C H A P T E R 4 7
Lipid-lowering agents
741
Pharmacokinetics
The statins are all absorbed from the GI tract and
undergo first-pass metabolism in the liver. They are
excreted through faeces and urine. The peak effect of
these drugs is usually seen within 2 to 4 weeks. These
drugs are most effective when taken at night when the
liver is processing the most lipids. These drugs cross
the placenta, and most have been found in breast milk.
Contraindications and cautions
These drugs are contraindicated in the presence of
allergy to any of the statins or to fungal by-products or
compounds
to avoid hypersensitivity reactions
. Statins
are also contraindicated in people with active liver
disease or a history of alcoholic liver disease,
which
could be exacerbated, leading to severe liver failure,
and
with pregnancy or breastfeeding,
because of the poten-
tial for adverse effects on the fetus or neonate.
These
drugs are labelled as pregnancy category X.
Atorvastatin levels are not affected by renal disease,
but individuals with renal impairment who are taking
other statins require close monitoring. Caution should
be used in individuals with impaired endocrine function
because of the potential alteration in the formation of
steroid hormones.
Adverse effects
The most common adverse effects associated with these
drugs reflect their effects on the GI system: flatulence,
abdominal pain, cramps, nausea, vomiting and consti-
pation. CNS effects can include headache, dizziness,
blurred vision, insomnia, fatigue and cataract develop
ment, and may reflect changes in the cell membrane and
synthesis of cholesterol. Increased concentrations of
liver enzymes commonly occur, and acute liver failure
has been reported with the use of atorvastatin and flu-
vastatin. Pravastatin and simvastatin are not associated
with some of the severe liver toxicity that is seen with
the other agents. Rhabdomyolysis, a breakdown of
muscles whose waste products can injure the glomerulus
and cause acute renal failure, is a rare adverse effect but
has been known to occur with the use of all of these
drugs. MEDSAFE New Zealand has also warned that
high dose (80 mg) of simvastatin increases the risk of
myopathies.
Clinically important drug–drug interactions
The risk of rhabdomyolysis increases if any of these
drugs is combined with erythromycin, cyclosporin, gem-
fibrozil, niacin or antifungal drugs; such combinations
should be avoided.
Increased serum levels and resultant toxicity can
occur if these drugs are combined with digoxin or
warfarin; if this combination is used, serum digoxin
levels and/or clotting times should be monitored care-
fully and the prescriber consulted for appropriate dose
changes.
Increased oestrogen levels can occur if these drugs
are taken with oral contraceptives; the person should be
monitored carefully if this combination is used.
Serum levels of the drug and the risk of toxicity
increase if combined with grapefruit juice.
Safe medication administration
Individuals who are taking HMG-CoA inhibitors need to
be cautioned to avoid using grapefruit juice while taking
these drugs. Grapefruit juice alters the metabolism of the
drugs, leading to an increased serum level of the drug and
increased risk for adverse effects, such as the potentially fatal
rhabdomyolysis with renal failure. The effects may last for
several days, so just drinking the grapefruit juice at a different
time of day does not protect the person from risk.
Prototype summary: Atorvastatin
Indications:
Adjunct to diet in the treatment of
elevated levels of cholesterol, triglycerides and
LDL; to increase HDL cholesterol in people with
primary hypercholesterolaemia; treatment of boys
and postmenarchal girls age 10 to 17 years of age
with familial hypercholesterolaemia and two or
more risk factors for CAD; prevention of CAD
in adults without clinically evident heart disease
but with multiple risk factors to reduce the risk of
cardiovascular events.
Actions:
Inhibits HMG-CoA, causing a decrease in
serum cholesterol levels, LDLs and triglycerides and
an increase in HDL levels.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Slow 1–2 hours
20–30 hours
T
1/2
:
14 hours; metabolised in the liver and cells and
excreted in bile.
Adverse effects:
Headache, flatulence, abdominal
pain, cramps, constipation, rhabdomyolysis with
acute renal failure.
Care considerations for people receiving
HMG-CoA reductase inhibitors
Assessment: History and examination
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Assess for contraindications and cautions: any
known allergies to these drugs or to fungal
