Acetylcysteine Compositions and Methods of use Thereof

Abstract

A pharmaceutical composition and method for providing a reduction in side effects for human patients in need of therapy comprising the administration of a pharmaceutical composition comprising acetylcysteine is disclosed.

What is claimed is: 
     
         1 . A method of treating a patient with a pharmaceutical composition, comprising:
 administering to a patient in need thereof a therapeutically effective amount of a pharmaceutically acceptable composition comprising acetylcysteine and a pH adjusting agent, wherein the composition is substantially free of chelating agents, the pharmaceutical composition providing for a reduction in side effects as compared to an acetylcysteine composition containing chelating agents.   
     
     
         2 . The method of  claim 1 , wherein the composition contains from about 0.1% to about 50% of acetylcysteine. 
     
     
         3 . The method of  claim 2 , wherein the composition comprised from about 1.0% to about 25% acetylcysteine. 
     
     
         4 . The method of  claim 3 , wherein the composition contains about 20% acetylcysteine. 
     
     
         5 . The method of  claim 3 , wherein the composition contains about 10% acetylcysteine. 
     
     
         6 . The method of  claim 2 , wherein the composition contains less than about 0.05% chelating agent. 
     
     
         7 . The method of  claim 1 , wherein the pH adjusting agent is present in an amount to provide a pH of the composition of about 6 to about 8. 
     
     
         8 . The method of  claim 7 , wherein the pH adjusting agent is present in an amount to provide a pH of the composition of about 6.8. 
     
     
         9 . The method of  claim 1 , wherein the reduction of side effect is selected from the group consisting of tachycardia, nausea, vomiting, pharyngitis, rhinorrhea, rhonci, pruritis, rash, flushing, anaphylaxis, and combinations thereof. 
     
     
         10 . The method of  claim 1 , wherein the composition is administered to treat acetaminophen overdose and the therapeutically effective amount is administered intravenously at a dose of about 200 mg/kg over a period of about 3 to about 5 hours followed by a second dose at 100 mg/kg over 16 hours. 
     
     
         11 . The method of  claim 10 , wherein the composition is administered intravenously at a dose of about 200 mg/kg over a period of about 4 hours followed by a second dose at 100 mg/kg over 16 hours. 
     
     
         12 . A method of treatment, comprising intravenously administering a 300 mg/kg dose of acetylcysteine to a patient in need of treatment with acetylcysteine over 20 hours via a 2-bag infusion regimen comprising a first dose of 200 mg/kg delivered over a time period from about 3 to about 5 hours, followed by a second dose of 100 mg/kg over 16 hours. 
     
     
         13 . The method of  claim 12 , further comprising determining if the patient has achieved clinically significant improvement in liver function over the course of the 20 hour treatment, and if not, continuing the administration of acetylcysteine to the patient beyond 21 hours to achieve significant clinical improvement in liver function. 
     
     
         14 . The method of  claim 12 , further comprising administering to the patient either a repeat course of the entire treatment protocol (300 mg/kg over 21 hours) or a repeat course of the maintenance dose (100 mg/kg over 16 hours). 
     
     
         15 . The method of  claim 12 , further comprising continuing the treatment with an acetylcysteine infusion at 6.25 mg/kg per hour beyond 21 hours. 
     
     
         16 . The method of  claim 12 , wherein the first dose is administered over a time period of about 4 hours. 
     
     
         17 . An improvement in a method of intravenously administering a 300 mg/kg dose of acetylcysteine to a patient in need of treatment with acetylcysteine over 20 hours, the improvement comprising decreasing the initial rate of acetylcysteine infusion to 50 mg/kg per hour and maintaining that rate of infusion for 4 hours. 
     
     
         18 . The method of  claim 17 , further comprising thereafter intravenously delivering a second dose of 100 mg/kg acetylcysteine to the patient over 16 hours. 
     
     
         19 . The method of  claim 18 , further comprising determining if the patient has achieved clinically significant improvement in liver function over the course of the 20 hour treatment, and if not, continuing the administration of acetylcysteine to the patient beyond 21 hours to achieve significant clinical improvement in liver function. 
     
     
         20 . The method of  claim 19 , further comprising administering to the patient either a repeat course of the entire treatment protocol (300 mg/kg over 21 hours) or a repeat course of the maintenance dose (100 mg/kg over 16 hours). 
     
     
         21 . The method of  claim 20 , further comprising continuing the treatment with an acetylcysteine infusion at 6.25 mg/kg per hour beyond 21 hours. 
     
     
         22 . A pharmaceutical composition, consisting of comprising 6 g acetylcysteine, an effective amount of sodium hydroxide to provide a pH in the range from about 6.0 to about 7.5, and a sufficient amount of sterile water for injection, USP to provide a total volume of 30 mL (200 mg/mL). 
     
     
         23 . The pharmaceutical composition of  claim 22 , having a pH from about 6.0 to about 7.0. 
     
     
         24 . The pharmaceutical composition of  claim 23 , which is packaged in 30-mL glass vials. 
     
     
         25 . A pharmaceutical composition, consisting of an amount of acetylcysteine effective to provide a dose of 200 mg per kg of weight of a human patient, an effective amount of sodium hydroxide to provide a pH in the range from about 6.0 to about 7.5, sterile water for injection, in 1000 mL 0.45% Sodium Chloride Injection. 
     
     
         26 . A pharmaceutical composition, consisting of an amount of acetylcysteine effective to provide a dose of 100 mg per kg of weight of a human patient, an effective amount of sodium hydroxide to provide a pH in the range from about 6.0 to about 7.5, sterile water for injection, in 500 mL 0.45% Sodium Chloride Injection. 
     
     
         27 . A pharmaceutical composition, consisting of an amount of acetylcysteine effective to provide an effective dose of acetylcysteine to a human patient, an effective amount of sodium hydroxide to provide a pH in the range from about 6.0 to about 7.5, sterile water for injection, and sodium chloride. 
     
     
         28 . The pharmaceutical composition of  claim 27 , which contains from about 10 to about 400 mg/mL acetylcysteine.