QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(二十一)
own as (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxytricyclo [3.3.1.1]dec-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, monohydrate or
(1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxy-1-adamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile hydrate. The empirical formula is C18H25N3O2•H2O and the molecular weight is 333.43. The structuralformula is:
Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is a biguanide. Themolecular formula is C4H11N5•HCl and the molecular weight is 165.63. The structural formula is:QTERNMET XR is available as film-coated tablets of four strengths:
•2.5 mg dapagliflozin/2.5 mg saxagliptin/1000 mg metformin HCl: Each tablet contains 2.5 mgdapagliflozin (equivalent to 3.08 mg dapagliflozin propanediol), 2.5 mg saxagliptin (exists in theform of HCl salt) and 1000 mg metformin HCl (equivalent to 779.86 mg metformin).
•5 mg dapagliflozin/2.5 mg saxagliptin/1000 mg metformin HCl: Each tablet contains 5 mgdapagliflozin (equivalent to 6.15 mg dapagliflozin propanediol), 2.5 mg saxagliptin (exists in theform of HCl salt) and 1000 mg metformin HCl (equivalent to 779.86 mg metformin).
•5 mg dapagliflozin/5 mg saxagliptin/1000 mg metformin HCl: Each tablet contains 5 mgdapagliflozin (equivalent to 6.15 mg dapagliflozin propanediol), 5 mg saxagliptin (exists in the formof HCl salt) and 1000 mg metformin HCl (equivalent to 779.86 mg metformin).
•10 mg dapagliflozin/5 mg saxagliptin/1000 mg metformin HCl: Each tablet contains 10 mgdapagliflozin (equivalent to 12.3 mg dapagliflozin propanediol), 5 mg saxagliptin (exists in the formof HCl salt) and 1000 mg metformin HCl (equivalent to 779.86 mg metformin).
ach tablet also contains the following inactive ingredients: carboxymethyl cellulose sodium,crospovidone, hypromellose 2208, iron oxides, lactose anhydrous, magnesium stearate, microcrystallinecellulose, polyvinyl alcohol, macrogol/polyethylene glycol, silicon dioxide, talc, and titanium dioxide.
Hydrochloric acid and sodium hydroxide (if needed) are added for pH adjustment.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
QTERNMET XR contains: dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor,saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin hydrochloride, a biguanide.
Dapagliflozin
Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for themajority of the reabsorption of filtered glucose from the tubular lumen. Dapagliflozin is an inhibitor ofSGLT2. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose and lowers the renalthreshold for glucose and thereby increases urinary glucose excretion.
Saxagliptin
Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) andglucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the smallintestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in aglucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowersglucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved.
Saxagliptin is a competitive DPP-4 |
