Atorsam-F Drug Interactions

Co-administration of Fenofibrate with Atorvastatin does not significantly affect Atorvastatin AUC.
Atorvastatin: Colestipol: Plasma concentrations of Atorvastatin decreased approximately 25% when colestipol and atorvastatin were co-administered. However, LDL-C reduction was greater when atorvastatin and colestipol were co-administered than when either drug was given alone. Since bile acid sequestrants may bind other drugs given concurrently, patients should take the fixed dose combination of Atorvastatin and Fenofibrate at least 1 hour before or 4-6 hours after a bile acid binding resin to avoid impeding its absorption.
Digoxin: Administration of multiple doses of Atorvastatin with digoxin increases the steady-state plasma digoxin concentrations by approximately 20%. Patients taking digoxin and fixed dose combination of Atorvastatin and Fenofibrate concomitantly should be monitored appropriately.
Erythromycin: In healthy individuals, plasma concentrations of atorvastatin increased by approximately 40% with co-administration of Atorvastatin and erythromycin, a known inhibitor of cytochrome P450 3A4. The risk of myopathy is increased when statins and erythromycin are concurrently administered. Caution should be exercised when co-administering the fixed dose combination of Atorvastatin and Fenofibrate with erythromycin.
Oral Contraceptives: Co-administration of Atorvastatin and an oral contraceptive containing norethindrone and ethinyl estradiol produces increased plasma concentrations of norethindrone and ethinyl estradiol. These increases should be considered when selecting an oral contraceptive for a woman taking the fixed dose combination of Atorvastatin and Fenofibrate.
Oral Anticoagulants: If coumarin anticoagulants and fixed dose combination of Atorvastatin and Fenofibrate are co-administered, the dosage of the anticoagulant should be reduced to maintain the prothrombin time/INR at the desired level to prevent bleeding complications. Frequent prothrombin time/INR determinations are advisable until it has been definitely determined that the prothrombin time/INR has stabilized.
Cyclosporine: Because cyclosporine can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of fibrate drugs including Fenofibrate, there is a risk that an interaction will lead to deterioration. The benefits and risks of using the fixed dose combination of Atorvastatin and Fenofibrate with immunosuppressants and other potentially nephrotoxic agents should be carefully considered. Also, the risk of myopathy during treatment with statins is increased with concurrent administration of cyclosporine. Hence, caution should be exercised when co-administering fixed dose combination of Atorvastatin and Fenofibrate with cyclosporine.
Azole antifungals/Niacin: The risk of myopathy during treatment with statins is increased with concurrent administration of these agents. Hence caution should be exercised when these drugs are co-administered with the fixed dose combination of Atorvastatin and Fenofibrate.
Fenofibrate: In vitro studies using human liver microsomes indicate that Fenofibrate and fenofibric acid is not an inhibitor of cytochrome (CYP) P450 isoforms; CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C8, CYP2C19 and CYP2A6, and mild-to-moderate inhibitors of CYP2C9 at therapeutic concentrations.
Oral Anti-coagulants: Potentiation of coumarin-type anticoagulants has been observed with prolongation of the prothrombin time/INR. The dosage of the anticoagulant should be reduced to maintain the prothrombin time/INR at the desired level to prevent bleeding complications. Frequent prothrombin time/INR determinations are advisable until it has been definitely determined that the prothrombin time/INR has stabilized.
Bile acid sequestrants: Bile acid sequestrants have been shown to bind to other drugs given concurrently. Therefore, fenofibrate should be taken at least 1 hour before, or 4-6 hours after, a bile acid binding resin to avoid impeding its absorption.
Glimepiride: Concomitant administration of Fenofibrate once daily for 10 days with glimepiride (1 mg tablet) single dose simultaneously with the last dose of Fenofibrate resulted in a 35% increase in mean AUC of glimepiride in healthy subjects. Glimepiride Cmax was not significantly affected by Fenofibrate co-administration. There was no statistically significant effect of multiple doses of Fenofibrate on glucose nadir or AUC with the baseline glucose concentration as the covariate after glimepiride administration in healthy volunteers. However, glucose concentrations at 24 hours remained statistically significantly lower after pretreatment with Fenofibrate than with glimepiride alone. Glimepiride had no significant effect on the pharmacokinetics of fenofibric acid.
Ezetimibe: Concomitant administration of Fenofibrate with ezetimibe (10 mg) once daily for 10 days in 18 healthy adults resulted in increases in total ezetimibe AUC, Cmax and Cmin of approximately 43%, 33% and 56%, respectively, and increases in ezetimibe glucuronide AUC, Cmax and Cmin of approximately 49%, 34% and 62%, respectively. The pharmacokinetics of fenofibric acid was not significantly affected by ezetimibe and the multiple-dose pharmacokinetics of free (unconjugated) ezetimibe was not significantly affected by Fenofibrate.