1. Home>
2. Specialties>
3. Emergency Medicine>
4. Summary and Comment

Aminotransferase Elevation in Healthy Adults Taking Acetaminophen

The clinical significance of the elevations is unclear.

Acetaminophen has a well-established safety record, and chronic treatment with 4 g per day has been confirmed to be safe. However, a recent trial found that a novel hydrocodone/acetaminophen combination was associated with a high incidence of serum alanine aminotransferase (ALT) elevations. To characterize the association between ALT levels and acetaminophen, researchers conducted a randomized, single-blind (participants), controlled, pharmaceutical–company-sponsored trial in 145 healthy adult volunteers (78% men; mean age, 34).

Every 6 hours for approximately 1 week, participants received one of five treatments: (1) placebo alone; (2) 1g of acetaminophen alone; and (3–5) 1g acetaminophen with 15 mg oxycodone, 4 mg hydromorphone, or 30 mg morphine, respectively. During the study, participants were housed in two inpatient clinical pharmacology facilities, and their diets were controlled. Treatment was discontinued if ALT concentrations exceeded three times the upper limit of normal (considered clinically significant elevation).

Trough acetaminophen concentrations did not exceed therapeutic limits in any participant. The incidence of clinically significant ALT elevations was 39% in all active-treatment groups combined (range, 31%–44%) versus 0% in the placebo cohort. After treatment discontinuation, ALT levels continued to increase for a median of 2 days and remained significantly elevated for a median of 6.5 days before returning to normal.

Comment: Given the exceptional safety profile of acetaminophen, the authors surmise that the ALT elevations observed in this study would have resolved with continued administration of acetaminophen. They call for longer-duration trials to address this issue. The incidence of ALT elevations found in this study was higher than that reported in other studies. This difference likely reflects the study population’s relatively high proportion of Hispanics (57%), as Hispanics have higher baseline ALT levels than do whites. Pending further investigation, there seems to be nothing here to discourage the routine use of acetaminophen as an analgesic.

— John A. Marx, MD, FAAEM, FACEP

Published in Journal Watch Emergency Medicine August 4, 2006

Citation(s):

Watkins PB et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: A randomized controlled trial. JAMA 2006 Jul 5; 296:87-93.

• Original article (Subscription may be required)
• Medline abstract (Free)