Anti-emetics in haemato-oncology patients with chemotherapy induced nausea and vomiting (CINV)

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Objectives

This guideline has been written to standardise the management of chemotherapy induced nausea and vomiting in children. It discusses the other causes of nausea and vomiting in this group of children, and also details the management of acute dystonic reactions.

Scope

This guideline should be in used in paediatric haemato-oncology patients who are receiving chemotherapy.

1. Introduction

Nausea and vomiting are common and can be debilitating in children with cancer. The prevention of symptoms should be the goal of modern anti-emetic therapy. The risk of emesis depends on the emetogenicity of drugs (see Table 1- section 4) and on the response of the patient. Oral and intravenous routes are equally efficacious providing that there are no barriers to drug absorption.

Selection of anti-emetic agents should be based on a sound, receptor based understanding of the pathophysiology of emesis. Common reasons for the failure of anti-emetic therapy in children are the selection of the wrong compound or the use of inadequate dosing.

The prescriber is responsible for calculating the dose of each anti-emetic drug for each admission/block of chemotherapy. It should not be assumed that the previously charted dose is correct.

2. Related Documentation

None.

3. Authorised Personnel / Specific Staff Competencies

The management of patients with nausea and vomiting will be directed by the Consultant/Associate Specialist or a senior member of the medical team.

The Medical/Nursing team will be responsible for administration and monitoring.

4. Equipment / Materials

Fluid balance charts and drug charts. 

5.1 Causes of vomiting

It should be remembered that patients receiving chemotherapy may have nausea or vomiting due to a cause other than the direct effect of the chemotherapy (CINV). These include:

  • Radiotherapy (NB: TBI, gut or cranio-spinal are most likely to provoke emesis)
  • Partial or complete bowel obstruction
  • Vestibular dysfunction
  • Brain metastases
  • Electrolyte imbalance: hypercalcemia, hyperglycemia, hyponatremia
  • Uraemia
  • Concomitant drug treatments including opiates
  • Gastroparesis
    • tumour or chemotherapy (vincristine etc) induced
  • Gastric Haemorrhage (coffee ground vomitus : may be steroid induced)
  • Psychophysiologic:
    • anxiety
    • anticipatory nausea and vomiting
  • Raised ICP
5.2 General information on treatment

5.2.1 Patients receiving chemotherapy with a high level of emetic risk should receive combination anti-emetic therapy with a 5HT3 blocker (ondansetron) and cortico steroid (dexamethasone). Intravenous anti-emetics should be given at least 30 minutes prior to starting chemotherapy or by the oral route at least 1 hour prior to starting treatment. These anti-emetics must be prescribed regularly on the patients prescription chart. Most patients moderately emetogenic chemotherapy will require dual therapy. Children receiving chemotherapy with low emetic risk should receive only Ondansetron. If the chemotherapy agents have minimal emetic risk then no routine prophylaxis is required.

5.2.2 Dexamethasone should not be given to patients who receive steroids as part of their treatment protocol. Patients with Acute Lymphoblastic Leukaemia (ALL) receive dexamethasone as part of induction and intensification therapy. Chemotherapy for ALL is not generally highly emetogenic and additional dexamethasone for emesis should not be prescribed.

Patients with brain tumours should not be started on dexamethasone as an anti emetic as it may prevent chemotherapy penetrating the blood brain barrier.

Patients receiving immunomodulatory therapy should not receive steroids during that part of their treatment eg Neuroblastoma - when receiving ch14.18 antibody and Osteosarcoma - when receiving mifamurtide. 

5.2.3 Dexamethasone should also be avoided in patients receiving conditioning treatment with chemotherapy and/or radiotherapy prior to stem cell transplantation, because steroid therapy will increase the risk of fungal infection in a population already at risk.

5.2.4 All children who face prolonged, profound neutropenia are at risk of invasive fungal infections and dexamethasone should be avoided in these patients. This particularly relates to children with Acute Myeloid Leukaemia (AML) who are receiving, or have received, chemotherapy regimens containing fludarabine and/or/-gemtuzumab ozogamicin (Mylotarg). After ensuring that ondansetron has been optimally prescribed, failure of non-steroid containing anti-emesis in these patients should be discussed with the consultant.

5.2.5 If standard anti-emetic therapy fails in any patient, exclude all other causes of nausea/vomiting and ensure that the anti-emetic drugs have been prescribed at optimal route, dosing and frequency. Check patient compliance/tolerance and consider if drug absorption might play a role in lack of response. If second line agents are considered necessary metoclopramide is generally the drugs of choice.

MHRA Update 2013

Metoclopramide is contra-indicated in children < 1 year. In children aged 1-18, Metoclopramide should only be used as a second-line option for prevention of delayed chemotherapy-induced nausea and vomiting. Metoclopramide should only be prescribed for short-term use (<5 days).

5.2.6 Consider using lorazepam prior to a treatment block if either anticipatory nausea is a problem or anxiety forms a large component of the nauseating trigger (particular issue in adolescents). This may need to commence before starting the journey to hospital.

5.2.7 Levomepromazine (Nozinan) is a receptor non-specific agent that is often helpful in refractory cases although sedation can be problem. Beware of increased risk of extra-pyramidal side-effects and increased sedative effects when combining metoclopramide with cyclizine. Nabilone and haloperidol may also be useful in these circumstances.

5.2.8 There is growing evidence that newer generation 5HT3 blockers eg Granisetron and Palonosetron and neurokinin receptor antagonists eg aprepitant may be of benefit in CINV. However these drugs should be discussed with a consultant and pharmacy prior to prescription. Granisetron has been used successfully in a small number of patients in whom optimised ondansetron treatment has failed. Apreptitant is added to chemotherapy regimens with a very high emetogenic potential at the agreement of the Consultant. 

