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DRUG INTERACTIONS

Antipyrine

Mean antipyrine concentrations in plasma after administration of a single, oral dose of antipyrine during coadministration of multiple doses of atorvastatin were nearly superimposible on concentrations after administration of antipyrine alone. Individual and mean parameter values for plasma pharmacokinetics of antipyrine were similar in both treatment periods. These results indicate that the recommended highest daily dose of atorvastatin has negligible effects on antipyrine pharmacokinetics and on oxidative pathways responsible for the metabolism of antipyrine.⁽²⁷⁾

Colestipol

The combination of atorvastatin and colestipol tended to produce larger reductions in LDL-cholesterol levels and smaller reductions in triglyceride levels than atorvastatin monotherapy.⁽²⁸⁾.  

Cimetidine

Pharmacokinetic parameters and lipid responses were similar following administration of atorvastatin alone and atorvastatin with cimetidine. The rate and extent of atorvastatin absorption and the effects of atorvastatin on LDL-cholesterol responses are not influenced by coadministration of cimetidine.⁽²⁹⁾

Digoxin

Mean steady-state plasma digoxin concentrations were unchanged by administration of 10 mg atorvastatin. Mean steady-state plasma digoxin concentrations following administration of digoxin with 80 mg atorvastatin were slightly higher than concentrations following administration of digoxin alone, resulting in 20% and 15% higher Cmax and AUC(0-24) values, respectively. Since tmax and renal clearance were not significantly affected, the results are consistent with an increase in the extent of digoxin absorption in the presence of atorvastatin.⁽³⁰⁾

Erythromycin 

When erythromycin was coadministered with atorvastatin, mean C_max and AUC_(0-infinity) increased by 37.7% and 32.5%, respectively. Possible mechanisms for this interaction include erythromycin inhibition of first-pass conversion of atorvastatin to inactive metabolites and erythromycin inhibition of P-glycoprotein-mediated intestinal or biliary secretion.⁽³¹⁾

Warfarin

Twelve patients chronically maintained on warfarin were administered 80 mg atorvastatin for 2 weeks. Mean prothrombin times decreased slightly, but only for the first few days of the two-week treatment period. Thus atorvastatin had no consistent effect on the anticoagulant activity of warfarin and adjustment in warfarin dosing should not be necessary.⁽³²⁾

Clopidogrel

Atorvastatin, attenuated the antiplatelet activity of clopidogrel in a dose-dependent manner. CYP3A4 activates clopidogrel. Atorvastatin, another CYP3A4 substrate, competitively inhibits this activation. Use of a statin not metabolized by CYP3A4 and point-of-care platelet function testing may be warranted in patients treated with clopidogrel.⁽³³⁾