Download Cardiovascular Disease + Hormonal Therapy Prostatepedia_February Volume No.

Cardiovascular Disease + Hormonal Therapy
Prostatepedia_February
2016
Volume 1 No.
6
February
2016
Volume 1 No. 6 P1
In this issue....
In our February issue, we take
a broader view of cardiovascular
disease risk among men on
a common form of hormonal
therapy called GnRH agonists.
(You may be more familiar with
the brand name Lupron.)
You’ll hear from Dr. Shellie Ellis
and Mr. Sean O’Farrell, researchers
who are looking at larger databases—
the American SEER database and
the Prostate Cancer Database,
Sweden—to gain insight into both the
relationship between cardiovascular
disease risk and GnRh agonists and
to discern patterns of GnRh agonist
use in the United States. As O’Farrell
points out, while these populationbased studies are interesting,
we really do need a randomized
clinical trial with many patients
to truly evaluate risk.
Of course, as most of you already
know, cardiovascular disease is an
enormous problem in the majority
of American men before they’re
even diagnosed with prostate
cancer. Whether or not any given
prostate cancer treatment adds
to risk is almost beside the point,
as Dr. Mark Moyad points out:
ignoring cardiovascular disease
in favor of prostate cancer is foolhardy
at best. More prostate cancer patients
die of cardiovascular disease than
prostate cancer itself. A cardiovascular
disease evaluation for every prostate
cancer patient before he even starts
hormonal therapy, as well as careful
monitoring during treatment, has
been a hallmark of my practice and
ought to be standard care for all men.
Charles E. Myers, Jr., MD
Contents:
Contributors:
P 4 Mark Moyad, MD:
Cardiovascular Disease
+ Hormonal Therapy
Editor-in-Chief:
Charles E. Myers, Jr., MD
P 7 Sean O’Farrell, BsC, MR:
Publisher
Jessica Myers-Schecter
Cardiovascular Disease Risk
P10 Shellie Ellis, PhD, MA:
GnRH Agonist
Prescription Patterns
Mission:
We aim to provide useful current
information about prostate cancer
and its treatment. This information
and the products and media advertised
in this publication are advisory only.
Individuals pictured are models and
are used for illustrative purposes only.
Please consult your physician for
specific medical or therapeutic advice.
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ISSN: 2381-4020
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Mark Moyad, MD:
Cardiovascular Disease
+ Hormonal Therapy
Dr. Mark Moyad, the Jenkins/
Pokempner Director of Preventive
& Complementary Medicine
at the University of Michigan
(Dept. of Urology), is a popular
speaker at patient-centered
prostate conferences in the
United States and abroad.
Moyad is dedicated to educating
prostate cancer patients about
the connections between diet,
supplements, lifestyle, and health.
Prostatepedia recently spoke with
him about the importance of addressing
cardiovascular disease in men on
hormonal therapy.
How much of a problem is cardiovascular
disease in men newly diagnosed with
prostate cancer?
Dr. Mark Moyad: It’s arguably the
number one cause of death in prostate
cancer patients. It’s the quiet elephant
in the room. Men have to be as concerned
about cardiovascular disease as they
are with their prostate cancer diagnosis.
Do some prostate cancer treatments,
like hormonal therapy, increase the risk
of cardiac disease?
Dr. Moyad: Whenever people ask
me that, I almost always say it doesn’t
matter. Because we already know
that cardiovascular disease going into
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“If cardiovascular
disease isn’t discussed,
you shouldn’t even
be treated for
prostate cancer.”
Androgen Deprivation Therapy (ADT)
is the number one cause of death
in men.
So even if ADT doesn’t increase
risk, I’m already going to treat that
patient as if he were at high risk for
a cardiovascular event. I’m still going
treat this person as if he’s just as
likely to die of a cardiac event.
You have to think heart-healthy
as much as ADT-healthy before
the first injection. It doesn’t mean
we’re downplaying the prostate
cancer. It means that life is a game
of probability, so in order to beat
the odds you need to do everything
possible to reduce your cardiac risk
to zero. If you do that, it takes care
of all the other business that you’re
worried about.
We also know that ADT has been
around for 30 years now because
“What¹s the point of
being treated for prostate
cancer if you’re going
to die of a cardiac event
five years later?”
it’s helped so many people. If we had
something better, ADT would be gone
tomorrow, because it does come
with a lot of side effects, especially
weight gain. Your triglycerides can
go way up; your glucose can go
way up. You’re going to want to work
out less. You’re not going to have
any testosterone.
