Vous êtes sur la page 1sur 68

Nausea and Vomiting in Palliative Care

Audit Presentation

January 15th 2015


Audit Group Members and Meetings
Dr Richard Latten 27th August 2014
Dr Seamus Coyle 10th September 2014
Dr Laura McGlynn 1st October 2014
Dr Paula Powell 27th October 2014
Dr Jamie Barfield 12th November 2014
Ann Griffiths 3rd December 2014
Sian Rae 17th December 2014
Agnes Noble 30th December 2014
Tracey Hindley 7th January 2015
Tania Forrester 14th January 2015
Dave Hewison
Session Overview

• Patient, Carer and Public Involvement


• Literature Search and Review
• Existing Standards
• Audit Results
• Recommendations
• Questions
Patient, Carer and Public Involvement

• Representative - Dave Hewison


• Willowbrook Hospice Volunteer
• Actively participated in several group audit
meetings
• No previous direct involvement with a specialist
palliative care team
• Key areas to recognise from a patient, public and carer view

1. COMMUNICATION

- Inform the patient of their management plan


- Discuss antiemetic choice and WHY
- Help the patient to understand WHY are they are nauseated/vomiting
- Assess how much information the patient would like
- If further information requested seek ways to direct the patient to
information sources
2. EXPECTATIONS

- Discuss various antiemetics may be required to achieve symptom


control
- Help the patient to remain confident that the healthcare professional
is reviewing and managing appropriately

3. HONESTY AND PROFESSIONALISM


- Open and honest approach
LITERATURE REVIEW
Question

What is the evidence for the use of

ANTIEMETIC ‘X’
in the management of nausea and vomiting in
palliative care?
ANTIEMETICS SEARCHED
• Aprepitant • Hyoscine butylbromide
• Cyclizine • Levomepromazine
• Dexamethasone • Lorazepam
• Domperidone • Metoclopramide
• Granisetron • Olanzapine
• Haloperidol • Ondansetron
• Hyoscine hydrobromide • Prochlorperazine
SELECTION CRITERIA
INCLUSION EXCLUSION

• Humans • < 18 years of age


• Adult patients • Animals
• Incurable conditions • Non palliative care conditions
• Cancer and NON cancer • Chemotherapy related nausea
diagnoses and vomiting
• Radiotherapy related N+V • Post operative nausea and
• Pharmacological management vomiting
• English language • Bowel obstruction
• Publication Year 0-current • Non pharmacological
management
• Non English language
METHOD
• Search via NHS Evidence search

• MEDLINE/PUBMED/EMBASE/COCHRANE databases

• Search terms:
“Nausea” OR “Vomiting” AND “Antiemetic” NOT
“chemotherapy”

• 2 reviewers for each antiemetic searched


• Filters: “Clinical Trials” “Evidence base” “Cochrane”
“Humans” “Evidence based medicine”

• If zero articles from standard search some filters not


selected and 2nd search

• Abstract selection…full text reviewed….2 reviewers


LITERATURE SEARCH RESULTS
Sian Rae; Clinical Pharmacist, Whiston Hospital & Willowbrook Hospice

Aprepitant
APREPITANT
• Substance P Neurokinin1 receptor antagonist
• Licensed for moderate/highly emetogenic CINV
– in combination with dexamethasone and ondansetron
• No other clinical trials published
• 120mg on day one; 80mg on days two and three
– IV fosaprepitant also available
• Weak/moderate CYP3A4 inhibitor
– e.g. 50% dexamethasone reduction required
• One palliative case study
Aprepitant 2005 Pharmacology NA
(EMEND): the role Journal of Pain & Study
Useful interactions
of substance P in Eric Prommer Palliative Care
summary
nausea and Pharmacotherapy
vomiting.

