only a substrate for CYP3A4 and a
moderate inhibitor of CYP2D6. 19
Because CYP3A4 is involved in
the metabolism of approximately
50% of marketed drugs, it is
not surprising that inducers or
inhibitors of this isoenzyme might
be involved in numerous DDIs. By
inhibiting CYP3A4, aprepitant can
decrease the elimination rate of
CYP3A4 substrates, leading to the
increased exposure and capacity
to exert AEs. Aprepitant DDIs that
involve this mechanism include:
corticosteroids (dexamethasone,
methylprednisolone),
chemotherapy agents (ifosfamide,
irinotecan, possibly etoposide,
vinorelbine), benzodiazepines
(midazolam, alprazolam,
triazolam), immunosuppresants
72 | 2018 | hospitalpharmacyeurope.com
(cyclosporine, tacrolimus,
everolimus), opioids (alfentanil,
fentanyl), ergot alkaloids, diltiazem
and others. 9,19 No clinically
significant effect of aprepitant on
either the pharmacokinetics of
standard doses of docetaxel and
cyclophosphamide or toxicity
of docetaxel were observed. 20
The concomitant use of
aprepitant with dexamethasone/
methylprednisolone requires the
dose reduction of corticosteroids
by approximately 50% if they
are administered orally, whereas
intravenous administration
might require a smaller dose
reduction. 1 Midazolam is
frequently a part of antiemetic
protocols and AEs with midazolam
when co-administered with