[india-drug] Celecoxib and Rofecoxib

[Raj Vaidya <pharmhin@sancharnet.in>]

Celecoxib and Rofecoxib
-----------------------

 http://www.mja.com.au/public/issues/179_08_201003/dow10457_fm-2.html

Editorials

Coax, COX and cola
John S Dowden
MJA 2003; 179 (8): 397-398

Declaring war and prescribing drugs are decisions dependent on
information, and the consequences can be calamitous if that 
information is incomplete or inaccurate.

The calamity which threatened the sustainability of the Pharmaceutical
Benefits Scheme (PBS) in 2000 and 2001 was the volume of prescriptions
for cyclooxygenase (COX)-2 inhibitors. Celecoxib was listed on the 
PBS on 1 August 2000, and by the end of December 2000 over 1.5 million
prescriptions had been written, costing the government more than $76
million.1 By the end of June 2001, the cost had exceeded $160 million.2

In this issue of the Journal (page 403), Kerr and colleagues confirm 
The rapid rise in prescriptions for celecoxib and rofecoxib.3 However, 
Their research cannot explain why the general practitioners in their
study
were so enthusiastic about the new drugs. The doctors' decisions to
prescribe would have been based on the available information. At the
time the drugs were launched in Australia, most of that information
would have been supplied directly or indirectly by the manufacturers.
There was little independent information, and the major randomised
trials of celecoxib (CLASS4) and rofecoxib (VIGOR5) were only 
published in late 2000.

The information from the manufacturers emphasised the relative safety 
Of the new drugs. Compared with non-selective non-steroidal
anti-inflammatory drugs (NSAIDs), the new drugs caused fewer peptic
ulcers. This was an important message, as doctors are often warned 
about the serious gastrointestinal complications of NSAIDs.

There is evidence that some patients were prescribed the new drugs
because they had suffered adverse effects from NSAIDs.6 However, this
did not result in a fall in the prescribing of NSAIDs. The availability
of celecoxib and rofecoxib increased the number of people being 
treated for musculoskeletal disorders,3 suggesting the new drugs were
being
prescribed for conditions beyond the restrictions of the PBS. Such
conditions include non-specific back pain, sprains and sports
injuries.3,6

Some general practitioners believe that COX-2 inhibitors are more
effective than NSAIDs.6 This belief is not confirmed by the clinical
trials, and now even the evidence of their improved safety is being
questioned.7 The published results of VIGOR5 and CLASS4 did not 
include all the data submitted to the United States Food and Drug 
Administration FDA).7,8 The favourable results of CLASS were based on
only the first 6 months of the trial. Analysis of the 12 months' data
that was 
Available to the FDA suggests that celecoxib was associated with a
similar 
Number of ulcer complications as were diclofenac and ibuprofen.7,9 
Similarly, analysis of the complete data for rofecoxib suggests it may
be
associated with an increased risk of cardiovascular events10 and that
serious adverse effects may be more frequent than with naproxen.8

The Therapeutic Goods Administration (TGA) probably had access to the
complete data when it evaluated the drugs for use in Australia. 
However, unlike the FDA data, which are published on its website,8,10
the 
TGA's evaluations are kept secret. Would publication of the TGA's 
Evaluations have alerted Australians to the possible problems with
COX-2 
inhibitors?

Concerns about the drugs only arose months after they were marketed.
Even if they had been aired earlier, they are likely to have been lost
in the excitement surrounding the launch of the drugs. Even the 
Minister for Health and Aged Care put out a press release listing some
of the
benefits of celecoxib and describing it as a "major breakthrough in
arthritis therapy".11

Enthusiasm for the COX-2 inhibitors waned slightly with experience. In
Kerr and colleagues' study, rofecoxib was not embraced to the same
extent as celecoxib. Nearly a third of the patients prescribed
rofecoxib had previously been prescribed celecoxib, suggesting they had
been disappointed by the response.3 Initial enthusiasm followed by a 
slower increase or plateau in prescribing is a common pattern with new 
drugs. If the new drugs are not as good as they were thought to be, can
they justify being twice the price of other NSAIDs?

What coaxes doctors to expose their patients to new products when so
little information is available? I believe that manufacturers'
marketing strategies play on doctors' desire to give their patients the
best possible care. Much of the variation in the prescribing of new
drugs depends on the personality of the doctors, and probably on their
susceptibility to these marketing techniques.12 The prospect of 
reduced adverse effects is likely to have a strong influence on
prescribing practice.

If adopting new drugs quickly actually puts patients at risk,
prescribers must be presented with information to balance the claims of
the drug companies. Achieving this balance is difficult, partly because
independent information (such as Therapeutic guidelines and the
Australian medicines handbook) sometimes comes at a cost, while drug
company information - supported by massive advertising budgets - is
free. In 2000, the amount spent on promoting rofecoxib to Americans
US$160 million) exceeded the advertising budgets for Pepsi and
Budweiser beer.13

In view of the popularity of the new drugs in the United States, 
Perhaps Australia should have been prepared for the demand. If the TGA
had 
Been able to provide its evaluations to publishers of independent
information, they could have prepared prescribing guidelines before the
drugs were marketed.

