CASE BASE LEARNING

Nausea and Vomiting Case Study

Created by:
I Gusti Putu Agus Anom
NIM. 2208612009

Lecturer
Dr. apt. Rini Noviyani, S.Si., M.Si

PHARMACY PROFESSIONAL STUDY PROGRAM

FACULTY OF MATHEMATICS AND NATURAL SCIENCES
UDAYANA UNIVERSITY
2023
Topic: Nausea and Vomiting

Case study

Mrs DM is a 47-year-old woman who has recently been diagnosed with non-small cell lung
cancer (NSCLC) of non-squamous histology. Staging of the cancer revealed a tumour in her
right lung, approximately 6 cm in diameter; there is local lymph node involvement, but no
distant metastasis.

After discussion with the oncologist, Mrs DM was prescribed four cycles of carboplatin and
pemetrexed. The administration schedule for the first cycle was as follows:

Dexamethasone 8 mg i.v. bolus

Ondansetron 8 mg i.v. bolus

Pemetrexed 500 mg/m2 i.v. infusion

Carboplatin: target AUC = 5 mg min mL1 i.v. infusion.

The discharge medication was given as follows:

Metoclopramide 10–20 mg four times daily (when required)

Ondansetron 8 mg twice a day for 2–3 days

Dexamethasone 4 mg twice a day for 1 day.

Around 36 hours after her first cycle, Mrs DM has severe nausea and vomits uncontrollably
despite having taken her discharge medication as prescribed. The nausea and vomiting
eventually subside over a number of days.

As Mrs DM experienced severe CINV after her first cycle of carboplatin and pemetrexed, a
decision is made to replace the ondansetron with palonosetron and add aprepitant to her
therapy.
SOAP Method Analysis:
Subjective
- Mrs DM is a 47-year-old woman who has recently been diagnosed with non-small cell
lung cancer (NSCLC) of non-squamous histology.
- Staging of the cancer revealed a tumour in her right lung, approximately 6 cm in
diameter; there is local lymph node involvement, but no distant metastasis.
- Around 36 hours after her first cycle, Mrs DM has severe nausea and vomits
uncontrollably despite having taken her discharge medication as prescribed. The nausea
and vomiting eventually subside over a number of days.
- Mrs DM experienced severe CINV after her first cycle of carboplatin and pemetrexed,
a decision is made to replace the ondansetron with palonosetron and add aprepitant to
her therapy.

Objective
No results of vital signs examination or laboratory examination.

Assessment
Problem Medic (PM) Therapy Drug Related Problem
(DRP)

Non-small cell lung − Pemetrexed 500 mg/m2 P 1.2 There is a (potential)

cancer (NSCLC) i.v. infusion problem with the effect of the
− Carboplatin: target AUC pharmacotherapy
= 5 mg min mL1 i.v. C 1.1 The drug selection is not in
infusion. accordance with the guidelines
I 4.1 Add Pembrolizumab.
Pembrolizumab is indicated in
combination with PEMEtrexed
and CARBOplatin for the first-
line treatment of metastatic
non-squamous NSCLC in adults
(Ettinger et al., 2021)

