The adverse effects which patients might experience when using over-the-counter analgesics could be anticipated from a knowledge of patients’ existing conditions, it was explained in a lecture sponsored by Crookes Healthcare given on September 10
The most important risk factor for adverse effects when taking over-the-counter
analgesics was the use of concomitant medication, Professor Nicholas Moore (professor
of clinical pharmacology, University of Bordeaux, France) said. The condition
that the analgesic was being used to treat also had an influence on whether
adverse effects might occur.
Professor Moore’s findings were taken from the results of the paracetamol,
aspirin and ibuprofen new tolerability (PAIN) study.1 This
was a randomised, blinded, parallel-group trial of paracetamol (P), aspirin
(A) and ibuprofen (I) administered to patients by French general medical practitioners
at doses equivalent to the OTC indications for the products in France at that
time. The maximum daily doses were 3g (P or A) or 1.2g (I) to be taken for up
to seven days. Patients completed diaries of drug use and adverse effects and
were given follow-up calls by their GP after 24 hours and seven to nine days.
In total 8,677 patients were randomised (P=2,888; A=2,900; I=2,886). The aim
of the trial was to show that ibuprofen was equal to paracetamol and superior
to aspirin in terms of tolerability.
Of the patients entering the trial, 99.5 per cent were evaluable and 95 per
cent complied with the “rather simple” protocol. This was “almost
as good a response as a phase I trial”, Professor Moore said. The most
common indications were musculoskeletal pain (33 per cent), colds or influenza
(20) and backache (16). Around 25 per cent of patients had concomitant diseases
and 45 per cent were taking other medicines during the study.
Looking at the primary end point of the trial, adverse effects were seen in
14.5 per cent (P), 18.5 per cent (A) and 13.7 per cent (I) of patients. This
was a significant difference with respect to A and the hypothesis was proven.
“Aspirin had more adverse effects in all categories,” Professor Moore
said.
Other risk factors
Presenting a more detailed analysis of the adverse effect profiles from the
trial, Professor Moore asked: “So, which patients should we look out for?”
Women had reported more adverse events than men, which could have been because
they either complained more or they were, it seemed, more resistant to the action
of analgesics, he said.
In terms of age, it was a case of “the older you get the more adverse effects
you have”, but Professor Moore noted that “the young complain more
than the middle aged”.
Patients with a higher temperature at the start of the trial had fewer adverse
events. This might be because patients treating feverish conditions had taken
shorter courses of treatment.
The condition which was being treated had an effect on the adverse effect profile.
Greater numbers of events were reported when the condition was backache, musculoskeletal
pain, headache or “other”.
However, the most important factor was the use of concomitant medication. The
greater the number of additional medicines that were being taken the greater
was the risk of adverse effects. The greatest risk came if any of the concomitant
medicines was “prohibited”, ie, contraindicated on the summary of
product characteristics or packaging. This showed that “forbidden medicines
were on the label for a good reason” and that OTC analgesics should not
be used if they were present.
“The greatest risk of adverse effects with aspirin is in patients with
as few as one concomitant medicine. Thus we should not give aspirin to patients
taking other drugs,” Professor Moore said. However, when more than three
concomitant medicines were being taken then the risk of adverse effects was
greater for paracetamol than for aspirin.
In conclusion, Professor Moore said that in common painful conditions, when
the product labelling was respected, paracetamol and ibuprofen had equal tolerability.
Aspirin as an analgesic
Answering questions after the lecture, Professor Moore said that when comparing
paracetamol and aspirin, then aspirin increased the risk of adverse effects
whatever the dose used was. It was not as well tolerated as paracetamol. In
his opinion, aspirin should be restricted to use for cardiovascular indications
and should no longer be sold over the counter as an analgesic.
Comparing paracetamol and the non-aspirin non-steroidal anti-inflammatory drugs
(NANSAIDs), such as ibuprofen, the perception that NANSAIDs were bound to cause
more adverse effects was a spill-over from long-term, high-dose studies. This
was not applicable to short-term, low-dose use.
“We have indications from the PAIN study that ibuprofen actually has fewer
gastrointestinal effects, such as dyspepsia, than paracetamol, which flies in
the face of accepted knowledge.”
Asked if the study validated the packaging warnings to “Always read the
label”, Professor Moore said that as long as the labelling criteria had
been followed the patient population in the study had been perfectly representative
of the normal population who purchased OTC analgesics. For example, aspirin
sensitivity or asthma had been exclusion criteria for the study.
“Thank God there are pharmacists to help patients read the labels,”
he added.