SJS & vasodilatation in modafinil (Provigil brand)
brucealan
As a new member I notice occasional mentions of Stevens-Johnson
Syndrome in regard to that of Provigil brand modafinil. It is in
large part due to pressure upon the FDA and Cephalon Corporation
applied by me that, in 2007, the FDA finally released a few (and only
a few OF MANY) instances of the report of multiple occurrences of SJS,
D.R.E.S.S. and other delayed reaction drug hypersensitivity instances
related specifically to (Provigil) branded modafinil.
Indeed, the reason that I happen to find myself on this discussion
group at all is due to signficant brain damage I suffered as a
consequence of my own personal experience with Provigil modafinil. At
that time, in January 2007, there were no bolded FDA warnings about
any severe consequences of taking Provigil. About 3 weeks after I
began taking it as a potential substitute for the Dexedrine I had
taken for a decade, and one day after my physician had upped my dose
to 400 mg daily, I went into spontaneous distributive shock, which
developed into cardiogenic shock (with no MI), left me on total life
support for at least 10 days (including mechanical ventilation) and
left me to deal with the extended hypoxic brain syndrome which has
left me disabled through to this day and, it would appear,
permanently.
Much has been written about Provigil and SJS (which does not always
manifest with severe skin rashes - mine were relatively mild). Little
has been written about Cephalon Corporation's own studies showing that
1 of 50 of all original test subjects developed vasodilitation, i.e.,
an inordinate expansion of their arterial wall diameters which in most
cases will do no more than lower blood pressure but which, if numerous
self-reports of cardiogenic shock with Provigil are to be believed,
causes death in a great many more people than the FDA has ever owned
up to.
Gwern Branwen
>
> As a new member I notice occasional mentions of Stevens-Johnson
> Syndrome in regard to that of Provigil brand modafinil. It is in
> large part due to pressure upon the FDA and Cephalon Corporation
> applied by me that, in 2007, the FDA finally released a few (and only
> a few OF MANY) instances of the report of multiple occurrences of SJS,
> D.R.E.S.S. and other delayed reaction drug hypersensitivity instances
> related specifically to (Provigil) branded modafinil.
If it was a few of only many, then why did their warning mention only
one case (not a few), and qualify it as a 'possible' case? If a small
trial of a few thousand patients produced 1 case of SJS, then given
the estimated millions of modafinil users since, there ought to be
more than that...
--
gwern
http://www.gwern.net
William Goudy
developed vasodilitation,"
publish them. If they didn't, where do we find them?
Quite curious. Thank you.
On Jun 26, 4:53 pm, Gwern Branwen <gwe...@gmail.com> wrote:
karnautrahl
month user of Modifinal. 200mg per day, self medicating-a matter
requiring no more discussion than suffice to say that I did my
homework first.
Results:
Negative-slight increase in mania at times, with extreme focus.
Very late night paranoia, regularly. This is mild BUT noticeable if I
am up very late and have slept little.
Taken after 9am, I'll be up until 3am.
Positive effects:
Extreme focus-again, this double edged sword.
Verbal fluency increased
Experience of multitasking increased, downside being distractability
when tired
Real world achievements then?
I didn't study piano formally, ever. Using Youtube clips I memorised
the 3rd movement of Moonlight Sonata and am able to play this quite
competently. This memorising in itself is nothing special, half an
hour daily or more of constant repetition. The fact I stuck to it is
the story. This piece is a Grade 8+ in the UK so I understand. I don't
read music and don't have any other basics apart from knowing the
names of the keys on the keyboard.
3 months of spare time work, built a tiny woodwork shop. We didn't do
any carpentry or similar at school; this is my first experience. The
extreme focus ALSO led me down 2k worth of tools and kit. All of which
is used a lot rather than gathering dust as an impulse project.
Workbenches and all sorts got built.
Programming and other skills were added during this time, all work
related.
I covered what would have taken me over 3 years to do, knowing me as I
do, in just 9 months.
Why did I start though?
Daily pain in the ass, work sapping, narcolepsy. Funnily enough,the
indicated usage.
Did my IQ increase though? I've no clue if that can be shown.
Motivation improved instead.
Please note, modifinal is very good with few obvious side effects (on
me at least). Doesn't make it perfect and I cannot be sure of long
term issues.