Nausea and vomiting The medicine for the DRP for the first cycle:
first cycle: P 1.2 There is a (potential)
− Dexamethasone 8 mg problem with the effect of the
i.v. bolus pharmacotherapy
− Ondansetron 8 mg i.v. C 1.4 There is a (potential) drug
bolus interaction
− Dexamethasone will
decrease the level or
effect of ondansetron by
affecting
hepatic/intestinal enzyme
CYP3A4 metabolism.
I 3.1 Replace the ondansetron
with palonosetron and aprepitant
The medicine after the DRP after the first cycle:
first cycle: P 1.2 There is a (potential)
− Dexamethasone 8 problem with the effect of the
mg i.v. bolus pharmacotherapy
− Palonosetron C 1.4 There is a (potential) drug
− Aprepitant interaction
− Aprepitant will increase
the level or effect of
dexamethasone by
affecting
hepatic/intestinal enzyme
CYP3A4 metabolism
− Dexamethasone will
decrease the level or
effect of aprepitant
I 4.1 Monitoring Therapy
The discharge DRP for the discharge
medication was given medication:
as follows: P 1.2 There is a (potential)
− Metoclopramide 10– problem with the effect of the
20 mg four times pharmacotherapy
daily (when required) C 1.4 There is a (potential) drug
− Ondansetron 8 mg interaction
twice a day for 2–3 − Dexamethasone will
days decrease the level or
− Dexamethasone 4 mg effect of ondansetron by
twice a day for 1 day. affecting
hepatic/intestinal enzyme
CYP3A4 metabolism.
I 4.1 Monitoring Therapy
Planning
1) Non-Small Cell Lung Cancer (NSCLC)
Pembrolizumab is indicated in combination with PEMEtrexed and
CARBOplatin for the first-line treatment of metastatic non-squamous NSCLC in adults
whose tumors have no EGFR or ALK positive mutations. Treatment is administered
every 21 days for up to 4 cycles in combination with CARBOplatin and then followed
by maintenance therapy of pembrolizumab and PEMEtrexed every 21 days up or until
disease progression or unacceptable toxicity develops. Atypical responses (i.e., an
initial transient increase in tumour size or small new lesions within the first few months
followed by tumour shrinkage) have been observed. It is recommended to continue
treatment for clinically stable patients with initial evidence of disease progression until
disease progression is confirmed. Facilities to treat anaphylaxis MUST be present when
chemotherapy is administered. The starting dose of the drugs detailed below may be
adjusted downward by the prescribing clinician, using their independent medical
judgement, to consider each patient individual clinical circumstances (Ettinger et al.,
2021).

