Possible decrease in efficacy of Parkinson’s treatment. Avoid combination
when possible
Increased risk of bleeding. Monitor patient for bruises or gastrointestinal
bleeding
Possible hyperglycaemia. Monitor blood glucose levels more frequently
Possible hypokalaemia. Monitor potassium levels
Possible hypertension. Adjust dose of antihypertensives if necessary
is increased, and the effectiveness
might be decreased. 18 It has been
suggested that granisetron might
be the preferred 5-HT 3 RA in
elderly patients because CYP2D6, a
highly polymorphic enzyme, is not
involved in its metabolism, thereby
avoiding the risk of AEs (in poor
metabolisers, representing 5–10%
of Caucasians), or reduced efficacy
(in ultra-rapid metabolisers). 13
Although partly metabolised
through CYP2D6, ondansetron
has not been associated with
pharmacokinetic interactions
via this isoenzyme. A possible
explanation for the lack of CYP2D6
interactions of ondansetron may be
that it is metabolised by more than
one CYP isoenzyme and therefore
no single mechanism dominates its
overall metabolism. 13
NK 1 RAs
This drug class includes aprepitant,
its prodrug for intravenous
use, fosaprepitant, netupitant
(marketed in a fixed combination
with palonosetron in NEPA, the
first fixed combination antiemetic)
and rolapitant.
In contrast to 5-HT 3 RAs, the
DDIs of NK 1 RAs are predominantly
pharmacokinetic. The interplay
between NK 1 RAs and CYP450
isoenzymes is complex. Aprepitant
is a substrate, a moderate inhibitor
and an inducer of CYP3A4, as well
as a weak inducer of CYP2C9.
Fosaprepitant is biotransformed
to aprepitant and exerts the same
influence on CYP450 isoenzymes.
Aprepitant acts as a CYP3A4
inhibitor within four days of
treatment, whereas an inductive
effect is observed approximately
a week later. Netupitant is
a substrate and moderate inhibitor
of CYP3A4, whereas rolapitant is
only a substrate for CYP3A4 and a
hospitalpharmacyeurope.com | 2019 | 75