aprepitant should be monitored.
It was shown that a five-day
aprepitant protocol increased
the concentrations of orally
administered midazolam (2mg)
significantly; however, there were
no clinically significant changes
in concentrations following
intravenous administration of
the same dose of midazolam.
For all aprepitant DDIs, caution
is warranted and additional
monitoring might be appropriate
but, so far, the recommendation
for dose-adjustment is limited only
to corticosteroids. 9,19 As an inducer
of CYP3A4 and CYP2C9, aprepitant
can increase the elimination
rate of substrates and decrease
their efficacy. Reduced efficacy
of hormonal contraceptives has
been reported and patients require
additional contraception during
treatment with aprepitant and
two months following the last
dose. The efficacy of warfarin
may be compromised and the
international normalised ratio
(INR) should be monitored within
two weeks of aprepitant use. 9,19
Because aprepitant itself
is metabolised via CYP3A4,
other inhibitors such as azole
antimycotics (ketoconazole,
itraconazole, voriconazole,
posaconazole), macrolide
antibiotics, nefazodone and
protease inhibitors might
increase plasma concentrations
of aprepitant several-fold and
potentiate AEs. In contrast, strong
CYP3A4 inducers might reduce
the efficacy of aprepitant and
their concomitant use should be
avoided. 9,19
Netupitant as a substrate and
moderate inhibitor of CYP3A4
has similar DDIs to aprepitant but
lacks the DDIs mediated by the
induction of CYP3A4 and CYP2C9.
When NEPA is administered,
all DDIs of netupitant and
palonosetron should be considered.
Increased exposure to docetaxel
and etoposide was observed
following co-administration
with netupitant (in NEPA) but no
consistent effect was seen with
cyclophosphamide. Increased
toxicity of cyclophosphamide,
etoposide and docetaxel in
the presence of NEPA was
not observed. 21,22 Netupitant
was associated with in vitro
P-glycoprotein (P-gp) inhibition, but
this effect was not seen in vivo with
digoxin. Similar to aprepitant, the
only recommended dose-reduction
applies to corticosteroids,
whereas all other concomitantly
administered interacting drugs
should be monitored for AEs. 8,19
Although rolapitant is a
substrate for CYP3A4, it seems that
only strong CYP3A4 inducers might
reduce its efficacy and concomitant
use should be avoided.
Rolapitant is not a CYP3A4
inhibitor, so there is no
requirement to reduce the dose
of dexamethasone. Rolapitant
is a moderate CYP2D6
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