By Daniel R. Matlis
Recently, I wrote an article calling for consistent federal regulatory requirements for the practice of compounding. Last month, the US District Court in Texas ruled against the FDA on this mater.
As I made clear in my previous article, I am a supporter of compounding. But in order to protect the public, it is imperative that the combination of FDA approved drugs into new compounds be tested for safety and effectiveness.
Critics may ask: Don’t two FDA approved compounds a safe new compound make?
Not always. Remember Fen-Phen?
Fen-Phen is the combination of fenfluramine or dexfenfluramine (marketed as Redux) and phentermine. All were prescription medications approved by the FDA as appetite suppressants. In 1996, physicians began prescribing the combination of Fen-Phen for use in weight loss programs. During that year, the number of prescriptions for Fen-Phen in the United States exceeded 18 million. The practice is known as “off-label use” since no studies are presented to the FDA to demonstrate the effectiveness or safety of the drugs taken in combination.
In July 1997, the New England Journal of Medicine published an article potentially linking heart valve disease with the use of Fen-Phen. Later in that year, the FDA found that of 291 asymptomatic patients screened, about 30 percent had abnormal valve findings, primarily aortic regurgitation. Based on these data, the manufacturers agreed to withdraw the products from the market and FDA recommended that patients stop taking the drugs.
But this is not a recent phenomenon. In 1937 the manufacturer of “Elixir Sulfanilamide” was seeking a palatable solvent for its new sulfa drug. It decided to use a combination of diethylene glycol and water with raspberry flavoring. Both the drug and the solvent are safe by themselves, but combined create they a lethal mixture that killed 107 people (mostly children) before the drug was recalled recalled. Similar to Fen-Phen the combination compound had not been tested prior to release to the public.
By contrast before the introduction of Caduet, the combination of high blood pressure medicine Norvasc and high cholesterol Lipitor, the manufacturer conducted a double blind placebo controlled clinical trial of 1660 patients to evaluate the safety of the combination therapy.
I believe there are two approaches to address this issue; the first is to required safety testing for new compounds comprised of already approved drugs, regardless of who makes them, big Pharma or your neighborhood pharmacist. This testing should focus on the safety and efficacy of the new compound.
The second alternative is to go the route of informed consent and experimental drugs. I believe that doctors should have the right to prescribe compounded medicines, pharmacist the right to make then and patients the right to take them as long as we can evaluated all known risks and have meaningful informed consent.
By the way, I checked with Andrew, my neighborhood pharmacist, and he will only mix in flavor for my kids prescriptions if the drug has been tested for safety in combination with the flavoring syrup.