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Risks of taking long-term paracetamol may be ‘underestimated’

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Clinicians may have underestimated the risks for patients who take paracetamol long-term, suggests a study by UK researchers.  

They are calling for a major review of evidence to ensure the effectiveness of the commonly taken drug – the most widely used over-the-counter and prescription analgesic – and how it is tolerated for certain conditions.

It is recommended as first-line therapy by a variety of international guidelines for a multitude of acute and chronic painful conditions and is generally considered to be safer than non-steroidal anti-inflammatory drugs or opiates.

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

“We believe the true risk of paracetamol prescription to be higher than that currently perceived”

Study authors

Researchers, led by Professor Philip Conaghan from the Leeds Institute of Rheumatic and Musculoskeletal Medicine, looked at eight existing studies that had assessed the association between chronic use of paracetamol and major adverse events in adults.

Of two studies that showed mortality, one found a dose-response and reported there had been an increased relative rate of mortality from 0.95 to 1.63 for increasing standard doses of paracetamol when comparing patients who had been prescribed paracetamol 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 adverse events also had 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 estimated glomerular filtration rate – a test used to check how well the kidneys are working – from 1.40 to 2.19.

The authors said 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 increasing incidence of mortality, cardiovascular, gastrointestinal and renal adverse events – though the overall risks of these problems remained small.

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

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

The authors said: “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,” they said in the journal Annals of the Rheumatic Diseases.

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Readers' comments (3)

  • Here we go again.
    Starting to look like the NSAID/COXIB controversy. The problems appear to greater for long term use and there is no need to panic and stop using paracetamol.
    All medications can be dangerous if used for too long or in exess but it is more dangerous to leave severe pain untreated.
    If we took all side effects into account we wouldn't use any drugs and we would still be biting on a stick for pain relief.

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  • 100% agree with previous comment. Sums up the article entirely.

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  • Anonymous- I think you mean "excess." Also "problems appear to be greater," or more economically "problems appear greater." There is a very simple trick to avoiding such errors: proofread before you hit the Submit button. Nevertheless, I completely concur.

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