the initial 5-HT 3 RA administered. 10
First-generation 5-HT 3 RAs
Ondansetron, granisetron,
tropisetron, dolasetron,
ramosetron and azasetron belong
to the first-generation setrons
and are available for oral and/
or intravenous administration.
Granisetron is also available
as transdermal patch which is
approved for prevention of CINV
in patients receiving multiday,
moderately or highly emetogenic
intravenous chemotherapy
for a planned duration of 3–5
consecutive days 3 when oral
antiemetic administration is
complicated by factors making
swallowing difficult. The patch
can be worn for up to seven days,
depending on the duration of the
applied chemotherapy course. 3
A number of randomised,
comparative trials have failed
to demonstrate any convincing
difference in efficacy or
tolerability when used at effective
recommended doses.
Key findings include: 3,11–16
• First-generation setrons
all appear equally effective
in preventing CINV at the
recommended dosages 1,3
• 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
54 | 2019 | hospitalpharmacyeurope.com
glucocorticosteroids
• Oral formulations and
intravenous setrons have
equivalent efficacy (at approved
and recommended doses and
intervals). 9 The decision as to
which formulation to use should
be based on patient-specific factors
and any associated costs for the
hospital.
5-HT 3 RAs have few adverse
effects and no limiting toxicity
at typical doses. Most commonly
reported adverse events are mild
and include low-grade headache,
malaise, transient elevation of
hepatic enzymes and constipation.
Caution is advised when using
5-HT 3 RAs concomitantly with
drugs that affect serotonin levels. 3
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-
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 .1,3 Revised
labelling recommends limiting
single IV doses of ondansetron to
no more than 16mg. 3
Paediatric experience is greatest