Acetaminophen Formulation With Protection Against Toxic Effects of Overdose

Abstract

An oral pharmaceutical dosage form that comprises both acetaminophen and a glutathione replenishing agent, such as N-acetylcysteine. This allows co-administering the glutathione replenishing agent along with acetaminophen, which may be beneficial in rapidly counteracting the toxic effects of acetaminophen overdose. The oral dosage form could be in the form of a tablet or capsule. The dosage form may be designed to compartmentally separate the glutathione replenishing agent from having chemical interaction with the acetaminophen. The dosage form may be designed to mask the taste or smell of the glutathione replenishing agent.

1 . A method of treating a patient with acetaminophen, comprising administering a solid oral dosage form that simultaneously provides acetaminophen and a glutathione replenishing agent to the patient, wherein the oral dosage form is a pharmaceutical capsule comprising:
 a degradable casing;   acetaminophen contained within the casing in an amount of 100 to 1,500 mg;   a glutathione replenishing agent contained within the casing in an amount of 50 to 800 mg as one or more discrete units.   
     
     
         2 . The method of  claim 1 , wherein orally administering the pharmaceutical capsule to the patient results in a peak drug level for acetaminophen and a peak drug level for the glutathione replenishing agent, wherein the peak drug level for the glutathione replenishing agent occurs after the peak drug level for acetaminophen. 
     
     
         3 . The method of  claim 1 , wherein the acetaminophen is compartmentally separated from the glutathione replenishing agent. 
     
     
         4 . The method of  claim 1 , wherein no significant chemical interaction occurs between acetaminophen and the glutathione replenishing agent. 
     
     
         5 . The method of  claim 1 , wherein acetaminophen is provided as multiple discrete units. 
     
     
         6 . The method of  claim 5 , wherein the multiple discrete units of acetaminophen are particles comprising acetaminophen. 
     
     
         7 . The method of  claim 6 , wherein the particles of acetaminophen and particles of glutathione replenishing agent have a size in the range of 100 μm to 2 mm. 
     
     
         8 . The method of  claim 7 , wherein the particles of acetaminophen and the particles of glutathione replenishing agent are granules, pellets, beads, grains, or microcapsules. 
     
     
         9 . The method of  claim 1 , wherein the one or more discrete units of the glutathione replenishing agent are mini-tablet(s) comprising the glutathione replenishing agent. 
     
     
         10 . The method of  claim 9 , wherein the mini-tablet(s) of glutathione replenishing agent comprise an inner mass of the glutathione replenishing agent and a protective coating around the inner mass. 
     
     
         11 . The method of  claim 10 , wherein the multiple discrete units of acetaminophen are particles comprising acetaminophen. 
     
     
         12 . The method of  claim 1 , wherein the amount of glutathione replenishing agent is less than 160 mg. 
     
     
         13 . The method of  claim 1 , wherein the ratio (by weight) of the glutathione replenishing agent to acetaminophen is in the range of 1:20 to 1:5. 
     
     
         14 . The method of  claim 1 , wherein the amount of glutathione replenishing is 50 to 800 mg. 
     
     
         15 . The method of  claim 1 , wherein the glutathione replenishing agent is is N-acetylcysteine.