Chemotherapy-induced NV antiemetic classes

Question 1

Serotonin receptor antagonists and SE

Answer 1

• Granisetron (Kytril®), ondansetron (Zofran®), palonosetron (Aloxi®) –available in Singapore
• Used principally for acute nausea/vomiting
• Effectiveness is significantly increased when used in combination with dexamethasone
• Few side effects.
• Headache is common, treat with paracetamol, instruct patient and monitor for this.
• Constipation
• Transient elevation in LFTs
• QT prolongation

Question 2

Serotonin receptor antagonists effectiveness is significantly ________when used in combination with ______________

Answer 2

Effectiveness is significantly increased when used in combination with dexamethasone

Question 3

Ondansetron (BD)
pki
half life
class

Answer 3

pki = 8.39

Half-life 4-6 hr

First gen

serotonin receptor antagonist

Question 4

Granisetron (OD)

pki
half life
class

Answer 4

pki = 8.91

Half-life 5-8 hr

First gen

serotonin receptor antagonist

Question 5

Tropisteron

pki
half life
class

Answer 5

pki = 8.81

Half-life 7 hr

First gen

serotonin receptor antagonist

Question 6

Palonosteron

pki
half life
class

Answer 6

pki = 10.5

Half-life 40 hr (give 1 day last 5 days)

second gen

serotonin receptor antagonist

Question 7

Cortiosteroids: Dexamethasone

and SE

Answer 7

•MOA unknown.
Effective as single agent and also increases efficacy of 5-HT3 antagonists.

•For these short courses, no need to taper dose, or monitor for HPA suppression (3-5 days)

•Some mood elevation, gastritis, energizing effect, appetite stimulant, sometimes irritability, insomnia, loss of glucose control in diabetics
- insomnia –> take early after breakfast or by 4pm

•Useful in both acute and delayed CINV

Question 8

Dopamine Receptor Antagonists

and SE

Answer 8

• Phenothiazine, prochlorperazine, haloperidol, droperidol, metoclopramide (Maxalon®), domperidone
• Side Effects:
• Sedation,
• Extra-pyramidal symptoms (EPS) : dystonia, dkathisia, pseudoparkinson, dyskinesia, dystonia
• QT prolongation (droperidol –FDA black box warning)

•Mainstay of anti-emetic therapy for highly emetic agents in the days before 5HT3 antagonists

•Used principally for breakthrough nausea, given intravenously
- to cover dopamine receptor that is not already covered.

•Recent HSA warnings with metoclopramide

Question 9

Benzodiazepine: lorazepam (Ativan®) and SE

Answer 9

• Patients tend to prefer this drug for PRN use
• It is the primary agent used to treat anticipatory nausea and vomiting
• Can be useful for acute and breakthrough emesis
• Sedation and tranquilizing effect

•Administer the night before and 30 mins prior to
chemotherapy.

Question 10

NK-1 Receptor antagonist

usage

Answer 10

•Aprepitant (Emend®), Fosaprepitant (IVEmend®, Rolapitant (Varubi®), Netupitant/Palonosetron (Akynzeo®)

Usages:
1. In combination with other anti-emetics, indicated for prevention of emesis caused by highly emetogenic chemotherapy

2. Unable to tolerate previous cycle of chemotherapy with adequate coverage of antiemetics
   - -> eg moderate risk = 5HT + Dex; if pt still NV = add on NK1 Receptor antagonist
3. For patients who possess multiple risk factors for nausea and vomiting

Question 11

Aprepitant (Emend®)

SE and DDI

Answer 11

• Locally available as 3 days dosing
• Generally well-tolerated
• Side effects:
• asthenia/fatigue,
• diarrhea,
• constipation,
• nausea,
• dizziness, and
• hiccups

•Aprepitant is a substrate, a moderate inhibitor (early), and an inducer (late) of CYP3A4 and CYP2C9
–Warfarin: may decrease INR (seen at around 7-10 days after aprepitant)
–Oral contraceptives: decreased efficacy
–Oral steroids: increases the AUC of dexamethasone 2.2 fold

Question 12

Aprepitant is a substrate, a moderate inhibitor (early), and an inducer (late) of _____ and _______

Answer 12

Aprepitant is a substrate, a moderate inhibitor (early), and an inducer (late) of CYP3A4 and CYP2C9

Question 13

tx for refractory emesis

Answer 13

Try other unconventional agents: haloperidol, olanzapine