page186
Ezetimibe
Ezetimibe inhibits the intestinal
absorption of
choles-
terol. It is licensed as an adjunct to dietary manipulation
in patients with primary hypercholesterolaemia in com-
bination with a statin or alone (if a statin is inappropri-
ate),
in
patients
with
homozygous
familial
hyper-
cholesterolaemia in combination with a statin,
and in
patients with homozygous familial sitosterolaemia (phy-
tosterolaemia). If ezetimibe is used in combination with
a statin,
there is an increased risk of
rhabdomyolysis
(see also Muscle Effects,
p.
162)
NICE guidance
Ezetimibe for the treatment of primary
hypercholesterolaemia (November 2007)
Ezetimibe,
used in accordance with the licensed
indications
for
Ezetrol
c
,
is
an
option
for
the
treatment of
adults with primary hypercholesterol-
aemia.
EZETIMIBE
Indications
adjunct to dietary measures and statin
treatment in primary hypercholesterolaemia and
homozygous familial hypercholesterolaemia (ezeti-
mibe alone in primary hypercholesterolaemia if statin
inappropriate or not tolerated);
adjunct to dietary
measures in homozygous sitosterolaemia
Cautions
interactions: Appendix 1 (ezetimibe)
Hepatic impairment
avoid in moderate and severe
impairment—may accumulate
Pregnancy
manufacturer advises use only if potential
benefit outweighs risk—no information available
Breast-feeding
manufacturer advises avoid—present
in milk in
animal
studies
Side-effects
gastro-intestinal disturbances;
headache,
fatigue;
myalgia;
rarely
arthralgia,
hypersensitivity
reactions (including rash,
angioedema,
and anaphy-
laxis), hepatitis;
very rarely
pancreatitis, cholelithiasis,
cholecystitis,
thrombocytopenia,
raised creatine
kinase,
myopathy,
and rhabdomyolysis
Dose
.
ADULT
and
CHILD
over 10 years,
10 mg once daily
Ezetrol
c
(MSD,
Schering-Plough) A
Tablets
,
ezetimibe 10 mg,
net price 28-tab pack =
£26.31
With simvastatin
See under Simvastatin
Fibrates
Bezafibrate, ciprofibrate, fenofibrate, and gemfibrozil
act mainly by decreasing serum triglycerides; they have
variable effects on LDL-cholesterol.
Although a fibrate
can reduce the risk of coronary heart disease events in
those with low HDL-cholesterol
or
with raised tri-
glycerides,
a statin should be used first.
Fibrates are
first-line therapy only in those whose serum-triglyceride
concentration is greater than 10 mmol/litre or in those
who cannot tolerate a statin. In type 2 diabetes a fibrate
can be added to a statin for those with a serum-trigly-
ceride concentration exceeding 2.3 mmol/litre,
despite
6 months of treatment with a statin and optimal glycae-
mic control.
Fibrates can cause a myositis-like syndrome, especially
if
renal
function is impaired.
Also,
combination of
a
fibrate with a statin increases the risk of muscle effects
(especially rhabdomyolysis)
and should be used with
caution (see Muscle Effects,
p.
162) and monitoring of
liver function and creatine kinase should be considered;
gemfibrozil
and statins should not
be used concomi-
tantly.
BEZAFIBRATE
Indications
hyperlipidaemias of types IIa,
IIb,
III,
IV,
and V in patients who have not responded adequately
to diet and other appropriate measures; also see notes
above
Cautions
correct hypothyroidism before initiating
treatment (see p.
161);
interactions: Appendix 1
(fibrates)
Contra-indications
hypoalbuminaemia,
primary
biliary cirrhosis,
gall bladder disease,
nephrotic
syndrome
Hepatic impairment
avoid in severe liver disease
Renal impairment
reduce dose to 400 mg daily if
eGFR 40–60 mL/minute/1.73 m
2
;
reduce dose to
200 mg every 1–2 days if eGFR 15–40 mL/minute/
1.73 m
2
;
avoid if eGFR less than 15 mL/minute/
1.73 m
2
;
avoid modified-release preparations if eGFR
less than 60 mL/minute/1.73 m
2
Myotoxicity
Special
care needed in patients
with renal
disease,
as progressive increases in serum creatinine con-
centration or failure to follow dosage guidelines may result in
myotoxicity (rhabdomyolysis); discontinue if myotoxicity
suspected or creatine kinase concentration increases signif-
icantly
Pregnancy
manufacturers advise avoid—embryotoxi-
city in
animal
studies
Breast-feeding
manufacturer advises avoid—no
information available
Side-effects
gastro-intestinal disturbances,
anorexia;
less commonly
cholestasis,
weight gain,
dizziness,
headache,
fatigue,
drowsiness,
renal impairment,
raised serum creatinine (unrelated to renal impair-
ment),
erectile dysfunction,
myotoxicity (with myas-
thenia or myalgia)—special risk in renal impairment
(see Cautions), urticaria,
pruritus, photosensitivity
reactions;
very rarely
gallstones,
hypoglycaemia,
anaemia,
leucopenia, thrombocytopenia,
increased
platelet count,
alopecia,
Stevens-Johnson syndrome,
and toxic epidermal necrolysis
Dose
. See preparations below
Bezafibrate
(Non-proprietary) A
Tablets
, bezafibrate 200 mg, net price 100-tab pack =
£6.86 Label:
21
Dose
200 mg 3 times daily;
CHILD over 10 years,
see
BNF for
Children
Bezalip
c
(Actavis) A
Tablets
,
f/c,
bezafibrate 200 mg,
net price 100-tab
pack = £8.63.
Label:
21
Dose
200 mg 3 times daily;
CHILD over 10 years,
see
BNF for
Children
Modified release
Bezafibrate
(Non-proprietary) A
Tablets
,
m/r,
bezafibrate 400 mg,
net price 28-tab
pack = £3.25.
Label:
21,
25
Dose
400 mg once daily (dose form not appropriate in patients
with renal
impairment)
Brands include
Fibrazate
c
XL
,
Zimbacol
c
XL
166
2.12 Lipid-regulating drugs
BNF 61
2
Cardiovascular system