inhibitor, and caution should
be taken in combination with
CYP2D6 substrates such as
dextromethorphan, propafenone,
tamoxifen, metoprolol,
thioridazine and others. CYP2D6
participates in the metabolism of
all 5-HT3 RAs except granisetron,
which may make granisetron a
better partner for rolapitant than
ondasetron. Nevertheless, a single
180mg dose of rolapitant had no
effect on the pharmacokinetics of
intravenous ondansetron when
administered on the same day. By
inhibiting breast cancer resistance
protein, rolapitant may increase
the occurence of AEs in substrates
such as methotrexate, sulfasalazine
and rosuvastatin. Rolapitant
may interact with digoxin and
dabigatran via P-gp inhibition.
However, the clinical relevance of
these interactions is questionable
because concomitant use is not
frequent. If necessary, monitoring
of AEs is recommended. 8,19
Olanzapine
Olanzapine antagonises
dopamine D2 receptors, and
pharmacodynamic interactions
with dopamine agonists
such as anti-Parkinsonian
drugs (levodopa, ropinirole,
pramipexole) are expected. 23
Although these DDIs should be
avoided in patients treated for
Parkinsonism and schizophrenia,
it is not clear whether the same
recommendation applies when
74 | 2018 | hospitalpharmacyeurope.com
olanzapine is used in a shorter
course for CINV, which lasts
≤five days and at a lower dose
(maximum 10mg). Moreover,
olanzapine prolongs the QTc
interval and all DDIs described
previously between QTc prolonging
drugs and 5-HT3 RAs also apply
to olanzapine. Therefore, if
olanzapine is used concomitantly
with 5-HT3 RAs, palonosetron
may be the preferred choice.
Caution should be exercised when
olanzapine is co-administered with
central nervous system depressants
such as benzodiazepines and
opioids. However, the interaction
with benzodiazepines seems to
be route-specific and is more
likely if both interacting drugs are
administered parenterally. 24
Olanzapine is a CYP1A2
substrate and, as such, susceptible
to alterations of the elimination
rate when co-administered with
CYP1A2 inducers or inhibitors.
CYP1A2 inducers such as smoking
and carbamazepine may reduce
the efficacy of olanzapine but the
clinical consequences are probably
limited. By contrast, strong CYP1A2
inhibitors such as fluvoxamine
and ciprofloxacin may require
dose lowering by 25%. 23 Activated
charcoal decreases the absorption
of orally administered olanzapine
and their administration should be
separated by at least 2 h. 24
Dexamethasone
Dexamethasone DDIs with