Possible role for acetylcysteine as a treatment for acute liver failure secondary to antitubercular medication use

Author:

Fox Ashley N1,Nation Brooke E2,Autry Marcus Tad3,Johnson Peter N4

Affiliation:

1. Department of Pharmacy, University of New Mexico Hospitals, Albuquerque, NM

2. Total Dose Community Pharmacy, Oklahoma City, OK

3. Department of Hematology/Oncology, Stevenson Cancer Center, Oklahoma City, OK

4. Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, OK

Abstract

Abstract Purpose Drug-induced liver injury (DILI) that progresses to acute liver failure (ALF) has a high mortality rate, and therapeutic options are limited. Acetylcysteine has a labeled indication for use as an antidote for acetaminophen toxicity and has also been used with limited success in treatment of non–acetaminophen-induced liver injury, with small clinical trials indicating an increase in transplant-free survival. Recommendations for management of non–acetaminophen-induced DILI include withdrawal of the offending agent and supportive care. Treatment guidelines generally discourage a rechallenge with an offending medication, except in cases where there are no other therapeutic options for management of a serious disease, such as active tuberculosis (TB). Summary This case report describes the reversal of ALF due to DILI in a patient receiving antitubercular agents for active TB. After withdrawal of initially prescribed antitubercular agents, the patient was switched to a less hepatotoxic anti-TB regimen and intravenous acetylcysteine pending results of antimicrobial susceptibility testing. After stabilization of the patient’s liver enzyme levels, intravenous acetylcysteine was discontinued and oral acetylcysteine was continued for 5 days without an increase in hepatic enzyme levels or clinical deterioration. After 5 days, oral acetylcysteine was discontinued due to patient-reported nausea and vomiting. Conclusion Given the limited number of therapeutic interventions shown to be beneficial in ALF and data suggesting a protective effect against DILI with initiation of acetylcysteine at the start of treatment with anti-TB medications, acetylcysteine can be considered for patients with anti-TB – associated DILI.

Publisher

Oxford University Press (OUP)

Subject

Health Policy,Pharmacology

Reference21 articles.

1. ACG clinical guideline: the diagnosis and management of idiosyncratic drug-induced liver injury;Chalasani;Am J Gastroenterol,2014

2. An official ATS statement: hepatotoxicity of antituberculosis therapy;Saukkonen;Am J Respir Crit Care Med.,2006

3. Use of acetylcysteine for non-acetaminophen-induced acute liver failure;Sales;Ann Hepatol,2013

4. Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model;Singh;Hum Exp Toxicol,2012

5. Efficacy of N-acetylcysteine on prevention of antitbuerculosis drug-induced hepatotoxicity;Farazi;World J Med Sci,2015

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