11. It is marketed by MSD PHARMA (SINGAPORE) PTE LTD, with the registration number of SIN15904P.
This product contains Ertugliflozin 5mg, and Sitagliptin 100MG in the form of TABLET, FILM COATED. It is approved for ORAL use.
This product is manufactured by Schering-Plough Labo NV in BELGIUM.
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
Ertugliflozin belongs to the class of potent and selective inhibitors of the sodium-dependent glucose cotransporters (SGLT), more specifically the type 2 which is responsible for about 90% of the glucose reabsorption from glomerulus.[A31581] This drug was developed under the collaboration of Merck and Pfizer. It was FDA approved as monotherapy and in combination with sitagliptin or metformin hydrochloride on December 22, 2017.[L1132]
Indication
Ertugliflozin as a monotherapy is indicated to improve the glycemic control in adult patients with type 2 diabetes.[FDA label] Ertugliflozin, in combination with metformin hydrochloride, is indicated to improve glycemic control in patients with diabetes type 2 who are not controlled on a regimen of ertugliflozin or metformin or in patients who are already treated with both ertugliflozin and metformin.[L1134] The administration of ertugliflozin in combination with sitagliptin is indicated to improve glycemic control in adult patients with type 2 diabetes when treatment with ertugliflozin and sitagliptin is appropriate.[L1135] It is pointed out that the use of ertugliflozin has to be an adjunct therapy to the use of diet and exercise. The type 2 diabetes mellitus is characterized by insulin resistance in muscle and liver, which results in the elevation of glucose levels in blood, or by presence of insulin deficiency. The insulin resistance is related to genetic factors, obesity, sedentary lifestyle or/and aging. This increase in the blood glucose can cause severe damage to kidney, eyes and vascular system.[A31582]
Mechanism of Action
As part of a normal process, the glucose from the blood is filtered for excretion and reabsorbed in the glomerulus so less than one percent of this glucose is excreted in the urine. The reabsorption is mediated by the sodium-dependent glucose cotransporter (SGLT), mainly the type 2 which is responsible for 90% of the reabsorbed glucose. Ertugliflozin is a small inhibitor of the SGLT2 and its activity increases glucose excretion, reducing hyperglycemia without the requirement of excessive insulin secretion.[A31581]
Pharmacokinetics
- Absorption
- Preclinical studies showed that ertugliflozin is well absorbed and had an oral bioavailability of 70-90%. The reported Tmax occurred at 0.5-1.5 hours after dosage.[A31583] Following oral administration, the Cmax and AUC appeared to be dose proportional.Administration of 15 mg reported values of Cmax and AUC of 268 ng/ml and 1193 ng h/ml respectively.[L1136]
- Distribution
- After oral administration of ertugliflozin, the apparent volume of distribution was reported to be 215.3 L. The steady-state volume of distribution after intravenous administration of etrugliflozin is 85.53 L.[L1136]
- Metabolism
- In vitro studies showed that the metabolic profile of ertugliflozin in liver microsomes and hepatocytes is formed by reactions of monohydroxylation, O-demethylation and glucuronidation. The metabolism of ertugliflozin is proposed to be formed by 8 different metabolites found in plasma, feces and urine. In plasma, the unchanged form of ertugliflozin was found to be the major component of the administered dose. There were also other six minor metabolites identified in circulating plasma.[A31583]
- Elimination
Clearance
The apparent total plasma clearance rate after oral administration of ertugliflozin is 178.7 ml/min and the systemic total plasma clearance after intravenous administration is reported to be 187.2 ml/min.[L1136]
Toxicity
The reports from clinical trials have portrait ertugliflozin to be well tolerated and abscent of significant side effects.[A31586] Carcinogenic studies have been performed and it has been reported an increased incidence of adrenal medullary pheochromocytoma; possibly related to carbohydrate malabsorption leading to altered calcium homeostasis. There were no reported cases of mutagenesis or impairment in fertility.[FDA label]
Active Ingredient/Synonyms
Ertugliflozin | Ertugliflozin |
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.
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.