Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Why is paracetamol (also known as acetaminophen) the most frequently used analgesic for the relief of pain in people with osteoarthritis?
Well, firstly, paracetamol has been the first-line recommended treatment for osteoarthritis pain for very many years and, secondly, it is readily available over the counter and can be bought in relatively large quantities.
There has been a lot of concern regarding the toxicity of paracetamol lately. Please can you give an overview of the recent studies that have prompted this?
The study that prompted the media release suggested that about 150 people every week, which is about 8,000 people every year in Australia, are being hospitalized as a consequence of taking paracetamol at toxic doses.
It’s not a particularly new finding that paracetamol causes quite a lot of toxicity, but I think the study is the last in a number of studies looking at the damage caused by paracetamol toxicity, particularly liver toxicity.
Could you also outline the research that has looked at paracetamol and gastrointestinal blood loss?
I think historically people have mainly been concerned about anti-inflammatories causing gastrointestinal blood loss among those using pain relief for their arthritis.
More recently however, there have been a few different studies suggesting that paracetamol may increase gastrointestinal blood loss, particularly when taken concomitantly with an anti-inflammatory.
I think it’s important that people be aware of that. Even concomitant use of a PPI in the context of using paracetamol and an anti-inflammatory may not reduce the risk of gastrointestinal blood loss.
Were you surprised by these findings?
No, although I think the gastrointestinal blood loss is a bit more surprising than the liver toxicity. The liver toxicity is something that most people have been aware of for a long time but I don’t think people were aware of the magnitude of the problem.
About half of patients who end up being scheduled for a liver transplant are in that situation as a consequence of taking too much paracetamol.
Do we really understand how paracetamol works?
I think from the perspective of treating arthritis, the primary effects are exerted through central analgesic mechanisms.
I think a lot of people believed paracetamol may work on peripheral nerve receptors or nerve fibres in and around the joints and/or by reducing inflammation in the joint, but the primary mechanism is really central analgesia i.e. acting on the brain directly.
Why have the main regulatory body in the US, the Food and Drug Authority (FDA), limited prescription paracetamol to 325mg per tablet?
For the FDA, I think the primary motivation was to try and reduce the number of people developing liver toxicity as a consequence not only of accidental overdose, but also of intentional overdose.
The accidental overdoses were happening because people were taking regular paracetamol at doses up to 4 grams per day (500mg or 2 tablets every 6 hours), but were then also taking a cold or a flu remedy containing paracetamol, therefore accidentally overdosing on the agent.
By reducing the size of the tablets, the FDA hope to make the maximum daily dosage closer to 3.2 grams per day and obviate some of the concerns that people have about potential overdose.
Why is paracetamol commonly found in cold and flu remedies and how important is it for people with arthritis to pay attention to what is in these remedies?
Paracetamol is a very common component of cold and flu remedies, mainly because when people have a cold or the flu, they also have concomitant symptoms such as headache or muscle ache and pain.
The majority of people take paracetamol to relieve pain but also to help to control the associated fever.
It’s incredibly important for people who have arthritis and/or who are taking paracetamol for other pain purposes to be aware of all the over-the-counter medications they are taking, particularly cold and flu remedies, which often contain paracetamol.
There have also been some studies published recently that question the efficacy of paracetamol in the relief of pain. Could you please outline these?
In recent meta-analyses of paracetamol studies, the effect size of paracetamol has been found to be almost indistinguishable from placebo in well-designed studies.
Studies looking at the recent osteoarthritis research society guidelines, (published in March of this year in Osteoarthritis and Cartilage) suggested the effect size was very close to 0.
Now, the guidelines no longer recommend paracetamol as the first-line treatment in osteoarthritis and we more strongly advocate the use of agents such as topical anti-inflammatories for the majority of people who have the condition.
What impact do you think this research will have?
The research has definitely had an impact on the recent guidelines, but disseminating guidelines and actually bringing about changes in practice is another matter altogether.
Although the guidelines have now been revised, I’m fairly sure most clinicians, pharmacists and others who advocate the use of paracetamol are probably not aware of the changes. It may well take a number of years to get the information out there, so that paracetamol is no longer advocated as the first-line analgesic for osteoarthritis.
What do you think the future holds for paracetamol?
I still think that it’s likely to be relatively widely used for other purposes including headache and fever, for example.
However, in the context of osteoarthritis, which is one of the most common reasons for taking paracetamol, I think it is likely people will start using it less frequently and replacing it with other agents, particularly topical anti-inflammatories.
Where can readers find more information?
To find good information about treating osteoarthritis pain, we would strongly recommend people refer to the Arthritis Australia, which has a website called myjointpain.org.au. The website is free to access and provides good information about the various arthritis treatments that are available for those suffering from joint pain.
About Professor David Hunter
Professor Hunter is a rheumatology clinician researcher whose main research focus has been clinical and translational research in osteoarthritis (OA).
He is the Florance and Cope Chair of Rheumatology and Professor of Medicine at University of Sydney, and Staff Specialist at Royal North Shore Hospital and North Sydney Orthopaedic and Sports Medicine Centre.
A native of New Zealand and an Australian citizen, he earned his Bachelor of Medicine, Bachelor of Surgery, and Master of Sports Medicine at the University of New South Wales.
He completed a fellowship in Rheumatology at the Royal Australian College of Physicians, a Masters of Sports Medicine from UNSW, and earned a Masters of Medical Science (Clinical Epidemiology) from the University of Newcastle.
He established a full-time career in medical research in 1999, received his PhD in 2001 and then maintained an academic faculty appointment in Boston University amongst the foremost OA clinical researchers. He returned to Australia in 2010.
His research is focused on a number of key elements in OA including (but not limited to) the epidemiology of osteoarthritis, the application of imaging to better understand structure and function with application to both epidemiologic research and clinical trials, novel therapies in disease management and heath service system delivery of chronic disease management.
He is an editor for leading international journals in his field. He has authored books on osteoarthritis and has over 300 publications in peer reviewed journals.