Crestor Drug Interactions

Effect of co-administered medicinal products on rosuvastatin: Transporter protein inhibitors: In vitro and in vivo data indicate that rosuvastatin has no clinically significant cytochrome P450 interactions (as a substrate, inhibitor or inducer). Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter OATP1B1 and efflux transporter BCRP. Concomitant administration of CRESTOR with medicinal products that are inhibitors of these transporter proteins may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy (see Table 2, Dosage & Administration and Precautions).
Ciclosporin: During concomitant treatment with CRESTOR and ciclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers (see Table 2). CRESTOR is contraindicated in patients receiving concomitant ciclosporin (see Contraindications). Concomitant administration did not affect plasma concentrations of ciclosporin.
Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant protease inhibitor use may strongly increase rosuvastatin exposure (see Table 2). For instance, in a pharmacokinetic study, co-administration of 10 mg rosuvastatin and a combination product of two protease inhibitors (300 mg atazanavir/100 mg ritonavir) in healthy volunteers was associated with an approximately three-fold increase in rosuvastatin AUC. The concomitant use of CRESTOR and some protease inhibitor combinations may be considered after careful consideration of CRESTOR dose adjustments based on the expected increase in rosuvastatin exposure (Table 2.)
Gemfibrozil and other lipid-lowering products: Concomitant use of CRESTOR and gemfibrozil resulted in a 2-fold increase in rosuvastatin C_max and AUC. Based on data from specific interaction studies no pharmacokinetic relevant interaction with fenofibrate is expected, however a pharmacodynamic interaction may occur. Gemfibrozil, fenofibrate, other fibrates and lipid lowering doses (> or equal to 1 g/day) of niacin (nicotinic acid) increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. The 40 mg dose is contraindicated with concomitant use of a fibrate. These patients should also start with the 5 mg dose.
Ezetimibe: Concomitant use of CRESTOR and ezetimibe resulted in no change to AUC for either drug when administered to healthy volunteers. There was a 1.2 fold increase in AUC of rosuvastatin when 10 mg CRESTOR and 10 mg ezetimibe was administered in hypercholesterolaemic subjects (Table 2). A pharmacodynamic interaction, in terms of adverse effects, between CRESTOR and ezetimibe cannot be ruled out.
Antacid: The simultaneous dosing of CRESTOR 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 CRESTOR. The clinical relevance of this interaction has not been studied.
Fusidic Acid: Interaction studies with rosuvastatin and fusidic acid have not been conducted. As with other statins, muscle related events, including rhabdomyolysis, have been reported in post-marketing experience with rosuvastatin and fusidic acid given concurrently. Patients should be closely monitored and temporary suspension of rosuvastatin treatment may be appropriate.
Erythromycin: Concomitant use of CRESTOR and erythromycin resulted in a 20% decrease in AUC and a 30% decrease in Cmax of rosuvastatin. This interaction may be caused by the increase in gut motility caused by erythromycin.
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. Therefore, drug interactions resulting from cytochrome P450-mediated metabolism are not expected. 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).
Interactions requiring rosuvastatin dose adjustments (see also Table 2): When it is necessary to co-administer CRESTOR with other medicinal products known to increase exposure to rosuvastatin, doses of CRESTOR should be adjusted. It is recommended that prescribers consult the relevant product information when considering administration of such products together with CRESTOR.
If medicinal product is observed to increase rosuvastatin AUC approximately 2 fold or higher, the starting dose of CRESTOR should not exceed 5 mg once daily. The maximum daily dose of CRESTOR should be adjusted so that the expected rosuvastatin exposure would not likely exceed that of a 40 mg daily dose of CRESTOR taken without interacting medicinal products, for example a 20 mg dose of CRESTOR with gemfibrozil (1.9-fold increase), a 10 mg dose of CRESTOR with combination ritonavir/atazanavir (3.1-fold increase), and a 5 mg dose of CRESTOR with ciclosporin (7.1 fold increase in exposure).
If medicinal product is observed to increase rosuvastatin AUC less than 2-fold, the starting dose need not be decreased but caution should be taken if increasing the CRESTOR dose above 20mg.
Protease Inhibitors: Coadministration of rosuvastatin with certain protease inhibitors or combination of protease inhibitors may increase the rosuvastatin exposure, (AUC) up to 7-fold (see Table2). Dose adjustment are needed depending on the level of effect on rosuvastatin exposure (see Dosage & Administration, and Precautions). (See Table 2.)


Click on icon to see table/diagram/image


Effect of rosuvastatin on co-administered medicinal products: Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, the initiation of treatment or dosage up-titration of CRESTOR in patients treated concomitantly with vitamin K antagonists (e.g. warfarin or another coumarin anticoagulant) may result in an increase in International Normalised Ratio (INR). Discontinuation or down-titration of CRESTOR may result in a decrease in INR. In such situations, appropriate monitoring of INR is desirable.
Oral contraceptive/hormone replacement therapy (HRT): Concomitant use of CRESTOR and an oral contraceptive resulted in an increase in ethinyl estradiol 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 CRESTOR 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.