5.2.9 Remember, anti-emetics have their own side effect profile (e.g. 5HT3 blockers are constipating and can cause headache).

NB: All episodes of refractory nausea and vomiting should be discussed with a consultant.

5.3 Acute dystonic reactions

5.3.1 Acute Dystonic reactions may occur with Phenothiazines and Metoclopromide, especially if these drugs are used at high dose or in combination.

5.3.2 Treatment of dystonic reactions – Procyclidine 10mg in 2ml Injection (stocked on RHC 2A and 2B):

Dose:

Single IV bolus dose is usually effective within 5 – 10 minutes (up to 30 minutes). Can be repeated after 20 minutes.

Age Group Single IV bolus dose
1 month - 1 year 500 micrograms - 2 mg
2-9 years 2 - 5mg
≥10 years 5-10 mg
5.4 Duration of anti-emetic treatment

When patients are discharged home following completion of a course of chemotherapy they should NOT be dispensed corticosteroid as an anti-emetic. Those requiring anti-emetics at home should be dispensed a maximum of TWO days of other regular anti-emetic in the first instance and then reviewed.

Pharmacy dispenses the patient's original packs of anti-emetic drugs so it is essential that parents/carers/patients are counselled appropriately to take anti-emetics regularly for the first two days only following chemotherapy and then only if required. 

Appendix 1: Emetogenicity of common chemotherapy agents (Tables 1 & 2)

Table 1: Adapted from POGO (Pediatric Oncology Group of Ontario) Classification of Acute Emetogenic Potential of Antineoplastic Medication in Pediatric Cancer Patients Given as Single Agents.

High Level of Emetic Risk
(>90% frequency of emesis in absence of prophylaxis)
Moderate Level of Emetic Risk (30-90% frequency of emesis in absence of prophylaxis) Low Level of Emetic Risk (10-30% frequency of emesis in absence of prophylaxis) Minimal (<10% frequency of emesis in absence of prophylaxis)

Carboplatin

Carmustine >250mg/m2

Cisplatin

Cyclophosphamide  > 1g/m2

Cytarabine >3g/m2

Dacarbazine

Methotrexate >12g/m2

Thiotepa > 300mg/m2

 

 

 

 

 

 

Aldesleukin >12million units/m2

Arsenic Trioxide

Azacitidine

Busulfan Carmustine <250mg/m2

Clofarabine

Cyclophosphamide <1g/m2

Cyclophosphamide (oral)

Cytarabine >200mg to < 3g/m2

Daunorubicin

Doxorubicin

Epirubicin

Etoposide (oral)

Idarubicin

Ifosfamide

Imatinib (oral)

Intrathecal therapy (methotrexate, hydrocortisone & cytarabine)

Irinotecan

Lomustine

Melphalan > 50mg/m2

Methotrexate >250mg to < 12g/m2

Oxaliplatin > 75mg/m2

Temozolomide (oral)

Amsacrine

Capecitabine

Cytarabine <200mg/m2

Docetaxel

Doxorubicin (liposomal)

Etoposide

5-Fluorouracil

Gemcitabine

Methotrexate >50mg/m2 to <250mg/m2

Mitomycin

Mitoxantrone

Paclitaxel

Teniposide

Thiotepa < 300mg/m2

Topotecan

 

Alemtuzumab

Alpha interferon

Asparaginase (IM/SC/IV)

Bevacizumab

Bleomycin

Bortezomib

Cladribine

Dasatinib

Erlotinib

Fludarabine

Gemtuzumab ozogamicin

Hydroxycarbamide (oral)

Mercaptopurine (oral)

Methotrexate <50mg/m2

Nelarabine

Rituximab

Sorafenib

Sunitinib

Thalidomide

Tioguanine (oral)

Vinblastine

Vincristine

Vindesine

Vinorelbine

Summary of Recommendations:

  • The single neoplastic agents provided in Table 1 have high, moderate, low or minimal emetogenic risk in children
  • With the exceptions noted in Table 2, the emetogenicity of multiple agent anti-neoplastic therapy given to children is classified based on the emetogenic potential of the most highly emetogenic agent in the combination to be given.
  • The emetogenicity of multiple day anti-neoplastic therapy is classified in children based on the emetogenetic potential of the most highly emetogenic agent on each day of therapy.

Table 2: Adapted from POGO (Pediatric Oncology Group of Ontario) Classification of Acute Emetogenic Potential of Antineoplastic Medication in Pediatric Cancer Patients Given as Single Agents.

High Level of Emetic Risk (>90% frequency of emesis in absence of prophylaxis)

  • Cyclophosphamide + anthracycline
  • Cyclophosphamide + Etoposide

  • Cytarabine 150-200mg/m2 + Daunorubicin

  • Cytarabine 300mg/m2+ Etoposide Doxorubicin + Ifosfamide

  • Doxorubicin + Methotrexate 5g/m2

  • Etoposide + Ifosfamide

Appendix 2: Anti-emetic drugs and doses

 

Prepared by: Karon McDOWALL
Checked by: Nicola CURRAN

Date: 14/08/17

Referenced from BNF, BNF for Children, Rainbow Guidelines, COG and POGO guidelines, & general information from other paediatric centres in the UK.

 

Editorial Information

Last reviewed: 01 December 2017

Next review: 01 December 2019

Author(s): Dr D Murphy

Version: 3

Approved By: Sch Clin Gov Group & Hosp Governance Group

Document Id: RHC-HAEM-ONC-017