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Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting - Pediatric - Inpatient/Ambulatory

Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting - Pediatric - Inpatient/Ambulatory - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Nausea and Vomiting


Prevention and Treatment of Chemotherapy-
Induced Nausea and Vomiting - Pediatric -
Inpatient/Ambulatory
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ................................................................................................. 2
SCOPE ............................................................................................................................. 2
METHODOLOGY ............................................................................................................ 2
DEFINITIONS .................................................................................................................. 3
INTRODUCTION ............................................................................................................. 4
RECOMMENDATIONS ................................................................................................... 4
UW HEALTH IMPLEMENTATION ................................................................................. 9
REFERENCES ................................................................................................................ 10
CPG Contact for Content:
Name: Mary Mably, RPh, BCOP – Pharmacy
Phone Number: (608) 263-1263
Email: mmably@uwhealth.org
Guideline Revision Author:
Lauren McGinty, PharmD
Original Guideline Author(s):
Heather Donovan, PharmD, BCOP; Kate
Simondsen, PharmD; Kenneth DeSantes, MD
Coordinating Team Members:
Mary Mably, RPh, BCOP – Pharmacy
CPG Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS –
Manager, Drug Policy Program
Phone Number: (608) 263-1328
Email address: ptrapskin@uwhealth.org
Review Individuals:
Nicole Lubcke, PharmD
Jennifer Piccolo, PharmD, BCOP
Margo Hoover-Regan, MD
Kathleen Montgomery, PhD, RN, PCNS-BC,
CPHON
Committee Approvals/Dates:
Pharmacy & Therapeutics Committee (Last Periodic Review: May 2016)
Release Date: May 2016 | Next Review Date: May 2019
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org

Executive Summary
Guideline Overview
This clinical practice guideline is intended to guide the prescribing of anti-emetics to prevent and treat
chemotherapy-induced nausea and vomiting (CINV). It is compiled from an extensive literature review of
current evidence and external clinical practice guidelines related to CINV. Literature on CINV in pediatric
patients is limited, and most treatments are derived from experience in adult populations.
Key Practice Recommendations
1. Emetogenic potential of single chemotherapy agents should be determined. (UW Health Class I, Level A)
2. For multi-drug chemotherapy regimens, emetogenic potential should be based on the drug with the
highest emetic risk. (UW Health Class I, Level A)
3. Recommended prophylactic anti-emetic regimens should be administered based on emetogenic
potential of the chemotherapy regimen for low, moderate, and high emetic risk regimens. (UW Health
Class I, Level A)
4. An additional agent from a different drug class than any scheduled anti-emetics is recommended for
treatment of breakthrough CINV. (UW Health Class I, Level A)
Scope
Disease/Condition(s): Pediatric patients receiving chemotherapy who may develop or have developed
CINV
Clinical Specialty: Bone marrow transplant, hematology, oncology, radiation oncology, pharmacy, nursing
Intended Users: Physicians, advanced practice providers, pharmacists, registered nurses
Objective(s): Minimize morbidity by preventing and treating nausea and vomiting caused by chemotherapy
Target Population: Patients less than 18 years of age who are receiving chemotherapy
Interventions and Practices Considered: This guideline provides recommendations for anti-emetic pre-
medication based on the emetic potential of chemotherapy and for management of acute-onset, delayed-
onset, anticipatory, breakthrough, and refractory nausea and vomiting associated with chemotherapy. Non-
medication therapies were not considered.
Major Outcomes Considered: Incidence and severity of nausea and vomiting with chemotherapy
Methodology
Methods Used to Collect/Select the Evidence:
Search methodology: A literature search was performed using Pubmed. Search terms included:
“Chemotherapy Induced Nausea and Vomiting,” “Anti-emetic,” “Pediatric,” “Palonosetron,” “Fosaprepitant,”
“Aprepitant,” “Olanzapine,” “Lorazepam,” “Diphenhydramine,” “Scopolamine,” “Cost analyses anti-emetic
therapy,” “Breakthrough Nausea and Vomiting,” and “Anticipatory Nausea and Vomiting.” The National
Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), European Society of
Medical Oncology (ESMO), and Children’s Oncology Group (COG) anti-emetic guidelines were also reviewed.
Studies were included as part of this guideline if they were done in humans, had clinical outcomes measured,
and offered information that was different from or not included in the national guidelines.
Methods Used to Formulate the Recommendations:
The workgroup members agreed to adopt recommendations developed by external organizations and/or
arrived at a consensus through discussion of the literature and expert experience. All recommendations
endorsed or developed by the guideline workgroup were reviewed and approved by other stakeholders or
committees (as appropriate).
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org

Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Internally developed recommendations, or those adopted from external sources without an assigned evidence
grade, were evaluated and assigned an evidence grade by the guideline workgroup.
Rating Scheme for the Strength of the Evidence/Recommendations:
A modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) developed by
the American Heart Association and American College of Cardiology has been used to assess the Quality and
Strength of the Evidence in this Clinical Practice Guideline (Figure 1).1
Figure 1. Grading Scheme
Definitions
1. Types of nausea and vomiting:
1.1. Acute onset: occurs within a few minutes to several hours of chemotherapy administration and
commonly resolves within 24 hours with peak intensity at 5-6 hours2-4
1.2. Delayed onset: occurs more than 24 hours after chemotherapy administration and commonly
resolves within six or seven days with peak intensity at 48-72 hours2-4
1.3. Anticipatory: occurs before patient receives the next chemotherapy treatment as a conditioned
response usually secondary to a negative experience with chemotherapy2, 4
1.4. Breakthrough: occurs despite prophylactic treatment, requiring rescue antiemetic therapy2
1.5. Refractory: occurs during subsequent cycles when antiemetic prophylaxis and rescue have
failed in earlier cycles2, 4
2. Emetogenic potential of chemotherapy
2.1. High emetic potential: 90% or more of patients experience acute emesis in the absence of
anti-emetic medications2, 4
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org

2.2. Moderate emetic potential: 30-90% of patients experience acute emesis in the absence of
anti-emetic medications2, 4
2.3. Low emetic potential: 10-30% of patients experience acute emesis in the absence of anti-
emetic medications2, 4
2.4. Minimal emetic potential: less than 10% of patients experience acute emesis in the absence of
anti-emetic medications2, 4
Introduction
Chemotherapy-induced nausea and vomiting is a serious side effect of chemotherapy that can
significantly impact a patient’s quality of life.2 Additionally, uncontrolled emesis can result in
electrolyte imbalances, nutrient depletion, anorexia, decline in functional status, poor compliance, and
withdrawal from potentially beneficial chemotherapy treatment.2, 4 Severe CINV can prolong
hospitalizations and increase health care costs. One review confirmed that the cost associated with
CINV prophylaxis was less than the cost of care for patients who did not receive adequate CINV
prophylaxis.5 The incidence and severity of CINV depends on a number of factors including
emetogenic potential of the drug, dosing and schedule of the chemotherapy and/or radiation therapy,
and patient-specific factors such as age, gender, and prior chemotherapy.2
The primary goal of anti-emetic therapy is to prevent nausea and vomiting completely, and
advances in medication therapy over the past decades have made this increasingly possible.4
More than 90% of patients receiving a highly emetogenic chemotherapy regimen will experience
emesis without anti-emetic therapy. This number falls to about 30% if patients receive appropriate
anti-emetic therapy prophylactically.2 If complete prevention of CINV is not possible, the secondary
goal is to minimize the morbidity associated with CINV as much as possible.
Recommendations
1. Classification of the emetogenic potential of select chemotherapy agents
1.1. Emetogenic potential of single chemotherapy agents should be determined based on Table
1.6 (UW Health Class I, Level A)
1.2. For multi-drug chemotherapy regimens, emetogenic potential should be based on the drug
with the highest emetic risk unless the regimen is listed in Table 2, in which case emetogenic
potential should automatically be considered high risk.6 (UW Health Class I, Level A)
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org