2) Nausea and Vomiting

Multiple medications may be required to solve the side effect such as nausea and
vomiting from NSCLC therapy.
− Dexamethasone
Corticosteroids have been used for CINV for decades and are amainstay
treatment for both acute and delayed CINV. Although the exact antiemetic
mechanism of action for corticosteroids is unknown, hypotheses include direct
action on the NTS and interactions with serotonin and neurokinin receptors that
 provide a “booster effect” for other antiemetics. Accordingly, corticosteroids are
often used in combination with other agents to increase antiemetic efficacy.
Dexamethasone is the corticosteroid of choice for CINV, although no studies have
been performed comparing available steroids. Common adverse effects of
corticosteroid therapy include insomnia, epigastric discomfort, agitation, weight
gain, and hyperglycemia, although most of these issues only emerge after
prolonged use.
− Ondansetron
The 5-HT3 antagonists act through central antagonism in the CTZ and
peripheral antagonism on intestinal vagal afferents. They are highly effective in
treating N/V because of activation of both central and peripheral pathways by broad
5-HT3 receptor expression. QT interval prolongation is an important consideration,
particularly in patients with arrhythmias and those concurrently taking additional
QT-prolonging drugs.
− Palonosetron
Serotonin receptor antagonists are most commonly used in acute CINV,
although palonosetron has demonstrated efficacy in delayed CINV as well. These
agents are considered to be well tolerated and have minimal side effects such as
headache, constipation, elevated liver enzymes, and QT interval prolongation on
electrocardiogram.
The first-generation 5-HT3 receptor antagonists, odansetron, dolasetron, and
granisetron, have half-lives of 3–9 h, while the second-generation compound,
palonosetron, has a half-life of approximately 40 h. A prospective randomized trial
evaluating the comparative efficacy of 5-HT3 receptor antagonists together with
dexamethasone during highly emetogenic chemotherapy reported that, whereas
palonestron produced the best treatment responses in both the acute and delayed
phases and was preferable due to single dosing, odansetron was favorable in terms
of cost. In contrast, palonestron and granisetron outperformed ondansetron for
moderately emetogenic regimens.
− Aprepitant
NK1 receptor antagonists act peripherally and centrally by blocking the binding
of substance P at the NK1 receptor. Approved NK1 antagonists in the United States
include aprepitant, fosaprepitant, and rolapitant. As aforementioned, these agents
 are typically administered in combination with a 5-HT3 antagonist and
dexamethasone; however, another regimen for delayed CINV is aprepitant with or
without dexamethasone. The most common adverse effects include fatigue,
headache, anorexia, diarrhea, hiccups, and increased liver enzymes. Noteworthy,
aprepitant is primarily metabolized by cytochrome P450 34A (CYP3A4) and to a
lesser extent by CYP1A2 and CYP2C9. Aprepitant inhibits CYP3A4, but after a
three-day treatment, it induces CYP2C9, and to a lesser extent CYP3A4. It can
therefore potentially influence the activity of other drugs metabolized by CYP3A4
or CYP2C9, such as the chemotherapeutic agents cyclophosphamide, docetaxel,
erlotinib, etoposide, gefitinib, ifosfamide, irinotecan, imatinib, paclitaxel, and
tamoxifen, and vinca alkaloids. Dose adjustments are required when
dexamethasone, a substrate of CYP3A4, is co-administered as well as warfarin, a
substrate of CYP2C9. Additionally, rolapitant is metabolized by CYP3A4, so co-
administration of CYP3A4 inducers (i.e. rifampin) can reduce rolapitant blood
levels and efficacy.
− Metoclopramide
Metoclopramide is a potent antiemetic with prokinetic properties and is
effective for gastroparesis. Its mechanism of action involves vagal and central 5-
HT3 and D2 receptor antagonism. Long-term use is limited by potential
extrapyramidal adverse effects (akathisia, parkinsonism, and tardive dyskinesia)
that may be irreversible. Neurokinin 1 receptor antagonists work by alleviating the
emetic effects of substance P and are Food and Drug Administration approved for
the treatment of CINV.
ANSWER FOR THE QUESTION
A. Does the drug given fulfil the right drug, right dose, right patient, right route of
administration and be aware of side effects?
Answer:
▪ First cycle:
Dexamethasone 8 mg i.v. bolus
Ondansetron 8 mg i.v. bolus
Pemetrexed 500 mg/m2 i.v. infusion
Carboplatin: target AUC = 5 mg min mL1 i.v. infusion
Then, for the second cycle Ondansetron will be replaced with Palonosetron and add
Aprepitant to her therapy.
▪ Second cycle therapy plan:
Dexamethasone 8 mg i.v. bolus
Palonosetron
Pemetrexed 500 mg/m2 i.v. infusion
Carboplatin: target AUC = 5 mg min mL1 i.v. infusion
Aprepitant
1. Right Drug
- First Cycle:
▪ In the first cycle patient only received two combination therapy, Permetrexed
and Carboplatin for the NSCLC treatment. But, in a cohort study evaluated the
efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) as a
three combination therapy versus PC alone as first-line therapy for advanced
nonsquamous NSCLC, Pembrolizumab plus PC, which has been granted
accelerated U.S. FDA approval, represents an effective and tolerable treatment
option for use as initial therapy for eligible patients with advanced
nonsquamous NSCLC (Borghaei et al., 2019).
▪ Pembrolizumab is indicated in combination with PEMEtrexed and
CARBOplatin for the first-line treatment of metastatic non-squamous NSCLC
in adults whose tumors have no EGFR or ALK positive mutations. Treatment
is administered every 21 days for up to 4 cycles in combination with
CARBOplatin and then followed by maintenance therapy of pembrolizumab
and PEMEtrexed every 21 days up or until disease progression or unacceptable
toxicity develops (Ettinger et al., 2021).
 - Second Cycle:
▪ Previous MASCC/ESMO consensus guidelines recommended a three-drug
regimen including single doses of a 5-HT3-receptor antagonist (RA),
dexamethasone and aprepitant given before chemotherapy to prevent acute
nausea and vomiting following chemotherapy of high emetic risk and
dexamethasone plus aprepitant or aprepitant alone to prevent delayed nausea
(Roila et al., 2016). Finally, a phase II open-label study evaluated aprepitant
combined with a 5-HT3 RA plus dexamethasone (8 mg on days 1–3) versus
a 5-HT3 RA plus dexamethasone alone in 134 patients with advanced non-
small-cell lung cancer who received carboplatin-based first-line
chemotherapy. Triple antiemetic therapy with aprepitant, a 5-HT3 receptor
antagonist, and dexamethasone improved the control of CINV prevention in
patients receiving carboplatin and pemetrexed chemotherapy (Ito et al.,
2014).
▪ A meta-analysis of randomised trials concluded that palonosetron in the
above reported patient population was superior to another 5-HT3 Ras.
Combination of a second-generation 5-HT3 receptor antagonist,
palonosetron (which has a greater binding affinity and a prolonged half-life),
and dexamethasone is superior to a first-generation 5- HT3 receptor
antagonist and dexamethasone (Saito et al., 2009).
2. Right Dose
Drugs name References Dose Prescription Information
Dose
Pembrolizum 200 mg IV infusion 200 mg IV 100 ml 0,9% NaCl
ab (additional every 21 days (or every infusion every over 30 mins using
drug for the 3 weeks for four 21 days (or a low protein
cycle 2) cycles) every 3 weeks binding 0,2 to 5
for four cycles) micrometre in line
or add on filter
PEMEtrexed 500 mg/m2 IV infusion 500 mg/m2 IV 100 ml 0,9% NaCl
infusion over 10 min
The recommended
dose of
pemetrexed is 500
mg/m2
administered as an
i.v. infusion over
 10 minutes on day
1 of each 21 day

