When to start tricor
Fenofibrate
hello I'm dr. Ken lanta thanks for
watching let's talk about trial or a fan
of fibrate this is a drug that was FDA
approved in 1993 to add to diet in order
to reduce blood lipids and triglycerides
so what does it do it reduces the total
cholesterol reduces the bad cholesterol
reduces the triglycerides and it
increases the HDL with the good
cholesterol but in spite of all of that
it hasn't been shown to reduce the
cardiovascular morbidity or mortality
rate in other words it doesn't prevent
deaths from cardiovascular disease it's
used pretty much for adults who have
very high levels of triglycerides but
first if you have very high
triglycerides you should try to find out
what the cause is sometimes it's due to
poor sugar control if you have diabetes
maybe it's because you weigh too much
you drink too much alcohol you have low
levels of thyroid hormone activity maybe
you're taking estrogen birth control
pill or a thigh as I diuretic or a beta
blocker irrespective of all of this
remember even if we reduce the
triglycerides I'm not going to save your
life the dose of the medicine 145
milligrams you take that once a day
that's the dose for a primary
hypercholesterolemia or for elevated
levels of triglycerides you check the
blood at four weeks and again at eight
weeks if the triglycerides aren't
appropriately controlled after two
months well then probably get off the
drug because it isn't going to work you
can take the drug either with meals or
without meals and if you have any
element of renal compromise for renal
function then you either have to reduce
the dose or not take it at all now there
are three drugs in the family that have
sort of the same side effects the same
clinical profile there trichloroethane
fibrate there's close irate and gunfire
brasil so if you have a side effect of
any one member of the family tenses are
you going to have it in the other so
what are some of the side effects one
the close Irate study
that was called the coronary drug
project that looked people who had heart
attacks and followed them for about five
years and didn't find any difference in
the mortality rate but it did find that
they had more gall stones they had about
three percent gallstones versus only a
little bit less than 2 percent gall
stones requiring surgery in the group
taking the placebo World Health
Organization did a study with 5000
individuals known own heart disease
followed the people for the five years
of the study and then one year after the
study and actually fine found that the
people who took the close i braid had a
slightly higher death rate total all
cause mortality taking the drug versus
taking placebo a little less than 6
percent versus a little less than 4
percent the excessive deaths were due to
malignancy complications of gallbladder
disease and pancreatitis again v Brazil
they did the Helsinki heart study looked
at about four thousand middle-aged men
no history of coronary artery disease
they followed him for the five years of
the study three and a half years
afterward and what they found again was
total mortality was increased but not
significantly in the gamify Brazil group
and the cancer deaths were increased
okay so now let's get back to tricor
realizing all of the drugs in the same
family might have the same side effects
so three to six month duration studies
have taken try Claus should that the
drug did modestly reduce the cholesterol
by about twenty percent the bad
cholesterol by about 20 percent boosted
the HDL good cholesterol by about eleven
percent and the total triglycerides fell
by about thirty percent if they started
off at a baseline of about a hundred and
ninety well that's not very dramatic but
if your triglycerides are very high say
somewhere between 500 and 1500
triglycerides should be less than 200
anyway so if they're fairly high then
the drug seems to work okay
it reduces the triglycerides by about
fifty five sixty percent so the
triglycerides could go from say mid 700s
down to low 300s that's pretty good
if
the triglycerides are only moderately
elevated say between 350 and 500 it's
gonna make the triglycerides fall by
again about 50% so that's pretty good
but remember if your triglycerides are
very high and as they get close to a
thousand that increases the risk for
pancreatitis you want to find out if you
have a secondary cause something that
you can change to bring the
triglycerides down so remember the
alcohol the drugs kidney disease a
variety of conditions well how do you
address high triglycerides and we'll
certainly diet decrease the fat you take
in maybe you take some fish oil and then
there are the fibrates by themselves
remember they don't cause a reduction in
overall mortality they don't decrease
the non cardiovascular mortality but
