Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of P450 isoenzyme 3A4

Abstract

The invention concerns safe non-interacting drug combinations of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which is (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid or a pharmaceutically acceptable salt thereof (the Agent) and a drug which is either an inducer, inhibitor or a substrate of cytochrome P450, in particular cytochrome P450 isoenzyme 3A4. Particular combinations are useful in treating hyperlipidaemia in humans who are receiving immunosuppressive chemotherapy. A preferred combination is the Agent and a fibrate drug, the use of such a combination in treating hyperlipidaemia in mammals, and medicaments containing such a combination for use in such treatments.

1 - 32 . (canceled)  
   
   
       33 . A method for reducing or avoiding adverse drug interaction in a patient in need of combination therapy, which therapy comprises the co-administration to said patient of a statin and at least one second drug that is an inducer, inhibitor or substrate of P450 isoenzyme 3A4, said method comprising administering as said statin the HMG-CoA reductase inhibitor (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid or a pharmaceutically acceptable salt thereof, whereby adverse interaction between said statin and said second drug through the mechanism of drug metabolism by P450 isoenzyme 3A4 is avoided.  
   
   
       34 . The method of  claim 33  wherein said second drug is a cholesterol lowering agent that is an inducer, inhibitor or substrate of P450 isoenzyme 3A4.  
   
   
       35 . The method of  claim 34  wherein said second drug is a fibrate.  
   
   
       36 . The method of  claim 34  wherein said second drug is selected from bezafibrate, clofibrate, ciprofibrate, fenofibrate and niacin.  
   
   
       37 . The method of any one of claims  34 - 36  wherein the condition treated by said combination therapy comprises hypercholesterolaemia or hyperlipoproteinaemia.  
   
   
       38 . The method of any one of claims  34 -36 wherein the condition treated by said combination therapy comprises atherosclerosis.  
   
   
       39 . The method of  claim 33  wherein said second drug is an immunosuppressant drug that is an inducer, inhibitor or substrate of P450 isoenzyme 3A4.  
   
   
       40 . The method of  claim 39  wherein said immunosuppressant drug is selected from cyclosporin and tacrolimus.  
   
   
       41 . The method of  claim 33  wherein said second drug is a cardiovascular treatment drug that is an inducer, inhibitor or substrate of P450 isoenzyme 3A4.  
   
   
       42 . The method of  claim 41  wherein said cardiovascular treatment drug is selected from digitoxin, diltiazam, losartan, nifedipine, quinidine, verapamil and warfarin.