Rezulin versus Avandia.
With the release of Avandia to compete head to head against Rezulin I think it is wise to discuss all aspects of these two drugs. I for one, believe that Rezulin should do quite well over the next several years
in competition against Avandia. I suspect this opinion is against the grain, but only time will tell.
First, the issue of liver toxicity seems to be a major concern. When Rezulin was first released, it had no liver toxicity warnings. The premarketing studies found no hepatotoxicity in the first 5000 or so patients that used Rezulin. Only later did toxicity appear. Looking back, we now know that the drug should not be used in patients with liver disease. Warner Lambert has since warned physicians not to give the drug to people with liver disease. The risk of serious liver toxicity with monthly liver enzyme checks is 1/55,000. Yes, I have had several patients with liver enzyme elevations. When they occurred, I simply stopped the drug and all was well.
It is not certain whether liver toxicity with this glitazone class of medications is confined to Rezulin or is a class effect of all medications in this class. The next year will help to answer this question because only by using Avandia and gaining clinical experience
with it, will this question be answered. If we assume that it is a class effect at the same rate as Rezulin, then it will take several hundred thousand patients up to one year to find out. We must remember that Rezulin had no liver toxicity when it entered the market because
only 5000 patients were exposed to the 1/55,000 chance of toxicity. My rough guess is that there was less that a 10% chance for toxicity to appear with Rezulin prior to its release because of the small sampling size in relation to the relative risk of liver toxicity.
The question I must ask is whether I should expose my patients to the unknown question of liver toxicity with Avandia. If one were to assume that Avandia is safe, then might one not be traveling the same path that Rezulin patients traveled on. That is, a risk of toxicity that remains hidden until further clinical experience is established with the drug. It seems to me, that the choice is between the devil that we know versus the devil that we do not yet know; Rezulin liver toxicity versus the known or unknown liver toxicity of Avandia. As a prudent physician, I think it will take more time to sort these issues out.
No one knows yet how it will play out, and until we do, I am choosing
Rezulin until further clinical experience is established with Avandia.
A second issue is cost. If all things are equal, then the less expensive drug usually wins out. I have heard some rumors that Avandia will be 20% cheaper than Rezulin. I do not yet know how they will be compared pricewise. If Avandia is significantly less expensive, then it may draw marketshare away from Rezulin. WLA could counter with a price reduction of their own if marketshare is eroded.
In closing, I will continue to use Rezulin until compelling data forces me to change my opinion. That data may come, but at least it is not self evident at the moment of launch for Avandia. I am sure that it will be guerilla warfare for both sales forces over the next two years. As for myself, I remain skeptical of claims made about drugs that are new to the market. |
