in absorption, distribution,
metabolism or excretion of one
or both interacting drugs. Most
common pharmacokinetic DDIs
involve the induction or inhibition
of CYP450 isoenzymes, involved
in the biotransformation of
drugs. The effects of induction
or inhibition of the isoenzymes
usually persist for longer than it
takes for the drug to be eliminated
from the body. This explains why
a drug that has been discontinued
from treatment still may affect,
in a defined time period, the
elimination of another drug. 4,5
DDIs can have therapeutic benefit.
An example is the better control
of CINV when two antiemetics
from different drug classes are
co-administered. Nevertheless,
there is concern when DDIs result
in less effective treatment or in the
occurrence of adverse effects (AEs)
of interacting drugs. 5 The most
important DDIs of antiemetics
used in the management of CINV
are addressed in the following text
and summarised in Table 1.
5-HT3 RAs
5-HT3 RAs are usually classified
as first generation (dolasetron,
ondansetron, tropisetron,
granisetron and ramosetron) or
second generation (palonosetron).
Electrocardiogram interval
changes, such as QTc prolongation,
table 1
DDIs of main antiemetic drugs 6–11
Antiemetic
Interacting drugs
Pharmacokinetic interactions
5-HT 3 RA (palonosetron,
ondansetron, etc) NK1 RA
(netupitant, aprepitant,
fosaprepitant), dexamethasone Strong CYP3A4 inducers (for
example, rifampicin, phenytoin,
carbamazepine
CYP2D6 inducers and inhibitors
Aprepitant, fosaprepitant,
netupitant, dexamethasone Strong CYP3A4 inhibitors (for
example, ketoconazole)
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