the chemotherapy cycle. 27,28
The drug–drug interaction
profile of aprepitant is complex.
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 corticosteroids,
(metabolised through the
CYP3A4 pathway) which can
lead to an increased exposure to
corticosteroids. Therefore, when
corticosteroids are administered
with aprepitant, doses should
be reduced by approximately
50%, except for those cases in
which corticosteroids constitute
part of the chemotherapeutic
regimen. 1,3,27,28
The possibility of increased
toxicity should be taken into
account when aprepitant is
administered with cytotoxics (for
example, doxorubicin) that are
metabolised by the same pathway.
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). 1,3,27,28
Common adverse reactions
reported for aprepitant and
fosaprepitant (in part of a
combination chemotherapy
regimen) include headache,
fatigue, anorexia, nausea,
constipation, transient mild
56 | 2018 | hospitalpharmacyeurope.com
elevation of serum transaminase
levels, weakness and hiccups. 1,3,27,28
Aprepitant has been studied
extensively in adults and the
pharmacokinetic disposition,
efficacy, safety and clinical
experience in children
and adolescents have been
investigated. 29–31
A powder for oral suspension
has been licensed for prevention
of nausea and vomiting associated
with MEC and HEC chemotherapy
in children, toddlers and infants
from the age of six months to
12 years. 30
Clinical trials to study its
efficacy in children are ongoing. 32
Netupitant
NEPA is an oral fixed dose
combination of the highly selective
NK1 RA netupitant 300mg and the
pharmacologically and clinically
distinct 5-HT3 RA, palonosteron
0.5mg.
NEPA was approved in the
United States (2014) and Europe
(2015) for prevention of CINV
in patients receiving MEC and
HEC (cisplatin HEC + MEC in
Europe) and is recommended in
international guidelines. 3,33–37
The positive effect in
improvement of quality of life of
patients has been assessed with
NEPA. NEPA plus a single dose of
dexamethasone was superior to
palonosetron plus dexamethasone
in preventing CINV following
MEC in acute, delayed and overall