QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(二十六)
ted by UDPglucuronosyltransferase 1A9 (UGT1A9).
In in vitro studies, dapagliflozin and dapagliflozin 3-O-glucuronide neither inhibited CYP 1A2, 2C9,2C19, 2D6, or 3A4, nor induced CYP 1A2, 2B6, or 3A4. Dapagliflozin is a weak substrate of theP-glycoprotein (P-gp) active transporter, and dapagliflozin 3-O-glucuronide is a substrate for the OAT3active transporter. Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp,OCT2, OAT1, or OAT3 active transporters. Overall, dapagliflozin is unlikely to affect the
pharmacokinetics of concurrently administered medications that are P-gp, OCT2, OAT1, or OAT3substrates.
Effects of Other Drugs on Dapagliflozin
Table 5 shows the effect of coadministered drugs on the pharmacokinetics of dapagliflozin.
Table 5: Effects of Coadministered Drugs on Dapagliflozin Systemic Exposure
Coadministered Drug
(Dose Regimen)*
Dapagliflozin
(Dose Regimen)*
Dapagliflozin
Change† in AUC‡ Change† in Cmax
Oral Antidiabetic Agents
Metformin (1000 mg) 20 mg ↓1% ↓7%
Pioglitazone (45 mg) 50 mg 0% ↑9%
Sitagliptin (100 mg) 20 mg ↑8% ↓4%
Glimepiride (4 mg) 20 mg ↓1% ↑1%
Voglibose (0.2 mg three times
daily)
10 mg ↑1% ↑4%
Saxagliptin (5 mg single dose) 10 mg (single dose) ↓2% ↓6%
Cardiovascular Agents
Hydrochlorothiazide (25 mg) 50 mg ↑7% ↓1%
Bumetanide (1 mg) 10 mg once daily
for 7 days
↑5% ↑8%
Valsartan (320 mg) 20 mg ↑2% ↓12%
Simvastatin (40 mg) 20 mg ↓1% ↓2%
Anti-infective Agent
Rifampin (600 mg once daily
for 6 days)
10 mg ↓22% ↓7%
Non-Steroidal Anti-inflammatory Agent
Mefenamic Acid (loading dose
of 500 mg followed by 14
doses of 250 mg every 6 hours)
10 mg ↑51% ↑13%
*Single dose unless otherwise noted.
† Percent change (with/without coadministered drug and no change=0%); ↑ and ↓ indicate the exposureincrease and decrease, respectively.
‡
AUC=AUC(INF) for drugs given as single dose and AUC=AUC(TAU) for drugs given in multiple doses.
Effects of Dapagliflozin on Other Drugs
Table 6 shows the effect of dapagliflozin on other coadministered drugs. Dapagliflozin did notmeaningfully affect the pharmacokinetics of the coadministered drugs.
Table 6: Effects of Dapagliflozin on the Systemic Exposures of Coadministered Drugs
Coadministered Drug
(Dose Regimen)*
Dapagliflozin
(Dose Regimen)*
Coadministered Drug
Change† in AUC‡ Change† in Cmax
Oral Antidiabetic Agents
Metformin (1000 mg) 20 mg 0% ↓5%
Table 6: Effects of Dapagliflozin on the Systemic Exposures of Coadministered Drugs
Coadministered Drug
(Dose Regimen)*
Dapagliflozin
(Dose Regimen)*
Coadministered Drug
Change† in AUC‡ Change† in Cmax
Pioglitazone (45 mg) 50 mg 0% ↓7%
Sitagliptin (100 mg) 20 mg ↑1% ↓11%
Glimepiride (4 mg) 20 mg ↑13% ↑4%
Cardiovascular Agents
Hydrochlorothiazide (25 mg) 50 mg ↓1% ↓5%
Bumetanide (1 mg) 10 mg once daily
for 7 days
↑13% ↑13%
Valsartan (320 mg) 20 mg ↑5% ↓6%
Simvastatin (40 mg) 20 mg ↑19% ↓6%
Digoxin (0.25 mg) 20 mg loading dose
then 10 mg once
daily for 7 days
0% ↓1%
Warfarin (25 mg)
S-w |