In the Mark Moyad perfect world,
you would never get an injection
of Lupron until you have had
a discussion about the fact that
if you don’t aggressively take care
of your heart health, your existing
heart disease will get worse. It may
not be the drug per se, but all the
indirect effects, such as lack of energy,
slowed metabolism, slight anemia,
weight gain, increased diabetes risk,
increased cardiac risk, and possibly
increased blood pressure. We’re not
saying the drug itself directly does
that, but if you add up all the little
things it does and the patient isn’t
very motivated, it can be bad.
I’ll add that this whole scare about
ADT and cardiovascular disease is
complex. To put this in perspective,
most of the randomized trials don’t
show that ADT makes cardiovascular
disease worse. The randomized
trials published a couple years ago
in Journal of the American Medical
Association showed no difference.
The observational studies show
that ADT does make cardiovascular
disease worse. That is why we’re
battling back and forth. That is why
you see one paper that says it makes
it worse and another paper that says
it doesn’t make it worse. The reason
why you’ll probably never come
to an answer is because it’s so
complex. The health of the patient
going into treatment matters.
Does he have five other diseases
that the ADT exacerbated? Is he
completely healthy?
You think a man’s doctor should aggressively
address any risk of cardiovascular
disease before he starts on ADT?
Dr. Moyad: I think so strongly
that it should be a part of it that if
cardiovascular disease isn’t discussed,
you shouldn’t even be treated for
prostate cancer. What’s the point
of being treated for prostate cancer
if you’re going to die of a cardiac
event five years later? In all honesty,
you might as well just enjoy life.
The idea, though, is not to have your
urologist or oncologist become your
cardiologist. The idea is for you to
go back to your primary care doctor
or cardiologist and say, “I’m about
to start on this androgen deprivation
therapy. I need to know my cardiac
risk as it stands right now so I have
a baseline and then we need to talk
about how we can monitor this the
whole time I’m on ADT.”
This is not difficult. You’re basically
setting up a meeting with your primary
care doctor or going back to your
cardiologist and saying, “I have to
go on ADT. We need to aggressively
monitor for any changes.”
Let’s talk about the details of careful
cardiovascular monitoring.
Dr. Moyad: Make sure you’re going
to be measured for what I call the
Big Four.
The first is weight: BMI and
waist circumference. The second
number is lipids: your LDL and HDL
cholesterol and triglycerides. Blood
sugar, hemoglobin A1c is number
three. Blood pressure is number four.
These are the only four numbers
I really want people to be obsessed
with. And they can work with their
primary care physicians to monitor these.
The mantra is: You need to know
how these four numbers change
during ADT as well as you know
how your PSA is doing.
What about diet and exercise?
Dr. Moyad: As I said, most people
going into ADT have some condition
that increases risk, like high blood
sugar. When your metabolism slows
while you’re on ADT, your lipid profile
gets worse, your weight gets worse,
your blood pressure increases, and
your triglycerides go up dramatically.
Everything just gets worse with this
weight gain problem.
There have been actual studies
of CT scans and other imaging scans
of weight gain in people on ADT.
Within very little time, they increase
not only their subcutaneous fat, the fat
right underneath the skins, but also
the fat around their organs. You can
get fat infiltration around liver and
pancreas. You’re making all these
organs work harder.
Caloric control and exercise become
important. And I’ll say that caloric
control is just as important as exercise
when you’re on ADT because what
you eat right now is really going
to matter in terms of weight gain.
It really is. But yes, aerobic and
resistance exercise are important.
Some men work with a trainer;
some do it by themselves.
But just because you exercise,
you can’t eat whatever you want or
drink whatever you want. That’s a big
problem, I think, in prostate cancer
patients. As they get older, a lot
of people turn to drinking as selfmedication. But alcohol is so
concentrated in calories.
What about medications—
like metformin or statins?
Dr. Moyad: If you need help beyond
diet and lifestyle, you can start
looking at the possibility of what
I call in my books and medical articles,
the easy to remember 3-letter acronym
for health care professionals and
patients known as S-A-M: Statin,
Aspirin, and Metformin.
