Rofecoxib / Vioxx

by drdoc on-line

Rofecoxib, VIOXX is a specific COX 2 inhibitor. Inhibition of COX 2 results in therapeutic benefit, in the presence of inflammation, where Cyclooxygenase 2 is induced.

In the process, Cyclooxygenase 1 is not inhibited and therefore the protective function of COX 1 on the stomach is not affected.

The drug is classified as a COXIB class drug and represented the second such drug produced in the therapy of pain and inflammation. Others in the class include CELEBREX and BEXTRA

However for reasons of cardiac side effect - increase risk of myocardial infarction, the drug has been voluntarily withdrawn by the pharmaceutical company - MERCK.

The COXIB class is being evaluated by the FDA.

 

Rofecoxib
Vioxx
The personal opinion of drdoc on-line regarding the COXIB class of drugs

 

STATEMENT / PERSONAL OPINION -  FROM DR GOTLIEB REGARDING CELEBREX / VIOXX / COXIBS

I feel that the COXIB group – the new class of Antiinflammatories - and this especially includes Celebrex and Bextra are getting an unwarranted attack since the withdrawal of the other COXIB, VIOXX.

 It must firstly be noted that VIOXX was voluntarily withdrawn by Merck. The big question is WHY ??? Even the European agency expressed surprise at the action of Merck. I have yet to see data that says the withdrawal was mandatory. Most of us do not understand WHY the company withdrew the product.

 The cardiac issue of COXIBs relates to a potential to enhance clotting.

 We felt that the already existing and known concern that VIOXX was associated with a slightly greater risk of heart attack was long ago identified and debated soon after its development and introduction onto the market. In addition, VIOXX also showed slight increase in Blood pressure in 4-6% of people and 6-8% incidence of fluid oedema. All Antiinflammatories as well as Celebrex also have a potential to retain fluid from kidney side effect. BUT Celebrex showed no difference compared to the old antiinflammatories.  The potential for fluid retention also might aggravate previous heart failure issues independent of heart attack risk.  BUT it was not a new issue for either the new or the old drugs (although it WAS more common with VIOXX). VIOXX was always seen as a problem in high risk cardiac patients.

 Old Antiinflammatories increase risk of bleeding. They also increase risk of stomach ulcers and bleeding.

What the public fail to be informed of and which the medical fraternity has apparent amnesia,  is the HUGE hazard of old Antiinflammatories.

OLD DATA in the PRE COXIB era showed:

 In the UK (population ~ 60 million) data suggested that 150 people are hospitalised every day for gastric bleeds

In 50 of these 150 the stomach bleed or perforation will be directly attributable to old Antiinflammatories.

15 (10%) of these 150 will die  from their complications – EVERY DAY.

 

In the USA Singh a prominent researcher in the field published data as follows

Old Antiinflammatory-related deaths and admissions to hospital

Event

UK

USA

Canada

Annual NSAID prescriptions

25 million

70 million

10 million

NSAID-related admissions

12,000

100,000

3,900

NSAID-related deaths

2,600

16,500

365

  

Importantly old Antiinflammatories can result in risk of ulcer and bleeding WITHIN DAYS of use and the problem of the ulcer is asymptomatic in ˝ of patients prior to sudden complication. Ulcers can occur if the anti-inflammatory is given by mouth, rectal suppository or even injection or topical application. Old Antiinflammatories cause stomach ulcers in 20 percent of patients and 2-3% haemorrhage severely resulting in hospitalisations and potential for death.

 
COXIBS do not produce ulcers to the same degree as Antiinflammatories.

THEY ARE / WERE STREETS AHEAD SAFER in my opinion and in the opinion, I would suggest of most rheumatologists.

The cardiologists do not see the patient in pain and in all likelihood would never be aware that the patients they want us to put on old Antiinflammatories will get stomach ulcers and potentially bleed to death.

 Old Antiinflammatories, by preventing clotting have therefore a degree of bleeding risk. This is utilised for cardiac protection - prevention of heart attack – especially using aspirin. The COXIBs were in fact designed NOT to bleed and to not affect the stomach. They therefore by design offer NO cardiac protection.

 BUT the VIOXX appears to overshoot risk of clotting in some at risk patients.

 This cardiac issue was demonstrated after the VIOXX primary trial showed a 0.4% risk of heart attack versus 0.1% risk after 15-18 months continual use of conventional anti-inflammatory. The trial data included elderly at risk people.  It was therefore already highlighted thereafter that people at risk of heart attacks should have coexisting aspirin in low dose with VIOXX to reduce risk of heart attack.

 In the recent bowel polyp trial that showed risk from VIOXX – the risk was again show only at 15 months continuous use. The population wasn’t looked at – ie number of at risk people. The study was not a study to assess cardiac risk and was not set up to really look at this. Again we note that the withdrawal was done by the company NOT the regulatory agencies.

 Celebrex showed no increase in heart attack risk in early studies and had the same incidence of blood pressure problems and fluid retention as old fashioned Antiinflammatories.  Nevertheless the same caution regarding aspirin in low dose plus Celebrex in high cardiac risk patients was suggested anyway in the past as a precaution based on science of theoretical risk, despite no evidence for increased risk.

 In the recent highlighted study of Celebrex at 4 times usual dose in bowel cancer / bowel polyp study a slight risk was noted after 15 months use. In another identical group NO risk was found. No other Celebrex study really shows risk.

 The interesting thing is that the drug in high dose shrinks precancerous polyps. It seems that the blinded doctors and public under pressure from irrational and almost hysterical media pressure are forgetting EVERYTHING good that these drugs do.

 As a rheumatologist I deal with elderly people in pain EVERY DAY.

I would personally use the newer drugs rather than the old ones. I consider the old ones POISONS, and feel that to prescribe them to elderly people or at risk people is NEGLIGENT. I maintain that the cost of using them is WARRANTED.

I feel that funders don’t like us to use them as they want to simply save money and don’t care a hoot about their patients.

 BUT we also note that all these drugs are for symptoms of arthritis only and we still have to treat the underlying disease. This is a fact we have tried to treat for years. Antiinflammatories do NOTHING to treat the underlying disease.

 The press does not realise the hazards of the older Antiinflammatories

Withdrawal of COXIBS means that we would be consigned to using old Antiinflammatories – essentially old poisons.

The cardiologists might be happy – but I assure you we, and the patients out there, will not be happy when we start to see the massive increase in deaths from stomach bleeding and perforations.

 I think that would be a most unbelievable state of regression to the dark ages.

Only the medical aids would go laughing all the way to the bank making higher profits.

 

·        I believe that the COXIBs should be available albeit with warning regarding cardiovascular risk. We are and have been aware of, and debated, this potential risk for the entire time they have been available.

·        I believe that VIOXX should have been especially red flagged but that it should not have been withdrawn.

·        I certainly believe they should not be used without aspirin if there is significant cardiac risk.

·        I believe that the almost “hysteria” regarding these drugs should be left to rational science to debate and that the practitioners should use the drugs appropriately.

·        I believe that they are a wonderful advance in science and are medications that have revolutionised use of Antiinflammatories for arthritis.

·        I believe that they are safer than the old ant inflammatory drugs which should be called on by the regulatory agencies to produce safety data regarding stomach ulcer and bleeding and mortality risk.

·        It is my belief that Celebrex is not associated with the same degree of risk as VIOXX and represents a much safer alternative to these old poisons

 

Such is the irony – the old drugs would NEVER be passed for human use if they had been developed today. I hate using the old drugs and will do so only with greatest resistance.

  

Dr Gotlieb
Cape Town
Jan 2005.

 

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