Perrigo Company was engaged in developing a pharmaceutical known as
Dayhist D, which contains phenylpropanolamine, or ?PPA?.  What
evidence is there that PPA was known to cause brain strokes or any
bleeding in the brain, prior to 2001, of which Perrigo could therefore
have been aware?

---

Request for Question Clarification by pafalafa-ga on 23 Sep 2005 09:11 PDT

dunfanighy-ga,

There is a fair amount of technical literature that predates 2001, and
that associates PPA with brain strokes and bleeding.

Can you tell me a bit more about what sort of answer you are expecting?

For instance, are you looking simply for a list of references, say,
that look like this:

==========
Kikta DG, Devereaux MW, Chandar K. Intracranial hemorrhages due to
phenylpropanolamine. Stroke. 1985;16:510-512.
==========

In this case, the reference tells you that the medical journal named
'Stroke' had an article in a 1985 issue (number 16, pages 510-512)
directly on the topic you asked about.


If that's the information you need, I would be glad to provide about a
dozen similar reference, or more if I can locate them.


But if you're looking for a different sort of answer, please let me
know how I can best help you.


Thanks,


pafalafa-ga

---

Clarification of Question by dunfanighy-ga on 23 Sep 2005 13:11 PDT

A list of references, like you gave as an example, is what I am
looking for.  Thank you for your assistance.

dunfanighy-ga,

Thanks for clarifying what you're looking for.


Concerns about a link between the use of phenylpropanolamine (as a
decongestant and/or weight loss drug) and strokes/bleeding in the
brain date back at least to the 1970's.  The concerns were large
enough to initially cause the Food and Drug Administration to withhold
final certification for PPA as "generally recognized as safe". 
Eventually, the concerns became concrete enough that FDA announced in
November 2000 that PPA was being withdrawn from the market.

The scientific literature that gave rise to these concerns is well
documented.  I have cited the key journal papers and government
reports in my answer, below. All of the documents are dated before
2001.

I believe this information should fully meet your needs.

However, please don't rate this answer if you find you would like
additional information.  Just post a Request for Clarification to let
me know how I can assist you further, and I am at your service.

All the best,

pafalafa-ga


===============



PHENYLPROPANOLAMINE & RISK OF HEMORRHAGIC STROKE:
Final Report of The Hemorrhagic Stroke Project
Horwitz, R. et al
May 10, 2000
http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3647b1_tab19.doc



Morgan JP. Phenylpropanolamine. A critical analysis of reported
adverse reactions and overdosage Fort Lee, New Jersey: Jack K.
Burgess, Inc.; 1986


Lake CR, Gallant S, Masson E, Miller P. Adverse drug effects
attributed to phenylpropanolamine: A review of 142 case reports.
American Journal of Medicine. 1990;89:195-208


King J. Hypertension and cerebral haemorrhage after Trimolets
ingestion. Medical Journal of Australia. 1979;2:258


Kikta DG, Devereaux MW, Chandar K. Intracranial hemorrhages due to
phenylpropanolamine. Stroke. 1985;16:510-512


Fallis RJ, Fisher M. Cerebral vasculitis and hemorrhage associated
with phenylpropanolamine. Neurology. 1985;35:405-407


Johnson DA, Etter HS, Reeves DM. Stroke and Phenylpropanolamine use.
Lancet. 1983:970


McDowell JR, LeBlanc HJ. Phenylpropanolamine and cerebral hemorrhage.
The Western Journal of Medicine. 1985;142:688-691


Lasagna L. Phenylpropanolamine: A review New York, NY: Wiley & Sons, Inc.; 1988


Maher LM. Postpartum intracranial hemorrhage and phenylpropanolamine
use. Neurology. 1987;37:1686


Forman HP, Levin S, Stewart B, Patel M, Feinstein S. Cerebral
vasculitis and hemorrhage in an adolescent taking diet pills
containing phenylpropanolamine: case report and review of literature.
Pediatrics. 1989;83:737-741


Kase CS, Foster TE, Reed JE, Spatz EL, Girgis GN. Intracerebral
hemorrhage and phenylpropanolamine use. Neurology. 1987;37:399-404


Traynelis VC, Brick JF. Phenylpropanolamine and vasospasm. Neurology. 1986;36:593


Chung Y-T, Hung D-Z, Hsu, C-P, Yang,  D-Y, Wu, T-C. Intracerebral
hemorrhage in a young woman with arteriovenous malformation after
taking diet control pills containing phenylpropanolamine: A case
report. Chinese Medical Journal. 1998;61:432-435


Humberstone PM. Hypertension and cold remedies. British Medical Journal. 1969;i:846


Sloan MA, Kittner MA, Rigamonti D, Price TR. Occurrence of stroke
associated with use/abuse of drugs. Neurology. 1991;41:1358-1364


Bernstein E, Diskant BM. Phenylpropanolamine: a potentially hazardous
drug. Annals of Emergency Medicine. 1982;11:311-315


Jick H, Aselton P, Hunter JR. Phenylpropanolamine and cerebral
haemorrhage. Lancet. 1984:1017


http://www.fda.gov/bbs/topics/ANSWERS/ANS01051.html
FDA ISSUES PUBLIC HEALTH WARNING ON PHENYLPROPANOLAMINE 
November 6, 2000


http://www.fda.gov/cder/drug/infopage/ppa/qa.htm
Questions and Answers
Safety of Phenylpropanolamine
November 6, 2000



http://www.fda.gov/cder/drug/infopage/ppa/science.htm
Food and Drug Administration
Science Background
Safety of Phenylpropanolamine
November 6, 2000


http://www.fda.gov/cder/drug/infopage/ppa/default.htm
Phenylpropanolamine (PPA) Information Page


http://www.fda.gov/ohrms/dockets/ac/00/slides/3647s1d/
Regulatory History of OTC Phenylpropanolamine Hydrochloride (PPA) 
10/30/00
[there are a lot of additional materials at this site, if you're
interested in a deeper history of PPA]



==============


Again, let me know if there's anything more I can do for you.


paf

---

Request for Answer Clarification by dunfanighy-ga on 26 Sep 2005 08:43 PDT

Excellent work.  Can you tell me if there is a web site where I can
view these references and if not, what you might suggest for me to
obtain the articles.  Thank you.

---

Clarification of Answer by pafalafa-ga on 26 Sep 2005 11:07 PDT

Glad to hear that these references met your needs.

The very first link I provided:


http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3647b1_tab19.doc


is a pretty detailed (46 pages) overview of the scientific information
on PPA as of 2000.  Be sure to look this over thoroughly, if you
haven't already.

As for the other papers, I provided links already where they were
available.  However, most of the papers are in journals that you would
need to access either in print form in a medical library, or through
online medical databases that are available to subscribers.

You can find abstracts for some of the articles online at the PubMed
library (a wonderful resource) maintained by the National Institutes
of Health.  For instance, here is the abstract for "Adverse drug
effects attributed to phenylpropanolamine: a review of 142 case
reports":



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2200264&dopt=Citation



Just copy the article titles into the PubMed search box to see if
other abstracts are available.



If you have access to a medical or university library, you should
certainly check with the librarian to see what sort of access to
databases is available.  Even many public libraries have database
access services that should be able to retrieve some, if not all, of
the full version of the listed articles.

 
Wish I could provide you all the articles directly, but as they are
copyright-protected, I'm afraid that's just not allowed!

Let me know if there's anything else I can do for you on this one.


paf

Thank you so much..your generosity is most appreciated.

paf