Table 1: Emetogenic potential of select chemotherapy agents6
High Moderate Low Minimal
Altretamine
Carboplatin@
Carmustine > 250 mg/m2
Cisplatin*@
Cyclophosphamide
≥ 1 g/m2*@
Cytarabine ≥ 3 g/m2@
Dacarbazine
Dactinomycin@
Mechlorethamine
Methotrexate ≥ 12 g/m2 @
Procarbazine (oral)
Streptozocin
Thiotepa ≥ 300 mg/m2@
Aldesleukin > 12-15
million units/m2
Amifostine > 300 mg/m2
Arsenic trioxide
Azacitidine
Bendamustine
Busulfan
Carmustine
≤ 250 mg/m2 @
Clofarabine@
Cyclophosphamide
< 1 g/m2*@
Cyclophosphamide (oral)
Cytarabine
> 200 mg/m2 to < 3 g/m2
Daunorubicin@
Dinutuximab
Doxorubicin*@
Epirubicin
Etoposide (oral)
Idarubicin
Ifosfamide
Imatinib (oral)
Irinotecan
Lomustine
Melphalan > 50 mg/m2
Methotrexate
≥ 250 mg to < 12 g/m2
Oxaliplatin > 75 mg/m2
Procarbazine
Temozolomide (oral)
Triple IT
Chemotherapy@:
Methotrexate,
Cytarabine,
Hydrocortisone
Aldesleukin ≤ 12 million
units/m2
Amifostine ≤ 300 mg/m2
Bexarotene
Busulfan (oral)@
Capecitabine
Cytarabine ≤ 200 mg/m2
Docetaxel
Doxorubicin (liposomal)
Etoposide
5-Fluorouracil
Gemcitabine
Ixabepilone
Methotrexate
> 50 mg/m2 to
< 250 mg/m2
Mitomycin
Mitoxantrone
Nilotinib
Paclitaxel
Paclitaxel-albumin
Pemetrexed
Teniposide
Thiotepa < 300 mg/m2
Topotecan
Vorinostat
Alemtuzumab
Alpha interferon
Asparaginase (IM or IV)
Bevacizumab
Bleomycin
Bortezomib
Cetuximab
Chlorambucil (oral)
Cladribine
Dasatinib
Decitabine
Denileukin diftitox
Dexrazoxane
Erlotinib
Fludarabine
Gefitinib
Gemtuzumab ozogamicin
Hydroxyurea (oral)
Lapatinib
Lenalidomide
Melphalan (oral
low-dose)
Mercaptopurine (oral)
Methotrexate
≤ 50 mg/m2
Nelarabine
Panitumumab
Pegaspargase
Pentostatin
Rituximab
Sorafenib
Sunitinib
Temsirolimus
Thalidomide
Thioguanine (oral)
Trastuzumab
Tretinoin
Valrubicin
Vinblastine
Vincristine
Vinorelbine
* Commonly associated with delayed nausea and vomiting @ Pediatric evidence available
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org

