I don’t know. However simply going through labels in the PDR it’s so prevalent that I’m sure that all companies (as well as the FDA toxicologists) must have been aware of these patterns for decades. Even though the toxicologists said I was ‘out of my mind and there was no such signal the first time I realized it’. It’s only a matter of degree of severity. So if you know you have a QT signal and cardiac problem with the drug in humans then you know you probably also have a bone problem.

As for FDA. Last spring Janet Woodcock made an announcement about safety with fluoruquinolone antibiotics (e.g. ciprofloxacin) causing tendon rupturing and stating she wondered why (she was promoting her new safety initiative. Well it took me 5 minutes to figure out it was likely due to effects on BRMP2, which is associated with Pulmonary arterial hypertention, and guess what moxifloxacin if the positive control used for QT studies, and Trovafloxacin has a huge amount of hepatotoxicity (hepatic fibrosis - think Ketek). I’m really disgusted because the drugs I reviewed all had big QT problems along with I then realized problems with PAH and hepatic fibrosis.

I think FDA has known for a long long time and simply wasn’t telling the reviewers. The senior pharm/tox reviewers I found out knew and put it in reviews for other drugs but when I mentioned it in my review the pharm/tox review management dismissed my concerns and indicated in a counter review that I was full of it. I believe that this is falsification of government documents which is a crime. Of course the evidence has been turned over to the proper authorities. You need to contact congress and see why nothing is being done.

Salmon - A soon to be former FDA reviewer and whistleblower

Opinions are my own and do not represent the opinions of the FDA.

Look at the labeling for many drugs and the preclinical fetal development studies you will see a pattern. Poor ossification, especially at the phylanges and where the ribs meet the sternum. It may get worse and show poor skeletal development and small pups, as well as a dimininshed number of pups.

These also will typically go together with human data showing prolongation of the QTc and sometimes hepatic fibrosis.

I suspect that this may have to do with effects on BMRP2 not only because it’s involved in bone growth and formation of fibrotic tissue but also mutations are associated with Pulmonary Arterial Hypertension.

Remember though if it’s labeled in the rabbits you’ll have no recourse to sue when your 88 yo mother places weight on her leg and it snaps and she tumbles down the stairs. The FDA will have reviewed it and says describing a little something about some rabbit digits not forming properly is enough of a warning for physicians to understand.

We wouldn’t want to overwarn anyone (espcecially small boned women) so they might switch to another agent that has less of effect on bone loss.

Salmon

Opinions are my own.