[tri-med] Strattera Side Effects Update

I finally got a 2 page letter from Eli Lilley Co regarding Penny's Vision
concerns, and their 26 page "official" report on the known & suspected side
effects of Strattera.

According to the company's letter to me:

"The event maps to the MedDRA term(s) of: blindness, transient blindness,
tunnel vision and blurred vision."

"The MedDRA term(s) mentioned above have been rarely reported in the
spontaneous
adverse event database, which is defined as an adverse event that occurs at
an
estimated rate of less than 0.01% according to the reporting system
information.
These data do not represent the rate of occurrence for an adverse event in a
treated population; they merely represent the rate of reporting of a
particular
adverse event to the company."

"This information was valid for data received up through November 26, 2005."

So Annie, your brand new 2007 Nursing Drug book, may not list these vision
problems as a possible side effect, but the company has known about them for
at
least a year and a half now.

Penny and I are both of the opinion that if parents actually read even a
portion
of this 26 page report there wouldn't be nearly as many kids taking this
drug as
there currently are.  And it doesn't even mention the vision problems above
in
their letter either.

Some hi-lites from the report:

Page #2

"...a half life of about 5 hours.  A fraction of the population (about 7% of
Caucasians and 2% of African Americans) are poor metabolizers (PMs) of
CYP2D6
metabolized drugs" (i.e. Strattera). "These individuals have reduced
activity in
this pathway resulting in...5-fold higher peak plasma concentrations, and
slower
elimination (plasma half-life of about 24 hours)...compared with people with
normal activity..."

This could mean that IF Devon is a "poor metabolizer" (and the odds of that
are
pretty darn good as unfortunately we all know who have one of these
kiddo's), he
would have been getting his next dose of Strattera just about the time the
previous
one had only just hit the half-life mark.  So Lord only knows just how much
"over
medicated" his blood levels rose to over the course of these weeks of
Strattera
trial.  Upping his odds of course for developing an "adverse event".

Page #6

Talking about ADHD treatment: "Drug treatment may not be indicated for all
patients
with this syndrome." And "The effectiveness of Strattera for long-term use,
i.e.,
for more than 9 weeks in a child and adolescent patients and 10 weeks in
adult
patients, has not been systematically evaluated in controlled trials.
Therefore,
the physician who elects to use Strattera for extended periods should
periodically
reevaluate the long-term usefulness of the drug for the individual
patient..."

Page #7

"Narrow Angle Glaucoma
In clinical trials, Strattera use was associated with an increase risk of
mydriasis"
(abnormal dilation of the pupil) "and therefore its use is not recommended
in
patients with narrow angle glaucoma."

The reason I included the above quote is because Penny and I think it may
well be
relevant in Devon's case.  Not that he necessarily has Narrow Angle
Glaucoma, as
he's never actually been tested for it, but that we think the drug may be
effecting
his pupil dilation.  Devon actually appears to have the "transient
blindness" listed
in Lilley's letter to me.  Some times, as in last Saturday morning, he seems
to see
just fine, but at others he appears to have suffered a total or partial set
back.
However, we think those set backs may just be only after he's been outside
in bright
sunlight.  Time will tell.

Page #8

"Postmarking reports indicate that Strattera can cause severe liver injury
in rare
cases.  Although no evidence of liver injury was detected in clinical trials
of about
6000 patients, there have been two reported cases of markedly elevated
hepatic enzymes
and bilirubin, in the absence of other obvious explanatory factors, out of
more than 2
million patients during the first two years of postmarketing
experience...and was
followed by recovery upon drug discontinuance providing evidence that the
Strattera
caused the liver injury...laboratory abnormalities may continue to worsen
for several
weeks after drug is stopped...The patients described above recovered from
liver injury,
and did not require a liver transplant.  However, in a small percentage of
patients,
severe drug-related liver injury may progress to acute liver failure
resulting in death
or the need for a liver transplant."

The "good news" there is that even the postmarketing patients that they've
seen thus far
who have developed "serious liver injury" totally recovered after the drug
was discontinued.
So, there IS an excellent chance that Devon will eventually regain his lost
vision too
once the drug is totally out of his system.

I'm not going to go into all of the "Serious Cardiac Events" for children &
adolescents
also listed on this page, but this is part of the reason why I will NEVER
let Miss P's
neuro talk me into a Strattera trial.

Pages #9 & 10

Under "Precautions", "General" talks about the pediatric increases in both
systolic &
diastolic blood pressures as well as heart rate.

"At the final study visit before drug discontinuance, 3.6% of
Strattera-treated subjects
had heart rate increases of at least 25 beats/minute and a heart rate of at
least 110
beats/minute...The mean heart rate increase...in poor metabolizer (PM)
patients 10.4
beat/minute."

They do make a point of stressing that "no pediatric patients had these
measurements at
more then one visit", but considering it was "the last visit" that's not
really saying
much!  And...

"At the final study visit before drug discontinuance, 6.8% of
Strattera-treated
pediatric subjects had high systolic blood pressure measurements...,
2.8%...had high
diastolic blood pressure measurements...(High systolic and diastolic blood
pressure
measurements were defined as those exceeding the 95th percentile, stratified
by age,
gender, and height percentile - National High Blood Pressure Education
Working Group
on Hypertension Control in Children and Adolescents.)"

