Product Information
Registration Status: ActiveGALVUS MET TABLET 50MG/850MG is approved to be sold in Singapore with effective from 2009-11-08. It is marketed by NOVARTIS (SINGAPORE) PTE LTD, with the registration number of SIN13685P.
This product contains Metformin 850mg, and Vildagliptin 50mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Novartis Pharma Stein AG in SINGAPORE,Novartis Pharma Produktions GmbH in TURKEY,NOVARTIS SINGAPORE PHARMACEUTICAL MANUFACTURING PTE. LTD. in SWITZERLAND, andNovartis Saglik 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
Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin may induce weight loss and is the drug of choice for obese NIDDM patients. Use of metformin is associated with modest weight loss. When used alone, metformin does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus metformin hydrochloride was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and metformin is appropriate.
Indication
For use as an adjunct to diet and exercise in adult patients (18 years and older) with NIDDM. May also be used for the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome (PCOS). Jentadueto is for the treatment of patients when both linagliptin and metformin is appropriate.
Mechanism of Action
Metformin's mechanisms of action differ from other classes of oral antihyperglycemic agents. Metformin decreases blood glucose levels by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. These effects are mediated by the initial activation by metformin of AMP-activated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, whole body energy balance, and the metabolism of glucose and fats. Activation of AMPK is required for metformin's inhibitory effect on the production of glucose by liver cells. Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors. Metformin administration also increases AMPK activity in skeletal muscle. AMPK is known to cause GLUT4 deployment to the plasma membrane, resulting in insulin-independent glucose uptake. The rare side effect, lactic acidosis, is thought to be caused by decreased liver uptake of serum lactate, one of the substrates of gluconeogenesis. In those with healthy renal function, the slight excess is simply cleared. However, those with severe renal impairment may accumulate clinically significant serum lactic acid levels. Other conditions that may precipitate lactic acidosis include severe hepatic disease and acute/decompensated heart failure.
Pharmacokinetics
- Absorption
- Absorbed over 6 hours, bioavailability is 50 to 60% under fasting conditions. Administration with food decreases and delays absorption. Some evidence indicates that the level of absorption is not dose-related, suggesting that absorption occurs through a saturable process. Limited data from animal and human cell cultures indicate that absorption occurs through a passive, non-saturable process, possibly involving a paracellular route. Peak action occurs 3 hours after oral administration.
- Distribution
- 654 L for metformin 850 mg administered as a single dose. The volume of distribution following IV administration is 63-276 L, likely due to less binding in the GI tract and/or different methods used to determine volume of distribution.
- Metabolism
- Metformin is not metabolized.
- Elimination
Clearance
718-1552 mL/minute following single oral dose of 0.5-1.5 g. Metformin is removed by hemodialysis at a rate of approximately 170 ml/min under good hemodynamic conditions.
Toxicity
Acute oral toxicity (LD50): 350 mg/kg [Rabbit]. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen.
Active Ingredient/Synonyms
1,1-Dimethylbiguanide | Dimethylbiguanid | Metformin | Metformina | Metformine | Metforminum | Metformin |
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
Vildagliptin, previously identified as LAF237, is a new oral anti-hyperglycemic agent (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucaon release by the alpha cells of the islets of Langerhans in the pancreas. It is currently in clinical trials in the U.S. and has been shown to reduce hyperglycemia in type 2 diabetes mellitus. While the drug is still not approved for use in the US, it was approved in Feb 2008 by European Medicines Agency for use within the EU and is listed on the Australian PBS with certain restrictions.
Indication
Used to reduce hyperglycemia in type 2 diabetes mellitus.
Mechanism of Action
Vildagliptin inhibits dipeptidyl peptidase-4 (DPP-4). This in turn inhibits the inactivation of GLP-1 by DPP-4, allowing GLP-1 to potentiate the secretion of insulin in the beta cells. Dipeptidyl peptidase-4's role in blood glucose regulation is thought to be through degradation of GIP and the degradation of GLP-1.
Pharmacokinetics
- Absorption
- Rapidly absorbed following oral administration with an oral bioavailability of greater than 90%.
- Distribution
- Metabolism
- Elimination
Active Ingredient/Synonyms
EQUA | Galvus | Jalra | LAF237 | NVP-LAF-237 | NVP-LAF237 | Vildagliptin | Xiliarx | Vildagliptin |
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.