QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(二十五)
t were 45%, 2.04-fold, and 3.03-fold higher, respectively, as compared topatients with type 2 diabetes with normal renal function. Higher systemic exposure of dapagliflozin inpatients with type 2 diabetes mellitus with renal impairment did not result in a correspondingly higher24-hour urinary glucose excretion. The steady-state 24-hour urinary glucose excretion in patients withtype 2 diabetes and mild, moderate and severe renal impairment was 42%, 80% and 90% lower,respectively, than patients with type 2 diabetes with normal renal function. The impact of hemodialysis on
dapagliflozin exposure is not known [see DOSAGE AND ADMINISTRATION (2.2), WARNINGS ANDPRECAUTIONS (5.5) and USE IN SPECIFIC POPULATIONS (8.6)].
Saxagliptin: A single-dose, open-label study was conducted to eva luate the pharmacokinetics ofsaxagliptin (10 mg dose) in subjects with varying degrees of chronic renal impairment compared tosubjects with normal renal function. The 10 mg dosage is not an approved dosage. The degree of renalimpairment did not affect Cmax of saxagliptin or its metabolite. In subjects with moderate renalimpairment (eGFR 30 to less than 45 mL/min/1.73 m2), severe renal impairment (eGFR 15 to less than
30 mL/min/1.73 m2) and ESRD patient on hemodialysis, the AUC values of saxagliptin or its activemetabolite were >2 fold higher than AUC values in subjects with normal renal function. QTERNMETXR is contraindicated in patients with an eGFR less than 45 mL/min/1.73 m2, ESRD, or on dialysis.
Metformin HCl: In patients with decreased renal function, the plasma and blood half-life of metformin isprolonged and the renal clearance is decreased [see CONTRAINDICATIONS (4) and WARNINGS ANDPRECAUTIONS (5.1)].
Hepatic Impairment
Dapagliflozin: In subjects with mild and moderate hepatic impairment (Child-Pugh classes A and B),mean Cmax and AUC of dapagliflozin were up to 12% and 36% higher, respectively, as compared tohealthy matched control subjects following single-dose administration of 10 mg dapagliflozin. Thesedifferences were not considered to be clinically meaningful. In patients with severe hepatic impairment (Child-Pugh class C), mean Cmax and AUC of dapagliflozin were up to 40% and 67% higher, respectively,
as compared to healthy matched controls.
Saxagliptin: In subjects with hepatic impairment (Child-Pugh classes A, B, and C), mean Cmax and AUCof saxagliptin were up to 8% and 77% higher, respectively, compared to healthy matched controlsfollowing administration of a single 10 mg dose of saxagliptin. The 10 mg dosage is not an approveddosage. The corresponding Cmax and AUC of the active metabolite were up to 59% and 33% lower,respectively, compared to healthy matched controls. These differences are not considered to be clinicallymeaningful.
Metformin HCl: No pharmacokinetic studies of metformin have been conducted in patients with hepaticimpairment [see DOSAGE AND ADMINISTRATION (2.3), WARNINGS AND PRECAUTIONS (5.1) andUSE IN SPECIFIC POPULATIONS (8.7)].
Pediatric
Pharmacokinetics of QTERNMET XR in the pediatric population has not been studied.
Drug Interactions
Specific pharmacokinetic drug interaction studies with QTERNMET XR have not been performedalthough such studies have been conducted with the individual dapagliflozin, saxagliptin and metformincomponents.
Dapagliflozin
In Vitro Assessment of Drug Interactions
The metabolism of dapagliflozin is primarily via glucuronide conjugation media |