when they're added to statins do they do
any good if the statins don't really
work as well as you want can you have
10:05 right the trial or and get better
result
probably not but now we have an
interesting trial and this drug is going
to get to be very interesting as we'll
talk about so we have the Accord trial
the accord lipid trial followed people
for a little less than five years it
looked at about fifty five hundred type
two diabetics who were already taking
statins and they gave some of them the
trial or and identify brayton others
they just took the placebo and there was
a non significant eight percent decrease
in the incidence of major adverse
coronary vascular events that means
non-fatal heart attacks a non-fatal
stroke and cardiovascular death in
people who were combining the statins
with the trial or versus people taking
the status by themselves so overall if
we look at just the men it seems that
the men had some extra benefit they had
about 18% reduction in the non-fatal
heart attack non-fatal stroke
cardiovascular death so that's pretty
good unfortunately the women had a
non-statistical 40 percent increase in
their risk of dying or having one of
those
kind of events okay so then they did
another study it's called the field
study looked at almost 10,000 people
followed him for five years and again
they found a little bit of reduction in
the secondary outcome secondary outcome
when they looked at the total
cardiovascular events but what they
didn't find was a decrease in the total
mortality actually the total mortality
rose in those people taking the drug
rose by about 11% and there was a non
significant increase in the coronary
heart disease death rate so the total
deaths and the heart related death
seemed to increase but not statistically
significantly so in diabetics who have
distal epidemia that almost goes
part-and-parcel diabetics about 70% of
diabetics going to have increased
triglycerides and they're going to have
low levels of HDL and not only do they
have abnormal lipids they have small
dense LDL and small dense LDL or the
worst of the LDL so in 2019 you know the
American College cardiology American
Heart Association said hey diabetics
you're at high risk you ought to take
something to reduce your risk of heart
disease since the major cause of death
and diabetics is heart disease and what
they said is take a statin and if you
have mild risk take mild or moderate
intensity statin and if you have a
significant risk take a high intensity
statin okay well one of the leading
causes of blindness in working aged
adults is diabetic retinopathy so it's
thought that you can reduce the diabetic
retinopathy if you control the high
blood pressure and control the blood
sugar they can decrease the incidence
and progression of the diabetic
retinopathy but the hypercholesterolemia
hypertriglyceridemia results are really
inconsistent so when you take the statin
to reduce your cholesterol reduce your
triglyceride
it really doesn't do much for diabetic
retinopathy but it seems like the fellow
fibrate the try clerk might and that's
the exciting part about this particular
kind of condition or this particular
drug
so the micro vascular complications of
diabetes involve the nerves involve the
eyes and involve the kidney and if we
look at people who have diabetes overall
about 30 percent of them are going to
have some form of retinopathy it's gonna
be probably everyone if we look close
enough in the type 1 diabetics and if we
look at type 2 diabetics probably 80%
especially in people who have had the
diabetes for at least twenty years
recently there's been a slight decrease
and that's because we're treating the
sugar more aggressively than we used to
20-30 years ago but vision threatening
diabetic retinopathy is still a
relatively common condition caused
either by diabetic macular oedema or
diabetic progressive retinopathy that
has to be treated by the injections into
the eye or laser photocoagulation well
those two recent studies that I just
mentioned showed that independent of the
effect of Fenna fibrate in reducing the
triglycerides and reducing the
cholesterol it might prevent or at least
the progression of diabetic
retinopathy the field study and the
Accord study showed basically the same
thing they showed that the drugs were
able to reduce the likelihood of
progression of diabetic retinopathy in
people who already have it it won't
prevent the development of diabetic
retinopathy but if you have diabetic
retinopathy overall there's about 30%
reduced likelihood that you're going to
progress so that sounds like it's pretty
impressive for a drug that overall isn't
very exciting so if we look overall at
the people who are taking the drug yes
it reduces the cholesterol that
yes it reduces a triglycerides a little
