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Risks of Long-Term Acetaminophen May Have Been Underestimated

Authors review adverse-event data

Doctors may have underestimated the risks for patients who take acetaminophen long-term, according to research published online in the Annals of the Rheumatic Diseases.

Acetaminophen –– the active ingredient in Tylenol (McNeil) –– is the most widely used over-the-counter and prescription analgesic worldwide and is recommended as first-line pharmacological therapy by a variety of international guidelines for numerous acute and chronic painful conditions. It is also generally considered to be safer than other commonly used analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or opiates.

However, the analgesic benefit of acetaminophen has recently been questioned in the management of acute lower-back pain and chronic osteoarthritis.

Researchers in the U.K. conducted a systematic review of studies that had assessed the association between the chronic use of paracetamol (the European name for acetaminophen) and major adverse events in the general adult population.

They identified eight suitable studies to analyze. Of two studies that showed mortality, one found a dose-response and reported an increased relative mortality rate from 0.95 to 1.63 for increasing standard doses of paracetamol in patients who had been prescribed the drug compared with those who had not.

Of four studies reporting cardiovascular adverse events, all showed a dose-response, with one study reporting an increased risk ratio of all cardiovascular adverse events from 1.19 to 1.68.

One study reporting gastrointestinal (GI) adverse events noted a dose-response with a higher relative rate of events or bleeds from 1.11 to 1.49.

Finally, of four studies reporting renal adverse events, three reported a dose-response, with one reporting a more likely decrease in the estimated glomerular filtration rate from 1.40 to 2.19.

The authors said that although the eight observational studies were likely to have biases related to people who needed long-term paracetamol (often people who already had multiple medical problems requiring other analgesics and medications), their findings demonstrated a consistent dose-response relationship between paracetamol at standard analgesic doses and adverse events typical of those often observed with NSAIDs. This included a dose-related relationship between paracetamol and an increasing incidence of mortality, cardiovascular, GI, and renal adverse events, although the overall risks of these disorders remained small.

The authors acknowledged that with every prescribing decision, there was a calculation of risk versus benefit or a trade-off of efficacy versus tolerability.

However, when the analgesic benefit was uncertain, as had been suggested in previous studies of paracetamol in the treatment of osteoarthritis joint pain and acute low-back pain, it was necessary for clinicians to take more a careful consideration before recommending or prescribing paracetamol for long-term use.

The authors concluded: “Based upon the data presented above, we believe the true risk of paracetamol prescription to be higher than that currently perceived in the clinical community. Given its high usage and availability as an over-the-counter analgesic, a systematic review of paracetamol’s efficacy and tolerability in individual conditions is warranted.”

Sources: Medical Xpress; March 2, 2015; and Annals of the Rheumatic Diseases; March 2, 2015.

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