CARBOplati [AUC] 5 mg/mL/min [AUC] 5 500 ml glucose 5%

n every 3 weeks for four mg/mL/min over 30 mins
cycles every 3 weeks
for four cycles
Palonosetron 0,25 mg IV 0,25 mg IV Infuse over 30
seconds beginning
approximately 30
min before the
start of
chemotherapy)
Dexamethasone 8 mg IV 8 mg IV Dexamethasone
was administered
30 minutes prior
to chemotherapy
treatment on Day
1 and in the
morning on Days 2
through 4.
Aprepitant 125 mg orally 125 mg orally The recommended
dose of Aprepitant
is 125 mg hour
prior to
chemotherapy
treatment (Day 1)
and 80 mg orally
once daily in the
morning on Days 2
and 3.

- In cohort study, patients were stratified were randomized to receive PC

(Pemetrexed, 500 mg/m2 , plus Carboplatin, area under the concentration time
curve [AUC] 5 mg/mL/min every 3 weeks for four cycles), alone or with
Pembrolizumab, 200 mg every 3 weeks for 2 years, Pembrolizumab plus PC
represents an effective and tolerable treatment option for use as initial therapy for
eligible patients with advanced nonsquamous NSCLC (Borghaei et al., 2019).

- Study evaluated aprepitant combined with a 5-HT3 RA plus dexamethasone (8 mg

on days 1–3) versus a 5-HT3 RA plus dexamethasone alone in 134 patients with
 advanced Non-Small-Cell Lung Cancer who received Carboplatin-based first-line
chemotherapy. Triple antiemetic therapy with Aprepitant, a 5-HT3 receptor
antagonist, and Dexamethasone improved the control of CINV prevention in patients
receiving Carboplatin and Pemetrexed chemotherapy (Ito et al., 2014).

- A phase II dose-finding study in US patients showed Palonosetron 3 μg/kg (fi xed

dose of about 0,25 mg) as the minimum eff ective dose for preventing CINV after
highly emetogenic chemotherapy, with doses up to 90 μg/kg (fi xed dose of about 6
mg) also safe and eff ective (Saito et al., 2009).
3. Right Patient
- Based on the prescription above, the administration of the drug prescribed by the
doctor is said to be appropriate for the patient because for the chemotherapy
treatment for NSCLC patient safe to be given to patient based on the evidence-
based medicine.
4. Right Route of Administration
- The drug given is said to be appropriate if the drug chosen is in accordance with
the patient's condition and the suitability between the dosage form and the age of
the patient. Based on the prescriptions screened above, it can be said that the patient
is right because its is NSCLC patient that need chemotherapy so that preparations
can be given in IV infusion.
5. Beware of side effect
- Aprepitant: The most common severe toxicity of aprepitant that reached grade 3 or
4 in both groups was leukopenia, neutropenia, and thrombocytopenia ((Ito et al.,
2014).
- Dexamethasone: Although corticosteroids in antiemetic therapy sometimes induce
adverse effects, an increased prevalence of infection and poor glycemic control was
not observed. The use of systemic corticosteroids or immunosuppressants before
starting pembrolizumab should be avoided because of their potential interference
with the pharmacodynamics activity and efficacy of pembrolizumab. However,
systemic corticosteroids or other immunosuppressants can be used after starting
pembrolizumab to treat immune-related adverse reactions.
- Pembrolizumab: In view of the serious and potentially life-threatening side effects
of pembrolizumab, it is mandatory that patients be carefully assessed prior to
 commencing on treatment. Patients must be monitored regularly for hepatic,
pulmonary, gastrointestinal toxicity and for endocrinopathies while on treatment.
- PEMEtrexed
▪ Myelosuppression: Usually the dose limiting toxicity with PEMEtrexed.
PEMEtrexed should not be given to patients until absolute neutrophil count
(ANC) returns to 1.5x109 /L and platelet count returns to 100x109 /L. Dose
reductions for subsequent cycles are based on nadir ANC, platelet count and
maximum non-haematologic toxicity seen from the previous cycle.
▪ Skin reactions: Pre-treatment with dexamethasone (or equivalent) can reduce
the incidence and severity of skin reactions.
▪ Cardiotoxicity: Serious cardiovascular events including MI and cerebrovascular
events have been uncommonly reported usually when PEMEtrexed is given in
combination with another cytotoxic agent. Most of the patients in whom these
events have been observed had pre-existing cardiovascular risk factors
- CARBOplatin
▪ Hypersensitivity: Reactions to CARBOplatin may develop in patients who have
been previously exposed to platinum therapy. However allergic reactions have
been observed upon initial exposure to CARBOplatin.
▪ Neurotoxicity and ototoxicity: Ototoxicity and sensory neural damage should
be assessed by history prior to each cycle (National Cancer Control Programme,
2019).

