at the recommended dosages, 1,3
and are considered to be equally
effective and interchangeable.
A meta-analysis performed
by Jordan et al indicated that
ondansetron, granisetron, and
dolasetron had similar clinical
efficacy for prevention of acute
chemotherapy-induced emesis. 11
For each setron, there is
a therapeutic efficacy plateau at
a definable dose level above which
further dose escalation does not
improve outcome. Their efficacy
is significantly improved when
combined with corticosteroids.
Oral formulations are
therapeutically equivalent
(at approved doses), and as
effective as the intravenous
route of administration. 3
The decision as to which
formulation to use should be based
on patient-specific factors and any
associated costs for the hospital.
5-HT3 RAs have few adverse
effects and no limiting toxicity
at typical doses. Most commonly
reported adverse events are mild
and include headache, transient
elevation of hepatic enzymes and
constipation. Electrocardiogram
interval changes and cardiac
arrhythmias are a class-effect.
Patients most at risk include
those with congenital long
QT syndrome, heart failure,
bradyarrhythmias, electrolyte
abnormalities (hypokalaemia,
hypomagnesaemia), and
concomitant use of other QT-
54 | 2018 | hospitalpharmacyeurope.com
prolonging medications. 1,3,11–16
Intravenous dolasetron and
the 32-mg intravenous dose
of ondansetron are no longer
indicated for the prevention of
CINV because they are associated
with dose-dependent increase in
the corrected QT interval. 1 This is
observed less with the oral form,
although there is still a potential
risk. 3
Paediatric experience is greatest
with ondansetron, granisetron
and tropisetron and, recently,
palonosetron. 16–19
Second-generation 5-HT3 RAs
The second-generation agent
palonosetron is structurally
unrelated to other available 5-HT3
RAs. It differs in having 30–100-
fold higher affinity for the 5-HT3
receptor and has a significantly
longer half-life (40 hours)
compared with first-generation
antagonists (ondansetron: children
<15 years: 2–7 hours; adults: 3–6
hours; granisetron: oral 6 hours;
intravenously 9 hours; dolasetron:
≤10 min; hydrodolasetron: adults:
6–8 hours; children: 4–6 hours;
tropisetron: 8 hours). 1,3,18,19
Clinical trials have
demonstrated the non-inferiority
and superiority of palonosetron
versus first generation 5-HT3
RAs. 20,21
Palonosetron is also indicated in
paediatric patients ≥1 month up to
17 years of age for the prevention
of acute nausea and vomiting