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MEDIA STATEMENT
10th October 2007
IIF response to:-
Loke et al. Meta-analysis: Gastrointestinal bleeding due to interaction
between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory
drugs. (Alimentary Pharmacology and Therapeutics Online)
The International Ibuprofen Foundation (IIF) has noted the above paper
and is grateful to the authors for this detailed meta analysis which includes
clinical papers already published in the literature.
What is the new evidence?
Loke et al have used a rigorous statistical technique to analyse four
studies (published between 1999 and 2007) that evaluated the risk of gastrointestinal
bleeding in patients treated with an SSRI antidepressant and an NSAID
at the same time. By pooling data from several studies, this technique
provides more reliable conclusions than is possible with a single study.
Loke et al also analysed individual case studies, both published and unpublished.
In summary, they estimate that the likelihood of gastrointestinal bleeding
is increased by a factor of 6.33 compared with someone of the same age
who is not taking either medicine. This increase in risk is greater than
that associated with either SSRIs (2.36) or NSAIDs (3.16) taken alone.
However, there was some variability between the findings of the studies
they analysed; after adjusting for this, the estimated risk was 4.46 for
SSRIs and NSAIDs taken together. These findings were broadly confirmed
by the case studies.
Their data suggests that, for every 82 people aged over 50 taking both
an SSRI and an NSAID for a year, one would experience an upper gastrointestinal
haemorrhage. Considering only those who had previously had such an event
and were therefore at increased baseline risk, there would be one event
per year per 70 patients treated with both drugs.
What do we already know about this problem?
Older people are at increased risk of gastrointestinal bleeding even without
drug treatment: Loke et al say the background level of such events is
23 per 10,000 per year. It was already well established that SSRIs increase
the risk of gastrointestinal bleeding in elderly people (1),(2) and three
of the four studies included in the new analysis had concluded that taking
an SSRIs and an NSAID together pose an increased risk.(2-4) This data
is already covered in product literature and the BNF.
In 2006, US researchers analysed four retrospective studies and estimated
that the risk of gastrointestinal bleeding was increased by a factor of
3.3 - 15.6 in people taking an NSAID plus an SSRI compared with people
taking neither.(5) They warned: "Clinicians must take care to avoid
these negative outcomes by altering NSAID or SSRI therapy, or by providing
ulcer-protective drugs".
The contribution of Loke et al is to provide a statistically more reliable
estimate of the risk associated with an accepted problem.
What are the implications for OTC ibuprofen?
Loke et al do not provide any information on how NSAIDs were used in the
studies they analysed, or which NSAIDs were involved; however, the NSAIDs
were prescribed. Analysing 22 individual cases reported to drug manufacturers,
they found that the median time for gastrointestinal bleeding to occur
was 25 weeks; 5 cases occurred within one month.
The IIF wishes to reemphasise that Ibuprofen used in the short-term at
the low dose available over the counter (OTC)* has a long history of use
as a safe and effective medicine. The general public can remain reassured
of this when purchasing ibuprofen for minor ailments and so have no concerns
about its safety.
Scientific evidence (6-8) shows that, when used as directed, ibuprofen
is a safe, well-tolerated medicine. In the majority of studies, where
NSAIDs have been compared, ibuprofen has consistently been associated
with the lowest risk of GI complications.
* The OTC dose of ibuprofen is
a maximum of 1,200mg per day for up to 10 days.
ENDS
References
1. van Walraven C, Mamdani MM, Wells PS, Williams JI. Inhibition of serotonin
reuptake by antidepressants and upper gastrointestinal bleeding in elderly
patients: retrospective cohort study. Br Med J 2001;323:1-6
2. de Abajo FJ, García Rodríguez LA, Montero D. Association
between selective serotonin reuptake inhibitors and upper gastrointestinal
bleeding: population based case-control study. Br Med J 1999;319:1106-9
3. Dalton SO, Johansen C, Mellemkjaer L, et al. Use of selective serotonin
reuptake inhibitors and risk of upper gastrointestinal tract bleeding:
A
population-based cohort study. Arch Intern Med 2003 Jan 13;163(1):59-64.
4. Helin-Salmivaara A, Huttunen T, Grönroos JM, Klaukka T, Huupponen
R.
Risk of serious upper gastrointestinal events with concurrent use of NSAIDs
and SSRIs: a case-control study in the general population. Eur J Clin
Pharmacol. 2007 Apr;63(4):403-8.
5. Mort JR, Aparasu RR, Baer RK. Interaction between selective serotonin
reuptake inhibitors and nonsteroidal antiinflammatory drugs: review of
the literature. Pharmacotherapy 2006;26:1307-13
6. Moore N, van Ganse E, Le Parc J-M et al. The PAIN study: paracetamol,
aspirin and ibuprofen new tolerability study. A large-scale, randomised
clinical trial comparing the tolerability of aspirin, ibuprofen and paracetamol
for short-term analgesia. Clin Drug Invest 1999;18:89-98
7. Rainsford KD, Roberts SC, Brown S. Ibuprofen and paracetamol: relative
safety in non-prescription dosages. J Pharm Pharmacol 1997;49:345-76
8. Fries JF, Bruce B. Rates of serious gastrointestinal events from low
dose use of acetylsalicylic acid, acetaminophen, and ibuprofen in patients
with osteoarthritis and rheumatoid arthritis. J Rheumatol 2003;30:2226-33
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