B. What is the difference between nausea and vomiting?

Answer:
Nausea is the subjective experience of an unpleasant, wavelike sensation in the back of
the throat and/or the epigastrium that may culminate in vomiting (emesis). Vomiting
(emesis) is the forceful expulsion of the contents of the stomach, duodenum, or jejunum
through the oral cavity. Retching involves the gastric and esophageal movements of
vomiting without expulsion of vomitus; it is also referred to as dry heaves. (Bethesda,
2002).
C. Explain how CINV is classified and the mechanism of CINV.
Answer:
- Clasification of CINV
CINV is classified into acute, delayed, anticipatory, breakthrough, and refractory
types based on the timing of onset and the effectiveness of antiemetic medications.
▪ Acute CINV: This type of CINV occurs within the first 24 hours after
chemotherapy treatment and is usually resolved within the next 24 to 48 hours.
▪ Delayed CINV: Delayed CINV usually occurs 24 to 72 hours after chemotherapy
treatment and can last up to 7 days. Delayed CINV is more common in patients
receiving highly emetogenic chemotherapy (HEC).
▪ Anticipatory CINV: Anticipatory CINV occurs before the start of chemotherapy
treatment due to the previous experiences of CINV. This type of CINV is more
common in patients who have experienced CINV in the past.
▪ Breakthrough CINV: Breakthrough CINV occurs when patients experience
nausea and vomiting despite receiving antiemetic medications.
▪ Refractory CINV: Refractory CINV is a type of CINV that is resistant to
antiemetic medications and continues to occur despite different antiemetic
treatments.
- The mechanism of CINV
CINV involves several factors, including the type of chemotherapy, dose,
schedule, and patient-related factors such as age, gender, and previous history of CINV.
Chemotherapy agents damage the lining of the gastrointestinal (GI) tract, causing the
release of neurotransmitters such as serotonin and substance P, which stimulate the
vomiting center in the brainstem. In addition, chemotherapy treatment can also cause
inflammation of the GI tract, which further contributes to the development of CINV.

D. What is the rationale for prescribing ondansetron, dexamethasone and

metoclopramide?
Answer:
The rationale for prescribing ondansetron, dexamethasone and metoclopramide
because patient received cancer treatment therapy, namely carboplatin and pemetrexed,
based on the ASCO Guideline (2023) these drugs were included in the category of
moderate emetic risk of single intravenous antineoplastic agents in adults. The rationale
for prescribing ondansetron and dexamethasone was adjusted based on Antiemetics:
 ASCO Guideline (2023) for moderate emetic risk CINV. In the guideline it is said that
adults treated with carboplatin area under the curve (AUC) ≥4 mg/mL/min should be
offered a 3-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist,
and dexamethasone (day 1). From these results, patients get suitability in choosing
antiemetics based on the risk of vomiting from the chemotherapy agents they get. The
problem that often occurs is acute type vomiting and delayed type. Delayed emesis is more
common in patients receiving Cisplatin, Carboplatin, or Cyclophosphamide. The use of
Ondansetron as a single agent to treat delayed emesis is not good. So, to reduce the risk of
delayed emesis, it can be combined with Dexamethasone. This antiemetic combination can
help prevent vomiting after the patient undergoes chemotherapy (NESCN, 2018; Cangemi
and Kuo, 2019).
Additionally, medications used in management of nausea and vomiting consist of two
major classes --- agents that suppress nausea and prevent vomiting generally by central
action (antiemetics) and those which act peripherally by modulating gastrointestinal
motility (prokinetics). Metoclopramide (10 mg three times daily) is a D2 receptor
antagonist that acts as an intestinal prokinetic and has antiemetic properties. Prokinetic
drugs are a very attractive treatment option in patients with nausea and/or vomiting in the
setting of delayed gastric emptying, so prescription metoclopramide is used for delayed
gastric emptying. However, the European Medicines Agency (EMA) has limited its use to
a maximum of five days due to the side effects it produces, so metoclopramide is only used
when needed (Cangemi and Kuo, 2019).

