C H A P T E R 5 9
Antiemetic agents
935
with emetogenic chemotherapy. These are relatively new
drugs, and the drug of choice depends on personal pref-
erence and experience.
Pharmacokinetics
The 5-HT
3
receptor blockers are rapidly absorbed,
reaching peak levels within 1 hour. They are metabo-
lised in the liver and excreted in urine. Ondansetron,
dolasetron, granisetron and tropisetron are available in
oral and IV forms; palonosetron is only available in an
IV form.
Contraindications and cautions
These drugs are contraindicated with known allergy to
any component of the drug
to prevent hypersensitivity
reactions.
Caution should be used during pregnancy
and breastfeeding
because of the potential for adverse
effects on the fetus or nursing baby.
Adverse effects
The adverse effects most frequently seen with these
drugs are headache, dizziness and myalgia related to
their CNS effects. Pain at the injection site, rash, con-
stipation, hypotension and urinary retention have also
been reported.
receptor antagonists aprepitant (
Emend
) and fosaprep-
itant (
Emend IV
). Aprepitant is available in oral form
while fosaprepitant is given intravenously.
Therapeutic actions and indications
These drugs act directly in the CNS to block receptors
associated with nausea and vomiting with little to no
effect on serotonin, dopamine or corticosteroid recep-
tors. They are approved for use in treating the nausea
and vomiting associated with highly emetogenic antineo-
plastic chemotherapy, including cisplatin therapy. They
are given orally, in combination with dexamethasone.
Pharmacokinetics
They are metabolised in the liver and excreted in urine
and faeces, and are known to cross the placenta and to
enter breast milk.
Contraindications and cautions
Aprepitant and fosaprepitant should not be used during
pregnancy and breastfeeding
because of the potential
for adverse effects on the fetus or breastfeeding infant
or with known allergy to any component of the drug
to
prevent hypersensitivity reactions.
Adverse effects
The adverse effects associated with aprepitant and fosa
prepitant include GI effects of diarrhoea, constipation,
gastritis, nausea; anorexia; headache; and fatigue.
Clinically important drug–drug interactions
There is a risk of serious increase in serum levels
of pimozide if these drugs are used together; this
Prototype summary: Ondansetron
Indications:
Control of severe nausea and vomiting
associated with emetogenic cancer chemotherapy,
radiation therapy; treatment of postoperative
nausea and vomiting.
Actions:
Blocks specific receptor sites associated with
nausea and vomiting, peripherally and in the CTZ.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
30–60 mins 60–90 mins 1.7–2.2 hours
IV Immediate 60–90 mins Duration of
infusion
T
1/2
:
3.5–6 hours; metabolised in the liver and
excreted in urine.
Adverse effects:
Headache, dizziness, drowsiness,
myalgia, urinary retention, constipation, pain at
injection site.
S
ubstance
P/
neurokinin
1
receptor
antagonists
Two drugs in the newest class of drugs for treating
nausea and vomiting are the substance P/neurokinin 1
Prototype summary: Aprepitant
Indications:
In combination with other agents for
the prevention of acute and delayed nausea and
vomiting associated with severely emetogenic
cancer chemotherapy.
Actions:
Selectively blocks human substance
P/neurokinin 1 (NK1) receptors in the CNS,
blocking the nausea and vomiting caused by highly
emetogenic chemotherapeutic agents.
Pharmacokinetics:
Route
Onset
Peak
Oral
Rapid
4 hours
T
1/2
:
9 to 13 hours; metabolised in the liver and
excreted in urine and faeces.
Adverse effects:
Anorexia, fatigue, constipation,
diarrhoea, liver enzyme elevations, dehydration.
