Cyclosporin: During concomitant treatment with rosuvastatin and cyclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers. Concomitant administration did not affect plasma concentration of cyclosporin.
Vitamin K antagonist: As with other HMG-CoA reductase inhibitors, the initiation of treatment of dosage up titration of rosuvastatin in patient treated concomitantly with vitamin K antagonist (eg, warfarin) may result in an increase in international normalized ratio. Discontinuation or down titration of rosuvastatin may result in a decrease in INR. In such situation, appropriate monitoring of INR is desirable.
Gemfibrozil: As with other HMG-CoA reductase inhibitors, concomitant use of rosuvastatin & gemfibrozil resulted in a 2-fold increase in rosuvastatin Cmax and AUC.
Antacid: The simultaneous dosing of rosuvastatin with an antacid suspension containing aluminium and magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%. This effect was mitigated when the antacid was dosed 2 hours after rosuvastatin. The clinical relevance of this interaction has not been studied.
Erythromycin: Concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in AUC0-t and a 30% decrease in Cmax of rosuvastatin. This interaction may be caused by the increase in gut motility caused by erythromycin.
Oral contraceptive/hormone replacement therapy (HRT): Concomitant use of rosuvastatin and an oral contraceptive resulted in an increase in ethinyl oestradiol and norgestrel AUC of 26% and 34%, respectively. These increased plasma levels should be considered when selecting oral contraceptive doses. There are no pharmacokinetic data available in subjects taking concomitant rosuvastatin and HRT and therefore a similar effect cannot be excluded. However, the combination has been extensively used in women in clinical trials and was well tolerated.
Other medicinal products: Based on data from specific interaction studies no clinically relevant interactions with digoxin or fenofibrate are expected. Gemfibrozil, other fibrates and lipid lowering doses (> 1g/day) of niacin (nicotinic acid) increase the risk of myopathy when given concomitantly with some HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone.
Cytochrome P450 enzymes: Results from in vitro and in vivo studies show that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a poor substrate for these isoenzymes. No clinically relevant interactions have been observed between rosuvastatin and either fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4). Concomitant administration of itraconazole (an inhibitor of CYP3A4) and rosuvastatin resulted in a 28% increase in AUC of rosuvastatin.
This small increase is not considered clinically significant. Therefore, drug interactions resulting from cytochrome P450-mediated metabolism are not expected.