Methods of treating headaches using 5-ht agonists in combination with long-acting nsaids

Abstract

The invention is directed to methods and compositions that can be used in the treatment of headaches. In particular, methods and compositions are described involving the combination of a long-acting NSAID and a 5-HT1 B /1 D agonist.

1 . A method of treating a patient for a migraine headache, comprising simultaneously administering to said patient:
 (a) a 5-HT1 B /1 D  agonist; and   (b) a nonsteroidal anti-inflammatory drug having a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours (“LA-NSAID”);   wherein:   said 5-HT1 B /1 D  agonist and said LA-NSAID are administered to said patient orally after the onset of migraine symptoms; and   the amount of said 5-HT1 B /1 D  agonist and said LA-NSAID administered to said patient are sufficient to produce longer lasting efficacy compared to the administration of said 5-HT1 B /1 D  agonist in the absence LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT1 B /1 D  agonist.   
     
     
         2 . The method of  claim 1 , wherein said 5-HT1 B /1 D  agonist and said LA-NSAID are administered together in a single dosage form. 
     
     
         3 . The method of  claim 2 , wherein said single dosage form is a tablet, capsule, dragee or trochee. 
     
     
         4 . The method of  claim 1 , wherein said 5-HT1 B /1 D  agonist is selected from the group consisting of: sumatriptan; eletriptan; rizatriptan; frovatriptan; almotriptan;
 zolmitriptan; and naratriptan.   
     
     
         5 . The method of  claim 1 , wherein said LA-NSAID is selected from the group consisting of: flurbiprofen; naproxen; oxaprozin; indomethacin; ketorolac; mefenamic acid;
 nabumetone, etodolac; and piroxicam.   
     
     
         6 . The method of  claim 1 , wherein said LA-NSAID inhibits COX-2 to a greater extent than it inhibits COX-1. 
     
     
         7 . The method of  claim 6 , wherein said LA-NSAID is either etodolac or mefenamic acid. 
     
     
         8 . The method of  claim 6 , wherein said 5-HT1 B /1 D  agonist is sumatriptan. 
     
     
         9 . The method of  claim 1 , wherein said 5-HT1 B /1 D  agonist is sumatriptan. 
     
     
         10 . The method of  claim 1 , wherein said 5-HT1 B /1 D  agonist and said LA-NSAID are administered in a single dosage form and wherein said 5-HT1 B /1 D  agonist is sumatriptan present at between 5 mg and 100 mg and said LA-NSAID is naproxen present at between 200 mg and 600 mg. 
     
     
         11 . A pharmaceutical composition useful in treating migraine headache which comprises in a single oral dosage form:
 (a) a 5-HT1 B /1 D  agonist; and   (b) a nonsteroidal anti-inflammatory drug having a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours (“LA-NSAID”);   wherein the respective amounts of said 5-HT1 B /1 D  agonist and said LA-NSAID in said pharmaceutical composition are effective upon co-timely or simultaneous administration of one or more single oral dosage forms to produce longer lasting efficacy compared to the administration of said 5-HT1 B /1 D  agonist in the absence of said LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT1 B /1 D  agonist.   
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein said oral dosage form is a tablet, capsule, dragee or trochee. 
     
     
         13 . The pharmaceutical composition of  claim 11 , wherein said 5-HT1 B /1 D  agonist is selected from the group consisting of: sumatriptan; eletriptan; rizatriptan; frovatriptan; almotriptan; zolmitriptan; and naratriptan. 
     
     
         14 . The pharmaceutical composition of  claim 11 , wherein said LA-NSAID is selected from the group consisting of: flurbiprofen; naproxen; oxaprozin; indomethacin; ketorolac; mefenamic acid; nabumetone; etodolac; and piroxicam. 
     
     
         15 . The pharmaceutical composition of  claim 11 , wherein said LA-NSAID inhibits COX-2 to a greater extent than COX-1. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein said LA-NSAID is either etodolac or mefenamic acid. 
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein said 5-HT1 B /1 D  agonist is sumatriptan. 
     
     
         18 . The pharmaceutical composition of  claim 11 , wherein said 5-HT1 B /1 D  agonist is sumatriptan present at between 5 mg and 100 mg and said LA-NSAID is naproxen present at between 200 mg and 600 mg. 
     
     
         19 . A therapeutic package comprising:
 (a) the pharmaceutical composition of  claim 11 ; and   (b) a finished pharmaceutical container containing said pharmaceutical composition and further comprising labeling directing the use of said pharmaceutical composition in the treatment of migraine headache.   
     
     
         20 . The therapeutic package of  claim 19 , wherein said pharmaceutical composition is in the form of a tablet, capsule, dragee or trochee.