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 (see sections 4.3 and 4.4). These patients should also start with the 5 mg dose.
Ezetimibe: Concomitant use of 10 mg Crestor and 10 mg ezetimibe resulted in a 1.2-fold increase in AUC of rosuvastatin in hypercholesterolaemic subjects (Table 1). A pharmacodynamic interaction, in terms of adverse effects, between Crestor and ezetimibe cannot be ruled out (see section 4.4).
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 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 1): When it is necessary to co-administer Crestor with other medicinal products known to increase exposure to rosuvastatin, doses of Crestor should be adjusted. Start with a 5 mg once daily dose of Crestor if the expected increase in exposure (AUC) is approximately 2-fold or higher. 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), and a 10 mg dose of Crestor with combination ritonavir/atazanavir (3.1-fold increase).
Table 1 Effect of co-administered medicinal products on rosuvastatin exposure (AUC; in order of decreasing magnitude) from published clinical trials
Interacting drug dose regimen
Rosuvastatin dose regimen
Change in rosuvastatin AUC*
Ciclosporin 75 mg BID to 200 mg BID, 6 months
10 mg OD, 10 days
7.1-fold ↑
Regorafenib 160 mg, OD, 14 days
5 mg, single dose
3.8-fold ↑
Atazanavir 300 mg/ritonavir 100 mg OD, 8 days
10 mg, single dose
3.1-fold ↑
Velpatasvir 100 mg OD
10 mg, single dose
2.7-fold ↑
Ombitasvir 25 mg/paritaprevir 150 mg/ Ritonavir 100 mg OD/ dasabuvir 400 mg BID, 14 days
5 mg, single dose
2.6-fold ↑
Grazoprevir 200 mg/elbasvir 50 mg OD, 11 days
10 mg, single dose
2.3-fold ↑
Glecaprevir 400 mg/pibrentasvir 120 mg OD, 7 days
5 mg OD, 7 days
2.2-fold ↑
Lopinavir 400 mg/ritonavir 100 mg BID, 17 days
20 mg OD, 7 days
2.1-fold ↑
Clopidogrel 300 mg loading, fo |
