associated with initial and repeat
courses of emetogenic cancer
chemotherapy, including HEC. 19
The safety of palonosetron
is similar to other currently
available 5-HT3 RAs. Common
adverse events include headache,
constipation, fever, abdominal
pain, diarrhoea, pruritus, pain,
asthenia and insomnia. As with
other 5-HT3 RAs, caution should
be exercised in the concomitant
use of palonosetron with medicinal
products that increase the QT
interval, or in patients who
have, or are likely to develop,
prolongation of the QT interval. 1,3,19
NK1 RAs
Substance P, an 11-amino acid
neuropeptide, is the endogenous
ligand for the NK1 receptor. NK1
RAs represent the newest class
of antiemetic agents effective for
the prevention of CINV and have
significantly improved the rate of
complete response in the overall,
acute and delayed phases. 3
Substance P is a neuropeptide
from the family of tachykinins
that is abundantly and widely
distributed in the central nervous
system and other tissues. NK1
receptors are localised in the
brainstem nuclei and the dorsal
vagal complex, regions of the brain
involved in the regulation process
of emesis. Substance P itself is able
to induce emesis.
The signals of substance P
are mediated through the NK1
receptor, classified as a G-protein-
coupled receptor, that is associated
to the inositol phosphate signal
transduction pathway. 1,3,22–26
Aprepitant/fosaprepitant
The first marketed NK1 inhibitors
were the oral capsule formulation
of aprepitant and its intravenously
administered water-soluble
phosphoryl prodrug, fosaprepitant.
Fosaprepitant is rapidly converted
(within 30 minutes of infusion) to
aprepitant by a nearly complete
conversion. As fosaprepitant
is a prodrug of aprepitant, the
pharmacological activity mirrors
that of aprepitant. 27,28
Both drugs are 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. They have
particular efficacy in the delayed
phase of CINV. 1,3,27,28
Although aprepitant has
improved control of CINV in
combination with a 5-HT3 RA and
dexamethasone, aprepitant plus
dexamethasone alone was not
as effective as the combination
of the three drugs. As outlined
in the Summary of Product
Characteristics, aprepitant must
be administered in combination
with a 5-HT3 RA and
dexamethasone for three days,
regardless of the duration of
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