Some of the drugs on the list are very familiar to me. Meridia, Redux were developed for obesity treatment. Redux had the same liabilities as fenfluramine whic

Some of the drugs on the list are very familiar to me. Meridia, Redux were developed for obesity treatment. Redux had the same liabilities as fenfluramine which back in the 90's was being very carelessly prescribed by inexperienced practitioners resulting in unnecessary fatal outcomes. OTOH fenfluramine had been on the market for decades without notable difficulties until overprescribed. Similarly PPA was a very old drug but bad outcomes were noticed after it was used extensively without proper medical supervison. Serzone was a different story. It was an unusual antidepressant drug insofar as it had many active and a great many inactive metabolites which made its effects less predictable. After millions of prescriptions worldwide, a handful of fatalities associated with hepatic toxicity slowly came to light. When a Canadian study reported 18 such cases the pattern became clear and ultimately Serzone use was discontinued. However it's not unprecedented that drugs can be metabolized to compounds that are extremely toxic to the liver. It is a very rare phenomenon because having the exact genetically determined combination of liver enzymes to produce the toxic product is strictly a matter of chance. There's a huge number of cytochrome enzymes that are highly variable subject to random genetic variation. Once in a while a person is born with a particular set of unfavorable variants when in comes to a specific compound. The issue is that very rare events, e.g., 1/100000 cases requires huge number of exposures before the adverse events can be correlated with use of the drug. The FDA tries to assure safety, but prior to marketing it's not possible to rule out the "one in a million" sort of event. That's the reason it's vitally important to report side-effects, especially serious or life-threatening incidents to the FDA. No question that all drugs have side-effects and therefore should be used knowledgeably and conservatively. But we must remain vigilant, there is always a chance of unanticipated outcomes, often for the worse, though occasionally for the better.