Table 2: Emetogenic potential of select combination chemotherapy regimens6
High
ξ Cyclophosphamide + anthracycline
ξ Cyclophosphamide + doxorubicin
ξ Cyclophosphamide + epirubicin
ξ Cyclophosphamide + etoposide
ξ Cytarabine 150-200 mg/m2 + daunorubicin
ξ Cytarabine 300 mg/m2 + etoposide
ξ Cytarabine 300 mg/m2 + teniposide
ξ Doxorubicin + ifosfamide
ξ Doxorubicin + methotrexate 5 g/m2
ξ Etoposide + ifosfamide
2. Selection and administration of prophylactic anti-emetic therapy
2.1. Recommended prophylactic anti-emetic regimens are listed in Table 3 and
should be administered based on emetogenic potential of the chemotherapy for
low, moderate, and high emetic risk regimens.2, 4, 6 (UW Health Class I, Level A) All
recommended dosing for anti-emetics is listed in Table 4.
2.1.1. No routine prophylaxis is recommended for minimal emetogenic
chemotherapy.2-4, 6 (UW Health Class I, Level A)
2.1.2. If patients are enrolled in a pediatric research protocol, the anti-emetics
recommended by the protocol should be used.
2.2. All prophylactic anti-emetics should be administered 30-60 minutes prior to
administration of chemotherapy unless otherwise specified. 2 (UW Health Class I,
Level A)
2.3. The oral route is the recommended route of therapy, as intravenous and oral
formulations have been found to be equally safe and effective.2-4 (UW Health Class
I, Level A)
2.4. Granisetron is indicated for patients who are unable to tolerate ondansetron due
to side effects.2, 4 (UW Health Class I, Level A)
2.5. Patients who experience refractory CINV should receive a higher level of
prophylactic anti-emetic therapy with subsequent chemotherapy cycles.2, 3 (UW
Health Class I, Level A)
Table 3: Recommended prophylactic anti-emetic regimens6
High Risk Moderate Risk Low Risk
Children receiving
agents which are not
known or suspected to
interact with aprepitant
Children receiving
agents which are
known or suspected to
interact with aprepitant
Children in whom
corticosteroids are
contraindicated
ondansetron +
dexamethasone ondansetron
Days 1-3:
ondansetron +
dexamethasone +
aprepitant
Day 4:
dexamethasone
Days 1-3:
ondansetron +
dexamethasone
Day 4:
dexamethasone
ondansetron +
dronabinol
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org

3. Selection of anti-emetic therapy for breakthrough CINV
3.1. Rescue anti-emetics for breakthrough CINV are reasonable for all patients
receiving chemotherapy. 2 (UW Health Class IIa, Level C)
3.2. An additional agent from a different drug class than any scheduled
anti-emetics is recommended for the treatment of breakthrough CINV.2-4
(UW Health Class I, Level A)
3.3. Doses of all anti-emetic medications should be maximized for the treatment of
breakthrough CINV.4 (UW Health Class I, Level A)
3.4. Anti-emetics found to be effective for a patient should be scheduled for the
duration of the emetic risk and incorporated into the anti-emetic regimen for
subsequent cycles of chemotherapy.2 (UW Health Class I, Level A)
4. Selection of anti-emetic therapy for anticipatory CINV
4.1. Effective emetic control with initial cycles of chemotherapy should be a
priority, as this is the major factor in preventing anticipatory CINV. 2-4
(UW Health Class I, Level A)
4.2. In patients with a history of anticipatory nausea and vomiting, pre-treatment
with lorazepam the night prior to chemotherapy and the morning of treatment
is reasonable.2, 4, 6 (UW Health Class IIa, Level A)
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org

Table 4: Anti-Emetic Dosing 6, 7
Class Agent Dosing Maximum
Neurokinin
antagonist
Aprepitant7
< 15 kg: 80 mg PO day 1, 40 mg PO days 2-3
15-20 kg: 80 mg PO days 1-3
> 20 kg: 125 mg PO day 1, 80 mg PO days 2-3
Deviation from recommended regimen not allowed
5HT3 antagonist
Ondansetron
Highly emetogenic chemotherapy:
0.15 mg/kg IV/PO pre-therapy x 1 then q8h
Moderately emetogenic chemotherapy:
0.15 mg/kg IV/PO pre-therapy x 1 then q12h
Low emetogenic chemotherapy:
0.15 mg/kg IV/PO pre-therapy x 1
8 mg/dose
Granisetron
Highly emetogenic chemotherapy:
40 mcg/kg IV daily
Moderately or low emetogenic chemotherapy:
40 mcg/kg IV daily or 40 mcg/kg PO q12h
1 mg IV daily
1 mg PO BID
Prokinetic
Metoclopramide
*give diphenhydramine or
benztropine concurrently
0.1 mg/kg IV/PO q6h PRN 10 mg/dose
Corticosteroids Dexamethasone
Patients not receiving aprepitant:
10 mg/m2 IV/PO daily
Patients receiving aprepitant:
5 mg/m2 IV/PO daily
Patients not receiving aprepitant:
20 mg/dose
Patients receiving aprepitant:
Day 1: 12 mg/dose
Days 2-4: 8 mg/dose
Benzodiazepines
Lorazepam
*for prevention of anticipatory
nausea/vomiting only
0.02-0.05 mg/kg IV/PO the night before
chemotherapy and immediately preceding
chemotherapy
2 mg/dose
Cannabinoids Dronabinol ≥ 40 kg: 5 mg/m2 PO q4h PRN 15 mg/m2/dose
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: CCKM@uwhealth.org 05/2016

