Product Information
Registration Status: ActiveXIGDUO XR TABLET 5MG/500MG is approved to be sold in Singapore with effective from 2016-08-30. It is marketed by ASTRAZENECA SINGAPORE PTE LTD, with the registration number of SIN15077P.
This product contains Dapagliflozin 5mg, and Metformin 500mg in the form of ORAL TABLET, FILM-COATED, EXTENDED-RELEASE. It is approved for ORAL use.
This product is manufactured by AstraZeneca Pharmaceuticals LP in UNITED STATES, andMerck Sante (Drug Product Intermediate - Metformin) in FRANCE.
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
Dapagliflozin is indicated for the management of diabetes mellitus type 2, and functions to improve glycemic control in adults when combined with diet and exercise. Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor, which prevents glucose reabsorption in the kidney. Using dapagliflozin leads to heavy glycosuria (glucose excretion in the urine), which can lead to weight loss and tiredness. Dapagliflozin was approved by the FDA on Jan 08, 2014. Dapagliflozin is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Indication
Dapagliflozin is indicated for adjunct management of glycemic control in patients with type 2 diabetes mellitus, in combination with diet and exercise.
Mechanism of Action
A competitive inhibitor of the sodium-glucose transport subtype 2 protein, dapagliflozin blocks glucose reabsorption into the kidney, resulting in the elimination of blood glucose through the urine.
Pharmacokinetics
- Absorption
- Cmax is about 1 hour. (Obtained from 6 adult men in a fasted state administered a 50mg dose). 1.6% of unchanged dapagliflozin was found in the urine. A high-fat meal (52% caloric content) had no significant effect on previous pharmacokinetic parameters.
- Distribution
- Metabolism
- Dapagliflozin 3-O-glucuronide is the primary metabolite of dapagliflozin, with 61% of the dapagliflozin dose recovered in the urine as this metabolite. The metabolism of dapagliflozin is primarily mediated by UGT1A9-dependent glucuronide conjugation. The major metabolite, dapagliflozin 3-O-glucuronide, is not an SGLT2 inhibitor.
- Elimination
Clearance
Oral plasma clearance of 4.9 mL/min/kg, and a renal clearance of 5.6 mL/min.
Toxicity
Compared to placebo-treated patients, patients with moderate renal impairment treated with dapagliflozin did not have improvement in glycemic control and had more renal-related adverse reactions and more bone fractures; therefore, dapagliflozin should not be initiated in this population. Based on its mechanism of action, dapagliflozin is not expected to be effective in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2) or ESRD.
Active Ingredient/Synonyms
(2S,3R,4R,5S,6R)-2-(4-Chloro-3-(4-ethoxybenzyl)phenyl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol | Dapagliflozin |
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
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.