QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(二十)
ifferences in responses between the elderly and young patients. Metforminis known to be substantially excreted by the kidney. In general, dose selection for an elderly patientshould be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency ofdecreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and thehigher risk of lactic acidosis. Assess renal function more frequently in elderly patients [seeCONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.1), and CLINICALPHARMACOLOGY (12.3)].
8.6 Renal Impairment
QTERNMET XR is contraindicated in patients with moderate to severe renal impairment (eGFR less than45 mL/min/1.73 m2), ESRD, or on dialysis [see DOSAGE AND ADMINISTRATION (2.2),CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.6)].
Dapagliflozin
In clinical studies dapagliflozin was associated with increases in serum creatinine and decreases in eGFR[see ADVERSE REACTIONS (6.1)].
Dapagliflozin was eva luated in a study that included patients with moderate renal impairment (an eGFRof 45 to less than 60 mL/min/1.73 m2). The safety profile of dapagliflozin in the study of patients with aneGFR of 45 to less than 60 mL/min/1.73 m2 was similar to the general population of patients with type 2diabetes. Although patients in the dapagliflozin arm had reduction in eGFR compared to the placebo arm,eGFR generally returned towards baseline after treatment discontinuation.
MetforminMetformin is substantially excreted by the kidney, and the risk of metformin accumulation and lacticacidosis increases with the degree of renal impairment.
8.7 Hepatic Impairment
Use of metformin in patients with hepatic impairment has been associated with some cases of lacticacidosis. QTERNMET XR is not recommended in patients with hepatic impairment [see CLINICALPHARMACOLOGY (12.3)].
10 OVERDOSAGE
In the event of an overdose, contact the Poison Control Center. Appropriate supportive treatment shouldbe initiated as dictated by the patient’s clinical status.
The removal of dapagliflozin by hemodialysis has not been studied. Saxagliptin and its major metabolitecan be removed by hemodialysis (23% of dose over 4 hours). Overdose of metformin has occurred,including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10%of cases, but no causal association with metformin has been established. Lactic acidosis has been reportedin approximately 32% of metformin overdose cases [see WARNINGS AND PRECAUTIONS (5.1)].
Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions.
Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom
metformin overdosage is suspected.
11 DESCRIPTION
QTERNMET XR extended-release tablets for oral use contain dapagliflozin, saxagliptin and metformin
HCl.
Dapagliflozin propanediol is an active inhibitor of sodium-glucose cotransporter 2 (SGLT2). It isdescribed chemically as D-glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-,(1S)-. Dapagliflozin is compounded with (2S)-1,2-propanediol, hydrate (1:1:1) with an empirical formulaas C21H25ClO6•C3H8O2•H2O and the molecular weight of 502.98. The structural formula is: Saxagliptin is an active inhibitor of the dipeptidyl-peptidase-4 (DPP-4) enzyme. It is isolated in the
monohydrate form chemically kn |
