The association between exacerbation of chronic obstructive pulmonary disease and timing of paracetamol use: a cohort study in elderly Australians

Background: In elderly populations, paracetamol may be used regularly for conditions such as osteoarthritis. Paracetamol has been associated with respiratory disease through a proposed mechanism of glutathione depletion and oxidative stress. Given that chronic obstructive pulmonary disease (COPD) is frequently co-morbid with osteoarthritis, this study investigated whether the dose and timing of paracetamol exposure may induce COPD exacerbations.

Methods: The study population was 3523 Australian Government Department of Veterans' Affairs full entitlement holders who had existing COPD on 1 January 2011, who were dispensed at least one prescription of paracetamol between 1 January 2011 and 30 September 2015, and had no paracetamol dispensed in the 6 months prior to 1 January 2011. The outcome was time to first hospitalisation for COPD exacerbation after initiation of paracetamol. A weighted cumulative exposure approach was used.

Results: The association between paracetamol exposure and COPD exacerbation was protective or harmful depending on the dose, duration, and recency of exposure. Compared to non-use, current use at the maximum dose of 4 g daily for 7 days was associated with a lower risk (HR = 0.78, 95% CI = 0.67-0.92) and a higher risk after 30 days (HR = 1.27, 95% CI = 1.06-1.52). Risk declined to baseline after 2 months. For past use, there was a short-term increase in risk on discontinuation depending of dose, duration and time since stopping.

Conclusions: Patients and doctors should be aware of the possible risk of COPD exacerbation with higher dose paracetamol 1 to 6 weeks after initiation or discontinuation, but no increased risk after 2 months.