Aprepitant--a 2003 Pharmacology NA


novel NK1- Expert Opinion on Study Useful interactions
receptor Pharmacotherapy table
antagonist.
2005 Pharmacology NA
Effect of M. Depré, A. Van Hecken, M.
Study
aprepitant on the Oeyen, I. De Lepeleire, T.
pharmacokinetics Laethem, P. Rothenberg, K. J. European Journal of
and Petty, A. Majumdar, T. Clinical Pharmacology
pharmacodynamic Crumley, D. Panebianco, A.
s of warfarin Bergman, J. N. de Hoon
2003 Pharmacology NA
Effects of the Study
neurokinin1
McCrea JB1, Majumdar AK,
receptor
Goldberg MR, Iwamoto M,
antagonist
Gargano C, Panebianco DL,
aprepitant on the Clinical Pharmacology
Hesney M, Lines CR, Petty KJ,
pharmacokinetics and Therapeutics
Deutsch PJ, Murphy MG,
of dexamethasone
Gottesdiener KM, Goldwater
and
DR, Blum RA.
methylprednisolo
ne
Tania Forrester; Community Palliative Care Nurse Specialist; WLS&F

Cyclizine
Cyclizine
• Well established antihistamine
• Exact mechanism unknown
– reduces lower oesophageal sphincter tone and
labyrinthine apparatus sensitivity
• 50mg TDS oral, IV, SC
• No relevant clinical trials
• Can cause hallucinations and enhance
euphoric effects of opioids
• Limited evidence in relation to use in heart
failure
Article title Authors Journal Year Type of study Level of Key points
evidence
The Jane W.A. Journal of Pain 2012 Pharmacokinetics NA
pharmacokinetics Vella-Brincat, and Symptom Study
and BSc, Pharma, Management
pharmacogenetics Evan J. Begg,
of the antiemetic MD, Berit P.
cyclizine in Jensen, PhD,
palliative care Paul K.L. Chin,
patients MBChB,
Rebecca L.
Roberts, PhD,
Mary Fairhall,
RN, MA,
Sandy (A.D.)
Macleod,
MBChBb,
Kate Reid, RN,
MAe,
Dr Laura McGlynn; Palliative Medicine ST4; Aintree Hospital

Metoclopramide
METOCLOPRAMIDE
• Prokinetic anti emetic
• D2 antagonist and 5HT4 agonist
• Triggers a cholinergic system in the wall of the GI tract
• Block the dopamine break on gastric emptying induced by
stress, anxiety and nausea
• Useful in N+V caused by
- GI disorders
- Chemotherapy and Radiotherapy
- Dysmotility dyspepsia, Heartburn, Migraine, Hiccups
MHRA guidance
Article title Authors Journal Year Type of study Level of Key points
evidence
Dexamethasone in Bruera E, Journal of Pain 2004 RCT Level 1- 1. N= 51
Addition to Moyano JR, and Symptom 2. Partial relief with oral
Metoclopramide for Sala R, Risco M, Management metoclopramide for 48hrs
Chronic Nausea in Bosnjak S et al. 3. Dexamethasone was not
Patients with significantly better than
Advanced Caner: A placebo in the management of
Randomized nausea
Controlled Trial

Comparison of the Mystakidou K, CANCER 1998 RCT Level 1- 1. N = 280


Efficacy and Safety of Befon S, Liossi 2. Control of N+V
Tropisetron, C and Vlachos
Metoclopramide and L. 23.6% of MET+DEX patients
Chlorpromazine in the 78.9% of TRO patients
Treatment of Emesis 84.2% of TRO+MET pts
Associated with Far 92.3% of TRO+MET+DEX pts
Advanced Cancer 33.3% of CHL+DEX pts
84.6% of TRO+CHL pts
92.5% of TRO+CHL+DEX pts