On Jun 29, 1:11 pm, William Goudy <williamwarrengo...@gmail.com>
wrote:
whoisbambam
not many doctors want to prescribe it long-term, if at all.
if i hadnt worked nites, i doubt i would have ever been able to try
it--i had to pay to go to several doctors because of the repeated
denial. excuse after excuse.
and then only short term--1 refill.
whatever.
karnautrahl
Docs don't know enough about it, scared of potential issues I guess.
Otherwise I would do it official. I don't like other people's hoops in
my way so I just hunted like fuck for a source.
Gwern Branwen
>
> Docs don't know enough about it, scared of potential issues I guess.
> Otherwise I would do it official. I don't like other people's hoops in
> my way so I just hunted like fuck for a source.
If anyone cares, modafinil is an interest of mine and I keep a
collection of online sources:
http://www.gwern.net/Modafinil#suppliers-prices
There's also modafinil on Silk Road, but all the sellers seem to
expect a lot for it.
--
gwern
http://www.gwern.net
Aman Idle
--
You received this message because you are subscribed to the Google Groups "Dual N-Back, Brain Training & Intelligence" group.
To post to this group, send email to brain-t...@googlegroups.com.
To unsubscribe from this group, send email to brain-trainin...@googlegroups.com.
For more options, visit this group at http://groups.google.com/group/brain-training?hl=en.
whoisbambam
were no longer in service.
furthermore, i believe Jonathan told me that thepharmacyexpress did
not deliver, refused to answer emails, etc, months of trying.
so what is a good source on Gwern's site is unknown, esp. when you
factor in the fact that i just watched something on the news over here
wherein they determined that approximately 50% of online drugs were
counterfeit--fakes--resulting in the death of some, and the harm of
others (some ppl had paid a doctor for botox, and the doctor used an
online source, and their faces were grossly deformed, they were placed
on ventilators in the icu for a couple weeks, were paralyzed for
awhile, etc etc)
it would be good to know about recommendations that have been used
over a period of time wherein the medication had the expected effect,
independent of price, etc
On Jun 30, 8:48 am, Gwern Branwen <gwe...@gmail.com> wrote:
Gwern Branwen
> well, if i recall, i went to some of those sites Gwern listed and they
> were no longer in service.
True enough. I mention explicitly that Airsealed seems to be getting
out of modafinil, and there have been various broken links and dead
sites in the past year. (No idea when you used the list.)
> furthermore, i believe Jonathan told me that thepharmacyexpress did
> not deliver, refused to answer emails, etc, months of trying.
What he told me was that he had ordered from EDAndMore; he canceled
his order and got a refund. He mentioned his order had come in 3 days
previously from The Pharmacy Express; he did not mention any concerns
about the TPE modafinil being fake.
> so what is a good source on Gwern's site is unknown, esp. when you
> factor in the fact that i just watched something on the news over here
> wherein they determined that approximately 50% of online drugs were
> counterfeit--fakes--resulting in the death of some, and the harm of
> others (some ppl had paid a doctor for botox, and the doctor used an
> online source, and their faces were grossly deformed, they were placed
> on ventilators in the icu for a couple weeks, were paralyzed for
> awhile, etc etc)
Well, to some extent you can deal with that problem by sending the
product to a lab. I recently learned of a testing service run by
Erowid (see http://www.gwern.net/Modafinil#assaying ) which will tell
you whether modafinil was present or not in a pill (but not its
concentration or whether there are any other problems with the pill
like heavy metals).
--
gwern
http://www.gwern.net
Aman Idle
brucealan
approval was given but rather when Cephalon did subsequent testing on
children for the purpose of obtaining approval to treat ADHD in people
under 18. Cephalon had plans to market it under different name. The
committee which reviewed the application turned it down but it had no
effect upon the already-approved uses of Cephalon for those 18 and
older.
Regarding vasodilitation in 1 out of 50, this appears in Cephalon's
physician Prescribing Notes. See Table 3 Emergent side effects,
showing 2% level of occurrence vs. 0% for placebo. I have always found
it remarkable that vasodilatation was even identifiable and in my
opinion it is used as medical code for the more known term,
hypotension.
http://www.provigil.com/media/PDFs/prescribing_info.pdf
whoisbambam
i thought Jonathan told me that 'the pharmacy express' was not
answering his emails and that it had been over a month.
i guess i could be wrong.
only Jonathan could confirm.