The National Prescribing Service has recently received funding to
provide doctors with independent information about new additions to 
the PBS. To ensure advertising does not swamp these messages, perhaps 
there should be limits on promotional activities around the date of PBS
listing. While governments are unlikely to ban advertising, they 
could at least mandate that it provides quantitative information about
the
outcomes for patients.14

Another approach to new drugs is not to use them. This will spare
patients from the serious adverse effects which sometimes only emerge
after marketing. The Health Research Group in the US now recommends
waiting 7 years before using a new drug that provides no clear 
advantage over current therapies.15 While this may be an extreme
position, 
there is no need to feel pressured into immediately prescribing the
latest
drug. New is not always better.

Competing interests: Australian Prescriber is published by the 
National Prescribing Service. John Dowden is an unpaid director of
Therapeutic
Guidelines Ltd, and a member of the Editorial Advisory Board of
Australian Medicines Handbook.

1. Analysis section. Pharmaceutical Benefits Branch. PBS 
expenditure and prescriptions January 2000 to December 2000. Available
at:
www.health.gov.au/pbs/general/pubs/pbbexp/pbdec00/index.htm (accessed
Sep 2003).
2. Pharmaceutical Benefits Pricing Authority. Annual report for 
the year ended 30 June 2001. Canberra: AGPS, 2001.
3. Kerr SJ, Mant A, Horn FE, et al. Lessons from early large-scale
adoption of celecoxib and rofecoxib by Australian general
practitioners.
Med J Aust 2003; 179: 403-407.<eMJA full text>
4. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal
toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for
osteoarthritis and rheumatoid arthritis: the CLASS study. A randomized
controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA
2000; 284: 1247-1255. <PubMed>
5. Bombardier C, Laine L, Reicin A, et al. Comparison of upper
gastrointestinal toxicity of rofecoxib and naproxen in patients with
rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343:
1520-1528. <PubMed>
6. Cutts C, LaCase A, Tett S. A clinical audit of the prescribing of
celecoxib and rofecoxib in Australian rural general practice. Br J 
Clin Pharmacol 2002; 54: 522-527. <PubMed>
7. Juni P, Rutjes AW, Dieppe PA. Are selective COX-2 inhibitors
superior to traditional non-steroidal anti-inflammatory drugs? BMJ 
2002; 324: 1287-1288. <PubMed>
8. Budenholzer BR. Rofecoxib did not provide unequivocal benefit 
over traditional NSAIDs [letter]. BMJ 2002; 325: 161. <PubMed>
9. Hrachovec JB, Mora M. Reporting of 6-month vs 12-month data in
clinical trial of celecoxib [letter]. JAMA 2001; 286: 2398. <PubMed>
10. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular 
events associated with selective COX-2 inhibitors. JAMA 2001; 286:
954-959.
PubMed>
11. Wooldridge M. Relief for half a million arthritis sufferers  [media
release]. Canberra: Commonwealth Department of Health and Aged Care; 
1June 2000. Available at 
www.health.gov.au/mediarel/yr2000/mw/mw20048.htm
accessed Sep 2003).
12. Jacoby A, Smith M, Eccles M. A qualitative study to explore
influences on general practitioners' decisions to prescribe new 
drugs. Br J Gen Pract 2003; 53: 120-125. <PubMed>
13. National Institute for Health Care Management Research and
Educational Foundation. Prescription drugs and mass media advertising
2000. Washington: NIHCM Foundation, 2001.
14. Loke TW, Koh FC, Ward JE. Pharmaceutical advertisement claims 
in Australian medical publications. Med J Aust 2002; 177: 291-293.
PubMed><eMJA full text>
15. Health Research Group. New research results on safety of newly
approved drugs causes Health Research Group to extend five-year 
waiting rule to seven years. Worst Pills Best Pills 2002; 8: 41-43.
Australian Prescriber, Deakin, ACT.
John S Dowden, MRCGP, FRACGP, Editor-in-Chief.

Correspondence: Dr John S Dowden, Australian Prescriber, Suite 3/2
Phipps Close, Deakin, ACT 2600. jdowdenATnps.org.au


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Forwarded by:

                      Raj Vaidya, M.Pharm,
                      Community Pharmacist,
                      Hindu Pharmacy,
                      Cunha Rivara Road, P.B.No. 149,
                      Panaji - Goa - India 403001.
                      Tel : 91-832- 2223176, 2432903 (O), 2463926 (R).
                      Email : pharmhin@sancharnet.in


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