are a class effect of the first-
generation 5-HT3 RAs, although
they have not been reported
with transdermal or extended-
release subcutaneous granisetron.
Moreover, QTc prolongation
has not been observed with
palonosetron. The most serious
consequence of QTc prolongation
is the occurence of life-threatening
ventricular arrhythmias, including
torsades de pointes. Numerous
other drugs have the ability to
prolong the QTc interval such as:
anti-arrhythmics (amiodarone,
dronedarone, sotalol, dofetilide),
antidepressants (citalopram,
escitalopram), gastroprokinetics
(domperidone, metoclopramide),
antipsyhcotics (thioridazine,
haloperidol, chlorpromazine),
antibiotics (clarithromycin,
azithromycin, ciprofloxacin),
methadone, lithium, tacrolimus
and others. The concomitant use
of first-generation 5-HT3 RAs and
QTc-prolonging drugs should be
avoided if possible. 12,13
Serotonin syndrome,
characterised by altered mental
status, autonomic instability and
neuromuscular abnormalities,
has been observed following
concurrent administration
of 5-HT3 RAs with selective
serotonin reuptake inhibitor
antidepressants (fluoxetine,
citalopram, escitalopram,
Effect and suggested action
Decreased exposure to antiemetics and consequently decreased efficacy. The
oral clearance of ondansetron might increase, leading to reduced efficacy.
In patients treated with potent inducers of CYP3A4 (that is, phenytoin,
carbamazepine, and rifampicin), the clearance of ondansetron was increased
and ondansetron blood concentrations were decreased. Other 5-HT3 RAs may
be an alternative. Concomitant administration of NK1 RAs or corticosteroids
with strong CYP3A4 inducers should be avoided as the combination may result
in their decreased efficacy.
Concomitant administration with strong CYP3A4 inhibitors may increase
exposure to NK1 RA (except rolapitant) and corticosteroids and consequently
the risk of AEs. Caution is warranted
hospitalpharmacyeurope.com | 2018 | 67