Rozact Drug Interactions



Full Prescribing Info
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 substrare, inhibitor or inducer). Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter OATP1B1 and efflux transporter proteins. Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter OATP1B1 and efflux transporter BCRP. Concomitant administration of Rosuvastatin 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 AND ADMINISTRATIONS).
Ciclosporin: Rosuvastatin is contraindicated in patients receiving concomitant Ciclosporin. 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. The concomitant use of Rosuvastatin and some protease inhibitor combinations may be considered after careful consideration of Rosuvastatin dose adjustments based on the expected increase in Rosuvastatin exposure.
Gemfibrozil and other lipid-lowering products: Concomitant use of Rosuvastatin and Gemfibrozil resulted in a 2-fold increase in Rosuvastatin Cmax and AUC. 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 Rosuvastatin 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 Rosuvastatin and 10 mg Ezetimibe was administered in hypercholesterolaemic subjects. A pharmacodynamic interaction, in terms of adverse effects, between Rosuvastatin and Ezetimibe cannot be ruled out.
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.
Erythromycin: Concomitant use of Rosuvastatin 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 in 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: When it is necessary to co-administer Rosuvastatin with other medicinal products known to increase exposure to Rosuvastatin, doses of Rosuvastatin should be adjusted. Start with a 5 mg once daily dose of Rosuvastatin if the expected increase in exposure (AUC) is approximately 2-fold or higher. The maximum daily dose of Rosuvastatin should be adjusted so that the expected Rosuvastatin exposure would not likely exceed that of a 40 mg daily dose of Rosuvastatin taken without interacting medicinal products, for example a 20 mg dose of Rosuvastatin with Gemfibrozil (1.9-fold increase), and a 10 mg dose of Rosuvastatin with combination Ritonavir/Atazanavir (3.1-fold increase). (See table.)

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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 Rosuvastatin 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 Rosuvastatin 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 Rosuvastatin and an oral contraceptive resulted in an increase in Ethinyl estradiol and Norgestrel. These increased plasma levels should be considered when selecting oral contraceptives doses.
Genetic polymorphisms: Genotypes of SLCOB1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA have been shown to be associated with an increase in Rosuvastatin exposure (AUC) compared to SLCO1B1 c.521TT and ABCG2 c.421CC. For patients known to have the c.521CC or c.421AA genotype, a maximum once daily dose of 20 mg of Rosuvastatin is recommended.
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