UW Health Implementation
Potential Benefits:
The primary benefit of implementation of this guideline is the standardization of identifying
the emetogenic risk of chemotherapy regimens and initiation of prophylactic anti-emetics
with the goal of preventing CINV.
Potential Harms:
The risks of implementing this guideline and administering anti-emetic medications include
side effects such as constipation, headache, extrapyramidal effects, and QT prolongation.
Qualifying Statements:
The above recommendations are based on national consensus guidelines, current evidence,
and expert opinion. Patient-specific characteristics and experiences may require deviation
from these recommendations. Furthermore, the recommendations included in this guideline
are subject to change with publication of additional evidence.
Pertinent UW Health Policies & Procedures
UWHC Policy 6.1.1: Chemotherapy Processes: Informed Consent, Ordering, Verification,
Administration, Documentation and Patient/Family Education
Guideline Metrics:
ξ Identification of emetogenic potential of chemotherapy regimens
ξ Initiation of prophylactic anti-emetic therapy based on emetogenic risk of the
chemotherapy regimen
ξ Ensuring availability of anti-emetics for breakthrough and refractory nausea and vomiting
Implementation Plan/Clinical Tools
1. Guideline will be housed on U-Connect in a dedicated folder for CPGs.
2. Links to this guideline will be updated and/or added in appropriate Health Link or
equivalent tools.
3. Beacon treatment protocols will be created with anti-emetic regimens consistent with
these CPGs.
Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and
treatment of patients. This guideline outlines the preferred approach for most patients. It is
not intended to replace a clinician’s judgment or to establish a protocol for all patients. It is
understood that some patients will not fit the clinical condition contemplated by a guideline
and that a guideline will rarely establish the only appropriate approach to a problem.
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org

References
1. Tricoci P, Allen JM, Kramer JM, Califf RM, Smith SC, Jr. Scientific evidence underlying
the ACC/AHA clinical practice guidelines. Jama. 2009;301:831-841.
2. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in
Oncology: antiemesis version 1.2015. 2015.
3. Basch E, Prestrud AA, Hesketh PJ, Kris MG, Somerfield MR, Lyman GH. Antiemetic
Use in Oncology: Updated Guideline Recommendations from ASCO. 2012:532-540.
4. Roila F, Herrstedt J, Aapro M, et al. Guideline update for MASCC and ESMO in the
prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of
the Perugia consensus conference. Ann Oncol. 2010;21 Suppl 5:v232-243.
5. Carlotto A, Hogsett VL, Maiorini EM, Razulis JG, Sonis ST. The economic burden of
toxicities associated with cancer treatment: review of the literature and analysis of
nausea and vomiting, diarrhoea, oral mucositis and fatigue. Pharmacoeconomics.
2013;31:753-766.
6. Children's Oncology Group (COG). Guideline for the prevention of nausea and vomiting
due to antineoplastic medication in pediatric cancer patients. Version 09/25/2015.
7. Choi MR, Jiles C, Seibel NL. Aprepitant use in children, adolescents, and young adults
for the control of chemotherapy-induced nausea and vomiting (CINV). J Pediatr
Hematol Oncol. 2010;32:e268-271.
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 05/2016CCKM@uwhealth.org