Product Information
Registration Status: ActiveGLYXAMBI FILM-COATED TABLET 10 MG/5 MG is approved to be sold in Singapore with effective from 2017-06-16. It is marketed by BOEHRINGER INGELHEIM SINGAPORE PTE LTD, with the registration number of SIN15273P.
This product contains Empagliflozin 10mg, and Linagliptin 5mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Boehringer Ingelheim Pharma GmbH & Co. KG in GERMANY.
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
Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, therefore resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia and also assists weight loss and blood pressure reduction.
Indication
Empagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes.
Mechanism of Action
Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia, assists weight loss, and reduces blood pressure.
Pharmacokinetics
- Absorption
- Following oral administration, peak plasma concentrations were reached at 1.5 hours post-dose and then declined in a biphasic manner with a rapid distribution phase and a relatively slow terminal phase. Administration following a high-fat and high-calorie meal results in a slightly lower exposure with AUC decreasing by approximately 16% and Cmax decreasing by approximately 37% compared to fasted condition.
- Distribution
- 73.8 L
- Metabolism
- In vitro studies suggest that empaglifozin is primarily metabolized by glucuronidation by 5'-diphospho-glucuronosyltransferases UG2B7, UGT1A3, UGT1A8, and UGT1A9. The most abundant metabolites are three glucuronide metabolites: 2-O-, 3-O-, and 6-O-glucuronide. Empagliflozin does not inhibit, inactivate, or induce CYP450 isoforms. It is a substrate for p-glycoprotein (p-gp), however in vitro studies suggest that it is unlikely to cause interactions with drugs that are p-gp substrates.
- Elimination
Clearance
Apparent oral clearance was found to be 10.6 L/h based on population pharmacokinetic analysis.
Toxicity
The most commonly reported adverse effects for empaglifozin were urinary tract infections, female genital mycotic infections, and dyslipidemia. Because empagliflozin causes osmotic diuresis adverse reactions related to volume depletion were also reported (decreased systolic blood pressure, dehydration, hypotension, orthostatic hypotension, hypovolemia, and syncope). Impaired renal function and hypoglycemia were also reported.
Active Ingredient/Synonyms
(1S)-1,5-anhydro-1-(4-chloro-3-{4-[(3S)-tetrahydrofuran-3-yloxy]benzyl}phenyl)-D-glucitol | 1-chloro-4-(glucopyranos-1-yl)-2-(4-(tetrahydrofuran-3-yloxy)benzyl)benzene | Empagliflozin |
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
Linagliptin is a DPP-4 inhibitor developed by Boehringer Ingelheim for the treatment of type II diabetes. Two pharmacological characteristics that sets linagliptin apart from other DPP-4 inhibitors is that it has a non-linear pharmacokinetic profile and is not primarily eliminated by the renal system. FDA approved on May 2, 2011.
Indication
Linagliptin is used for the management of type 2 diabetes mellitus.
Mechanism of Action
Linagliptin is a competitive and reversible dipeptidyl peptidase (DPP)-4 enzyme inhibitor that slows the breakdown of insulinotropic hormone glucagon-like peptide (GLP)-1 for better glycemic control in diabetes patients. GLP and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones that increase the production and release of insulin from pancreatic beta cells and decrease the release of glucagon from pancreatic alpha cells. This results in a overall decrease in glucose production in the liver and increase an of insulin in a glucose-dependent manner.
Pharmacokinetics
- Absorption
- Cmax, 5 mg, healthy subjects = 8.32 nmol/L; Tmax, 5 mg, healthy subjects = 1.75 hours; AUC(0-24 hours), 5 mg, healthy subjects = 119 nmol · h/L; Bioavailability, healthy subjects = 30%. When a dose of 5 mg once daily is given, steady state is achieved by the third dose. Although a high fat meal reduces Cmax and increases AUC, this interaction with food is not clinically significant. Linagliptin may be administered with or without food.
- Distribution
- Vd = 1110 L
- Metabolism
- Linagliptin is not extensively metabolized, 90% of dose is excreted unchanged. The small portion of drug that is metabolized, the main metabolite is CD 1790 and is pharmacologically inactive. Glucuronidation forms some of its other minor metabolites.
- Elimination
Clearance
Renal clearance, steady state = 70 mL/min
Active Ingredient/Synonyms
(R)-8-(3-Aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methylquinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione | Trajenta | Linagliptin |
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.