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.

image