Salmon never disappoints -- and always has additional (and generally deeper) observations, in the comments. This time, it was in respone to my partial listing of the labeling/warnings as part of the FDA approval, this morning. Do take a look:
. . . .Unforunately, the bold AEs that you put forward are class effects and include class effects known among the older classical antipsychtics. So:
Increased risk of death in elderly. They all have black box warnings now. But we knew this from Zyprexa just look at the summary basis of approval. It was only after Lilly pushed it off-label for years that FDA finally did something.
Asenapine. Avoided studying in the elderly but just place it on the tongue It's so easly) and voila "no more grandma." That of course can be explained away as a class effect or inapproriate administration (not for dementia or not sublingual).
CVAs - strokes, TIAs might be due to those pesky effects on serotonin or also possibly narrowing of arteries and veins -- now wasn't SP looking at intimal media thickness. Yes?
Probably won't be picked up up as anything unusual.
NMS - nasty. Your body cooks itself. Interesting how this appears related to effects on mitochondrial as is effects on diabietes, lipids, etc.. Hard to tease out and hard to tell which drug it's worse with. Oh Well just label it, and hope for the best: asenapine -- just like we do with the others.
TD - long term may be 25% with OD of older antipsychotics like haldol less with appropriate dosing. May be 10-15% with newere atypicals. This this due to better dosing or different receptor profiling. Doesn't matter -- may be better -- but this is largely not life-threatening.
Phen-Fen like cardiovascular toxicity. NOT MENTIONED.HEPATOTOXICITY -- Dose and time dependent -- NOT MENTIONED.
BIRTH DEFECTS - NOT MENTIONED.
Other lesser effects not mentioned.
It's the comparisons and risks in certain populations with the not mentioned I'm really interested in. If they mention a couple of nasty things you've got to wonder why they're so afraid to mention other nasty AEs.
-- Salmon
August 14, 2009 4:24 PM. . . .
I do wonder, though, whether it will matter at all, to prescribing physicians, that the FDA has (as of today) only approved Saphris in acute settings -- not longer term maintenence.
4 comments:
Condor,
It won't matte to physicians in practice settings. To them it's another antipsychotic to try unless they personally get burned. Let's see death in 1 in 100, Maybe 500 patients in your practice maybe 20% on antipsychotics most on antidepressants etc.. Any death may not get followed up on or attrib to CV effects.
As to labeling for short term. That's a joke shizophrenica and bipolar are both considered chronic diseases. As Tom Laughren the head of the Psych group said at the asenapine advisory committee it would be unreasonable to expect someone to switch to a different med after short term use. So he'll likely just label so that if you do it's at your own risk but keep monitoring. HA!
Salmon
Pandora's box opens again, with another drug we will read about in less than 10 years that will have caused death and side effects that could have been prevented. The FDA is a worthless entity, bought and paid for by PhARMA, it is truly disgusting that we do not have any safety net to watch out for our lives except for our own knowledge and savvy reading and research.
Another score for big pharma and Lauhren, and another "take at your own risk" drug approved for the most vulnerable populations: the people who end up in psych wards and long term institutions and end up on these drugs w/out informed consent.
The drug industry has created the myth that SZ and BP are chronic illness only to be made well by a drug. Of course they would say that, it's billions of $$$ at stake.
God forbid someone got well on their own w/out chemicals! (that don't work!)
Thanks for the Saphris discussion here.
Thanks for stoppin' by, Stephany!
For those who may not know it, she runs a first-rate blog, herself -- called Soulful Sepulcher. . . .
Do check in over there, and search "asenapine" -- for much more.
Again, thanks -- and do stop back!
Namaste
PS: I hear ya', Salmon. And I do trust your take.
Thanks for the vote of confidence Condor.
Actually I think that for some people 3 weeks of asenapine for bipolar might be OK. As for acute Schizophrenia, MIGHY be OK too, but when you look at the studies the evidence for efficacy simply does not meet the level needed for approval. I mean when you have a minimum level that's been in place for 40 years and you start going over it, where does it end? You need to draw the line somewhere. In retrospect I think that when Pfizer said they were dropping it because of mixed results this is what they meant. I think they thought they could cover up the side effects. Look it wasn't SP that did the development program that the FDA reviewer claimed was designed to hide safety issues it was Pfizer. SP just picked up Pfizer's garbage.
As for long term safety this one has issues. Phen-fen we won't know how bad for a long time. Liver problems that's for sure. FDA is covering it by claiming no problems seen in clinical trials but when you read the package the reviewer found some indications of elevated bilirubins in a study that used 20 mg doses but it turned out the labs hadn't been submitted with the study. The reviewer asked for the labs but Gwen Zornberg the medical team leader (ex-Pfizer employee until shortly before asenapine was killed) makes a big deal that the OCP reviewer is 'lying' and she was never informed. Yet the e-mail to her with the request is included in the background package.
Then they claim that there were no Hy's law cases but even medical team admits there is a subject with elevated bilirubind 1.7x's normal. Man any elevation in bili with increased LFTs should be of concern even if it doesn't meet a magic number of 2 fold. So maybe the person only has a 7% chance of death instead of 10%. Plus the company says it's dose related and there was some child psychiatrist AC member who kept repeating we need it, we need it, because we have lots of patients in Connecticut who can't swallow. Who can't swallow except kids approximately 8 and younger and the elderly in nursing homes who are demented. Why to me this guy on the AC committee is an advertisement for off label use with dangerous ODing in vulnerable pops yet under the FD&CA that should prohibit approval.
Now SP is saying check blood for the first couple of months because of possible agran class effects but if you look at the actual plots the decreases to neutropenia and deaths didn't occur until after a year.
Truthfully you can't know for sure how bad something will actually be. But when you've worked on as many drugs as I have and you see nasty nasty stuff over and over certain things start to really jump out as really out of the ordinary both in simply being present and in this case the shear numbers of cases.
Plus going through the background package I am simply amazed at how much effort the FDA is putting into simply not looking at the data and trying to push this through no matter what.
Well I guess when you have companies like Pfizer sending PI's to threaten whistleblower's children, maybe some FDA reviewers are afraid of similar things. Then again they probably wouldn't need to be afraid if more than one person would stand up.
Salmon
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