On Jun 30, 4:40 pm, Gwern Branwen <gwe...@gmail.com> wrote:
> > well, if i recall, i went to some of those sites Gwern listed and they
> > were no longer in service.
>
> True enough. I mention explicitly that Airsealed seems to be getting
> out of modafinil, and there have been various broken links and dead
> sites in the past year. (No idea when you used the list.)
>
> > furthermore, i believe Jonathan told me that thepharmacyexpress did
> > not deliver, refused to answer emails, etc, months of trying.
>
> What he told me was that he had ordered from EDAndMore; he canceled
> his order and got a refund. He mentioned his order had come in 3 days
> previously from The Pharmacy Express; he did not mention any concerns
> about the TPE modafinil being fake.
>
> > so what is a good source on Gwern's site is unknown, esp. when you
> > factor in the fact that i just watched something on the news over here
> > wherein they determined that approximately 50% of online drugs were
> > counterfeit--fakes--resulting in the death of some, and the harm of
> > others (some ppl had paid a doctor for botox, and the doctor used an
> > online source, and their faces were grossly deformed, they were placed
> > on ventilators in the icu for a couple weeks, were paralyzed for
> > awhile, etc etc)
>
> Well, to some extent you can deal with that problem by sending the
> product to a lab. I recently learned of a testing service run by
☉
Gwern Branwen
> I believe that this case of SJS was noted, not when original Provigil
> approval was given but rather when Cephalon did subsequent testing on
> children for the purpose of obtaining approval to treat ADHD in people
> under 18. Cephalon had plans to market it under different name. The
> committee which reviewed the application turned it down but it had no
> effect upon the already-approved uses of Cephalon for those 18 and
> older.
If you look at the relevant section of the prescribing material:
> In clinical trials of modafinil, the incidence of rash resulting in discontinuation was approximately 0.8%
(13 per 1,585) in pediatric patients (age <17 years); these rashes
included 1 case of possible Stevens-
Johnson Syndrome (SJS) and 1 case of apparent multi-organ
hypersensitivity reaction. Several of the cases
were associated with fever and other abnormalities (e.g., vomiting,
leukopenia). The median time to rash that
resulted in discontinuation was 13 days. No such cases were observed
among 380 pediatric patients who
received placebo. No serious skin rashes have been reported in adult
clinical trials (0 per 4,264) of modafinil.
Rare cases of serious or life-threatening rash, including SJS, Toxic
Epidermal Necrolysis (TEN), and Drug Rash
with Eosinophilia and Systemic Symptoms (DRESS) have been reported in
adults and children in worldwide
post-marketing experience. The reporting rate of TEN and SJS
associated with modafinil use, which is
generally accepted to be an underestimate due to underreporting,
exceeds the background incidence rate.
Estimates of the background incidence rate for these serious skin
reactions in the general population range
between 1 to 2 cases per million-person years.
As I previously said, that SJS case was and apparently remains
unconfirmed. Notice that in the previous adult trial, with ~3x as many
patients, no rashes whatsoever were reported and certainly no SJS.
With a background incidence rate of 1 to 2 cases per
million-person-years, to be distinguishable, the rate would only have
to rise a little. Too bad they don't tell us exactly how many but
given the reporting biases at play (both for and against reporting),
perhaps the FDA doesn't permit more details; for example, I'd
especially want to know whether those 'adults and children' is really
just 'children'. As it stands, it looks like the problem is primarily
in juveniles.
(Page 4 also seems to imply that those pediatric trials were being
conducted on kids with ADHD. Important? Dunno.)
> Regarding vasodilitation in 1 out of 50, this appears in Cephalon's
> physician Prescribing Notes. See Table 3 Emergent side effects,
> showing 2% level of occurrence vs. 0% for placebo. I have always found
> it remarkable that vasodilatation was even identifiable and in my
> opinion it is used as medical code for the more known term,
> hypotension.
>
> http://www.provigil.com/media/PDFs/prescribing_info.pdf
I'm more amused by how the vasodilation/hypotension increase to 2% of
patients is exactly matched by an increase in hypertension from 1% to
3%. (Modafinil! It does stuff to blood pressure! But don't ask me
what.)
--
gwern
http://www.gwern.net