table 1
(Continuation)
Olanzapine Levodopa, pramipexol, ropinirole
Dexamethasone NSAIDs, anticoagulant
Antidiabetics
Diuretics
Antihypertensives
paroxetine) as well as serotonin
norepinephrine reuptake
inhibitors (duloxetine, etc). 14,15
Concomitant use of ondansetron
with apomorphine hydrochloride
should be avoided because of
possible profound hypotension
and loss of conciousness. 16 The
mechanism of this interaction
is unclear, and it is also unclear
whether it involves other members
of the drug class. As a precaution,
combined use of apomorphine
with all 5-HT3 RAs should be
avoided. The analgesic effect of
tramadol may be reduced when
it is co-administered with 5-HT3
RAs. The suggested mechanism for
this potential interaction involves
antagonism of spinal 5-HT3
receptors by RAs, which, in turn,
opposes the action of tramadol,
because the non-opioid analgesic
effect of tramadol occurs through
inhibition of presynaptic reuptake
70 | 2018 | hospitalpharmacyeurope.com
of serotonin, which leads to
increased impact of the descending
inhibitory pathways associated
with pain transmission in the
spinal column. 17
5-HT3 RAs are metabolised by
the following isoenzymes:
• Ondansetron: CYP1A1, CYP1A2,
CYP3A4 and CYP2D6
• Dolasetron and tropisetron:
largely by CYP2D6 with a
smaller contribution by CYP3A4;
• Granisetron: only by CYP3A4
• Palonosetron: by CYP2D6
(mainly), CYP3A4 and CYP1A2
(minor).
Pharmacokinetic interactions
of 5-HT3 RAs involve mainly
concomitant administration of
ondansetron with potent inducers
of the isoenzyme CYP3A4 such
as phenytoin, carbamazepine,
rifampicin and St John’s Wort.
As a potential consequence, the
elimination rate of ondansetron