Treatment of Dyslipidemia

The most serious side effects are liver failure
and rhabdomyolysis. Serious liver damage
caused by statins is rare. More often, statins
cause abnormalities of liver tests.

Abnormal tests usually return to normal
even if a statin is continued, but if the
abnormal test value is greater than three
times the upper limit of normal, the statin
usually is stopped. Liver tests should be
measured before statins are started and if
there is a medical concern about liver
damage thereafter.

Statins have some important drug interactions.
The first type of interaction involves the
enzymes responsible for the elimination of
statins by the liver. Liver enzymes (specifically,
the cytochrome P-450 liver enzymes) are responsible
for eliminating all statins from the body with the
exception of pravastatin and rosuvastatin.

Therefore, drugs that block the action of these liver
enzymes increase the levels of simvastatin,
lovastatin, fluvastatin, and atorvastatin (but not
pravastatin or rosuvastatin) in the blood and can lead
to the development of rhabdomyolysis.

Rhabdomyolysis is a rare serious side effect which involves
damage to muscles. Rhabdomyolysis often begins as
muscle pain and can progress to loss of muscle
cells, kidney failure, and death.

It occurs more often when statins are used in combination
with other drugs that themselves cause rhabdomyolysis or
with drugs that prevent the elimination of statins and raise
the levels of statins in the blood. Since rhabdomyolysis
may be fatal, unexplained joint or muscle pain that occurs
while taking statins should be brought to the attention of a
health care professional for evaluation.

Statins must not be used during pregnancy because of the
risk of serious adverse effects to the developing fetus.

Another important drug interaction occurs between
statins and niacin and fibric acids
(forexample, gemfibrozil [Lopid], clofibrate [Atromid-S],
andfenofibrate [Tricor]). Niacin and the fibric acid drugs
can cause rhabdomyolysis or liver failure when used
alone, and combining them with statins increases the
likelihood of rhabdomyolysis or liver failure. Gemfibrozil
should not be combined with statins. Other fibric acids and
niacin are used, with caution, in combination with statins.

Cholestyramine (Questran) as well
as colestipol (Colestid) bind statins in the intestine
and reduce their absorption into the body. To prevent
this binding within the intestine, statins should be taken
one hour before or four hours after cholestyramine or
colestipol.

Stains increase the effect of warfarin(Coumadin).
Patients taking statins and warfarin should their
blood clotting ability monitored carefully.

Fibric acid derivatives (fibrates) are a class
of medication that lowers bloodtriglyceride
levels. Fibrates lower blood triglyceride levels by
reducing theliver's production of VLDL (the
triglyceride-carrying particle that circulates in the
blood) and by speeding up the removal
of triglycerides from the blood.

Fibrates also are modestly effective in increasing
blood HDL cholesterol levels; however, fibrates
are not effective in lowering LDL cholesterol.

The side effects of fibrates include nausea,
stomach upset, and sometimes diarrhea. Fibrates
can irritate (inflame) the liver. The liver
irritation usually is mild and reversible, but
it occasionally can be severe enough to require
stopping the drug.

Fibrates can cause gallstones when
used for several years.

Fibrates can increase the effectiveness of blood
thinners, such as warfarin (Coumadin), when both
medications are used together. Thus, the dose of warfarin
should be adjusted to avoid over-thinning of the blood
which can lead to excessive bleeding.

Fibrates can cause muscle damage particularly
when taken together with statin medications.

Gemfibrozil interferes with the breakdown of
certainstatins (for example, simvastatin [Zocor]
or lovastatin [Mevacor, Altoprev]), resulting in
higher statin blood levels, and hence a higher
likelihood of muscle toxicity from the statin

Fibrates can increase the effectiveness of blood
thinners, such as warfarin(Coumadin), when
both medications are used together. Thus, the
dose of warfarin should be adjusted to avoid
over-thinning of the blood which can lead to
excessive bleeding.

Having enough niacin, or vitamin B3, in the body is
important for general good health. As a treatment, higher
amounts of niacin can improve cholesterol levels and lower
cardiovascular risks.

As a cholesterol treatment, niacin has strong evidence.
Several studies have shown that it can boost levels of
good HDL cholesterol and lower triglycerides as well or
better than some prescription drugs. Niacin also modestly
lowers bad LDL cholesterol. It's often prescribed in
combination with statins for cholesterol control, such
as Crestor, Lescol, orLipitor.

Side effects. Niacin can cause flushing -- harmless but
uncomfortable redness and warmth in the face and neck -especially when you first begin taking it. Your health care
provider will probably suggest increasing the dose slowly to
reduce this problem. He or she might also offer a time-release
prescription formulation to control flushing. Niacin can
cause upset stomach and diarrhea. However, all of these side
effects tend to fade over time.

Risks. Niacin does have risks. It can cause liver problems,
stomach ulcers, changes to glucose levels, muscle damage, low
blood pressure, heart rhythm changes, and other issues. People
with any health condition including liver or kidney
disease, diabetes,high blood pressure, or cardiovascular problems
need to talk to a doctor before using niacin supplements. Do not
treat high cholesterol on your own with over-the-counter niacin
supplements.

Interactions. If you take any medicines or supplements
regularly, talk to your doctor before you start using niacin
supplements. They could interact with medicines like
diabetes drugs, blood thinners, anticonvulsants, blood
pressure medicines, thyroid hormones, and antibiotics as
well as supplements like ginkgo biloba and some
antioxidants.

