ASK DR. BAUGHAN                                      March 24, 2000

BEAT UP DRUGS

Feeling sympathy for a drug company is about as difficult as sympathy for a managed care company, but in the new millenium, several drugs have taken a beating.  I recently wrote about the woes Propulsid has faced.  This week, Cardura and Rezulin are getting knocked about, and Rezulin may be down for the count.

The Cardura (doxazosin) story has a few interesting twists in how a decent drug may get a bad rep.  Cardura is a blood pressure medicine of the “alpha blocker” family.  Other members of the same family include prazosin (Minipress) and Hytrin.  They have also been found to be helpful in relieving some of the symptoms of BPH (Benign Prostatic Hypertrophy), a common ailment of older men.  They work pretty well to lower blood pressure and for BPH.

An on-going question in medicine is, “Which types of blood pressure medicine are best to start with?”  The reason for treating blood pressure is to decrease the risk of heart attacks, strokes and congestive heart failure.  A currently on-going study involving over 40,000 patients is called the ALLHAT study (an acronym for Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial).  This study compared a calcium-channel blocker (Norvasc), an ACE Inhibitor (Lisinopril), Cardura, and a diuretic.  After running the study for several years, the researchers found that patients in one group were having congestive heart failure (CHF) at higher rates than another group.  They then opened the code and found that the patients on Cardura were having more CHF than the diuretic group.  This does not mean that Cardura was causing CHF, since there is a higher risk of getting CHF without any treatment.  But it was not doing as good, BY ITSELF, in preventing CHF.  Many patients are on more than one medicine for hypertension.  Interestingly, if a person took both Cardura and a diuretic, the risk was no different than taking a diuretic alone.  But if the blood pressure was lower using both medicines, presumably there will be less risk of heart attack and stroke long term.

There is also no evidence that patients taking Cardura for BPH are at any higher risk for congestive heart failure.  So patients taking Cardura by itself for hypertension may want to discuss with their providers whether a change is warranted if they are able to tolerate other types of blood pressure medicines, but if they are taking it for BPH, or in combination with other medicines, they do NOT have to consider it a “bad” drug and get off it immediately.  The worst thing to do is stop the drug and not consult your doctor.

Rezulin is the prototype of a family of drugs used in diabetes.  It has been followed closely because of concerns that it may cause liver damage.  It has been used in Europe for years.  It has allowed thousands of people to remain on pills instead of taking insulin.  Last year a warning was issued urging anyone taking it to get a monthly blood test to ensure that liver problems were not developing.  The FDA finally decided that enough cases had surfaced that they should pull it off the market.  The number of deaths linked to Rezulin is around 60, compared with the thousands taking it.  Establishing a threshold for what is too much risk is tricky when it is so difficult to monitor the thousands of people necessary to find a pattern in a few. 

There are two alternatives to Rezulin in the same family, Avandia and Aptos.  Both are newer to the market than Rezulin.  Both “seem” to have less liver risk, so patients on Rezulin may be switched to them.  With wider usage, time will tell if the same problems surface with them.

An interesting footnote to diabetes management was the history of another family of medicines, phenformins, that were taken off the market in the early 1980s.  Fifteen years went by before a modification in phenformin was re-introduced, Glucophage, which is now widely used safely.