bit but the most important thing that
drug does is it seems to prevent the
progression of diabetic retinopathy and
so much so that in 2013 the Australian
authorities actually approved it
specifically for that purpose in type 2
diabetics in type 2 diabetics who had
existing diabetic retinopathy so in
America for some reason it's not really
caught on and additionally not only does
it seem to protect the eye but it also
seems at least to some extent to protect
the kidney and to protect the nerves so
overall we might have a good drug with
thinner fibrate additionally what it
might do is it might might prevent
amputations so in the amputations for
people who have microvascular now it
gets confusing a little bit because
there are two types of problems that the
vessels have you have the microvascular
in the macro vascular complications
macrovascular complications are just the
hardening of the arteries
well this drug doesn't seem to do much
about that but it does seem to do
something about the micro vascular
complications and the micro vascular
complications can lead to the amputation
especially if the toes or the foot well
the contraindications people shouldn't
take it if they have active liver
disease or gallbladder disease or if
they have severe kidney disease dialysis
women who are nursing or people who are
hyper sensitive the drug obviously
shouldn't take it the drug may and some
people that 5% increase some of the
liver tests happens bad 1% in people
taking placebo usually there's no
problem with that you can continue the
drug and the liver function tests seem
to get back to normal but rarely after a
period of weeks two years there could be
some sort of liver injury and a very
small percentage of people so
periodically you need some blood tests
and in some individuals there may be
some
down of the muscle we call it
rhabdomyolysis so if you're taking the
drug and all of a sudden you develop
diffuse aches and pains and your muscles
or unexplained muscle tenderness or some
weakness mmm you probably ought to go
and talk to your doctor it seemed like
maybe if you were taking a statin drug
it could increase the incidence but now
we think well it's probably just more
unique to the gamify Brazil but even so
you're probably at increased risk if
you're elderly if you have diabetes if
you have renal failure if you have low
level of thyroid hormone and again you
check the blood test periodically now
there's a caution if you're taking a
blood thinner like warfarin you might
need to reduce the dose of warfarin and
since there's more cholesterol that's
going to be excreted into the bile when
you take the phenol fibrate it might
predispose the gallstone so if you're at
risk you have to be extra careful and
then of course there are in a phylactery
actions that people can have if they
happen to be hypersensitive to the
medicine or its components and in some
people they develop pancreatitis and the
question is is the pancreatitis due to
the elevated levels of the triglycerides
certainly possible is it a drug effect
certainly possible or is it because of
too much biliary sludge that blocks the
pancreatic duct all of that's possible
so we don't really know what the
association is does not increase the
risk of deep vein thrombosis but might
just by a little bit increase the
likelihood of pulmonary embolism 1%
versus 0.7 percent of people taking
placebo so not as significant incidence
blood count will might be reduced in a
very small percentage of people who are
taking the drug so again need periodic
blood monitoring what are the standard
kind of side effects well there aren't
really all that much different from
placebo the reason that people stopped
taking a placebo well about 3% because
of the side effects 5% because of the
side effects from the Fenno fibrates so
really close to placebo some people
complain a back pain or headache or some
nausea but that's the exception rather
than the rule after
the medicine was on the market for a
while what they found was but yeah some
people develop some muscle spasms or
some rhabdomyolysis or some pain in the
joints or pancreatitis but the numbers
are so small that that's not really a
significant problem now there is a
problem in a very small percentage of
the people instead of raising the HDL
the good cholesterol might reduce the
good cholesterol might reduce the good
cholesterol Banta two milligrams you
normally wanted somewhere in 40
milligrams or higher that's what we
think might help protect you from having
a heart attack so low levels are of
concern and they can occur either
shortly after you start taking the drug
or for not appear till you've been on it
for several years
so again periodically blood checks it
can interact with some kind of medicines
