Crestor Drug Interactions

Effect of co-administered medicinal products on rosuvastatin: 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 Table 4, Dosage & Administration and Precautions).
Cyclosporin: Co-administration of CRESTOR with cyclosporin resulted in no significant changes in cyclosporin plasma concentration. However, rosuvastatin steady state AUC (0-t) increased up to 7-fold over that seen in healthy volunteers administered the same dose. Concomitant use of CRESTOR and cyclosporin is contraindicated (see Table 4 and Contraindications).
Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant protease inhibitor use may strongly increase rosuvastatin exposure (see Table 4). 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 3-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 (See Table 4, Dosage & Administration and Precautions).
Gemfibrozil and other lipid-lowering products: Concomitant use of CRESTOR and gemfibrozil resulted in a 2-fold increase in rosuvastatin C_max and AUC (0-t). Based on data from specific interaction studies, no pharmacokinetic relevant interaction with fenofibrate is expected, however pharmacodynamic interaction may occur.
Gemfibrozil, fenofibrate, other fibrates and lipid lowering doses (≥ 1g/day) of niacin (nicotinic acid) increase the risks of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. Therefore, the dose of CRESTOR should not exceed 10 mg/day when given in combination with fibrates or niacin. (See Dosage & Administration and Precautions.)
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.
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 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 the recommended maximum daily dose of CRESTOR taken without interacting medicinal products.
For example, where the recommended dose of CRESTOR is 20mg; the dose of CRESTOR taken with a ritonavir/atazanavir combination (3.1-fold increase) should not exceed 5 mg, and the dose of CRESTOR taken with gemfibrozil (1.9-fold increase) should not exceed 10 mg.
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. (See Table 4.)

Click on icon to see table/diagram/image

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 200mg 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.
Effect of rosuvastatin on co-administered medicinal products: Warfarin: As with other HMG-CoA reductase inhibitors, co-administration of CRESTOR and warfarin may result in a rise in INR compared to warfarin alone. In patients taking vitamin K antagonists monitoring of INR is recommended both at initiation or cessation of therapy with CRESTOR or following dose adjustment.
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.
Other medicinal products: Based on data from specific interaction studies, no clinically relevant interaction with digoxin is expected.
Endocrine function: Although clinical studies have shown that rosuvastatin alone does not reduce basal plasma cortisol levels or impairs adrenal reserve, caution should be exercised if any HMG-CoA reductase inhibitor or other lipid-lowering agent is administered concomitantly with drugs that may decrease levels or activity of endogenous steroid hormones (ketoconazole, spironolactone, cimetidine).
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. Therefore, the combination rosuvastatin and fusidic acid is not recommended. If possible, temporary suspension of rosuvastatin treatment is recommended. If unavoidable, patients should be closely monitored.