New Scrutiny of Drugs in Vioxx’s Family

One major question in pharmacology involves deciding which effects and side effects are unique to a drug, and which are class effects. If a study finds benefit from one ACE inhibitor when treating CHF, should we extrapolate to all ACE inhibitors. If one Cox-2 inhibitor, taken for 18 months, leads to heart attacks and strokes, should we condemn the entire class?

But it is part of Pfizer’s effort to distance itself from Merck’s problems and provide an answer to what has become a central question: Is it a class effect? Do all the drugs in the widely prescribed group known as COX-2 inhibitors carry the same risk as Vioxx?

Millions of patients and billions of dollars in sales could be affected by the answer. Spurred by heavy advertising, COX-2 inhibitors took off faster than any other group of drugs after Celebrex and Vioxx went on sale in 1999. Sales of the two medications, plus those of the newer Bextra, exceeded $6 billion worldwide last year.

Patients discontinuing Vioxx can now decide whether to switch to one of the other COX-2 inhibitors on the market – Celebrex or Bextra, another Pfizer product.

And it is possible that safety concerns could delay approval of two other drugs that are in advanced stages of development – Merck’s Arcoxia and Prexige from Novartis – as well as several further behind.

Merck said last week that it would no longer sell Vioxx because a study showed a higher risk of heart attacks and strokes among patients who had taken it for longer than 18 months. The reason for the greater risk is not known.

Many experts say that Celebrex, the oldest and biggest seller in the category, is somewhat different chemically from Vioxx and has not shown signs of increasing cardiovascular risk in clinical trials or in studies examining medical records of people who have taken the drug.

Dr. Daniel Solomon, a rheumatologist and epidemiologist at Brigham and Women’s Hospital in Boston, said, “I feel comfortable as a clinician, as someone prescribing these drugs, that it has a clean bill of health.” By contrast, he and others said, several studies dating to 2000 pointed to a risk for Vioxx.

But Dr. Eric J. Topol, chairman of the cardiovascular medicine department at the Cleveland Clinic, said that the drugs had not been tested adequately in people with heart disease, even though such people use them. “The real answer is we don’t know,” he said.

So these data give me pause. Cox-2 inhibitors really have only one specific indication – using NSAIDs when patients have had, or are at great risk of, bleeding gastritis. Marketing, especially Direct to Consumer Advertising (DCA), portrayed them as “better” NSAIDs. But NSAIDs are already very good. They have side effects, but so do the Cox-2s.

The “hype” spurred on sales of this class greatly out of proportion to their indications. Many of my golfing buddies took them, assuming that they were better anti-inflammatory drugs. But these drugs still cause sodium retention, renal insult and hypertension. They are not benign drugs. And now we find that at least one has a significant adverse effect when used long term.

I would not take a Cox-2 at this time for more than a short course. But then, I would not have taken these drugs chronically prior to the Vioxx announcement. I will avoid prescribing this class except under very clear, narrow indications.

Because I love to rant about DCA, I would hold Vioxx up as a clear example of the dangers of DCA. DCA tries to spur demand. It did. And now Merck will probably pay. And maybe some patients have paid dearly.

Related posts:

1. Risks and benefits – what if Merck starts selling Vioxx again?
2. New health wikio rankings
3. Public service announcement – beware of C diff
4. Celebrex – as I predicted
5. 17 days at the VA – Day 2

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