I think the bottom line is even that the experts don't know everything. The Univ. of Arizona's work in this area is ongoing, meaning they add to it all the time. I remember many years ago how simple their website was. Not anymore!

Quinidine was popular 30 yrs ago... long before the new waves of sophisticated drugs arrived. Once the liver enzyme research heated up, and the new drugs became available, the QT and interaction data started to be compiled.

In fact the story behind how Seldane was discovered to be a deadly risk is pretty interesting. Seldane had been on the market for over 10 yrs and was losing its patent. Rugby generic already had it available and it was being dispensed. A professor at Georgetown Medical school discovered this cardiac sudden death thing by accident (meaning he wasn't looking for it). He started investigating this, and a brief period during which doctors were notified about this serious interaction and cardiac QT potential. They ignored the warning letters, and I remember a news show like 20/20 or Dateline going to pharmacies in NY with RXs for both Seldane and Erythromycin and none of the pharmacists caught it either, or called the doctors to change the combo. Since the parent company already had the active metabolite of Seldane ready to market (Allegra), it dropped its drug application for Seldane, which then made generics illegal in US. (generic Seldane is still available in other countries today however). And Allegra does not have this interaction potential either.

Some people genetically just cannot handle drug metabolism well. And it is difficult to predict still today. Not everyone who took Seldane with Erythromycin died...but many did, and it was attributed to "some other reason".

What I think the harmful potential of this drug combo is involves several potential areas for harm.
1)Used by people with genetic long QT situations, it is a risk. Something to watch and monitor and measure at the doctor's office. The FDA is putting the responsibility on the doctor.

2) people without genetic QT issues, can still have problems. The actual QT may occur when this drug combo is mixed with other medication. The Univ of Arizona has lists of high risk to low risk medications that when combined may affect heart rhythm. Anna Nicole Smith's son Daniel died from a combo of Lexapro and methadone...no overdoses, just a combo affecting his heart.

3) People without QT issues, can still have one if they become low in potassium and magnesium. Both these electrolytes affect conductivity in the heart. So throwing up alot, or having alot of diarrhea or not eating enough foods with adequate magnesium in them (very common in US)... can combine with this drug combo, to cause issues. Also many drugs may deplete potassium and magnesium. For example, diabetics excrete magnesium from the urine daily. Steroids deplete both electrolytes as well as diuretics.

4) this drug combo will interact with other drugs based on quinidine's effects on drug metabolism. That you have to look up on the charts, where quinidine is listed as a substrate inhibitor.

5) foods like grapefruit cannot be taken with this drug... because of its liver metabolism. Grapefruit paralyzes the GI lining which contains some of the Cytochrome P450 enzymes, so that a dose of drug appears higher in the blood than when grapefruit is not consumed.

So you see it is hard to predict what will happen. But for those who take many drugs, the risk increases. This is why having the charts is important. Some DNA testing sites have downloads for these enzyme systems, since they sell the tests. They also breakdown % based on ethnic race distribution if that is a factor. Some drugs are metabolized differently in Asians vs Africans vs Caucasians.