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GPs told to be aware of potential harm of paracetamol as researchers call safety into question

Specialists in musculoskeletal medicine have called on NICE to look again at paracetamol use after their study found long-term use of paracetamol is associated with increased renal and cardiovascular toxicity, particularly at higher doses.

The team said GPs should be more aware of the potential harms of the drug when used for chronic pain relief, especially for conditions such as knee osteoarthritis where paracetamol seems not to be effective.

They said they have submitted their study to the MHRA, which is currently reviewing the safety of over-the-counter analgesics

However, GP prescribing leads warned GPs against changing practice on the basis of one observational study, as the results could be biased and may not reflect how differently individual patients respond to paracetamol.

The study was led by Professor Philip Conaghan from the Leeds Institute of Rheumatic and Musculoskeletal Medicine, who previously chaired a NICE panel that tried to demote paracetamol from being the recommended first-line therapy for pain relief in osteoarthritis, which was forced to back down from advising against paracetamol use, after objections from GP experts who warned the move could put patients at risk from alternative drugs

However, he has called on NICE to conduct a wide-ranging review of the pharmacological management of osteoarthritis once the UK medicines regulator has completed an ongoing review of the safety of over-the-counter analgesics.

To re-open the debate on paracetamol, Professor Conaghan’s team carried out a systematic review of the literature on adverse events associated with its use, identifying eight studies that could be analysed.

There were not enough data to carry out a full meta-analysis, but the researchers found a dose-response effect of long-term paracetamol use on cardiovascular, renal and gastrointestinal adverse events. There was also a link between paracetamol dose and mortality.

The team wrote: ‘Prescribers need to be more aware of patients’ individual responses to paracetamol and the observed increased toxicity with regular and higher dosing within standard dose ranges.

‘Based upon the data presented… 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.’

Professor Conaghan told Pulse: ‘We have submitted the study to the MHRA.’

The MHRA was due to make an announcement on the review by the end of last year, but a spokesperson told Pulse that the review is still ‘ongoing’ and that no date has been set for its completion.

Dr Andrew Green, chair of the GPC’s clinical and prescribing subcommittee, said the study was ‘interesting’ but warned against swapping treatments on the basis of one study.

He said: ‘GPs will always need to balance the risks and benefits for all treatments they provide. The study in interesting but we do have to take some care when applying population studies to individuals, who can vary enormously both in their response to treatments and in their attitude to risk.

‘We must not drift into a sort of theraputic nihilism where the fear of causing a side-effect leads to under-treatment of conditions that cause great distress, or into theraputic instability where every new study leads to changed treatments and the swapping one set of potential problems for another.’

Dr Martin Duerden, a GP in Conwy, North Wales, and prescribing advisor to the RCGP, said GPs should not change clinical practice based on the data.

He said: ‘It’s an interesting study and suggests that paracetamol taken in the long-term may not be as safe as we once thought. However, it is based on observational studies and as the researchers admit, it may be subject to bias, as long term paracetamol users may be sicker than those that don’t take them. The harms reported are mainly cardiovascular events and effects on renal function.

‘I wouldn’t make a change in clinical practice based on these data. The key take home message for me is that if people get good pain relief with paracetamol, they should take it, if they don’t they should stop it. In long term, users it might be worth suggesting a holiday from the drug to see if they are still getting benefit.’

Ann Rheum Dis 2015; available online 2 Mar

Readers' comments (16)

  • Vinci Ho

    I am surprised that there was not enough data to do a full meta-analysis . One would presume there would have been good numbers of studies , though small , already existed.
    What about data on patients taking combined preparations regularly e.g. cocodamol. My impression is that is far more prevalent to take cocodamol two qds daily.

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  • The risks of long term paracetamol therapy I thought were well known.
    Surprising therefore that paracetamol has been so vigorously promoted as a first line long term analgesic.
    A cost issue??

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  • Just thinking about the new amazing wonder drug that some pharma company is getting ready to promote as an expensive replacement prompting funding for this useless observational research.

    Otherwise without any sensible alternatives back to treating pain with a cup of tea and a hug.

    Wait tea is also now dangerous, as is giving a patient a hug!

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  • Took Early Retirement

    Given that every analgesic we use seems to have negative effects I wonder why nobody, other than me, has been thinking that maybe it ISN'T always the drugs, but effects of all the pain-causing & inflammation-causing chemicals coursing round the body that have the negative effects. We know that inflammation in itself is bad news- associated with decline in function in Alzheimer's patients for example?

    And what is the alternative from our academic colleagues? Leave everyone in pain? Watch the suicide rate rise?

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  • "And what is the alternative from our academic colleagues? Leave everyone in pain? Watch the suicide rate rise?"

    They don't deal with solutions, only problems....

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  • The longterm effect of breathing is death. 80 years olds dont die of Paracetamol they die of ageing organs.

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  • I sense an overwhelming air of despair, are there any conventional drugs left in the cupboard that do not harm patients?

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  • I am confident that one day Paracetamol will become a controlled drug.

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  • Wouldn't paracetamol in excess cause liver damage before kidney??????

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  • NICE has stated that Pracetamol is as good as Placebo in musculoskeletal disease .With PPI inhibitors Ibuprofen,now available over the counter has been said by NICE to be more effective.

    one should watch for hypersensitivity reactions,gastric sideefects ,avoid in Renal Impairment.BNF mentionsRarely papillary necrosis,or interstional nephrosis associated with NSAIDS may lead to Renal failure.
    We can do little else with pains of slipped discs sciatica etc after diclofenac gel application

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