ST. LOUIS—The only antidote for acetaminophen toxicity that has FDA approval is oral N-acetylcysteine. However, intravenous (IV) N-acetylcysteine has been administered for more than 20 years in Europe and Canada, and physicians in this country sometimes use the inhalant preparation as an IV formulation (9.1% of 14,021 patients who were treated for acetaminophen poisoning in the United States in 2001 were given IV N-acetylcysteine). Recently, researchers from Washington University and Barnes-Jewish Hospital, both in St. Louis, evaluated the stability and microbial susceptibility of the inhaled form of N-acetylcysteine prepared as an IV formulation and found that it is an acceptable alternative to oral or inhaled versions.[1]

Eight N-acetylcysteine solutions were made from vials of 20% N-acetylcysteine that were injected through a filter into a 5% dextrose solution. Three solutions were compounded at room temperature and used for stability testing, and one was prepared at high temperature and humidity to induce decomposition. Four others were prepared at room temperature and used for microbiological studies and pyrogen testing. The solutions were assayed according to US Pharmacopeia XXIV methodology.

Test solutions were analyzed at zero, four, eight, 12, 24, 36, 48, 60, and 72 hours, and the percentage of N-acetylcysteine remaining in each solution was recorded. Stability was defined as the time to 10% decomposition.

IV FORMULATION MEETS STABILITY STANDARDS

In the three solutions compounded at room temperature, time to 10% decomposition was between 60 and 72 hours. In the solution that was compounded at high temperature and humidity, time to 10% decomposition was greater than 72 hours. In fact, in this sample at 72 hours, the N-acetylcysteine concentration was 96.6%. All solutions remained free of particulate matter and discoloration at 72 hours. All of the solutions that were used for microbiological testing remained free of any bacterial growth on culture mediums at seven days.

Inhalation N-acetylcysteine prepared as a 2.6% IV formulation remained stable for a minimum of 60 hours, the researchers also found.

This study supports the safety and efficacy of IV N-acetylcysteine as an antidote for acetaminophen toxicity. Studies that have examined the adverse events occurring with IV N-acetylcysteine have found that they are infrequent, mild, and easily treated, causing either no interruption or only a short delay in infusion.

“In addition to its demonstrated safety profile, the use of IV N-acetylcysteine has been shown to be an effective treatment for acetaminophen ingestions and might be the only viable option for antidotal therapy in some cases because of the high incidence of nausea and vomiting in poisoned patients,” wrote the investigators.

—Gale Jurasek

Reference
1. Dribben WH, Porto SM, Jeffords BK. Stability and microbiology of inhalant N-acetylcysteine used as an intravenous solution for the treatment of acetaminophen poisoning. Ann Emerg Med. 2003;42:9-13.

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