QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(二十七)
arfarin
R-warfarin
20 mg loading dose
then 10 mg once
daily for 7 days ↑3%
↑6%
↑7%
↑8%
* Single dose unless otherwise noted.
† Percent change (with/without coadministered drug and no change=0%); ↑ and ↓ indicate the exposure increaseand decrease, respectively.
‡ AUC=AUC(INF) for drugs given as single dose and AUC=AUC(TAU) for drugs given in multiple doses.
Saxagliptin
In Vitro Assessment of Drug Interactions
The metabolism of saxagliptin is primarily mediated by CYP3A4/5.In in vitro studies, saxagliptin and its active metabolite did not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19,
2D6, 2E1, or 3A4, or induce CYP1A2, 2B6, 2C9, or 3A4. Therefore, saxagliptin is not expected to alterthe metabolic clearance of coadministered drugs that are metabolized by these enzymes. Saxagliptin is aP-glycoprotein (P-gp) substrate but is not a significant inhibitor or inducer of P-gp.
Effects of Other Drugs on Saxagliptin and its Active Metabolite, 5-hydroxy Saxagliptin
Table 7: Effect of Coadministered Drugs on Systemic Exposures of Saxagliptin and its
Active Metabolite, 5-hydroxy Saxagliptin
Coadministered
Drug
Dosage of
Coadministered
Drug*
Dosage of
Saxagliptin*
Saxagliptin
Change†
in AUC‡
Change† in
Cmax
Metformin 1000 mg 100 mg saxagliptin
5-hydroxy saxagliptin
↓2%
↓1%
↓21%
↓12%
Glyburide 5 mg 10 mg saxagliptin
5-hydroxy saxagliptin
↓2%
ND
↑8%
ND
Pioglitazone§ 45 mg QD for 10
days
10 mg QD
for 5 days
saxagliptin
5-hydroxy saxagliptin
↑11%
ND
↑11%
ND
Dapagliflozin 10 mg single
dose
5 mg single
dose
saxagliptin
5-hydroxy saxagliptin
↓1%
↑9%
↓7%
↑6%
Digoxin 0.25 mg q6h first
day followed by
q12h second day
followed by QD
for 5 days
10 mg QD
for 7 days
saxagliptin
5-hydroxy saxagliptin
↑5%
↑6%
↓1%
↑2%
Simvastatin 40 mg QD for 8
days
10 mg QD
for 4 days
saxagliptin
5-hydroxy saxagliptin
↑12%
↑2%
↑21%
↑8%
Diltiazem 360 mg LA QD
for 9 days
10 mg saxagliptin
5-hydroxy saxagliptin
↑109%
↓34%
↑63%
↓43%
Rifampin¶ 600 mg QD for 6
days
5 mg saxagliptin
5-hydroxy saxagliptin
↓76%
↑3%
↓53%
↑39%
Omeprazole 40 mg QD for 5
days
10 mg saxagliptin
5-hydroxy saxagliptin
↑13%
ND
↓2%
ND
Aluminum
hydroxide +
magnesium
hydroxide +
simethicone
aluminum
hydroxide:
2400 mg
magnesium
hydroxide:
2400 mg
simethicone:
240 mg
10 mg saxagliptin
5-hydroxy saxagliptin
↓3%
ND
↓26%
ND
Famotidine 40 mg 10 mg saxagliptin
5-hydroxy saxagliptin
↑3%
ND
↑14%
ND
Saxagliptin coadministered with strong CYP3A4/5 inhibitors [see DRUG INTERACTIONS (7) and
DOSAGE AND ADMINISTRATION (2.3)]:
Ketoconazole 200 mg BID for 9
days
100 mg saxagliptin
5-hydroxy saxagliptin
↑145%
↓88%
↑62%
↓95%
Ketoconazole 200 mg BID for 7
days
20 mg saxagliptin
5-hydroxy saxagliptin
↑267%
ND
↑144%
ND
Table 7: Effect of Coadministered Drugs on Syst |
