Clinic Diabetes

Fixed_Dose-XigduoXR

Dapagliflozin propanediol monohydrate/metformin hydrochloride

  • XIGDUO XR is available for oral administration as tablets containing the following active ingredients:
    -XIGDUO XR 10/500: 10 mg dapagliflozin (as dapagliflozin propanediol monohydrate) and 500 mg metformin hydrochloride.
    -XIGDUO XR 10/1000: 10 mg dapagliflozin (as dapagliflozin propanediol monohydrate) and 1000 mg metformin hydrochloride.
    -XIGDUO XR 5/1000: 5 mg dapagliflozin (as dapagliflozin propanediol monohydrate) and 1000 mg metformin hydrochloride.

The results of bioequivalence studies in healthy subjects demonstrated that XIGDUO XR combination tablets are bioequivalent to coadministration of corresponding doses of dapagliflozin and metformin hydrochloride modified release as individual tablets. The following statements reflect the pharmacokinetic properties of the individual active substances of XIGDUO XR.

  • Dapagliflozin: Dapagliflozin was rapidly and well absorbed after oral administration and can be administered with or without food. Maximum dapagliflozin plasma concentrations (Cmax) were usually attained within 2 hours after administration in the fasted state. The Cmax and AUC values increased proportional to the increment in dapagliflozin dose. The absolute oral bioavailability of dapagliflozin following the administration of a 10 mg dose is 78%.
  • Metformin hydrochloride Following a single oral dose of metformin extended release, Cmax is achieved with a median value of 7 hours and a range of 4 to 8 hours.

  • Dapagliflozin: Dapagliflozin is approximately 91% protein bound. Protein binding was not altered in various disease states (e.g., renal, or hepatic impairment).
  • Metformin hydrochloride
  • Distribution studies with extended-release metformin have not been conducted; however, the apparent volume of distribution (V/F) of metformin following single oral doses of immediate release metformin 850 mg averaged 654 ± 358 L. After repeated administration of metformin extended-release, metformin did not accumulate in plasma. Metformin is negligibly bound to plasma proteins, in contrast to sulfonylureas, which are more than 90% protein bound.

  • Dapagliflozin: Dapagliflozin is extensively metabolised, primarily to yield dapagliflozin 3-O-glucuronide. Dapagliflozin 3-O-glucuronide, with a molar plasma AUC 52% higher than that of dapagliflozin itself at the clinical dose, is an inactive metabolite and does not contribute to the glucose lowering effects.
  • Metformin hydrochloride Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) or biliary excretion.

  • Dapagliflozin:
    Dapagliflozin and related metabolites are primarily eliminated via urinary excretion, of which less than 2% is unchanged dapagliflozin. After oral administration of 50 mg [14C]-dapagliflozin dose, 96% was recovered, 75% in urine and 21% in faeces. In faeces, approximately 15% of the dose was excreted as parent drug. The mean plasma terminal half-life (t1/2) for dapagliflozin was 12.9 hours following a single oral dose of dapagliflozin 10 mg to healthy subjects.
  • Metformin hydrochloride:
    Renal clearance is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution. When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.

For more detailed information on this product please consult the product information.
https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2014-PI-02269-1