Central  South  Dakota  Medical News
The Clinical View
by Phillip Hoffsten
3 November 2004

THE VIOXX MESS:  A VERY COMPLEX PROBLEM

     Last month an arthritis medication called Vioxx (rofecoxib) was withdrawn from the market by Merck Pharmaceutical because of an increased incidence of heart attacks in patients taking this medication.  In the United States alone this was a $2.5 billion loss and Merck stock dropped a full 25% of its value in one day.  Vioxx was a very effective arthritis medication but also had considerable side effects of its own.  When the information became clear that Vioxx not only contributed to higher blood pressure and fluid retention but also contributed to an increase incidence of heart attack, the drug was withdrawn from the market.  The background for this story and what arthritic sufferers should do now is described below.

     The story really begins 40 years ago when it was discovered that aspirin was associated with a decreased likelihood of heart attack and stroke.  That information is still valid today.  Unless a person is allergic to aspirin or simply can’t tolerate it because of other symptoms, the use of 160 mg a day of aspirin is highly recommended for the general population.  Dr. John Vane was given the Nobel Prize in Medicine for his discovery of how aspirin seemed to work.  Specifically, it inhibits a chemical that made platelets stick together to form large blood clots.  This chemical is called thromboxane.  Unfortunately, aspirin also inhibits the production of a chemical called prostacyclin which lowers blood pressure, allows salt to be secreted from the body and prevents blood clots that might cause strokes or heart attacks from ever forming.  Fortunately aspirin’s effect of thromboxane exceeds it effect on prostacyclin and there is benefit from aspirin with a decrease in the incidence of stroke and heart attack.

     But everyone knows that aspirin can cause gastric irritation and, if taken in high doses for a long time, can cause actual stomach ulcers. 

 And yet aspirin is a fairly decent arthritis medication.  So drug companies like Merck and Pfizer did research to see if there was a way to separate the gastric irritation effect of aspirin from its good arthritic treatment effect.   Thus came on the market products such as Vioxx, Celebrex, and Bextra.  As always with new brand name medications, these were very expensive.  But with direct “to the consumer” advertising on television, these products boomed.  They really did seem to have a less irritating effect on the stomach and fewer bleeding ulcers.

     So what went wrong?  The basic flaw in the use of Vioxx, Celebrex and Bextra was their failure to inhibit the production of the bad chemical thromboxane which allowed clots to form that cause heart attacks and strokes.   Like aspirin, Vioxx, Celebrex and Bextra, all cause a decrease in the chemicals that produce arthritis and also cause a decrease in the production of blood-vessel protecting prostacyclin.  Without the decrease of thromboxane as aspirin does, Vioxx allowed for an increased incidence of blood clots in the brain and the heart causing heart attacks and strokes.  At this time Celebrex has been shown not to cause an increased incidence of stroke or heart attack at the 200 mg daily dose.  It is being restudied in light of the Vioxx problem.  Bextra has not been extensively studied in this regard.

     Initially when Vioxx was pulled from the market, I received countless phone calls from patients wanting to know what they could take now for their arthritis.  Is there anything that is safe?  The following points are offered as an answer to these questions:

     1.  Naproxen was the first aspirin-like arthritis drug on the market.  It was touted as better than aspirin in the late 1960’s.  To this time there has not been a more effect medication in the last 40 years.  True, some patients prefer Ibuprofen or ketorolac or a host of other prescription medications that seem to work for the individual patient.  Those are personal choices.  But Aleve, which is an over-the-counter form of naproxen, costs only $ .20 cents a day if a person takes two of the 200-mg. size tablets twice a day.  They are a nickel a tablet.

     2.  Vioxx, Celebrex, and Bextra were never touted to be better arthritis medications than naproxen, ibuprofen or ketorolac.  The advantage of Vioxx, Celebrex and Bextra was simply that they were more protective of the stomach than the older drugs.  Thus, there is not a predictable loss of effectiveness of the old drug as compared to Vioxx, which is now off the market.

     3.  If Aleve or ibuprofen or ketorolac cause gastric irritation, the use of Prilosec OTC will markedly decrease this side effect.  Prilosec OTC (over-the-counter) is relatively expensive but much cheaper than Vioxx.  The use of Naprosyn and Prilosec together is cheaper than Vioxx and will be protective of the stomach in some but not all people.  At this point, I am advising patients to try Aleve 2 tablets twice a day along with Prilosec OTC to treat their arthritis if the pain warrants that kind of intervention.

     4.  Should a person continue to use aspirin if they are taking naproxen, ibuprofen or ketorolac?  In my opinion, patients more than 50 years of age who have significant coronary risk factors should take an aspirin per day no matter what else they do, assuming the aspirin is tolerated.   Whereas naproxen has been shown to treat arthritis very well, it has not been shown to prevent heart attacks as aspirin has.

     5.  Is there an alternative to using the aspirin, ibuprofen, naprosyn, ketorolac, Vioxx, Bextra, Celebrex family of medications?  All of the above drugs are called non-steroidal anti-inflammatory drugs.  For any number of reasons, these drugs are sometimes not effective for an individual person or they may cause side effects that an individual finds unacceptable.  In that case if arthritic pain is still a problem, I recommend that the person try a product called propoxyphene/acetaminophen.  The trade name of this product is called Darvocet and it comes as a generic.  The cost is around $ .40 cents a pill and very frequently 3 pills per day will very effectively treat a person’s arthritic pain. The beauty of this drug is it acts on command.  You take it when you hurt and it makes the pain better.  It does not have side-effect dangers of heart attack or stroke, does not cause fluid retention, does not cause hypertension and does not cause gastric irritation.

     Arthritis pain can be severe and debilitating.  It seems a shame that in order to treat it, one trades pain relief for potential side effects and complications.  But that is the nature of medicine.  No medication is completely side effect free.  The healthcare providers at your local clinics are aware of the risks and benefits of medication schedules. They can be a significant help in alleviating arthritic pain while providing the safest medication schedule.