but not usual there's the warfarin I
mentioned that you might have to modify
the dose and if you're taking a medicine
like tacrolimus or cyclosporine that can
lead to other kind of issues and if
you're taking a bio acid binding resin
maybe a drug like quest strain you have
to be careful because it's gonna bind
the fan of fibrate and both of them are
going to go out in the stool and you're
not going to absorb well there is a
problem if you happen to take colchicine
colchicine can increase the risk of
muscle problems and there's a little bit
of an increase in the amount of a
diabetic medicine that is glimepiride or
previs that and the cholesterol reducing
medicine there increased by somewhere
between 10 and 30% that's not a
significant increase in concentration in
the system and by the same token if
you're taking lipitor torva statin it's
going to be reduced in your blood by
about 20% limited data if you happen to
be pregnant probably shouldn't take the
drug if you're breastfeeding probably
shouldn't take the drug it's not really
for pediatric population if you happen
to be an older individual or somebody
who has impaired renal function have to
be a little careful of taking the drug
liver conditions haven't really been
evaluated interestingly the phenyl
fibrate is a pro drug it's totally
inactive it has to be altered in the
blood stream it's altered to phenol
fabric acid benefiber cassidy is the
active moiety it's active compound the
drug works by dilating the vessels by
acting as an anti-inflammatory by
blocking the cox-2 enzyme that that's
important for aspirin function it also
seems to stop the death of some of the
endothelial cells the cells that line
the blood vessels in the eye protects
the parasites the cells around those
blood vessels seems to stop the
leakiness of the retinal vessels all of
that very good
well additionally it seems to reduce the
level of uric acid and its
anti-inflammatory from a number of
standpoint so it might have some extra
benefit when you take the drug it's well
absorbed you can take it either with
food or without food
that's 60 percent of it's gonna appear
in the urine is Fanta firebrick acid
about 25% is gonna be in the feces
there's no unchanged phenol fibrate that
happens to be able to be detected inside
the bloodstream
it's not gonna be acted on by those
liver drug enzymes drug metabolizing
enzymes that happen to be in the liver
that we talked about so often leave the
3 a 4 and the 2 v6 unrelated to that you
reach a steady state in the bloodstream
after you've been taking it for about
nine days and that steady state is about
twice as great as it is if you just took
a single dose most of the drug 99% is
going to be bound to proteins when it
floats around in the system
the half-life of the drug is gonna be 20
hours so you only have to take one a day
as I mentioned if you happen to have
renal impairment have to reduce the drug
and if you really have significant renal
impairment you shouldn't take the drug
in rapt studies it was shown that it
might increase the incidence of liver
cancer and pancreatic cancer and
pancreatic adenoma is and even
testicular cell tumors testicular
interstitial cell tumors well how much
does all of this cost well for one
hundred forty five milligrams for
supply you could get it at Costco cash
for $56 if you go to wobbling the same
drug the same a man is gonna cost you
three hundred fifty nine dollars thirty
fifty six fifty six dollars at Costco
and almost three hundred sixty dollars
at Walgreens doesn't make any sense if
you happen to have a coupon like you can
get it good rx
you could go over to Walmart get it for
$24 you could get it at Walgreens for
seventy two dollars but if you make a
mistake and go over to CVS it's gonna be
a hundred seventeen dollars the brand
name itself the tricor that's 125 to a
$280 for cash but if you have a coupon
again free at good rx it's less than
$100 so fibrate 1005 rate is an old drug
it's mostly used to reduce the
triglycerides some time to reduce the
cholesterol but it might have new life
and it might have new life in protecting
against some of the complications of
diabetes especially the diabetic eye
disease the proliferative retinopathy
remember doesn't prevent the development
of proliferative retinopathy but it
prevents the progression and since we
don't have much else that's easy and
simple rather than an injection into the
eye every month it's very expensive it
seems that this relatively inexpensive
drug it has some very new and
interesting potential something you
should know about anyway thanks for
watching you enjoyed the show please
tell a friend maybe consider subscribing
so you'll be notified when we post new
shows I appreciate your interest
I'm dr. Kenan Lanza
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