start

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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