The benefit that I see with these
drugs is not necessarily their potential
ability to slow the progression of the
disease. We don’t necessarily know
if they do that, but we do know they
can reduce the potential toxicity
of ADT due to any potential increase
in cardiovascular disease.
For example, if you are exercising and
reducing calories, but are still gaining
weight with a blood sugar level in the
pre-diabetes range (100-125 mg/dl),
then you may qualify for metformin
to help with weight loss and blood
sugar control. Taking a statin, aspirin,
or metformin makes more sense
February
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Volume 1 No. 6 P5
than worrying about which of the
100+ different supplements you
should take during ADT.
All three of these medications came
from a natural source. They’re all
dirt-cheap. They’re all generic.
I am not saying you have to be on
any of these medications, but many
patients qualify for at least one going
into ADT or during ADT.
How do you think stress and depression
factor into all this? Just hearing you’ve
been diagnosed with prostate cancer
can be incredibly stressful.
Dr. Moyad: Acute stress or stress once
in a while can be good. Acute stress
can sometimes motivate you: “I’m not
going to let this disease get me.”
Sean O’Farrell, BsC, MR :
Cardiovascular Disease Risk
Sean O’Farrell, of King’s College
London, is an author on a recent
Journal of Clinical Oncology article
on the risk of cardiovascular disease
in men on ADT.
Prostatepedia recently spoke with
Chronic stress, which can happen with
a diagnosis, can really make the whole
situation worse. You become stoic.
You’re stuck. You’re not motivated
to do anything. You’re mentally and
physically shackled.
If men go back to their primary care
physician for a cardiovascular evaluation
before going on ADT, we can identify
more of those suffering from depression
or chronic stress, can we not?
Dr. Moyad: It would catch all of it.
A lot of times, patients will say, “I have
a fog. I just feel like I’m in slow motion.
I just don’t feel cognitively up to
speed like I used to.” These are all
significant things to tell a physician
you trust.
Knowing your objective numbers
and discussing your subjective
feelings (mood, stress, and anxiety)
with the doctor you trust the most
with your health is crucial and
can make the difference between
a tolerable or good experience
with ADT and a miserable one.
P6 February
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him about cardiovascular disease risk
in men on hormonal therapy.
GnRH is a gonadotropin-releasing
hormone receptor that is primarily
located in the brain. You can target
that receptor in two ways: through
the use of GnRH antagonists like
Firmagon, or through the use
of GnRH agonists like Lupron.
The antagonists like Firmagon are
the newer form and have slightly
fewer side effects.
How is hormonal therapy used to treat
prostate cancer?
Mr. Sean O’Farrell: Your prostate
cancer is very much dependent on
testosterone and other hormones—
androgens—for growth. One very
effective treatment, particularly
in the earlier stages of the disease,
is to block testosterone. This is called
androgen deprivation therapy (ADT).
ADT comes in multiple forms. You can
have surgical androgen-deprivation,
also known as an orchiectomy,
or you can be given drugs.
In terms of the drugs, there are
three arms. In one arm are antiandrogens, which only act on the
tumor itself. In the other arm are
GnRH agonists, such as Lupron,
which globally inhibit androgens.
The use of these GnRH agonists
is commonly referred to as medical,
or pharmacological, castration.
“Being aware that
this is actually a risk
with GnRH agonists
is where it starts.”
We have focused on drugs like Lupron.
GnRH agonists are particularly
associated with side effects like
sexual dysfunction. And, as we
at King’s College London recently
pointed out, together with others,
these drugs are also associated with
cardiovascular issues.
Despite the side effects associated with
these drugs, they are quite an effective
treatment for prostate cancer.
Your group published a series of
papers analyzing the Prostate Cancer
Database, Sweden. What is this
database and why is it important?
O’Farrell: Prostate Cancer Database,
Sweden, or PCBaSe Sweden,
is a comprehensive register of 96-98%
of prostate cancer patients in Sweden.
This database is possible in Sweden
because every citizen has a tendigit personal identification number.
PCBaSe links different databases
through that ten-digit number. You can
link up things like information about
other diseases, their particular
prostate cancer diagnosis, lifestyle
factors, educational level, marital
status, and so on.
What made our study quite unique
is that we looked at patient drug
information in addition to other
factors. We were able to track
outpatient ADT prescriptions per
person without linking to name.
