Acetaminophen, a widely used analgesic, has long been considered a safe first-line treatment for managing chronic pain, especially in older adults. However, a recent large-scale study conducted on 180,483 acetaminophen users and 402,478 non-users aged 65 years and older in the UK primary care population raises significant concerns regarding its safety profile. The study’s findings published in Arthritis Care and Research highlight an increased incidence of gastrointestinal (GI), cardiovascular (CV), and renal adverse events associated with acetaminophen use, challenging its standing as the go-to oral analgesic for long-term pain management in older populations.
The study found an increased risk of gastrointestinal, cardiovascular, and renal adverse events. Acetaminophen users experienced a significantly higher incidence of peptic ulcer bleeding (PUB), uncomplicated ulcers, and lower GI bleeding. The study also found increased risks of heart failure and hypertension with acetaminophen. Chronic renal failure was also more common among acetaminophen users. A clear dose-response relationship was observed for PUB, uncomplicated ulcers, and chronic renal failure, with risks escalating with the number of acetaminophen prescriptions.
The study suggests potential mechanisms to explain these associations. For GI complications, prolonged acetaminophen use may inhibit prostacyclin synthesis, reducing vascular protection in the gastrointestinal lining and increasing susceptibility to bleeding. Similarly, the nephrotoxic effects of acetaminophen are thought to result from tubular cell stress, endoplasmic reticulum dysfunction, and caspase-mediated apoptosis.
There is a pressing need to reassess clinical guidelines recommending acetaminophen as the first-line analgesic for chronic pain conditions in older adults. Alternative pain management strategies, including non-pharmacological approaches and selective pharmacological agents, may offer safer and more effective options.
These findings challenge the long-held perception of acetaminophen as a universally safe option. While the incidence of adverse events associated with acetaminophen is lower than that of NSAIDs and COX-2 inhibitors, the similarity in their side effect profiles underscores the need for more nuanced prescribing practices. Clinicians must weigh the risks and benefits of acetaminophen, particularly for older patients with comorbidities that heighten their vulnerability to GI, CV, and renal complications.
Sources: Arthritis Care and Research, MedPage Today
