Effects of Other Drugs on the Pharmacokinetics of Alogliptin

There are no clinically meaningful changes in the pharmacokinetics of alogliptin when alogliptin is administered concomitantly with the drugs described below (Figure 2).

Figure 2. Effect of Other Drugs on the Pharmacokinetic Exposure of Alogliptin

Pioglitazone
Table 8. Effect of Pioglitazone Coadministration on Systemic Exposure of Other Drugs
 
 Coadministered Drug
 
Pioglitazone Dosage Regimen (mg) *
 Name and Dose Regimens
 Change in AUC †
 Change in Cmax †
 
45 mg(N=12)
 Warfarin ‡
 
Daily loading then maintenance doses based PT and INR valuesQuick's Value=35 ± 5%
 R-Warfarin
 ↓3%
 R-Warfarin
 ↓2%
 
S-Warfarin
 ↓1%
 S-Warfarin
 ↑1%
 
45 mg(N=12)
 Digoxin
 
0.200 mg twice daily (loading dose) then0.250 mg daily (maintenance dose, 7 days)
 ↑15%
 ↑17%
 
45 mg daily for 21 days(N=35)
 Oral Contraceptive
 
[Ethinyl Estradiol (EE) 0.035 mg plusNorethindrone (NE) 1 mg] for 21 days
 EE
 ↓11%
 EE
 ↓13%
 
NE
 ↑3%
 NE
 ↓7%
 
45 mg(N=23)
 Fexofenadine
 
60 mg twice daily for 7 days
 ↑30%
 ↑37%
 
45 mg(N=14)
 Glipizide
 
5 mg daily for 7 days
 ↓3%
 ↓8%
 
45 mg daily for 8 days(N=16)
 Metformin
 
1000 mg single dose on 8 days
 ↓3%
 ↓5%
 
45 mg(N=21)
 Midazolam
 
7.5 mg single dose on day 15
 ↓26%
 ↓26%
 
45 mg(N=24)
 Ranitidine
 
150 mg twice daily for 7 days
 ↑1%
 ↓1%
 
45 mg daily for 4 days(N=24)
 Nifedipine ER
 
30 mg daily for 4 days
 ↓13%
 ↓17%
 
45 mg(N=25)
 Atorvastatin Ca
 
80 mg daily for 7 days
 ↓14%
 ↓23%
 
45 mg(N=22)
 Theophylline
 
400 mg twice daily for 7 days
 ↑2%
 ↑5%
 
Daily for seven days unless otherwise noted
change (with/without coadministered drug and no change=0%); symbols of ↑ and ↓ indicate the exposure increase and decrease, respectively
Pioglitazone had no clinically significant effect on prothrombin time
Table 9. Effect of Coadministered Drugs on Pioglitazone Systemic Exposure
 
Coadministered Drug and Dosage Regimen
 Pioglitazone
 
Dose Regimen (mg) *
 Change in AUC †
 Change in Cmax †
 
Gemfibrozil 600 mgtwice daily for 2 days(N=12)
 30 mgsingle dose
 ↑3.4-fold ‡
 ↑6%
 
Ketoconazole 200 mgtwice daily for 7 days(N=28)
 45 mg
 ↑34%
 ↑14%
 
Rifampin 600 mgdaily for 5 days(N=10)
 30 mgsingle dose