Effectiveness of Corli O, Journal of Pain 1995 Double blind, Level 2+ 1. N = 30


Levosulpiride versus Cozzolino A, and Symptom randomised 2. Control of nausea was
Metoclopramide for Battatiotto L. Management crossover achieved 84.6% of pts treated
Nausea and Vomiting Study with Levosulpiride and 42.3%
in Advanced Cancer Metoclopramide
Patients: A Double-
Blind, Randomized,
Crossover Study
A Double Blind Crossover Bruera E, Journal of Pain and 2000 Double blind Level 2+ 1. N = 26
Study of Controlled Release Belzile M, Symptom crossover study 2. Nausea was lower in
Metoclopramide and Neumann C, Management controlled release
Placebo for the Chronic Harsanyi Z, Metoclopramide group
Nausea and Dyspepsia of Babul N et compared to placebo (12+/-
Advanced Cancer al. 10mm, 17 +/-12mm) VAS 0-
100mm

A double blind, Support Hardy J, Daly S, 2002 Randomised parallel Level 2+ 1. N= 92 patients
randomised, parallel group, Care Cancer McQuade B, groups 2. No significant difference
multinational, multicentre Albertsson M et al. between any of the
study comparing a single treatment groups in the
dose of Ondansetron 24mg control of nausea or emesis
PO, with placebo and
metoclopramide 10mg TDS
PO in the treatment of
opioid induced nausea and
emesis in cancer patients

Prophylactic use of Aass N, Radiotherapy and 1997 Open trial Level 2+? 1. N = 23
tropisetron or Hatun D, Oncology 2. 3 week period of
Metoclopramide during Thoresen M, radiotherapy, Monday –
adjuvant abdominal Fossa S. Friday
radiotherapy of seminoma 3. Nausea+Emesis lower in the
stage I: a randomised open TROP group compared with
trial in 23 patients the MET group
The Effect of Clinical Khoo V, 1997 Pilot Study Level 2+ 1. N = 30
Antiemetics and Oncology Rainford K, 2. Ondansetron group experienced less
Reduced Radiation Horwich A and nausea+ vomiting
Fields on Acute Dearnaley D.
Gastrointestinal
Morbidity of
Adjuvant
Radiotherapy in
Stage I seminoma
of the Testis: A
Randomised Pilot
Study

Long Term Safety Wilson J, Journal of 2002 Open label Level 2- 1. N = 48 patients
and Clinical Plourde J, Palliative Care evaluation 3 2. 40-60% decrease in the severity of nausea
Effectiveness of Marshall D, months over the first 2/52
Controlled Release Yoshida S et 3. 50% reduction in severity of vomiting over
Metoclopramide in al. the first 4/52
Cancer Associated 4. Most frequent adverse events: asthenia
Dyspepsia n=11, anorexia n=5, nausea n=5
Syndrome: a
Multicentre
Evaluation

Chronic Nausea in Bruera E, Journal of Pain 1996 Non Level 3 1. 4 Step approach to management of nausea
Advanced Cancer Seifert L, and Symptom analytical 2. Nausea improved with stepwise fashion
Patients: A Watanabe S, Management Case note
Retrospective Babul N et al review
Assessment of a
Metoclopramide
Based Antiemetic
Regimen
Prescribing for Timothy H.M. JOURNAL OF 2014 Survey of Level 4 105 responders
Nausea in Palliative 1,2 Meera PALLIATIVE palliative care For first-line therapy,
Care: Agar, MEDICINE clinician 69% chose metoclopramide
A Cross-Sectional Patsy Yates, practice and 26% haloperidol. For
Volume 17,
National Survey and David C. second-
Number 9, 2014
of Australian Currow, line therapy, 47% chose
Palliative Medicine haloperidol with much wider
Doctors variation in the other
nominated agents.
Pharmacovigilance David C. JOURNAL OF 2012 Prospective Level 2- N=53 patients
in Hospice / Currow, 1 Jane PALLIATIVE observational Across 12 hospices in AUS
Palliative Care: Vella-Brincat, MEDICINE cohort study Majority cancer.
Rapid Report of Belinda Volume 15, Majority prescribed for
Net Clinical Effect Fazekas, Number 10, prevention of N&V
of Metoclopramide Katherine 2012 Average dose: 32.9mg/24hr
Clark, Matthew (range 10-60mg)
Doogue, and After 48hrs overall benefit
Debra Rowett, reported in 43% (23/53)
32% (17/53) patients
experienced 24 harms (Table
4). The most frequently
encountered harms were
akathisia (restlessness
and motor agitation) (4
patients),
headache (4 patients), and
abdominal pain (4 patients)
Bowel perforation (2
patients)
Initial selection of McMath, Alt, International 2006 Retrospective Level 3 584 patient records evaluated
antiemetics in end of Weschules & journal of analysis of
life care: A Knowlton pharmaceutical hospice cancer population
retrospective compounding pharmacy
analysis records in US Prochlorperazine most
Mar/Apr 2006;
hospices commonly prescribed 1st line
10(2):147
anti-emetic
Then ABHR gel (Lorazepam /
Diphenhydramine /
metoclopramide /
haloperidol) followed by
metoclopramide

