E-DRUG: Differences in Drug Datasheets (3)
Andrew Herxheimer and some others did work in this area a number of years
ago I believe looking at the difference in data sheets for NSAIDs. I think
that this work was published in Pharmaceutical Journal. If Andrew is on this
discussion group perhaps he could fill in more details.
[the moderator has copied an editorial by Andrew below, it is from BMJ 1998]
Joel Lexchin MD
121 Walmer Rd.
Canada M5R 2X8
E mail: firstname.lastname@example.org
BMJ 1998;316:492 (14 February)
Many NSAID users who bleed don't know when to stop
Uncomprehending "adherence" is dangerous
Upper gastrointestinal bleeding and perforation are common and serious adverse
effects of non-steroidal anti-inflammatory drugs. About a third of all ulcer
bleeding in older people is associated with these drugs1 2; the same may apply
to perforation. The most important predisposing influences are the type and
dose of drug (and use of two non-steroidal anti-inflammatory agents together),
which can increase the risk up to 20-fold. Other risk factors include prior
ulcer,3 anticoagulants, systemic corticosteroids,4 smoking,5 alcohol
consumption,6 and old age.1 3 Some of these are independent, so that treatment
with non-steroidal anti-inflammatory drugs increases an already high risk. As
we look for ways of lowering the risk of bleeding in patients using non-steroid
anti-inflammatory drugs, an ingenious investigation from Newcastle offers a new
Wynne and Long studied 50 consecutive patients admitted to hospital with an
acute gastrointestinal bleed who had taken any of four commonly used
non-steroidal anti-inflammatory drugs in the preceding three days and 100
controls from local practices?matched for age, sex, drug, and dosage?who had
not bled.6 All patients were visited at home by a nurse to assess their
knowledge of their arthritis treatment. The nurse asked whether the patients
had received any information about possible side effects of the drug, if so
from where, and what they had been advised to do if side effects occurred. She
asked the index patients, "Did you have any stomach problems, such as
indigestion or pain before your stomach bleed?" and the controls, "Have you had
any stomach problems, such as indigestion or pain?" The nurse also asked the
patients to estimate how much of the prescribed dose they actually took and, if
it was less than prescribed, why so.
It turned out not only that the patients who had bled into the gut knew less
about the side effects of their drugs or what to do when they occurred than did
the controls but also that they stuck more closely to the prescribed dosage.
Fewer index patients (16%) than controls (41%) remembered having been told of
the potential side effects or about what to do if they developed an adverse
effect (4% v 21%). "Full compliance" was commoner among the index patients
(96%) than among the controls (70%). Furthermore, 18 (36%) of the index
patients had had epigastric pain before the bleed and all but two had continued
to take the drug, whereas only 15 (15%) of the controls had had dyspepsia, of
whom 10 had reduced their intake.
Perhaps this study should be interpreted cautiously: it was fairly small;
patients with a complication may be more likely to claim that they were
inadequately warned; and dyspepsia is widely accepted to be a poor guide to
ulceration?though this has not been critically examined in relation to use of
non-steroidal anti-inflammatory drugs. Nevertheless, it looks as if ignorance
about side effects led to failure to recognise warning symptoms and to
inappropriate compliance. Ten of the 16 patients who had pain but continued
their drug and bled might not have bled if they had stopped the drug at once.
Ten bleeds fewer out of 50 would be a useful reduction.
As the authors say, we need effective methods of increasing patients' knowledge
and understanding of side effects?and this applies not only to non-steroidal
anti-inflammatory drugs. In particular we must try to ensure that patients and
doctors share the same goals in medicine taking and move from compliance to
concordance.7 8 Establishing what works best will take time and effort. But for
a start, whenever doctors, pharmacists, and nurses see a patient who is using a
non-steroidal anti-inflammatory drug they could check whether the patient
understands two things. Firstly, they should understand that the drug is for
symptomatic relief and should be used only when arthritic pain or inflammation
is troublesome. Some patients with severe rheumatoid arthritis may have to take
the drug all the time, but most others do not. Prescribers and patients should
not aim at complete relief by using high doses because this increases the risk
of damaging the gut; they should accept partial relief. Secondly, they should
know that stomach pain or indigestion is a signal to stop taking the drug if
possible; if this is not possible, they and the doctor should consider whether
to reduce the dose.
Of 21 patient information leaflets for oral non-steroidal anti-inflammatory
drugs, nine tell the patient to stop taking the drug if such symptoms occur;
the others say "tell your doctor" or something similar.* The points about
symptomatic relief and using moderate doses whenever possible are almost
completely absent. The Medicines Control Agency should insist that the leaflets
are clear and consistent on these points.
Andrew Herxheimer, Adviser a
a Health Action International?Europe, 9 Park Crescent, London N3 2NL
*I did the survey in spring 1997 and I thank Andrew King and David Scott for
obtaining leaflets not in the ABPI Compendium of Patient Information Leaflets
1. Somerville K, Faulkner G, Langman M. Non-steroidal anti-inflammatory drugs
and bleeding peptic ulcer. Lancet 1986;i:462-4.
2. Faulkner G, Prichard P, Somerville K, Langman MJS. Aspirin and bleeding
ulcers in the elderly. BMJ 1988;297:1311-3.
3. Laporte J-R, Carné X, Vidal X, Moreno V, Juan J. Upper gastrointestinal
bleeding in relation to previous use of analgesics and non-steroidal
anti-inflammatory drugs. Lancet 1991;337:85-9.
4. Piper OM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic
ulcer disease: role of non-steroidal anti-inflammatory drugs. Ann Intern Med
5. Henry D, Dobson A, Turner C. Variability in the risk of major
gastrointestinal complications from non-steroidal anti-inflammatory drugs.
6. Wynne HA, Long A. Patient awareness of the adverse effects of non-steroidal
anti-inflammatory drugs (NSAIDs). Br J Clin Pharmacol 1996;42:253-6.
7. Mullen PD. Compliance becomes concordance. BMJ 1997;314:691-2.[Free]
8. Marinker M. From compliance to concordance: achieving shared goals in
medicine taking. BMJ 1997;314:747-8.[Free]