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222
Whelton a. et
al, Am J
Ther. 2000
Searl
By using the Celecoxib
clinical trial program, data
from more than 50
clinical trials,
preponderantly
randomized and controled
ones, were review.
To represent a post hoc
analyses of the renal
safety of celecoxib, using
the safety database
generated during its
clinical development
program.
226
McMorran et
al., CMAJ.
2000
This review is based on
the Canadian Adverse
Drug Reaction
Monitoring Programm
(CADRMP).
Cele. was approved in
April 1999 in Canada.
Between April 14 –
December 23, 1999, the
CADRMP received 220
reports of suspected
adverse drug reactions
associated with Celecoxib
in which 562 adverse
reactions were described.
228
Blondon H.,
Presse Med.
2000
Comments on 2
publications (studies) by
Laine et al. and Emery et
al.
To evaluate gastrotoxicity
of the COX-2 inhibitors
Rofecoxib and Celecoxib.
• Studies include more than 13 000 subjects with a mean age of 62 years in OA and 55
years in RA patients.
• More than 5000 subjects received Celecoxib for 2 years in a long-term, open-label
study at twice the maximum recommanded doseage.
• The overall incidence of renal adverse events after Celecoxib was greater than after
Placebo, but similar to that after NSAIDs.
• Most common events reported after Celecoxib were peripheral edema (2,1%),
hypertension (0,8%), exacerbation of preexisting hypertension (0,6%), and were not
time- or dose-related.
• Peripheral edema was not associated with increase weight or blood pressure.
• No evidence of drug-drug interaction with ACE inhibitors, β-blockers, Ca2+ channel
blockers, or diuretics.
→ Celecoxib is well tolerated by patients who may be at risk for NSAID-induced renal
toxicity, such as the elderly and those with hypertension or preexisting chronic heart
disease.
• 101 serious reports (59 women, age range 21-92). 48% of these reports occurred in
patients aged 70 years or older.
• 6 deaths were associated with Cele. Cause of death and direct relation to drug therapy
unclear in most cases. In all cases recommanded Cele. doses were used. 3 cases involved
concomitant Warfarin use.
• A number of adverse drug reactions included use of other drugs, such as ASA,
Warfarin, glucocortioids and other NSAIDs.
• The 220 reports occurred most frequently in the following organ systems (some appear
in more than one category):
GI 34%, dermatological 34%, body 30%, CNS and peripheral nervous system 19%,
respiratory 12%, psychiatric 12%, metabolic and nutritional 9%, cardiovascular 8%,
urinary system 8% and hematological 7%.
• 12 of 220 reports involved concomitant Warfarin, 11 of these were serious.
• 49 of 75 involving GI disorders were serious.
• 74 reports were of suspected allergic type reaction, 2 of them anaphylactoid reactions,
in 16 reports patient had a previous AE to sulfa drugs.
• Patients at risk for ulcerations with NSAIDs were not excluded in this studies (elder
than 65 years, history of ulcers or GI bleedings).
• The 2 studies confirm that COX-2 inhibitors have less toxicity on gastric mucosa than
traditional NSAIDs. However in clinical practice not the frequency of endoscopically
detected ulcers, but the incidence rate of clinical complications caused by this ulcers is
important.
→ Risk reduction, as well as the probability of GI complications has to be demonstrated
in further studies.
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