Acetaminophen Might Not Be As Safe As You Think

Authors: Roberts E et al., Ann Rheum Dis 2015 Mar 2;

In a review of observational studies, acetaminophen was associated with elevated risks for death and other adverse events.

Acetaminophen generally is considered to be safer than nonsteroidal anti-inflammatory drugs and other commonly used analgesics, but randomized controlled trial–level data to support this idea are limited. To assess acetaminophen’s adverse events profile, researchers conducted a systematic review of eight long-term cohort studies (duration range, 2–20 years; 664,000 adults) in which researchers reported adverse event rates associated with standard-dose acetaminophen therapy (i.e., 500–1000 mg every 4–6 hours; maximum, 4000 mg daily).

In the two studies in which overall mortality was assessed, mortality was elevated among acetaminophen users (with an apparent cumulative dose-response effect in 1 study). Dose-response effects also were noted in studies that showed associations between acetaminophen use and adverse cardiovascular events (e.g., myocardial infarctions, strokes; 4 studies), adverse upper gastrointestinal events (e.g., ulcers, upper gastrointestinal bleeds; 1 study), and adverse kidney events (i.e., decreases in estimated glomerular filtration rates, acute kidney failure, and increases in serum creatinine; 3 studies). Notably, all studies adjusted for potential confounders.

Comment

This review suggests that acetaminophen might not be as safe as we have generally assumed. However, the results should be interpreted with caution because of the likelihood of “confounding by indication” in these observational studies (i.e., acetaminophen is a first-line analgesic for patients with chronic or serious illness who can’t take other analgesics, and therefore it might be associated with — but not cause — higher risk for death). This limitation remains probable although, in each of the included studies, researchers did attempt to control for confounding factors. Nonetheless, clinicians and patients should be aware of potential adverse effects of regular long-term use of acetaminophen.