"Effects on Growth --- ...In general, the weight and height gain of
pediatric patients
treated with Strattera lags behind that predicted by normative population
data for the
first 9-12 months of treatment.  Subsequently, weight gain rebounds and at
about 3 years
of treatment, patients treated with Strattera have gained 17.9 kg on
average, 0.5 kg
more than predicted by their baseline data.  After about 12 months, gains in
height
stabilizes, and at 3 years, patients treated with Strattera have gained 19.4
cm on
average, 0.4 cm less than predicted by their baseline data."

So it appears Strattera stunts their growth and adds weight in addition to
everything
else!

Page #11

"Priapism"

Do we all recognize this term for the Cialis commercials?

"Rare postmarketing cases of priapism, defined as painful and nonpainful
penile erection
lasting more than 4 hours, have been reported for pediatric and adult
patients treated
with Strattera.  The erections resolved in cases in which follow-up
information was
available, some following discontinuance of Strattera.  Prompt medical
attention is
required in the event of suspected priapism."

Gee folks, don't we all just want our male pediatric triers sent home from
school with a
nurse's note on this one?

Page #12

"Strattera is an ocular irritant.  Strattera capsules are not intended to be
opened.  In
the event of capsule content coming in contact with the eye, the effected
eye should be
flushed immediately with water, and medical advice obtained."

It is stressed repeatedly in the literature that capsules are NOT to be
opened, making it
harder to administer to rare trisomy patients.

Also under "Laboratory Tests".  "Routine laboratory tests are not required."

Now that's a scary comment, considering the possibility of "severe liver
injury" listed
back on page #8!

Pages #13 & 14 relate to animal testing.  They were of course given higher
doses/per body
weight then would be 'normal' in human subjects.  But I'm not sure how that
relates to
the dose given to poor metabolizers who have residuals.

"Mutagenesis ---...there was a slight increase in the percentage of Chinese
hamster ovary
cells with diplochromosomes, suggesting endoreduplication (numerical
aberration)."

Chromosomal abnormalities!

"Pregnant rabbits...a decrease in live fetuses...Slight increases in the
incidence of
atypical origin of carotid artery and absence of subclavian artery were
observed."

Increased stillbirths & blood vessel defects in offspring!

"Rats...lactation...decreases in pup weight and pup survival were observed.
In a study
in which rats were treated with atomoxetine" (the main component of
Strattera) "in the
diet from 2 weeks (females) or 10 weeks (males) prior to mating throughout
the period
of organogenesis, a decrease in fetal weight (female only) and an increase
in the
incidence of incomplete ossification of the vertebral arch in fetuses were
observed...
No adequate and well-controlled studies have been conducted in pregnant
women.
Strattera should not be used during pregnancy unless the potential benefit
justifies
the potential risk to the fetus."

"Pediatric Use"
"The efficacy of Strattera beyond 9 weeks and the safety of Strattera beyond
1 year of
treatment have not been systematically evaluated."

Page #15

"Strattera was administered to 2067 children or adolescent patients with
ADHD and 270
adults with ADHD in clinical studies."

Under "Reasons for discontinuation of treatment due to adverse events in
children and
adolescent clinical trials --- ...For all studies,...5% of extensive
metabolizer (EM)
patients and 7% of poor metabolizer (PM) patients discontinued because of
adverse event.

"Strattera has not been systematically evaluated in pediatric patients with
seizure
disorder as these patients were excluded from clinical studies during the
product's
premarketing testing...In these clinical trials, the seizure risk among poor
metabolizers was 0.3% compared to 0.2% for extensive metabolizers.

Page #19

"The following postmarketing adverse events have been reported in temporal
association
with Strattera treatment and were not associated with Strattera use during
the pre-
marketing evaluation of Strattera.  Given the limitations associated with
spontaneous
reporting, it is difficult to accurately estimate the incidence rates for or
causality
of these events...Cardiovascular System ---QT prolongation, syncope.
Seizures ---
Seizures have been reported in the postmarketing period.  The post marketing
seizure
cases include patients with pre-existing seizure disorders and those with
identified
risk factors for seizures, as well as patients with neither a history of nor
identified
risk factors for seizures."

Page #20

"There was no evidence of symptom rebound or adverse events suggesting a
drug
discontinuation or withdrawal syndrome."

So yes, it IS evidently safe to abruptly stop this drug!  And...

"In some cases of overdose involving Strattera, seizures have been
reported."

Page #22

"1. Suicidal thoughts and actions in children and teenagers:...Although no
suicides
occurred in these studies, 4 out of every 1000 patients developed suicidal
thoughts."

Page #23

"3. Heart rate problems: sudden death in patients who have heart problems or
heart
defects..."

"4. New mental (psychiatric) problems in children and teenagers: new
psychotic symptoms
(such as hearing voices, believing things are not true, being suspicious) or
new manic
symptoms"

Page #24

"Do not chew, crush, or open the capsules.  Swallow Strattera capsules whole
with water
or other liquids.  Tell your doctor if you or your child cannot swallow
Strattera whole.
A different medicine may need to be prescribed."

Any takers?

Fawna, Research coordinator TRIS Project, mom
to Thom & Rhonda, Lara, & Philina 24yrs (PT6p
& Moya Moya Syndrome), Escondido, CA USA
http://home.mindspring.com/~fawna33/










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