Incidence of side effects associated with acetaminophen in people aged 65 years or more: a prospective cohort study using data from the Clinical Practice Research Datalink.

Objective: The main objective of this study is to examine the safety of oral acetaminophen at its therapeutic dose in adults aged 65 years or more.

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 non-exposure 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 weighted (IPTW) 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 (CI) were calculated using the Cox-proportional hazards regression model.

Results: In total, 180,483 acetaminophen-users and 402,478 non-users were included in this study. Acetaminophen use was associated with an increased risk of peptic ulcer 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, the use of acetaminophen as the first-line oral analgesic for long-term conditions in older people requires careful reconsideration.