Crestor Drug Interactions

Transporter protein inhibitors: 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 Dosage & Administration, Precautions and Table 4 as follows).
Cyclosporin: During concomitant treatment with CRESTOR and cyclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers (see Table 4). CRESTOR is contraindicated in patients receiving concomitant cyclosporin (see Contraindications). Concomitant administration did not affect plasma concentrations of cyclosporin.
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 Table 4). Dose adjustment is needed depending on the level of effect on rosuvastatin exposure (see Dosage & Administration and Precautions).
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.
Gemfibrozil and other lipid lowering products: Concomitant use of CRESTOR and gemfibrozil resulted in a 2-fold increase in rosuvastatin C_max and AUC (see Precautions).
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 (see Precautions). These patients should also start with the 5 mg dose.
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.
Erythromycin: Concomitant use of CRESTOR and erythromycin resulted in a 20% decrease in AUC(0-t) and a 30% decrease in C_max 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 CRESTOR 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 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.
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.
Ticagrelor: Ticagrelor has been shown to increase rosuvastatin concentrations, which may result in increased risk of myopathy. Consideration should be given to the benefits of prevention of major adverse cardiovascular events by use of rosuvastatin and the risks with increased rosuvastatin plasma concentrations.
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 (> or equal to 1 g/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 (see Precautions).
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.
Interactions requiring rosuvastatin dose adjustments (see also Table 4): 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 5 mg dose of CRESTOR with cyclosporin (7.1-fold increase in exposure), a 10 mg dose of CRESTOR with ritonavir/atazanavir combination (3.1-fold increase) and a 20 mg dose of CRESTOR with gemfibrozil (1.9-fold increase).
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 20 mg. (See Table 4.)

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The following medicinal product/combinations did not have a clinically significant effect on the AUC ratio of rosuvastatin at coadministration: Aleglitazar 0.3 mg 7 days dosing; Fenofibrate 67 mg 7 days TID dosing; Fluconazole 200 mg 11 days OD dosing; Fosamprenavir 700 mg/ritonavir 100 mg 8 days BID dosing; Ketoconazole 200 mg 7 days BID dosing; Rifampin 450 mg 7 days OD dosing; Silymarin 140 mg 5 days TID dosing.