UK rheumatologists have reopened the debate on the long-term safety of paracetamol, particularly for osteoarthritis and lower back pain.
Philip Conaghan from the Leeds Institute of Rheumatic and Musculoskeletal Medicine and colleagues called for a review of the popular analgesic’s efficacy and tolerability in individual conditions after their review of the literature found an increased risk of cardiovascular and renal adverse events with long-term use.
Professor Conaghan has previously chaired a NICE panel that recommended paracetamol not be used as a first line therapy for osteoarthritis. The guidelines were not changed because of fears the move could encourage greater opioid use.
In a review of eight observational cohort studies the research team found a dose-response relationship between paracetamol and increasing incidence of mortality, cardiovascular, GI and renal adverse events often seen with NSAIDs (see chart below for exact risks).
Some of the risks were higher than expected for certain events, for example hypertension and renal impairment, Professor Conaghan told the limbic.
Every prescribing decision involves a calculation of risk versus benefit, a trade off of efficacy versus tolerability, the authors wrote in the Annals of the Rheumatic Diseases.
“If providing adequate analgesia or antipyresis, clinicians and patients may be willing to accept the risk at the level of AEs demonstrated in this review”.
“However when analgesic benefit is uncertain, which has recently been suggested for paracetamol in the treatment of OA joint pain and low back pain more careful consideration of its usage is required,” they said.
Prescribers needed to be more aware of patients’ individual responses to paracetamol and the observed increased toxicity with regular and higher dosing within standard dose ranges, they said.
“Based upon the data presented… we believe the true risk of paracetamol prescription to be higher than that currently perceived in the clinical community,” they concluded.
The researchers noted that the review was based on observational studies and may therefore be subject to bias.
Professor Conaghan’s advice for people taking regular paracetamol is to stop taking it for a few days and see if it makes a difference to their symptoms.
“If it is helping, then they and their doctor need to be aware they could have slightly increased risks of certain problems,” he told the limbic.
“For most people with OA and back pain, having strong supporting muscles (e.g thigh muscle for knee pain) and keeping active, losing weight if required, are more effective than pills and have few side effects – but it means putting some time aside every day to look after yourself and many people find that hard,” he added.
Main findings:
Two studies that showed mortality, one found a dose–response relationship with an increased relative rate of mortality from 0.95 to 1.63 for increasing standard doses of paracetamol.
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 reported a dose–response with a higher relative rate of events or bleeds from 1.11 to 1.49.
Of four studies reporting renal adverse events, three reported a dose–response with one reporting a more likely decrease in estimated glomerular filtration rate from 1.40 to 2.19.