E. What advantages does palonosetron offer over ondansetron?

Answer:
The advantages offered by palonosetron compared to ondansetron are:
Aspect Based on Research Information
Therapeutic Based on research by Parathoduvil et al. (2017) regarding Therefore, Palonosetron
Effectiveness the Comparison of Antiemetic Effectiveness of was found to be superior
Palonosetron Versus Ondansetron in Patients on Cancer to Ondansetron in
Chemotherapy stated that the palonosetron group shows preventing nausea and
clinically better antiemetic efficacy than ondansetron group vomiting especially in
in preventing CINV and has significantly higher efficacy delayed phase (24-120
than ondansetron group in preventing delayed emesis. hours) and overall
 Palonosetron has shown superior results in controlling period (0-120 hours)
CINV in the present study. Palonosetron can be considered after several days of
as a better choice for control of CINV, especially delayed carboplatin-based
CINV. chemotherapy.
Besides that, other evidence supports the benefits of
palonosetron namely:
1. Palonosetron was found to be highly selective, with a
strong binding affinity and a long plasma elimination
half-life. It has shown its efficacy in preventing CINV in
both HEC (Highly Emetogenic Chemotherapy) and
MEC (Moderately Emetogenic Chemotherapy) settings
along with other drugs such as Palonosetron 0.25 mg
single dose IV on the first 3 days of cisplatin therapy,
combined with dexamethasone has shown higher
complete response rates (no emetic episodes, no rescue
medications), better control and protection against longer
nausea and emetic episodes and less use of rescue drugs
(Anusha and Saravanan, 2019).
2. Statistically significant difference in antiemetic response
to these two types of prophylaxis was observed,
palonosetron being more efficient particularly in delayed
phase and overall CINV (p = 0.006 for delayed phase,
and p = 0.008 for overall response). Complete response
was observed in 82.1 and 65.1% patients in palonosetron
and ondansetron groups, respectively (Vaid et al., 2020).
Side Effects Based on drug side effects, reported an 18 (17%) patients Therefore, the use of
experienced headache, 9 (8.5%) had constipation, 2 (1.9%) palonosetron has lower
had diarrhoea, 5 (4.7%) had abdominal pain and 3 (2.8%) side effects compared to
had dry mouth during treatment in ondansetron group, the use of ondasetron.
whereas, in palonosetron group 10 (9.4%) patients However, there was no
experienced headache, 5 (4.7%) had constipation, nobody statistically significant
experienced diarrhoea, 1 (0.9%) had abdominal pain and 6 difference between the
(5.7%) had dry mouth (Parathoduvil et al., 2017). two groups in relation to
 adverse effects and both
groups tolerated the
drugs well.
Drug Costs Based on the research of Chaudhary, et al. (2019) regarding Therefore, it is obtained
the comparison of the cost of the drug palonosetron with that palonosetron is
ondansetron, the results were obtained the median cost of more cost-effective
the drug and consumables was INR 279 (169 to 499) in the compared to
PG group (Palonosetron) as against INR 395 (76 to 1395) in ondansetron
the OG group (Ondansetron). PG (5 µg/kg) seemed to be as
efficacious and safe as OG for the prevention of CINV. It is,
however, a better choice in terms of cost and utilization of
manpower for centers in resource-limited countries.

