Actos - Clinical Pharmacology

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Fexofenadine HCI:

Co-administration of ACTOS for 7 days with 60 mg fexofenadine administered orally twice daily resulted in no significant effect on pioglitazone pharmaco-kinetics. ACTOS had no significant effect on fexofenadine pharmacokinetics.

Glipizide:

Co-administration of ACTOS and 5 mg glipizide administered orally once daily for 7 days did not alter the steady-state pharmacokinetics of glipizide.

Digoxin:

Co-administration of ACTOS with 0.25 mg digoxin administered orally once daily 7 days did not alter the steady-state pharmacokinetics of digoxin.

Warfarin:

Co-administration of ACTOS for 7 days with warfarin did not alter the steady-state pharmacokinetics of warfarin. ACTOS has no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin therapy.

Metformin:

Co-administration of a single dose of metformin (1000 mg) and ACTOS after 7 days of ACTOS did not alter the pharmacokinetics of the single dose of metformin.

Midazolam:

Administration of ACTOS for 15 days followed by a single 7.5 mg dose of midazolam syrup resulted in a 26% reduction in midazolam Cmax and AUC.

Ranitidine HCI:

Co-administration of ACTOS for 7 days with ranitidine administered orally twice daily for either 4 or 7 days resulted in no significant effect on pioglitazone pharmacokinetics. ACTOS showed no significant effect on ranitidine pharmacokinetics. ER: Co-administration of ACTOS for 7 days with 30 mg nifedipine ER adminis-tered orally once daily for 4 days to male and female volunteers resulted in least square mean (90% Cl) values for unchanged nifedipine of 0.83 (0.73-0.95) for Cmax and 0.88 (0.80-0.96) for AUC. In view of the high variability of nifedipine pharmacokinetics, the clinical significance of this finding is unknown.

Ketoconazole:

Co-administration of ACTOS for 7 days with ketoconazole 200 mg adminis-tered twice daily resulted in least square mean (90% Cl) values for unchanged pioglitazone of 1.14 (1.06 -1.23) for Cmax, 1.34 (1.26 -1.41) for AUC and 1.87 (1.71 -2.04) for Cmin. Atorvastatin Calcium: Co-administration of ACTOS for 7 days with atorvastatin calcium (LIPITOR ® ) 80 mg once daily resulted in least square mean (90% Cl) values for unchanged pioglitazone of 0.69 (0.57 -0.85) for Cmax, 0.76 (0.65 -0.88) for AUC and 0.96 (0.87 -1.05) for Cmin. For unchanged atorvastatin the least square mean (90% Cl) values were 0.77 (0.66 -0.90) for Cmax, 0.86 (0.78 -0.94) for AUC and 0.92 (0.82 -1.02) for Cmin.