My eyes almost popped out of my head when I read this article (here) concerning FDA’s move to place hydroxychloroquine in Category 1 for use by compounders based on a potential drug shortage created mostly by the administration’s hope that the drug may have some effect on COVID 19. It is one thing to use FDA-approved drug products to treat off labeled conditions, but this, in my opinion, is going too far.
FDA-approved hydroxychloroquine sulfate tablets have a lot of warnings, and there are some potential serious adverse events associated with the drug’s use such as irreversible retinal damage in some patients who had received hydroxychloroquine sulfate. Significant risk factors for retinal damage include daily doses of hydroxychloroquine sulfate greater than 6.5 mg/kg (5 mg/kg base) of actual body weight, life-threatening and fatal cardiomyopathy have been reported with the use of hydroxychloroquine, as well as with use of chloroquine. These drugs prolong the heart’s QT interval, which can lead to potentially fatal ventricular arrhythmias and torsades de pointes which has been reported in patients taking the drugs.
FDA drug products that are multisource must be shown to be bioequivalent to each other, meaning that the rate and extent of absorption are the same. This assures that approved products of the same drug, including strength, dosage form and active ingredient, can be expected to have the same therapeutic effect and adverse event profile when taken in the same molar dose as the innovator or brand name product. There is no bioequivalence testing performed or required for compounded drugs. This is a critical issue when considering a drug with significant adverse events, especially for a drug where the adverse events are dose-mediated and where toxic levels can be close to therapeutic levels.
There are a lot of good compounders out there, but even the best cannot assure the bioavailability of compounded solid oral dosage forms so, just imagine if a pharmacy or outsourcing compounder unwittingly makes a drug that is 20% or 50% more bioavailable than the currently approved products. I am a pharmacist as well as a former regulator and this scares the you-know-what out of me and it should scare you too! I recognize the need to use compounders to assist in drug shortage issues, but don’t you think the time to use them is certainly not when the drug has such potentially devastating adverse events associated with the approved products for which the bioavailability is known?