F. What is the rationale for using aprepitant?

Answer:
Aprepitant is a neurokinin-1 receptor antagonist (NK1RA) that is used to prevent
chemotherapy-induced nausea and vomiting (CINV). According to a review article
published in the journal Therapeutic Advances in Medical Oncology, aprepitant is
effective in reducing the incidence and severity of acute and delayed CINV in patients
receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy
(Hasketh, 2017). Aprepitant is often used in combination with other antiemetic
medications such as corticosteroids and serotonin receptor antagonists to provide optimal
control of CINV (Roila et al, 2016).
Chemotherapy drugs can cause the release of neurotransmitters, such as substance P,
which stimulate the vomiting center in the brain and trigger nausea and vomiting.
Aprepitant works by blocking the binding of substance P to NK1 receptors in the brain,
thereby reducing the incidence and severity of CINV (Navari, 2009).
Overall, aprepitant is an effective medication for preventing CINV and improving the
quality of life of cancer patients undergoing chemotherapy. However, its use should be
individualized based on the patient’s chemotherapy regimen, risk factors for CINV, and
other medical conditions, and should be monitored by healthcare professionals.
 References

Anusha, S. and Saravanan, P., 2019. A Comparative Study of Ondansetron and Palonosetron
in The Control of Cisplatin Induced Emesis. The Pharma Innovation Journal. 8, 300-
305.

Aprepitant [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2021.

Bethesda. (2002). Nausea and Vomiting Related to Cancer TreatmentNo Title. Published
online: November 8, 2022. https://www.ncbi.nlm.nih.gov/books/NBK66056/

Borghaei, H. et al. (2019) “24-Month Overall Survival from KEYNOTE-021 Cohort G:

Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy
for Advanced Nonsquamous Non–Small Cell Lung Cancer,” Journal of Thoracic
Oncology, 14(1), hal. 124–129. doi: 10.1016/j.jtho.2018.08.004.

Cangemi, D. J. and Kuo, B., 2019. Practical Perspectives in the Treatment of Nausea and
Vomiting. Journal of Clinical Gastroenterology. 53, 170-178.

Chaudhary, N. K., et al., 2019. Palonosetron is a Better Choice Compared with Ondansetron
for the Prevention of Chemotherapy-induced Nausea and Vomiting (CINV) in a
Resource-limited Pediatric Oncology Center: Results from a Randomized Control
Trial. Journal of Pediatric Hematology/Oncology. 41, 294-297.

Ettinger, D. S., Wood, D. E., Aisner, D. L., Akerley, W., Bauman, J. R., Bharat, A., ... &
Hughes, M. (2021). NCCN guidelines insights: non–small cell lung cancer, version
2.2021: featured updates to the NCCN guidelines. Journal of the National
Comprehensive Cancer Network, 19(3), 254-266.

Hesketh, P. J. et al., 2023. Antiemetics: ASCO Guideline Update. Journal of Clinical

Oncology. 38, 2782-2797.

Ito, Y. et al. (2014) “Aprepitant in patients with advanced non-small-cell lung cancer
receiving carboplatin-based chemotherapy,” Lung Cancer, 84(3), hal. 259–264. doi:
10.1016/j.lungcan.2014.03.017.

National Cancer Control Programme (2019) “NCCP - Pembrolizumab, PEMEtrexed and

CARBOplatin (AUC 5) Therapy,” 2019, (Auc 5), hal. 1–11.

Navari RM. Pharmacological management of chemotherapy-induced nausea and vomiting:

focus on recent developments. Drugs. 2009;69(5):515-533. doi:10.2165/00003495-
200969050-00002
NESCN. 2018. Anti-emetic Guidelines for Chemotherapy Induced Nausea and Vomiting
(CINV). England: Northern Cancer Alliance.

Parathoduvil, A. A., Sisupalan, A., and Rema, P. L., 2017. Comparison of Antiemetic
Effectiveness of Palonosetron Versus Ondansetron in Patients on Cancer
Chemotherapy: A Prospective Observational Study in South Indians. Journal of
Clinical and Diagnostic Research. 11, 10-14.

Roila, F. et al. (2016) “2016 MASCC and ESMO guideline update for the prevention of
chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and
vomiting in advanced cancer patients,” Annals of Oncology, 27(Supplement 5), hal.
v119–v133. doi: 10.1093/annonc/mdw270.

Saito, M. et al. (2009) “Palonosetron plus dexamethasone versus granisetron plus

dexamethasone for prevention of nausea and vomiting during chemotherapy: a
double-blind, double-dummy, randomised, comparative phase III trial,” The Lancet
Oncology, 10(2), hal. 115–124. doi: 10.1016/S1470-2045(08)70313-9.

Vaid, A. K. et al., 2020. Expert Consensus on Effective Management of Chemotherapy-

Induced Nausea and Vomiting: An Indian Perspective. Journal Frontiers in Oncology.
10, 1-11.