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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…