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CONTINUING PROFESSIONAL DEVELOPMENT
group. Only the combination-therapy
group showed a significant decrease in
Rosuzet is currently available in
composite packs containing ezetimibe
10 mg and rosuvastatin in strengths
two separate tablets. It is indicated as
adjunctive therapy to diet in patients
with primary (heterozygous familial and
not appropriately controlled with
rosuvastatin or ezetimibe alone.
To be eligible for PBS-subsidised Rosuzet,
the patient must have high cholesterol
levels that are inadequately controlled
after at least three months of treatment
at a maximum tolerated dose of a statin,
in conjunction with dietary therapy
and exercise. Details of PBS eligibility
criteria for lipid-lowering medicines can
be found on the PBS website (at: www.
Contraindications to Rosuzet therapy
myopathy secondary to other
pregnancy (category D) – statins are
contraindicated in pregnancy; women
of childbearing age must be using
adequate contraceptive measures
breastfeeding – lack of human data
active liver disease, including
unexplained persistent elevations in
serum transaminases and any serum
transaminase elevation exceeding
three times the upper limit of normal
combination with fenofibrate in
patients with gall bladder disease
(risk of cholelithiasis)
systemic sodium fusidate therapy
(risk of myopathy/rhabdomyolysis).
Rosuzet 10 mg + 40 mg strength is
also contraindicated in patients with
predisposing factors for myopathy/
personal or family history of
hereditary muscular disorders
severe renal impairment (CrCl
Asian race (pharmacokinetic studies
indicate that people of Asian ancestry
may achieve higher plasma levels of
concomitant use of fibrates.
Ezetimibe is rapidly absorbed and is
metabolised in the small intestine
and liver via glucuronide conjugation.
Food has no effect on its absorption.
The glucuronide metabolite has
been shown to have a higher binding
affinity for NPC1L1 than ezetimibe.
The metabolite and the remaining
ezetimibe are secreted in the bile
back into the intestine. They are then
repeatedly recirculated through the
liver and back into the intestine.
This enterohepatic circuit is responsible
for its long half-life of 22 hours.
About 90% of ezetimibe and its
metabolite are excreted in the faeces
and 10% in the urine.
Peak plasma levels occur 3–5 hours
after administration, and absolute
bioavailability is 20%. Food and dosing
time do not affect plasma levels, and
it can be taken in the morning or the
evening. It has a half-life of 19 hours
and is 90% protein-bound. About 10%
of a dose is metabolised by CYP2C9
to N-desmethyl rosuvastatin, which
has one-sixth to one-half the activity
of rosuvastatin. The unchanged drug
(90%) is excreted in the faeces, and the
metabolite (10%) in the urine.
Table 2. Ezetimbe and rosuvastatin drug interactions9,19,23
Interacting medicine Interaction
Increased plasma levels of all three
drugs (rosuvastatin by 7-fold)
Maximum rosuvastatin dose
Monitor cyclosporin levels and
for ezetimibe adverse effects
Increased risk of cholelithiasis; both
ezetimibe and fibrates can increase
cholesterol excretion into the bile.
Increased risk of myopathy and
rhabdomyolysis with statins
Increased rosuvastatin levels
Limit rosuvastatin dose to
10 mg (however, see above)
Possible significant increased
Monitor INR closely
Increased rosuvastatin levels
Start rosuvastatin with 5 mg
dose; monitor for adverse
effects; measure creatine
kinase (CK) if indicated
Increased risk of rhabdomyolysis
Reduced absorption of rosuvastatin Separate dosing by at least
Reduced absorption of ezetimibe
Take at least 2 hours before or
4 hours after resin.
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