This was all done anonymously
to maintain privacy. We tracked
how many times an individual’s
prescription was actually picked up,
thereby getting a comprehensive
picture of drug adherence. PCBaSe
Sweden is a database that links
together a lot of health care
information about prostate cancer
patients. It’s being extended to other
diseases, as well.
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Volume 1 No. 6 P7
Can you talk about your group’s study,
as well as the follow-up published
in March 2015?
O’Farrell: Mieke Van Hemelrijck
published the original study
in the Journal of Clinical Oncology.
We published this follow-up five
years later, also in the Journal
of Clinical Oncology.
In the first publication, Van Hemelrijck
and her colleagues looked at everyone
with prostate cancer—whether
you had ADT or not, whether you
were undergoing watchful waiting
or not, etc. They found that the
highest risk for cardiovascular
disease was among those on
hormone therapy.
“The best thing is to get
advice from your physician.
See a cardiovascular
specialist, if you can.”
By the time I started working on
the project in 2013, we had a drug
register. That drug register started
in 2005; by the time we were able
to look at the data, there was quite
a comprehensive amount of information.
We were able to split patients on ADT
into those who had had orchiectomy,
anti-androgens, or GnRH agonists.
We also had a control cohort of
patients. We had five age- and county
area-matched controls per prostate
cancer case as a comparison group.
We were able to do a very
comprehensive analysis of the different
types of ADT, compare the types to
their respective controls, determine
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where the risk of a cardiovascular
incident was really high, and determine
if there was any difference in risk
between types of androgen deprivation
therapy. We tried to distill which form
of ADT might be more associated with
an increased risk of other diseases,
such as cardiovascular disease.
What are the implications for patients?
Which is pretty common, isn’t it?
O’Farrell: Being aware that this
is actually a risk with GnRH
agonists is where it starts. The more
counseling you can get and advice
you get as early as possible, the
better and more you can prevent
future cardiovascular events.
O’Farrell: In Sweden, it is. In our
dataset, something like 24%
of people underwent that switch.
Twenty-four percent of those who
started on antiandrogens eventually
moved on.
Did you find that dose and duration
of different types of ADT increased
risk more than others?
You published a paper on thromboembolic
disease, as well, correct?
O’Farrell: We didn’t look at dosage
too much, but we did look at duration.
We found, to our own surprise,
that the risk for any cardiovascular
event was at its highest within
the first year on ADT, regardless
of which type the patient was on.
Cardiovascular risk was highest
for those who had anti-androgens,
GnRH agonists, or orchiectomy.
O’Farrell: We looked at venous
thrombosis and embolisms—blood
clots in your veins that can be fatal.
Thrombosis is a side effect that
has also been associated with ADT.
It’s a much more rare disease than
overall cardiovascular disease,
but it’s certainly something that can
happen, and when it does happen,
it can be dangerous.
We stratified our analysis by how
many cardiovascular events a man
had had before being diagnosed with
prostate cancer or before being given
ADT. We found that those who had
two or more cardiovascular events
before treatment were the ones
at highest risk during treatment.
The other groups remained quite flat.
Those with a history of cardiovascular
disease who then get ADT—
regardless of type—had the highest
risk of cardiovascular disease in the
first year on therapy. That was the
seminal finding.
We looked at the different types
of ADT—GnRH agonists and surgical
castration. We found that the risk
for a thromboembolic event was
also higher for those on GnRH
agonists and those who had had
an orchiectomy.
What do you think is behind
the increased risk during the first
six months?
O’Farrell: There are a number
of different potential reasons,
but I would stress that studies
like ours are very much hypothesisgenerating. We need lab studies
and clinical trials to really understand
this association.
Thrombosis experts may say there
are other things, particularly with
prostate cancer, that may affect this.
The prostate cancer itself is known
to be associated with increased
thromboembolic events. If your
disease progresses quickly, that
can lead to an increased risk for
thromboembolic events. We tried
to account for any indication that
your prostate cancer may have moved
a bit faster than one would hope.
Interestingly, the risk remained high
after they switched to GnRH agonists.
It wasn’t like the cardiovascular disease
story, where the risk peaked and then
dropped back to baseline. In this case,
the risk went up very early and
it stayed high.
The main message we would gather
from that is that hormone should
really only be given to patients
in whom it is indicated. Active
surveillance may be better for
people with earlier-stage disease.
