- lumiracoxib pulled from Canadian
market following Health Canada review. It was noted that there
were 4 hepatic failure cases at the 100mg/day dose, 2 of which were in
Canada. (Oct 04, 2007)
- lumiracoxib pulled from Australian market due to liver
deaths. (Aug 12, 2007): http://www.tga.gov.au/alerts/prexige.htm
- lumiracoxib - hepatic toxicity link to 200-400mg/day
doses?? (Aug 2007) http://www.crikey.com.au/Politics/20070815-Prexige-and-liver-damage-were-Australian-patients-over-dosed.html;
-Initial Synopsis: Elevation of LFTs with lumiracoxib
was seen in the TARGET trial, and was noted in the Health Canada
"Summary Basis of Decision" (http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/phase1-decision/drug-med/sbd_smd_2007_prexige_102465_e.html).
Potential hepatic toxicity was dose related, seen especially at 200-400mg/day
doses used. Australia has now had some fatalities secondary to liver
failure prompting the withdrawal of the drug from the Australian market.
It is important to note that strengths used in Australia appear to be 200mg or
more. In Canada, prescribing information and availability of the
100mg strength has likely resulted in lower strengths being used relative to
Australia. If using lumiracoxib, it would be prudent to avoid doses
>100mg/day, and add liver function to list of cautions.
- Summary from Rapid Rx & RxFiles (SHR) -
- Summary (pdf) from SDIS (Saskatchewan Drug
Information Service) - Aug07: http://www.rxfiles.ca/acrobat/Lumiracoxib-LFTs-SDIS-07.pdf
Lessons of Vioxx June 23, 2005 NEJM http://content.nejm.org/cgi/content/full/352/25/2576;
Insight on aggressive marketing of Vioxx after studies
indicated risk (cardiovascular) including Merck documents. http://www.democrats.reform.house.gov/story.asp?ID=848
- Cardiovascular News Release Company Link (Oct 04)
"...In the letter to healthcare professionals, Pfizer
also reviewed information about the cardiovascular profile of Bextra. The
information is based on analyses of a comprehensive clinical trial database of
nearly 8,000 patients treated with Bextra for durations ranging from six to 52
weeks. Available clinical information for Bextra suggests there is no increased
risk of cardiovascular thromboembolic events in people treated for
osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, Bextra has
been studied in several surgical settings. In studies in general surgery, Bextra
in combination with the investigational drug parecoxib (an IV formulation)
showed no increased risk of cardiovascular thromboembolic events. However, in
two trials in a high-risk surgery known as coronary artery bypass graft (CABG),
an increase in cardiovascular events was observed in patients receiving Bextra
alone or in combination with parecoxib..." See link for complete
Risk of hospitalization for myocardial infarction among users
of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control
Intern Med. 2005 May 9;165(9):978-84.
NEJM original articles & editorials from the 3 recent
Cox-2 trials Feb 15, 2005 http://content.nejm.org/early_release/index.shtml#2-15
FDA brief shows CV risk with
etoricoxib and uncertainty over lumiracoxib (Food and Drug Administration
Joint Meeting With the Arthritis Advisory Committee and the Drug Safety and Risk
Management Advisory Committee February 16-18, 2005 Briefing Information)
David J Graham, David Campen, et al. Risk of acute
myocardial infarction and sudden cardiac death in patients treated with
cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory
drugs: nested case-control study Lancet Published online January 25, 2005 http://www.thelancet.com/journal/vol365/iss9456/full/llan.365.9456.early_online_publication.32122.1
More Evidence on Cardiovascular Risks of COX-2 Inhibitors (Four studies and an
editorial in the Jan. 24,2005 issue of the Archives of Internal Medicine)
"House of Coxibs" JAMA editorial, Dec 30
Health Canada Advisory - Bextra (valdecoxib), Celebrex
(celecoxib), Mobicox (meloxicam); Dec 22, 2004: http://www.hc-sc.gc.ca/english/protection/warnings/2004/2004_69_e.html
Naproxen warning of cardiac risks following an NIH
sponsored Alzheimer's trial Dec20,2004.
Celebrex (celecoxib) shown to have increase CV risk in one (APC trial) and
not in the other (PreSAP trial) long term cancer trials on Dec 17,2004.
New FDA official Bextra (valdecoxib) contraindication in open heart surgery (CABG)
patients on Dec 9,2004.
BMJ article criticizing Pfizer for delaying release of negative information
about Bextra's heart adverse effects right away Oct 23,
Celebrex will conduct a 4000 patient over ~2yr trial to see if in fact the
drug is safe in high cardiovascular risk osteoarthritis patients (since
currently we do not have an answer for this question) on Oct 18,2004.
Vioxx (rofecoxib) Withdrawal: Not a surprise to InfoPOEMs Nov 2001.
Vioxx FDA submission which included MI data from the VIGOR trial on Feb ,8 2001.