Report all were effective in


reducing N&V
Comparison of Dragan Ljutic´ Kidney Blood 2002 double-blind Level 2+ 10 patients with uraemia
Ondansetron with Dijana Perkovic´ Press Res crossover study 5 metoclopramide / 5
Metoclopramide in Zvonko 2002;25:61–64 was done in 10 ondansetron
the Symptomatic Rumboldt uremic
Relief of Jugoslav Bagatin patients The antiemetic efficacy of
Uremia-Induced Izet Hozo ondansetron was clearly
Nausea and Nediljko Pivac superior to that of
Vomiting metoclopramide scored either
objectively (2.80 B
0.422 vs. 1.40 B 0.699; p !
0.005) or subjectively (4.10 B
0.738 vs. 2.10 B 0.994; p !
0.005).
Comparison of the Eduardo D. Cancer: 2006 Randomized Level 2+ Thirty-four patients with
Efficacy, Safety, Bruera, Tara Volume 74, double blind advanced cancer
and J.MacEachern, Issue 12, 29 cross over with nausea lasting more
Pharmacokinetics Kathy A. JUN 2006 study than 1 month and with no
of Controlled Spachynski, comparing evidence
Release and Donald F. controlled of involvement of the
Immediate LeGatt, R. Neil release gastrointestinal tract,
Release MacDonald, metocloprami peptic
Metoclopramide Najib Babul, de with ulcer or gastritis, brain
for the Zolfan immediate metastases, or metabolic
Management of Harsanyi, and release abnormalities
Chronic Nausea Andrew C. metocloprami were randomized, in a
in Patients with Darke, de double-blind cross-over
Advanced Cancer study, to receive 40 mg of
CRM every 12 hours or 20
mg of IRM every 6 hours for
3 days.

In 29 evaluable patients,
the intensity of nausea
on Day 3, measured by a 0-
100-mm visual analogue
scale and 0-3 categoric
scale was 15 5 17 and 0.6 f
0.6
after IRM, versus 8 f 9 (P =
0.033) and 0.4 * 0.5 (P =
0.055)
after CRM, respectively.
Dr Richard Latten

Hyoscine Hydrobromide
HYOSCINE HYDROBROMIDE

• Antimuscarinic drug
• Smooth muscle relaxant and anti secretory properties
• Indicated for prevention of motion sickness, drying
secretions, smooth muscle spasm and paraneoplastic
pyrexia and sweating
• Drug available as oral, subcut and transdermal
preparations
• No evidence from literature search regarding use in
nausea and vomiting
HYOSCINE HYDROBROMIDE

