Hepatotoxicity associated with chronic acetaminophen administration in patients without risk factors

OBJECTIVE: To evaluate the literature regarding the potential of acetaminophen to cause toxicity in adult patients without risk factors, when used chronically in daily doses < or = 4 g. DATA SOURCES: Key tertiary literature was reviewed, along with searches of MEDLINE (1966-July 2001). International Pharmaceutical Abstracts (1970-May 2001), and PREMEDLINE (July Week 5, 2001). Key search terms included acetaminophen, paracetamol, toxic hepatitis, hepatotoxicity, liver dysfunction, overdose, drug toxicity, and poisoning. DATA SYNTHESIS: Most tertiary references state that the maximum daily dose of acetaminophen is 4 g. Patients taking more than this amount, especially those with certain risk factors, are more likely to develop toxicity. However, a few patients may develop toxicity regardless of risk. An evaluation of the literature regarding the toxic potential of acetaminophen when given at doses < or = 4 g/d chronically (> or = 4 d) to adult patients without risk factors was conducted. CONCLUSIONS: Acetaminophen should be used cautiously on a chronic basis because several case reports show that it may be hepatotoxic at therapeutic doses.