CO-ADMINISTRATION OF WARFARIN AND ETHYL EICOSAPENTAENOATE
In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of reducing triglycerides in a subject on warfarin therapy, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.
1 . A pharmaceutical composition comprising warfarin, the composition providing a similar at least one pharmacokinetic endpoint of warfarin and/or at least one anticoagulation pharmacodynamic endpoint of warfarin, when co-administered with ethyl eicosapentaenoate, compared to a second pharmaceutical composition comprising warfarin administered without the ethyl eicosapentaenoate.
2 . The pharmaceutical composition of claim 1 , wherein the at least one pharmacokinetic endpoint of warfarin and/or the at least one anticoagulation pharmacodynamic endpoint of warfarin is about 70% to about 135% compared to the second pharmaceutical composition comprising warfarin administered without ethyl eicosapentaenoate.
3 . The pharmaceutical composition of claim 1 , wherein the at least one pharmacokinetic endpoint of warfarin is blood plasma C max and/or blood plasma AUC 0-inf .
4 . The pharmaceutical composition of claim 1 , wherein the at least one anticoagulation pharmacodynamic endpoint of warfarin is blood plasma INR max and/or blood plasma AUC INR .
5 . The pharmaceutical composition of claim 1 , wherein the ethyl eicosapentaenoate is administered at a daily dose of about 2 g or about 4 g per day.
6 . The pharmaceutical composition of claim 1 , wherein the ethyl eicosapentaenoate is in a capsule.
7 . The pharmaceutical composition of claim 6 , wherein the capsule comprises at least about 1 g of the ethyl eicosapentaenoate.
8 . The pharmaceutical composition of claim 6 , wherein the capsule comprises no more than about 20%, by weight of all fatty acids (and/or derivatives thereof) present, docosahexaenoic acid or esters thereof.
9 . The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition alters the blood plasma C max and/or the blood plasma AUC 0-inf of warfarin by no more than about 30% compared to administration of warfarin without the pharmaceutical composition.
10 . The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition alters the blood plasma INR max and/or the blood plasma AUC INR by no more than about 35% compared to administration of warfarin without the pharmaceutical composition.
11 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises at least about 80%, by weight of all fatty acids (and/or derivatives thereof) present, ethyl eicosapentaenoate.
12 . A method of treating or preventing a cardiovascular-related disease or disorder in a subject on warfarin therapy, the method comprising administering to the subject a pharmaceutical composition comprising ethyl eicosapentaenoate.
13 . The method of claim 12 further comprising identifying the subject as being on warfarin therapy before administering to the subject the pharmaceutical composition comprising ethyl eicosapentaenoate.
14 . The method of claim 12 , wherein a C max , an AUC max , an INR max and/or an AUC INR level of warfarin is not significantly altered compared to a C max , an AUC max , an INR max and/or an AUC INR level of warfarin in a second subject or a second subject group who has received warfarin but not the pharmaceutical composition comprising ethyl eicosapentaenoate.
15 . The method of claim 14 , wherein a C max , an AUC max , an INR max and/or an AUC INR level of warfarin is altered by no more than about 35% compared to a C max , an AUC max , an INR max and/or an AUC INR level of warfarin in the second subject or second subject group.
16 . The method of claim 12 , wherein the warfarin and the ethyl eicosapentaenoate are co-administered in a single dosage unit.
17 . The method of claim 16 , wherein the dosage unit is a capsule.
18 . The method of claim 12 , wherein the warfarin and the ethyl eicosapentaenoate are co-administered in separate dosage units.
19 . The method of claim 12 , wherein the ethyl eicosapentaenoate represents at least about 80%, by weight, of all fatty acids (and/or derivatives thereof) administered to the subject.
20 . The method of claim 12 , wherein docosahexaenoic acid and its esters thereof represent no more than about 20%, by weight of all fatty acids (and/or derivatives thereof) present.