Sign Out
Concomitant administration of Otagil 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).
Ciclosporin: Ciclosporin increased Rosuvastatin exposure and may result in increased risk of myopathy (see Table 4). Therefore, in patients taking Ciclosporin, the dose of Otagil should not exceed 5 mg once daily (see Dosage & Administration and Precautions).
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 three-fold and seven-fold increase in Rosuvastatin AUC and Cmax respectively. The concomitant use of Otagil and some protease inhibitor combinations may be considered after careful consideration of Otagil dose adjustments based on the expected increase in Rosuvastatin exposure (see Dosage & Administration, Precautions and Table 4 as follows).
Gemfibrozil and other lipid-lowering products: Concomitant use of Otagil and Gemfibrozil resulted in a 2-fold increase in Rosuvastatin Cmax 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 1g/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. These patients should also start with the 5 mg dose.
Ezetimibe: Concomitant use of 10 mg Otagil and 10 mg Ezetimibe resulted in a 1.2 fold increase in AUC of Rosuvastatin in hypercholesterolemic subjects (Table 4). A pharmacodynamic interaction, in terms of adverse effects, between Rosuvastatin and Ezetimibe cannot be ruled out (see Precautions).
Antacid: The simultaneous dosing of Otagil 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 Otagil. 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 Otagil and Erythromycin resulted in a 20% decrease in AUC(0-t) 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: 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 4): When it is necessary to co-administer Otagil with other medicinal products known to increase exposure to Rosuvastatin, doses of Otagil should be adjusted. It is recommended that prescribers consult the relevant product information when considering administration of such products together with Otagil.
If medicinal product is observed to increase Rosuvastatin AUC approximately 2-fold or higher, the starting dose of Otagil should not exceed 5 mg once daily. The maximum daily dose of Otagil should be adjusted so that the expected Rosuvastatin exposure would not likely exceed that of a 40 mg daily dose of Otagil taken without interacting medicinal products, for example a 5 mg dose of Otagil with Ciclosporin (7.1-fold increase in exposure), a 10 mg dose of Otagil with Ritonavir/Atazanavir combination (3.1-fold increase) and a 20 mg dose of Otagil 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 Otagil dose above 20 mg.
Protease inhibitors: Co-administration of Rosuvastatin with certain protease inhibitors or combination of protease inhibitors may increase the Rosuvastatin exposure, (AUC) up to 7-fold (see Table 1 under Dosage & Administration). Dose adjustment are needed depending on the level of effect on Rosuvastatin exposure (see Dosage & Administration and Precautions). (See Table 4.)
Click on icon to see table/diagram/imageThe following medicinal product/combinations did not have a clinically significant effect on the AUC ratio of Rosvustatin at co-administration: 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.
Other medications: Concurrent use of fibrates may cause severe myositis and myoglobinuria.
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 Otagil in patients treated concomitantly with Vitamin K antagonists (e.g. Warfarin or another coumarin anticoagulant) may result in an increase in International Normalized Ratio (INR). Discontinuation or down-titration of Otagil 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 Otagil 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 Otagil 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.
Pediatric population: Interaction studies have only been performed in adults. The extent of interactions in the pediatric population is not known.