What about people who have already
followed the treatment pattern you
describe and feel they may be at risk?
What should they do?
O’Farrell: The best thing is to get advice
from your physician. See a cardiovascular
specialist, if you can. A lot of patients
may not know that this is potentially
an issue,
But I would caution that these
are epidemiological studies.
They’re retrospective. They’re on
big datasets. They’re not randomized.
We need a randomized clinical trial
with a very high number of patients
to really say if the risk is there.
We found that the group at highest
risk for thromboembolic disease
was those who started on antiandrogens and then switched
to GnRH agonists because their
disease was progressing.
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Volume 1 No. 6 P9
Shellie Ellis, PhD, MA:
GnRH Agonist
Prescription Patterns
“As time goes on, you
will have more and
more information about
the physicians you see.”
users in general and they remained
low users.
Shellie Ellis is an Assistant Professor
at the University of Kansas.
Her research focuses on physician
decision-making and how health
care policies and reimbursement
influence treatment decisions.
Prostatepedia recently spoke
with her about her study on GnRH
prescription patterns from 2000-2009.
Talk to us about the reimbursement
cuts associated with the Medicare
Modernization Act (MMA).
Shellie Ellis: Most people are familiar
with the Medicare Modernization Act
because it gave prescription benefits
to Medicare beneficiaries, but it was
actually a very wide-ranging piece of
legislation. It reformed the logistics
of how Medicare payments were
delivered. At the same time, the
MMA issued reimbursement cuts
that affected some of the care that
prostate cancer patients received.
Within one portion of Medicare—
Medicare Part B—physicians are
directly reimbursed for drugs
they administer to patients in the
office. Some policymakers thought
that many of these drugs were
reimbursed at rates that exceeded
the cost of administering and buying
the drugs. There were a whole host
of these drugs in Medicare Part B.
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GnRH agonists like Lupron were
part of that class of drugs for which
reimbursements were cut as a result
of the changes enacted in 2004.
Then, a slightly more aggressive change
happened in 2005 with a two-part
reduction in reimbursement
for physicians.
This particular action was not necessarily
taken with the intent to improve quality
of care. Policymakers thought physicians
were being reimbursed at rates far
greater than physicians were spending
on buying and keeping these drugs.
It just so happened that GnRH agonists
were one of the most widely prescribed
drugs and so they rose to the top
of the list of those considered highcost for the Medicare program.
But, coincidentally, the drugs were being
used to treat low-risk prostate cancer
patients, which wasn’t recommended.
Tell us about the paper you published
last year.
Ellis: We started by looking at the
SEER-Medicare database. This database
is a collection of administrative claims.
Once physicians submit their Medicare
claims to the Centers for Medicare &
Medicaid Services (CMS), CMS makes
those claims available to researchers.
In particular, the National Cancer
Institute (NCI) takes data from SEER
registries, the state- and locality-
based registries that collect all
information about anyone diagnosed
with cancer in their catchment area.
SEER comprehensively searches
hospital records and physician
records to document cancer stage,
grade, and any other kinds of clinical
indicators about the cancer. They also
collect data about patients themselves—
where they live, and the communities
in which they live. Then they de-identify
that data and match it to the Medicare
claims data.
Others had looked at this database
to see what happened when the
reimbursement cuts went into effect.
There appeared to be a 65% decrease
in the use of GnRH agonists among
men with localized prostate cancer.
We noticed this large decrease in GnRH
agonist use and were interested in
understanding how physicians were
responding to the reimbursement
cut as well as the characteristics
of physicians who did not respond
to the reimbursement cut.
We characterized GnRH agonist use
from 2000 to 2009 and identified
different groups of physicians.
There were some physicians who
really didn’t use GnRH agonists at all
for their low-risk, localized prostate
cancer patients; their use of the
drug didn’t really change after the
reimbursement cut. They were low
We also identified a group of
physicians who used the drug quite
a bit, but when the reimbursement
cut happened, they decreased their
use of the drug dramatically.
We also noticed a group of physicians
who didn’t use the drug a lot, but when
the reimbursement changes happened,
they actually increased their use of the
drug substantially, much higher than
even the users who had used it quite
a bit prior to the reimbursement cuts.
These were doctors who, despite
the reimbursement cuts, were still
electing to use drugs that might not
be appropriate for their patients.
