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.’