Duvaztor-20/Duvaztor-40 Drug Interactions

Effect of co-administered medicinal products on atorvastatin: Atorvastatin (Duvaztor) is metabolised by cytochrome P450 3A4 (CYP3A4) and is a substrate of the hepatic transporters, organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) transporters. Metabolites of atorvastatin (Duvaztor) are substrates of OATP1B1. Atorvastatin (Duvaztor) is also identified as a substrate of the multi-drug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP), which may limit the intestinal absorption and biliary clearance of atorvastatin (Duvaztor). Concomitant administration of medicinal products that are inhibitors of CYP3A4 or transport proteins may lead to increased plasma concentrations of atorvastatin (Duvaztor) and an increased risk of myopathy. The risk might also be increased at concomitant administration of atorvastatin (Duvaztor) with other medicinal products that have a potential to induce myopathy, such as fibric acid derivatives and ezetimibe.
CYP3A4 inhibitors: Moderate CYP3A4 inhibitors (e.g. erythromycin, diltiazem, verapamil and fluconazole) may increase plasma concentrations of atorvastatin (Duvaztor). An increased risk of myopathy has been observed with the use of erythromycin in combination with statins. Interaction studies evaluating the effect of amiodarone or verapamil on atorvastatin (Duvaztor) have not been conducted. Both amiodarone and verapamil are known to inhibit CYP3A4 activity and co-administration with atorvastatin (Duvaztor) may result in increased exposure to atorvastatin (Duvaztor). Therefore, a lower maximum dose of atorvastatin should be considered and appropriate clinical monitoring of the patient is recommended when concomitantly used with moderate CYP3A4 inhibitors. Appropriate clinical monitoring is recommended after initiation or following dose adjustments of the inhibitors.
CYP3A4 inducers: Concomitant administration of atorvastatin (Duvaztor) with inducers of cytochrome P450 3A4 (e.g. efavirenz, rifampin, St. John's Wort) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, cytochrome P450 3A4 induction and inhibition of hepatocyte uptake transporter OATP1B1, simultaneous co-administration of atorvastatin (Duvaztor) with rifampin is recommended, as delayed administration of atorvastatin (Duvaztor) after administration of rifampin has been associated with a significant reduction in atorvastatin (Duvaztor) plasma concentrations. The effect of rifampin on atorvastatin (Duvaztor) concentrations in hepatocytes is, however, unknown and if concomitant administration cannot be avoided, patients should be carefully monitored for efficacy.
Transport inhibitors: Inhibitors of transport proteins (e.g., ciclosporin) can increase the systemic exposure of atorvastatin. The effect of inhibition of hepatic uptake transporters on atorvastatin (Duvaztor) concentrations in hepatocytes is unknown. If concomitant administration cannot be avoided, a dose reduction and clinical monitoring for efficacy is recommended.
Gemfibrozil/fibric acid derivatives: The use of fibrates alone is occasionally associated with muscle-related events, including rhabdomyolysis. The risk of these events may be increased with the concomitant use of fibric acid derivatives and atorvastatin (Duvaztor). If concomitant administration cannot be avoided, the lowest dose of atorvastatin (Duvaztor) to achieve the therapeutic objective should be used and patients should be appropriately monitored.
Ezetimibe: The use of ezetimibe alone is associated with muscle-related events, including rhabdomyolysis. The risk of these events may therefore be increased with concomitant use of ezetimibe and atorvastatin (Duvaztor). Appropriate clinical monitoring of these patients is recommended.
Colestipol: Plasma concentrations of atorvastatin (Duvaztor) and its active metabolites were lower (by approx. 25%) when colestipol was co-administered with atorvastatin (Duvaztor). However, lipid effects were greater when atorvastatin (Duvaztor) and colestipol were co-administered than when either medicinal product was given alone.
Fusidic acid: The risk of myopathy including rhabdomyolysis may be increased by the concomitant administration of systemic fusidic acid with statins. The mechanism of this interaction (whether it is pharmacodynamic or pharmacokinetic, or both) is yet unknown. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination.
If treatment with systemic fusidic acid is necessary, atorvastatin treatment should be discontinued throughout the duration of the fusidic acid treatment.
Colchicine: Although interaction studies with atorvastatin (Duvaztor) and colchicine have not been conducted, cases of myopathy have been reported with atorvastatin (Duvaztor) co-administered with colchicine, and caution should be exercised when prescribing atorvastatin (Duvaztor) with colchicine.