We wanted to know more about
this phenomenon, specifically,
the characteristics of the doctors
using the drug inappropriately,
as well as the patients that they
saw. One thing that was really
interesting was that the patients
who were being prescribed the drug
inappropriately were more vulnerable
patients than you might typically
see. They were more likely to be
African American. They were more
likely to be older. They were more
likely to be in communities with low
socioeconomic status and education.
use of a drug in certain ways. They might
suggest that when a physician is faced
with a reimbursement cut, he or she
might actually increase the number
of times the drug is given to make
up for lost revenue. You get less per
administration, but you’re doing it more
often to compensate. But few of the
economic theories actually partner
the clinical data with the theoretical
data about the physicians’ behavior.
practitioners funneling information
and knowledge to them. They don’t
have time to pursue educational
opportunities because they’re the
only doctor in the practice. They might
just be behind on some of the data
that was coming out at the time about
the harms of GnRh agonists or the
guidelines published in 2000 that
suggested this particular treatment
was not appropriate for low-risk patients.
What we saw is that these patients
were very different from the patients
of the doctors who decreased their use.
It is well established that men who are
older are more likely to be prescribed
these drugs. They may be exhibiting
other symptoms or have other diseases
to which the physicians are responding.
Or perhaps they’re not candidates for
surgery. If these patients are of lower
socioeconomic status, perhaps they
can’t afford surgery or have other barriers
to care. The patients themselves may
not want radiation therapy, but want
some type of therapy to relieve
symptoms or simply because they
have anxiety about a prostate cancer
diagnosis. It is possible these physicians
were responding to things we can’t
see in the SEER-Medicare data.
You’ve only looked at patients diagnosed
through 2007. Any plans to look at what
has happened between 2009 and now?
But even though these things might
explain the uptick in drug use, they still
aren’t appropriate for the patient,
so we wanted to identify which
physicians were more likely to overuse
the drugs. We found physicians in
solo practice and those without any
affiliation with a medical school were
more likely to do so. We think it’s
really important to reach out to those
particular physicians and make sure
that they’re aware of the risks.
Why do you think this phenomenon is more
likely to happen among solo practitioners?
Ellis: We looked at patients diagnosed
through 2007, but we had data through
2009. And yes. I just applied for the
updated SEER-Medicare dataset.
What do you think patients should take
away from this?
Ellis: As time goes on, you will have
more and more information about the
physicians you see. Try to stay informed
and work with your physician. If at all
possible, understand what guidelines
are available. What evidence do we
have to support that this is the best
treatment possible? Organizations
like the National Comprehensive
Cancer Network publish guidelines
available to you, so you can identify
what treatments are appropriate for
your particular stage of disease.
About 20% of urology care is delivered
in solo practices. Most of our traditional
efforts to reach physicians, such as
medical school affiliations or professional
societies, have improved quality of care.
Those kinds of opportunities may not
be reaching solo doctors. We need to
figure out new strategies for reaching
those particular physicians.
What do you think is behind that?
Ellis: Some economists might explain
this behavior of physicians’ increasing
Ellis: We can’t tell exactly from the data
we have. It may be because they’re
by themselves and don’t have other
February
2016
Volume 1 No. 6 P11
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XTANDI is not for use in women. Do not take XTANDI if you are
pregnant or may become pregnant. XTANDI can harm your unborn
baby. It is not known if XTANDI is safe and effective in children.
Before you take XTANDI, tell your healthcare provider
if you:
• Have a history of seizures, brain injury, stroke or brain tumors.
• Have any other medical conditions.
• Have a partner who is pregnant or may become pregnant. Men who
are sexually active2016
with a pregnant
woman must use a condom
1
P12and
February
Volume
No. 6
during
for 3 months
after treatment
with XTANDI. If your sexual
partner may become pregnant, a condom and another form of birth
control must be used during and for 3 months after treatment.
Talk with your healthcare provider if you have questions about birth
control. See “Who should not take XTANDI?”
• Take any other medicines, including prescription and
over-the-counter medicines, vitamins, and herbal supplements.
XTANDI may affect the way other medicines work, and other
medicines may affect how XTANDI works. You should not start
or stop any medicine before you talk with the healthcare provider
that prescribed XTANDI.
How should I take XTANDI?
• XTANDI is four 40 mg capsules taken once daily.
• Take XTANDI exactly as your healthcare provider tells you.
