Oral Contraceptives: Administration of another thiazolidinedione with an oral
contraceptive containing ethinyl estradiol and norethindrone reduced the plasma
concentrations of
both hormones by approximately 30%, which could result in loss of contraception.
The pharmacokinetics of coadministration of ACTOS and oral contraceptives have
not been
evaluated in patients receiving ACTOS and an oral contraceptive. Therefore,
additional
caution regarding contraception should be exercised in patients receiving ACTOS
and
an oral contraceptive.
Glipizide: In healthy volunteers, coadministration of ACTOS (45 mg once daily)
and glipizide (5.0 mg once daily) for seven days did not alter the steady-state
pharmacokinetics of glipizide.
Digoxin: In healthy volunteers, coadministration of ACTOS (45 mg once daily)
with digoxin (0.25 mg once daily) for seven days did not alter the steady-state
pharmacokinetics of digoxin.
Warfarin: In healthy volunteers, coadministration of ACTOS (45 mg once daily)
for
seven days with warfarin did not alter the steady-state pharmacokinetics of
warfarin. In
addition, ACTOS has no clinically significant effect on prothrombin time when
administered to patients receiving chronic warfarin therapy.
Metformin: In healthy volunteers, coadministration of metformin (1000 mg) and
ACTOS
(45 mg) after seven days of ACTOS (45 mg once daily) did not alter the pharmacoki-
netics of the single dose of metformin.
Theophylline: Coadministration of ACTOS for 7 days with theophylline 400 mg
administered twice daily resulted in no changes in the pharmacokinetics of
either drug.
Atorvastatin Calcium: Coadministration of ACTOS for 7 days with atorvastatin
80 mg
once daily resulted in no clinically relevant effect upon atorvastatin pharmacokinetics.
Coadministration of atorvastatin with ACTOS had no clinically relevant effect
on pioglitazone pharmacokinetics.
Ketoconazole: Coadministration of ACTOS for 7 days with ketoconazole 200 mg
administered twice daily resulted in no clinically relevant effect on pioglitazone
pharmacokinetics.
ACTOS does not inhibit metabolism of the CYP3A4 substrates midazolam, nifedipine
and atorvastatin. ACTOS coadministration results in a clinically insignificant
decrease
in the AUC of these drugs. Coadministration of ACTOS with ketoconazole (CYP3A4
inhibitor) showed clinically insignificant increases in AUC of pioglitazone.
Urinary 6ß-hydroxycortisol/cortisol ratios measured in patients treated
with ACTOS indicate no
CYP3A4 enzyme induction (see PRECAUTIONS, Drug Interactions and CLINICAL PHARMACOLOGY,
Metabolism).