Hepatotoxicity Associated with Chronic Acetaminophen Administration in Patients without Risk Factors

Abstract

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 ≤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 ≤4 g/d chronically (≥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.