• Take your prescribed dose of XTANDI one time a day, at the same
time each day.
• Your healthcare provider may change your dose if needed.
• Do not change or stop taking your prescribed dose of XTANDI
without talking with your healthcare provider first.
• XTANDI can be taken with or without food.
• Swallow XTANDI capsules whole. Do not chew, dissolve, or open
the capsules.
• If you miss a dose of XTANDI, take your prescribed dose as soon
as you remember that day. If you miss your daily dose, take your
prescribed dose at your regular time the next day. Do not take
more than your prescribed dose of XTANDI in one day.
• If you take too much XTANDI, call your healthcare provider or go
to the nearest emergency room right away. You may have an
increased risk of seizure if you take too much XTANDI.
What are the possible side effects of XTANDI?
XTANDI may cause serious side effects including:
• Seizure. If you take XTANDI you may be at risk of having a seizure.
You should avoid activities where a sudden loss of consciousness
could cause serious harm to yourself or others. Tell your healthcare
provider right away if you have loss of consciousness or seizure.
Your healthcare provider will stop XTANDI if you have a seizure
during treatment.
• Posterior Reversible Encephalopathy Syndrome (PRES).
If you take XTANDI you may be at risk of developing a condition
involving the brain called PRES. Tell your healthcare provider right
away if you have a seizure or quickly worsening symptoms such
as headache, decreased alertness, confusion, reduced eyesight,
blurred vision or other visual problems. Your healthcare provider
will do a test to check for PRES. Your healthcare provider will stop
XTANDI if you develop PRES.
The most common side effects of XTANDI include weakness or feeling
more tired than usual, back pain, decreased appetite, constipation, joint
pain, diarrhea, hot flashes, upper respiratory tract infection, swelling in
your hands, arms, legs, or feet, shortness of breath, muscle and bone
pain, weight loss, headache, high blood pressure, dizziness, and a
feeling that you or things around you are moving or spinning (vertigo).
XTANDI may cause infections, falls and injuries from falls. Tell your
healthcare provider if you have signs or symptoms of an infection
or if you fall.
Tell your healthcare provider if you have any side effect that bothers
you or that does not go away. These are not all the possible side
effects of XTANDI. For more information, ask your healthcare provider
or pharmacist.
You are encouraged to report negative side effects of prescription
drugs to the FDA. Visit www.fda.gov/medwatch, or call
1-800-FDA-1088.
Please see the Brief Summary on the following page and the
Full Prescribing Information on XTANDI.com.
QUESTIONS
ABOUT XTANDI?
Call 1-855-8XTANDI
(1-855-898-2634)
XTANDI, Astellas, and the flying star logo are trademarks
of Astellas
Inc.
1 Pharma
February 2016 Volume
No. 6 P13
© 2015 Astellas Pharma US, Inc. 076-1030-PM 8/15
PATIENT INFORMATION
XTANDI® (ex TAN dee)
(enzalutamide)
capsules
What is XTANDI?
XTANDI is a prescription medicine used to treat men with
prostate cancer that no longer responds to a medical or
surgical treatment that lowers testosterone and that has
spread to other parts of the body.
It is not known if XTANDI is safe and effective in children.
Who should not take XTANDI?
XTANDI is not for use in women.
Do not take XTANDI if you are pregnant or may become
pregnant. XTANDI can harm your unborn baby.
What should I tell my healthcare provider before taking XTANDI?
Before you take XTANDI, tell your healthcare provider if you:
• have a history of seizures, brain injury, stroke, or brain tumors
• have any other medical conditions
• have a partner who is pregnant or may become pregnant.
Men who are sexually active with a pregnant woman must
use a condom during and for 3 months after treatment
with XTANDI. If your sexual partner may become pregnant,
a condom and another form of effective birth control must
be used during and for 3 months after treatment. Talk with
your healthcare provider if you have questions about birth
control. See “Who should not take XTANDI?”
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. XTANDI may affect the
way other medicines work, and other medicines may affect
how XTANDI works.
You should not start or stop any medicine before you talk
with the healthcare provider that prescribed XTANDI.
Know the medicines you take. Keep a list of them with you to
show your healthcare provider and pharmacist when you get
a new medicine.
How should I take XTANDI?
• Take XTANDI exactly as your healthcare provider tells you.
• Take your prescribed dose of XTANDI one time a day, at
the same time each day.
