Aprepitant
Oral formulation
The first marketed NK 1 inhibitor
was the oral formulation of
aprepitant, licensed for the
prevention of acute and delayed
nausea and vomiting associated
with MEC and HEC courses
in combination with other
antiemetics, and for the prevention
of postoperative nausea and
vomiting in adults. Being an NK 1
RA, aprepitant has particular
efficacy in the delayed phase of
CINV. 1,3,28
Although aprepitant has
improved control of CINV in
combination with a 5-HT 3 RA and
dexamethasone, aprepitant plus
dexamethasone alone was not
as effective as the combination
of the three drugs. As outlined
in the label, aprepitant must be
administered in combination with
a 5-HT 3 RA and dexamethasone
for three days (mainly due to the
short half-life of 9–13 hours),
regardless of the duration of the
chemotherapy cycle. 28
The drug–drug interaction
profile of aprepitant (and its
intravenous formulation) is
complex. 29,30 Aprepitant is a
substrate and inhibitor of CYP3A4
and an inducer of CYP3A4, CYP2C9
and potentially other isoenzymes.
Drug–drug interactions
might become relevant when
aprepitant is co-administered
with glucocorticosteroids,
(metabolised through the
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CYP3A4 pathway) which can
lead to an increased exposure to
glucocorticosteroids. Therefore,
when glucocorticosteroids are
administered with aprepitant,
doses should be reduced by
approximately 50%, except
for those cases in which
glucocorticosteroids constitute
part of the chemotherapeutic
regimen. 1,3,28–30
The possibility of increased
toxicity should be taken into
account when aprepitant is
administered with cytotoxics (for
example, doxorubicin, ifosfamide)
that are metabolised by the same
pathway. 31
Aprepitant is a weak inducer
of CYP2C9, a pathway through
which drugs such warfarin and
other medications are metabolised
(for example, oral contraceptives
such as ethinyl estradiol-
levonorgestrel). 1,3,28,29
Common adverse reactions
reported for aprepitant (in part
of a combination chemotherapy
regimen) include headache,
fatigue, anorexia, nausea,
constipation, transient mild
elevation of serum transaminase
levels, weakness and hiccups. 1,3,28
Aprepitant has been studied
extensively in adults and the
pharmacokinetic disposition,
efficacy, safety and clinical
experience in children
and adolescents have been
investigated. 32,33
A powder for oral suspension