Pharmaceutical compositions

Abstract

Pharmaceutical compositions and methods are provided to treat headache, headache-associated symptoms, photophobia, or adverse effects associated with the headache. Also provided herein are small smooth particulates comprising a 5HT1B/1D receptor agonist. Compositions for oral administration are described herein wherein the compositions comprise a combination of active agents, such as a 5HT1B/1D receptor agonist and one or more antiemetics.

What is claimed is: 
     
         1 . A method for treating a headache or photophobia in a subject in need thereof, comprising administering to the subject a pharmaceutical composition, an oral dosage thereof, and a capsule thereof, wherein the pharmaceutical composition comprises:
 a plurality of first particulates, wherein each first particulate comprises a 5HT 1B/1D  receptor agonist that comprises rizatriptan or a pharmaceutical acceptable salt thereof, wherein: (a) each first particulate has an average diameter of less than about 500 μm; or (b) each first particulate comprises from about 55% to about 65% of the 5HT 1B/1D  receptor agonist (w/w); and   a plurality of second particulates, wherein each second particulate comprises:   (i) a core; and   (ii) a layer enclosing the core, wherein said layer comprises an antiemetic.   
     
     
         2 . The method of  claim 1 , wherein the 5HT 1B/1D  receptor agonist comprises the pharmaceutical acceptable salt of rizatriptan that is rizatriptan benzoate. 
     
     
         3 . The method of  claim 1 , wherein the method treats a headache that is a migraine headache. 
     
     
         4 . The method of  claim 1 , wherein the treatment is acute or prophylactic. 
     
     
         5 . The method of  claim 1 , wherein the administering treats a light sensitivity. 
     
     
         6 . The method of  claim 1 , wherein the administering treats nausea associated with a headache or vomiting associated with a headache. 
     
     
         7 . The method of  claim 1 , wherein the administering occurs one, two, or three times daily. 
     
     
         8 . The method of  claim 1 , wherein the administering occurs about every 4 to about every 6 hours. 
     
     
         9 . The method of  claim 1 , wherein the administering occurs about every 8 to about every 12 hours. 
     
     
         10 . The method of  claim 1 , wherein a second dose of the pharmaceutical composition, oral dosage, or capsule is administered after response to a first dose in the subject. 
     
     
         11 . The method of  claim 1 , wherein doses after a first dose of the pharmaceutical composition, oral dosage, or capsule are separated by at least 2 hours. 
     
     
         12 . The method of  claim 1 , wherein the rizatriptan or the pharmaceutically acceptable salt thereof is present at from about 1 mg to about 200 mg. 
     
     
         13 . The method of  claim 1 , wherein the rizatriptan or the pharmaceutically acceptable salt thereof is present at from about 35 mg to about 140 mg. 
     
     
         14 . The method of  claim 1 , wherein the antiemetic is present in an amount of about 15 mg to about 35 mg. 
     
     
         15 . The method of  claim 1 , wherein the antiemetic is present in an amount of about 35 mg to about 55 mg. 
     
     
         16 . The method of  claim 1 , wherein the antiemetic is present in an amount of about: 18, 18.5, 19, 19.5, 36, 37, 38, or 39 mg. 
     
     
         17 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 1 , wherein the antiemetic is ondansetron or a pharmaceutically acceptable salt thereof. 
     
     
         23 . The method of  claim 1 , wherein each first particulate has an average diameter of less than about 500 μm. 
     
     
         24 . The method of  claim 1 , wherein each first particulate comprises from about 55% to about 65% of the 5HT 1B/1D  receptor agonist (w/w).