• Your healthcare provider may change your dose if needed.
• Do not change or stop taking your prescribed dose of
XTANDI without talking with your healthcare provider first.
• XTANDI can be taken with or without food.
• Swallow XTANDI capsules whole. Do not chew, dissolve,
or open the capsules.
• If you miss a dose of XTANDI, take your prescribed dose
as soon as you remember that day. If you miss your daily
dose, take your prescribed dose at your regular time the
next day. Do not take more than your prescribed dose of
XTANDI in one day.
• If you take too much XTANDI, call your healthcare provider or
go to the nearest emergency room right away. You may have
an increased risk of seizure if you take too much XTANDI.
What are the possible side effects of XTANDI?
XTANDI may cause serious side effects including:
• Seizure. If you take XTANDI you may be at risk of having a
seizure. You should avoid activities where a sudden loss
of consciousness could cause serious harm to yourself or
P14 February
2016
Volume 1 No.
others. Tell your healthcare provider right away if you have
loss of consciousness or seizure. Your healthcare provider
will stop XTANDI if you have a seizure during treatment.
• Posterior Reversible Encephalopathy Syndrome (PRES).
If you take XTANDI you may be at risk of developing a
condition involving the brain called PRES. Tell your
healthcare provider right away if you have a seizure or
quickly worsening symptoms such as headache,
decreased alertness, confusion, reduced eyesight,
blurred vision or other visual problems. Your healthcare
provider will do a test to check for PRES. Your healthcare
provider will stop XTANDI if you develop PRES.
The most common side effects of XTANDI include:
• weakness or feeling more
• swelling in your hands,
tired than usual
arms, legs, or feet
• back pain
• shortness of breath
• decreased appetite
• muscle and bone pain
• constipation
• weight loss
• joint pain
• headache
• diarrhea
• high blood pressure
• hot flashes
• dizziness
• upper respiratory tract
• a feeling that you or things
infection
around you are moving or
spinning (vertigo)
XTANDI may cause infections, falls and injuries from falls.
Tell your healthcare provider if you have signs or symptoms
of an infection or if you fall.
Tell your healthcare provider if you have any side effect that
bothers you or that does not go away.
These are not all the possible side effects of XTANDI. For more
information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You
may report side effects to FDA at 1-800-FDA-1088.
How should I store XTANDI?
• Store XTANDI between 68°F to 77°F (20°C to 25°C).
• Keep XTANDI capsules dry and in a tightly closed container.
Keep XTANDI and all medicines out of the reach of children.
General information about XTANDI.
Medicines are sometimes prescribed for purposes other
than those listed in a Patient Information leaflet. Do not use
XTANDI for a condition for which it was not prescribed. Do
not give XTANDI to other people, even if they have the same
symptoms that you have. It may harm them.
This Patient Information leaflet summarizes the most
important information about XTANDI. If you would like more
information, talk with your healthcare provider. You can ask
your healthcare provider or pharmacist for information about
XTANDI that is written for health professionals.
For more information go to www.Xtandi.com or
call 1-800-727-7003.
What are the ingredients in XTANDI?
Active ingredient: enzalutamide
Inactive ingredients: caprylocaproyl polyoxylglycerides,
butylated hydroxyanisole, butylated hydroxytoluene, gelatin,
sorbitol sorbitan solution, glycerin, purified water, titanium
dioxide, black iron oxide
Manufactured by:
Catalent Pharma Solutions, LLC, St. Petersburg, FL 33716
Marketed by:
Astellas Pharma US, Inc., Northbrook, IL 60062
Medivation Inc., San Francisco, CA 94105
14L082-XTA-BRFS
© 2015 Astellas Pharma US, Inc.
XTANDI® is a registered trademark of Astellas Pharma Inc.
076-1121-PM
This Patient Information has been approved by the U.S. Food
and Drug Administration.
Revised: August 2015
Personalized
Treatment
Your prostate cancer is as
individual as you are.
For an Appointment With Dr. Myers at AIDP, Contact
Tel. 434-964-0212 (For appointments, press option #1) Fax. 434-964-0216
www.prostateteam.com
February
6
Individuals pictured are models and are used for illustrative purposes only.
2016
Volume 1 No. 6 P15
274 Redwood Shores, #739
Redwood City, CA 94065
434-220-3774
[email protected]
www.prostatepedia.net