Pharmaceutical composition comprising eicosapentaenoic acid and nicotinic acid and methods of using same

Abstract

The present invention relates to, inter alia, pharmaceutical compositions comprising eicosapentaenoic acid and/or derivatives thereof and nicotinic acid, to methods of manufacturing such compositions, and to therapeutic methods for treating carious diseases and disorders.

1 . A pharmaceutical composition comprising nicotinic acid in an amount of not more than about 1200 mg and eicosapentaenoic acid or a derivative thereof, wherein the composition contains not more than 10%, by weight, docosahexaenoic acid, if any. 
     
     
         2 . The composition of  claim 1  wherein the composition contains substantially no docosahexaenoic acid. 
     
     
         3 . The composition of  claim 1  wherein the eicosapentaenoic acid or derivative thereof is present in an amount of about 100 mg to about 5000 mg. 
     
     
         4 . The composition of  claim 1  wherein the eicosapentaenoic acid or derivative thereof is present in an amount of about 100 mg to about 1000 mg. 
     
     
         5 . The composition of  claim 1  wherein the eicosapentaenoic acid or derivative thereof comprises an eicosapentaenoic acid ethyl ester. 
     
     
         6 . The composition of  claim 1  wherein the nicotinic acid is suspended in the eicosapentaenoic acid or derivative thereof to form a suspension. 
     
     
         7 . The composition of  claim 6  wherein the suspension is present in a capsule. 
     
     
         8 . The composition of  claim 1  wherein the composition further comprises a statin. 
     
     
         9 . A pharmaceutical composition comprising nicotinic acid in an amount of not more than about 800 mg and eicosapentaenoic acid ethyl ester, wherein the composition contains substantially no amount of docosahexaenoic acid or derivative thereof. 
     
     
         10 . A pharmaceutical composition comprising nicotinic acid in an amount of not more than about 500 mg and about 100 mg to about 1000 mg of eicosapentaenoic acid ethyl ester, wherein the composition contains no docosahexaenoic acid, the nicotinic acid is suspended in the eicosapentaenoic acid ethyl ester, and the composition is present in a capsule. 
     
     
         11 . The composition of  claim 10  wherein the nicotinic acid is present in an amount of about 50 mg to about 400 mg and the eicosapentaenoic acid ethyl ester is present in an amount of about 300 to about 800 mg. 
     
     
         12 . A method of treating or preventing a cardiovascular-related disease or disorder in subject in need thereof, comprising: administering to the subject a pharmaceutical composition according to  claim 1 . 
     
     
         13 . A method of treating a cardiovascular-related disease or disorder in a subject in need thereof, comprising: co-administering to the subject a first pharmaceutical composition comprising nicotinic acid in an amount of not more than about 800 mg and a second pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof wherein said second pharmaceutical composition contains substantially no docosahexaenoic acid or derivative thereof. 
     
     
         14 . The method of  claim 13  wherein the co-administering step comprises administering the first and second pharmaceutical compositions to the subject within a period of about 24 hours. 
     
     
         15 . The method of  claim 13  wherein the co-administering step comprises administering the first and second pharmaceutical compositions to the subject within a period of about 12 hours. 
     
     
         16 . The method of  claim 13  wherein the co-administering step comprises administering the first and second pharmaceutical compositions to the subject substantially simultaneously. 
     
     
         17 . The method of  claim 13  wherein the subject does not ingest a non-steroidal anti-inflammatory agent within about 3 hours prior to or after said co-administration step. 
     
     
         18 . The method of  claim 13  wherein the eicosapentaenoic acid or a derivative thereof is present in the second pharmaceutical composition in an amount of about 100 mg to about 2000 mg. 
     
     
         19 . The method of  claim 13  wherein the eicosapentaenoic acid or a derivative thereof comprises eicosapentaenoic acid ethyl ester. 
     
     
         20 . A method of decreasing serum low-density lipoprotein-C and serum triglyceride levels and increasing serum high-density-lipoprotein-C levels in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising: (a) nicotinic acid in an amount of not more than 1000 mg and (b) an oil comprising at least about 95%, by weight, eicosapentaenoic acid ethyl ester; wherein the pharmaceutical composition contains no docosahexaenoic acid or derivative thereof. 
     
     
         21 . The method of  claim 20  wherein the eicosapentaenoic acid ethyl ester is present in the composition in an amount of about 100 mg to about 2000 mg. 
     
     
         22 . The method of  claim 21  where the composition is administered to the subject in about 1 to about 4 dosage units per day. 
     
     
         23 . A pharmaceutical composition comprising nicotinic acid in an amount of about 1 mg to about 200 mg dispersed in about 100 mg to about 1000 mg of an oil comprising at least about 95%, by weight, eicosapentaenoic acid ethyl ester, wherein the composition contains no docosahexaenoic acid or derivative thereof and is enclosed in a capsule shell. 
     
     
         24 . A method of reducing risk of cardiac arrest in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising (a) nicotinic acid in an amount of not more than 1000 mg and (b) an oil comprising at least about 95%, by weight, eicosapentaenoic acid ethyl ester, wherein the composition contains no docosahexaenoic acid or derivative thereof. 
     
     
         25 . A kit comprising a first pharmaceutical composition comprising nicotinic acid in an amount of not more than 1200 mg and a second pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof, wherein the second pharmaceutical composition contains not more than 10%, by weight, docosahexaenoic acid, if any. 
     
     
         26 . A method of preventing or reducing incidence or severity of niacin-induced flushing in a subject, comprising (a) providing a subject that has not yet initiated niacin therapy, (b) pre-treating the subject with a pharmaceutical composition comprising at least about 95% by weight EPA or derivative thereof and (c) subsequently administering niacin to the subject. 
     
     
         27 . The method of  claim 26  wherein the subject is pre-treated with the pharmaceutical composition in an amount sufficient to provide about 1 mg to about 5000 mg of EPA or derivative thereof per day for a period of about 1 to about 30 days. 
     
     
         28 . The method of  claim 26  wherein the subject is pre-treated with the pharmaceutical composition in an amount sufficient to provide about 1 mg to about 2000 mg of EPA or derivative thereof per day for a period of about 1 to about 10 days. 
     
     
         29 . A method of treating or reducing severity of niacin-induced flushing in a subject comprising (a) providing a subject on niacin therapy that experiences flushing and (b) treating the subject with a pharmaceutical composition comprising at least about 95% by weight EPA or derivative thereof in an amount sufficient to prevent reduce severity of said flushing.