Abstract
OBJECTIVE: The main objective of this study is to examine the safety of oral acetaminophen at its therapeutic dose in adults aged ≥65 years. METHODS: This population-based cohort study used the Clinical Practice Research Datalink-Gold data. Participants were aged ≥65 years registered with a UK general practice for at least 12 months between 1998 and 2018. Acetaminophen exposure was defined as at least two acetaminophen prescriptions within six months of the first acetaminophen prescription, the first prescription date being the index date. Acetaminophen nonexposure was defined as the absence of two acetaminophen prescriptions within six months over the study period. We calculated propensity score (PS) for acetaminophen prescription and undertook inverse probability treatment weighting using PS and PS-matched analyses to account for confounding. Missing data were handled using multiple imputation. The adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) were calculated using the Cox proportional hazards regression model. RESULTS: In total, 180,483 acetaminophen exposed and 402,478 unexposed participants were included in this study. Acetaminophen exposure was associated with an increased risk of perforation or ulceration or bleeding (aHR 1.24; 95% CI 1.16-1.34), uncomplicated peptic ulcers (aHR 1.20; 95% CI 1.10-1.31), lower gastrointestinal bleeding (aHR 1.36; 95% CI 1.29-1.46), heart failure (aHR 1.09; 95% CI 1.06-1.13), hypertension (aHR 1.07; 95% CI 1.04-1.11), and chronic kidney disease (aHR 1.19; 95% CI 1.13-1.24). CONCLUSION: Despite its perceived safety, acetaminophen is associated with several serious complications. Given its minimal analgesic effectiveness, acetaminophen as the first-line oral analgesic option for long-term conditions in older people requires careful reconsideration.