Combination composition comprising oxycodone and acetaminophen for rapid onset and extended duration of analgesia

Abstract

The present disclosure provides an extended release pharmaceutical composition comprising oxycodone and acetaminophen that provides a rapid onset of analgesia, and reduced levels of acetaminophen near the end of the dosing interval. Also provided are methods for reducing the risk of acetaminophen-induced hepatic damage in a subject being treated with an acetaminophen containing composition, as well as methods for treating pain in a subject in need thereof.

What is claimed: 
     
         1 . An extended release pharmaceutical composition, comprising:
 an immediate release portion comprising oxycodone or a pharmaceutically acceptable salt of oxycodone, acetaminophen, or a combination thereof; and an extended release portion comprising oxycodone or a pharmaceutically acceptable salt of oxycodone, acetaminophen, or a combination thereof;   wherein when the composition is orally administered to a subject in need thereof the composition delivers the oxycodone or the pharmaceutically acceptable salt thereof and the acetaminophen to the subject's upper gastrointestinal tract for at least about 4 hours to about 12 hours; and   wherein either the oxycodone or the pharmaceutically acceptable salt thereof or the acetaminophen produces a plasma profile characterized by at least one pharmacokinetic parameter that differs by less than about 30% when the subject is in a fasted state as compared to a fed state.   
     
     
         2 . The extended release pharmaceutical composition of  claim 1 , wherein the pharmacokinetic parameter differs by less than about 20%. 
     
     
         3 . The extended release pharmaceutical composition of  claim 1 , wherein the pharmacokinetic parameter is selected from the group consisting of AUC and Cmax. 
     
     
         4 . The extended release pharmaceutical composition of  claim 1 , wherein both the oxycodone and the acetaminophen produces a plasma profile characterized by at least one pharmacokinetic parameter that differs by less than about 30% when the subject is in a fasted state as compared to a fed state. 
     
     
         5 . The extended release pharmaceutical composition of  claim 1 , wherein the extended release component comprises at least one extended release polymer. 
     
     
         6 . The extended release pharmaceutical composition of  claim 5 , wherein the at least one extended release polymer is a polyethylene oxide. 
     
     
         7 . The extended release pharmaceutical composition of  claim 6 , wherein the polyethylene oxide has a molecular weight from about 500,000 Daltons to about 10,000,000 Daltons. 
     
     
         8 . The extended release pharmaceutical composition of  claim 1 , wherein the total amount of the acetaminophen in the composition is from about 250 mg to about 1300 mg and the total amount of the oxycodone or the pharmaceutically acceptable salt thereof in the composition is from about 5 mg to about 30 mg. 
     
     
         9 . The extended release pharmaceutical composition of  claim 1 , wherein the total amount of the acetaminophen in the composition is about 325 mg and the total amount of the oxycodone or the pharmaceutically acceptable salt thereof in the composition is about 7.5 mg. 
     
     
         10 . The extended release pharmaceutical composition of  claim 1 , wherein the composition is administered to a subject in need thereof at least twice a day. 
     
     
         11 . The extended release pharmaceutical composition of  claim 1 , wherein the composition delivers the oxycodone or the pharmaceutically acceptable salt thereof and the acetaminophen to the subject's upper gastrointestinal tract for at least about 6 hours. 
     
     
         12 . An extended release therapeutically effective pharmaceutical composition comprising:
 at least one immediate release portion comprising oxycodone or a pharmaceutically acceptable salt thereof and acetaminophen and at least one extended release portion comprising an extended release component, oxycodone or a pharmaceutically acceptable salt thereof, and acetaminophen;   wherein the sum of the amounts of the acetaminophen in the immediate release and the extended release portions is about 325 mg;   wherein the sum of the amounts of the oxycodone or pharmaceutically acceptable salt thereof in the immediate release and extended release portions is about 7.5 mg; and   wherein the composition can be administered to a subject in need thereof without regard to food.   
     
     
         13 . A method for treating pain in a subject in need thereof comprising:
 orally administering an effective amount of an extended release pharmaceutical composition comprising oxycodone or a pharmaceutically acceptable salt thereof and acetaminophen to the subject in a fasted state;   wherein the oxycodone or the pharmaceutically acceptable salt thereof in the composition produces a plasma profile characterized by at least one pharmacokinetic parameter that differs by less than about 30% when the subject is in a fasted state as compared to a fed state; and   wherein the subject achieves and maintains analgesia for at least about 12 hours.   
     
     
         14 . The method of  claim 13 , wherein the subject in need thereof is suffering from pain or diagnosed with a condition associated with pain, the pain being acute pain or chronic pain. 
     
     
         15 . The method of  claim 13 , wherein the subject in need thereof is suffering from moderate to severe acute pain. 
     
     
         16 . The method of  claim 13 , wherein the pharmacokinetic parameter differs by less than about 20%. 
     
     
         17 . The method of  claim 13 , wherein the pharmacokinetic parameter is selected from the group consisting of AUC and Cmax. 
     
     
         18 . The method of  claim 13 , wherein the acetaminophen produces a plasma profile characterized by at least one pharmacokinetic parameter that differs by less than about 30% when the subject is in a fasted state as compared to a fed state. 
     
     
         19 . The method of  claim 18 , wherein the pharmacokinetic parameter differs by less than about 20%. 
     
     
         20 . The method of  claim 19 , wherein the pharmacokinetic parameter is selected from the group consisting of AUC and Cmax.