Scimex: UK researchers say doctors may be underestimating the risks associated
with prescribing paracetamol for long-term use. The authors, who
reviewed a number of existing studies, say due to the drug's
availability as an over the counter medicine, more research into the
drug is required.
Doctors may have underestimated the risks for patients who take
paracetamol long-term, suggests research published online in the
journal Annals of the Rheumatic Diseases.
There should also be a systematic review carried out to ensure the
effectiveness of the commonly taken drug and how it is tolerated for
certain conditions.
Paracetamol is the most widely used over-the-counter and prescription
analgesic worldwide and is recommended as first-line pharmacological
therapy by a variety of international guidelines for a multitude of
acute and chronic painful conditions. It is also generally considered to
be safer than other commonly used analgesics such as non-steroidal
anti-inflammatory drugs (NSAIDs) or opiates.
However, the analgesic benefit of paracetamol has recently been
questioned in the management of acute lower back pain and the chronic
painful condition of osteoarthritis and a recent estimate of the true
risks of paracetamol at standard analgesic doses has not been available.
A UK team of researchers, led by Professor Philip Conaghan of the
Leeds Institute of Rheumatic and Musculoskeletal Medicine, set out to
conduct a systematic review of existing studies that had assessed the
association between chronic use of paracetamol and major adverse events
in the general adult population.
They identified eight suitable studies to analyse. 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 reported 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 that although the eight observational studies were
likely to have biases related to those people who needed long-term
paracetamol (often people who already had multiple medical problems
requiring other analgesics and medications), their findings demonstrated
a consistent dose–response relationship between paracetamol at standard
analgesic doses and adverse events typical of those often observed with
non-steroidal anti-inflammatory drugs.
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.
However, when analgesic benefit was uncertain, as had been suggested
in previous studies of paracetamol in the treatment of osteoarthritis
joint pain and acute low back pain, it was necessary for clinicians to
take more careful consideration before recommending or prescribing it
for long-term use.
The authors concluded: “Based upon the data presented above, 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.