Drug interactions
Cytochrome P450 3A4: In vitro and in vivo data indicate that rosuvastatin clearance is not
dependent on metabolism by cytochrome P450 3A4 to a clinically significant extent. This has
been confirmed in studies with known cytochrome P450 3A4 inhibitors (ketoconazole,
erythromycin, itraconazole).
Ketoconazole: Coadministration of ketoconazole (200 mg twice daily for 7 days) with
rosuvastatin (80 mg) resulted in no change in plasma concentrations of rosuvastatin.
Erythromycin: Coadministration of erythromycin (500 mg four times daily for 7 days) with
rosuvastatin (80 mg) decreased AUC and Cmax of rosuvastatin by 20% and 31%, respectively.
These reductions are not considered clinically significant.
Itraconazole: Itraconazole (200 mg once daily for 5 days) resulted in a 39% and 28% increase
in AUC of rosuvastatin after 10 mg and 80 mg dosing, respectively. These increases are not
considered clinically significant.
Fluconazole: Coadministration of fluconazole (200 mg once daily for 11 days) with
rosuvastatin (80 mg) resulted in a 14% increase in AUC of rosuvastatin. This increase is not
considered clinically significant.
Cyclosporine: Coadministration of cyclosporine with rosuvastatin resulted in no significant
changes in cyclosporine plasma concentrations. However, Cmax and AUC of rosuvastatin
increased 11- and 7-fold, respectively, compared with historical data in healthy subjects. These
increases are considered to be clinically significant (see PRECAUTIONS, Drug Interactions,
WARNINGS, Myopathy/Rhabdomyolysis, and DOSAGE AND ADMINISTRATION).
Warfarin: Coadministration of warfarin (25 mg) with rosuvastatin (40 mg) did not change
warfarin plasma concentrations but increased the International Normalized Ratio (INR) (see
PRECAUTIONS, Drug Interactions).
Digoxin: Coadministration of digoxin (0.5 mg) with rosuvastatin (40 mg) resulted in no change
to digoxin plasma concentrations.
Fenofibrate: Coadministration of fenofibrate (67 mg three times daily) with rosuvastatin (10
mg) resulted in no significant changes in plasma concentrations of rosuvastatin or fenofibrate
(see PRECAUTIONS, Drug Interactions, and WARNINGS, Myopathy/Rhabdomyolysis).
Gemfibrozil: Coadministration of gemfibrozil (600 mg twice daily for 7 days) with rosuvastatin
(80 mg) resulted in a 90% and 120% increase for AUC and Cmax of rosuvastatin, respectively.
This increase is considered to be clinically significant (see PRECAUTIONS, Drug Interactions,
WARNINGS, Myopathy/Rhabdomyolysis, DOSAGE AND ADMINISTRATION).
Antacid: Coadministration of an antacid (aluminum and magnesium hydroxide combination)
with rosuvastatin (40 mg) resulted in a decrease in plasma concentrations of rosuvastatin by
54%. However, when the antacid was given 2 hours after rosuvastatin, there were no clinically
significant changes in plasma concentrations of rosuvastatin (see PRECAUTIONS, Information
for Patients).
Oral contraceptives: Coadministration of oral contraceptives (ethinyl estradiol and norgestrel)
with rosuvastatin resulted in an increase in plasma concentrations of ethinyl estradiol and
norgestrel by 26% and 34%, respectively.