Alcohol might increase the risk of liver problems. Though
niacin is often used along with statins for high cholesterol,
this combination may increase the risk for side effects. Get
advice from your health care provider.

Labels have been revised to remove the need for
routine periodic monitoring of liver enzymes in
patients taking statins.

The labels now recommend that liver enzyme
tests should be performed before starting statin
therapy and as clinically indicated thereafter.

FDA has concluded that serious liver injury with
statins is rare and unpredictable in individual
patients, and that routine periodic monitoring of
liver enzymes does not appear to be effective in
detecting or preventing serious liver injury.

The NLA or NCEP ATP-III guidelines do not
provide specific recommendations for liver
function monitoring with fibrate therapy.

However, baseline measures, periodic follow-up
monitoring, and reduction or discontinuation of
therapy with transaminase levels ≥3 times the
ULN is prudent.

Additionally, clinicians should be cognizant of
factors that may increase risk of hepatotoxicity
such as drug interactions or pre-existing liver
disease.

Check lipids (fasting specimens required
to quantify LDL fraction and triglycerides
(TGs) accurately) and LFTs prior to
starting treatment.

Take statins at night when they have a
slightly greater effect.

Check U&Es prior to treatment, particularly if using in
combination with a statin, as renal insufficiency
increases the risk of myotoxicity. Adjust the dose if
there is evidence of renal insufficiency. Routine
ongoing monitoring of creatinine levels, etc is not
required.

Discontinue the fibrate if serum aminotransferases
are three or more times the upper limit of normal.

Check CK level only if myopathy or rhabdomyolysis is
suspected: stop treatment if the CK level is five times
the upper limit of normal or more.

The FDA recommends dose adjustment or
cessation when these liver enzymes reach
three times the upper limit of normal
levels. Because of their once-a-day
dosing, minimal side effects, and efficacy,
the statins are considered a first-line drug
therapy for dyslipidemias.

The fibrates work preferentially on the liver to reduce triglyceride
synthesis and very low-density lipoprotein (VLDL) production.
Fibrates also stimulate the uptake and metabolism of VLDL from
the plasma, which can lead to increased LDL levels in patients
who have very high baseline triglyceride levels.

They can reduce triglyceride levels markedly, and often produce a
modest increase in HDL-C. However, they usually are dosed
multiple times per day and may produce side effects, such as
gallstones and gastrointestinal (GI) disturbances, including
nausea and rash. However, for patients who predominantly have
elevated triglycerides (type IV and V hyperlipidemias), they are
considered first-line agents. Fibric acid derivatives should not be
prescribed if a patient is receiving a statin.

early symptoms of myopathy include muscle weakness,
muscle pain or tenderness, muscle pain during exercise, and
muscle fatigue. In some cases, patients with myopathy fall often,
have trouble walking, or experience difficulty getting out of a
chair.
Types of muscle proteins include the following:
 Creatine kinase (CK)
 Lactic dehydrogenase (LDH)
 Pyruvate kinase (PK)
As the disease progresses and muscle tissue wastes away, there is
less and less protein to circulate and the amount in the blood
drops to a normal level. The CK level is especially important in
diagnosing Duchenne MD and the metabolic myopathies.
Patient Case #3: AL is a 57-year-old African
American man with chronically elevated liver
transaminases. He also has a history of type 2
DM and stroke.
His physician calls your pharmacy asking if you
have any idea if he can use a statin medication
in this patient. Currently he is taking colestipol
for hyperlipidemia, but has discontinued this
medication due to severe constipation. Patient
denies any other complaints, including nausea,
vomiting, abdominal pain or jaundice.
AL’s labs are as follows: LDL 168 mg/dL, TC 276
mg/dL, TG 332 mg/dL, and HDL 42 mg/dL.
Patient’s AST and ALT have been consistently
elevated between 1.1-1.4 times the upper
limit of normal (ULN) for years.
His total and direct bilirubin, INR, platelets, and
albumin are all normal. Ultrasound of liver shows
probable non-alcoholic fatty liver disease
(NAFLD).

Elevations in liver aminotransferases, alanine
aminotransferase (ALT) and aspartate
aminotransferase (AST) have been demonstrated
with all statins at all doses.
if elevations in AST and ALT are seen prior to statin
initiation, the etiology should be determined and
referral to a hepatologist or gastroenterologist
may be necessary.
If AST and ALT become elevated at any time
during statin therapy, it remains prudent to
determine the etiology of the abnormal tests to
avoid discontinuation of statin therapy in high
risk individuals.
if the AST and ALT are elevated between one to
three times the ULN, then there is no need to
change the patient’s lipid-lowering regimen.
The panel does believe decompensated cirrhosis
and acute liver impairment are contraindications
to statin therapy. Decompensated cirrhosis is
cirrhosis associated with impaired liver function.
Patients would not only have elevated liver
aminotransferases, but also have elevated
indirect bilirubin, decreased albumin, decreased
platelets, increased INR, and possibly bleeding
varices

SOAP THIS CASE

Determine LDL goal

If the aminotransferases, alanine
aminotransferase (ALT) and aspartate
aminotransferase (AST) are elevated you should
stop Statins ( T / F )
