FARXIGA (Page 5 of 13)

Effects of Age, Gender, Race, and Body Weight on Pharmacokinetics

Based on a population pharmacokinetic analysis, age, gender, race, and body weight do not have a clinically meaningful effect on the pharmacokinetics of dapagliflozin and thus, no dose adjustment is recommended.

Pediatric

Pharmacokinetics in the pediatric population has not been studied.

Drug Interactions

In Vitro Assessment of Drug Interactions

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 the P-glycoprotein (P-gp) active transporter, and dapagliflozin 3-O-glucuronide is a substrate for the OAT3 active 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 OAT3 substrates.

Effects of Other Drugs on Dapagliflozin

Table 5 shows the effect of coadministered drugs on the pharmacokinetics of dapagliflozin. No dose adjustments are recommended for dapagliflozin.

Table 5: Effects of Coadministered Drugs on Dapagliflozin Systemic Exposure
Coadministered Drug (Dose Regimen) * Dapagliflozin (Dose Regimen) * Effect on Dapagliflozin Exposure (% Change [90% CI])
Cmax AUC
*
Single dose unless otherwise noted.
AUC = AUC(INF) for drugs given as single dose and AUC = AUC(TAU) for drugs given in multiple doses.

No dosing adjustments required for the following:

Oral Antidiabetic Agents

Metformin (1000 mg)

20 mg

Pioglitazone (45 mg)

50 mg

Sitagliptin (100 mg)

20 mg

Glimepiride (4 mg)

20 mg

Voglibose (0.2 mg three times daily)

10 mg

Other Medications

Hydrochlorothiazide (25 mg)

50 mg

Bumetanide (1 mg)

10 mg once dailyfor 7 days

Valsartan (320 mg)

20 mg

↓12%[↓3%, ↓20%]

Simvastatin (40 mg)

20 mg

Anti-infective Agent

Rifampin (600 mg once daily for 6 days)

10 mg

↓7%[↓22%, ↑11%]

↓22%[↓27%, ↓17%]

Nonsteroidal Anti-inflammatory Agent

Mefenamic Acid (loading dose of 500 mg followed by 14 doses of 250 mg every 6 hours)

10 mg

↑13%[↑3%, ↑24%]

↑51%[↑44%, ↑58%]

↔ = no change (geometric mean ratio of test: reference within 0.80 to 1.25); ↓ or ↑ = parameter was lower or higher, respectively, with coadministration compared to dapagliflozin administered alone (geometric mean ratio of test: reference was lower than 0.80 or higher than 1.25)

Effects of Dapagliflozin on Other Drugs

Table 6 shows the effect of dapagliflozin on other coadministered drugs. Dapagliflozin did not meaningfully affect the pharmacokinetics of the coadministered drugs.

Table 6: Effects of Dapagliflozin on the Systemic Exposures of Coadministered Drugs
*
Single dose unless otherwise noted.
AUC = AUC(INF) for drugs given as single dose and AUC = AUC(TAU) for drugs given in multiple doses.

Coadministered Drug (Dose Regimen) *

Dapagliflozin (Dose Regimen) *

Effect on Coadministered Drug Exposure (% Change [90% CI])

Cmax

AUC

No dosing adjustments required for the following:

Oral Antidiabetic Agents

Metformin (1000 mg)

20 mg

Pioglitazone (45 mg)

50 mg

↓7%[↓25%, ↑15%]

Sitagliptin (100 mg)

20 mg

Glimepiride (4 mg)

20 mg

↑13%[0%, ↑29%]

Other Medications

Hydrochlorothiazide (25 mg)

50 mg

Bumetanide (1 mg)

10 mg once dailyfor 7 days

↑13%[↓2%, ↑31%]

↑13%[↓1%, ↑30%]

Valsartan (320 mg)

20 mg

↓6%[↓24%, ↑16%]

↑5%[↓15%, ↑29%]

Simvastatin (40 mg)

20 mg

↑19%

Digoxin (0.25 mg)

20 mg loading dosethen 10 mg once dailyfor 7 days

Warfarin (25 mg)

20 mg loading dosethen 10 mg once dailyfor 7 days

↔ = no change (geometric mean ratio of test: reference within 0.80 to 1.25); ↓ or ↑ = parameter was lower or higher, respectively, with coadministration compared to the other medicine administered alone (geometric mean ratio of test: reference was lower than 0.80 or higher than 1.25).

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