taken into account and a reduced
dose of dexamethasone (acting as
a CYP3A4 substrate) should be used
when combined with aprepitant
and NEPA. 1,3,33–39
phases of observation. As a fixed-
dose antiemetic drug combination,
NEPA along with a single dose of
dexamethasone on day 1 offers
guideline-based prophylaxis with a
convenient, single-day treatment. 38
In addition to the oral fixed
combination, the intravenous
equivalent (IV NEPA) consisting of
235mg fosnetupitant free-base, a
prodrug of netupitant, plus 0.25mg
palonosetron, has been approved
by the FDA (in 2018) for prevention
of CINV in patients receiving
cisplatin HEC.
Netupitant has a half-life of
90 hours and a high binding
affinity. Similar to aprepitant, it
inhibits CYP3A4, so the possibility
of drug–drug interactions must be
Rolapitant
Rolapitant is a potent and selective
NK1 inhibitor, approved by the
FDA (2015) and granted marketing
authorisation in Europe (2017) for
prevention of delayed CINV.
Rolapitant has a long plasma
half-life (approximately 180 hours)
and is metabolised primarily
by CYP3A4. Unlike aprepitant,
fosaprepitant and netupitant, it
does not inhibit CYP3A4, so no
dose adjustment of dexamethasone
is required. Rolapitant moderately
inhibits CYP2D6, breast-
cancer resistance protein and
P-glycoprotein. Caution should
be exercised when rolapitant
is combined with a medicinal
product metabolised by CYP2D6,
notably those having a narrow
therapeutic margin. It is approved
in adults, in combination with
other antiemetic agents (5-HT3
RAs and corticosteroid) to prevent
delayed CINV and effectively
prevents nausea during the overall
and delayed phases in patients
receiving HEC and MEC. 40
The most common side effects
are fatigue and headache. Post-
marketing surveillance revealed
that anaphylaxis, anaphylactic
shock, and other serious
hypersensitivity reactions due to
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