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VBCR - April 2015, Volume 4, No 2 - In the News

Paracetamol (acetaminophen in the United States) appears to have more cardiovascular, gastrointestinal (GI), and renal toxicity, as well as increased risk of mortality, than has been previously assumed, especially at high doses, according to a systematic review of the literature published online.

Paracetamol is the most widely used over-the-counter and prescription analgesic worldwide. It is currently recommended as a first-line medication by a variety of international guidelines for a wide range of acute and chronic pain. A previous study questioned the analgesic benefit of paracetamol in osteoarthritis, and the authors of the present study sought to characterize adverse events associated with use of the drug.

This review demonstrates a consistent dose-response relationship between paracetamol at standard analgesic doses and adverse events often observed with nonsteroidal anti-inflammatory drugs (NSAIDs). This includes a dose-response relationship between paracetamol and increasing incidence of mortality and cardiovascular, GI, and renal adverse events in the general adult population, according to the authors.

They acknowledge the limitations of an observational review but state that the trends they found were “striking.” Acknowledging that every prescription decision entails balancing risks versus benefit, the authors suggest that when adequate analgesia is a priority, the risks may be acceptable to patients and physicians, but in situations in which analgesic benefit is uncertain (as in osteoarthritis), more careful consideration of paracetamol usage is required. Prescribers need to be aware of these data showing a higher risk than that currently perceived in the clinical community, they stated.

The observational study was based on searches of Medline and Embase from inception of the databases until May 1, 2013. Of 1888 studies retrieved, 8 met the inclusion criteria, and all were cohort studies. The inclusion criteria were as follows: the study population was aged 18 years or older and the study investigated 1 or more of the adverse events of interest in people taking oral paracetamol at standard therapeutic doses of 0.5-1 g every 4-6 hours to a maximum of 4 g/day compared with nonuse.

Two studies reporting mortality compared paracetamol use with nonuse; 1 showed a dose response and found an increased relative rate of mortality from 0.95 to 1.63. Of 4 studies that looked at cardiovascular adverse events, all showed a dose response, and 1 found an increased risk ratio for all cardiovascular adverse events from 1.19 to 1.68. One study that reported GI adverse events found a dose response with increased relative rate of GI adverse events or bleeds from 1.11 to 1.49. Of 4 studies that looked at renal adverse events, 3 reported a dose response, with 1 reporting an increased odds ratio of 30% or greater decrease in glomerular filtration rate from 1.40 to 2.19. Roberts E, et al. Ann Rheum Dis. Published online: March 2, 2015.

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Last modified: May 21, 2015
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