Article title Authors Journal Year Type of Level of Key points


study evidence

Transdermal S.P. Drugs 1985 Expert Level 4 1. Adverse systemic


Hyoscine Clissold, Opinion effects include dry
(Scopolamine) R. C. Heel mouth, blurred vision,
drowsiness,
A preliminary
impairment of ocular
review of its
accommodation,
pharmacodynam
blurred vision,
ics properties
mydriasis, difficulty
and therapeutic
urinating, rashes and
efficacy.
erythema.
Dr Richard Latten; Consultant in Palliative Medicine; Marie Curie

Ondansetron
ONDANSETRON

• 5HT3 antagonist

• Block the amplifying effect of 5HT on vagal nerve fibres

• Useful when excess 5HT are released from the body’s


stores eg after chemotherapy or radiation induced
damage of GI mucosa
Article title Authors Journal Year Type of study Level of evidence Key points

A double blind, Support Care Hardy J, Daly S, 2002 Randomised Level 2+ 1. Randomised to
randomised, parallel Cancer McQuade B, parallel groups Oral
group, Albertsson M et al. Ondansetron
multinational, 24mg OD,
multicentre study Metoclopramid
comparing a single e 10mg TDS or
dose of placebo TDS
Ondansetron 24mg 2. Treatment of
PO, with placebo opioid induced
and emesis in cancer
metoclopramide patients
10mg TDS PO in the 3. 24hr study
treatment of opioid treatment
induced nausea and 4. N= 92 patients
emesis in cancer 5. 30 received
patients placebo, 29
received
Ondansetron
and 33 received
Metoclopramid
e
6. No significant
difference
between any of
the treatment
groups in the
control of
nausea/emesis
Comparison of Dragan Ljutic´ Dijana Kidney Blood Press Res 2002 double-blind crossover 10 patients with uraemia
Ondansetron with Perkovic´ Zvonko 2002;25:61–64 study was done in 10 5 metoclopramide / 5
Metoclopramide in the Rumboldt Jugoslav uremic ondansetron
Symptomatic Relief of Bagatin patients
Uremia-Induced Nausea Izet Hozo Nediljko The antiemetic efficacy of
and Vomiting Pivac ondansetron was clearly
superior to that of
metoclopramide scored
either objectively (2.80 B
0.422 vs. 1.40 B 0.699; p !
0.005) or subjectively (4.10 B
0.738 vs. 2.10 B 0.994; p !
0.005).

Prophylaxis of Kristopher Dennis & Support Care Cancer 2012 Observational study Patients receiving single (SF)
radiotherapy-induced Janet Nguyen & (2012) 20:1673–1678 or multiple fraction
nausea and vomiting Roseanna Presutti & (MF) palliative radiotherapy
in the palliative treatment Carlo DeAngelis & (RT) of moderate or low
of bone metastases May Tsao & emetogenic risk for bone
Cyril Danjoux & metastases were prescribed
Elizabeth Barnes & prophylactic Ondansetron.
Arjun Sahgal & Lori The frequency and duration of
Holden & Florencia prophylaxis and the use of
Jon & rescue antiemetics were left
Shun Wong & to the discretion of the
Edward Chow treating physicians.

Despite prophylaxis, RINV was


common
among patients receiving
palliative radiotherapy for
bone metastases, especially
during the delayed phase.
Ondansetron in A. D. Journal of Pain 2000 Case report 2 x case report of
Multiple Sclerosis Macleod, and Symptom ondansetron
Management relieving symptoms
Vol. 20 No. 5
November 2000
Ondansetron in Sebastiano Journal of Pain 1998 Case report 1 x case report of
Nausea and Mercadante, and Symptom response to
Vomiting MD, Monica Management ondansetron
Induced by Spinal Sapio, MD, Vol. 16 No. 4
Morphine and Roberto October 1998
Serretta,
Successful Control Roger M. Journal of Pain 1994 Case report 1 x case report of
of Intractable Cole, FRACP, and Symptom response to
Nausea and Frances Management ondansetron
Vomiting Robinson, Vol. 9No. 1
Requiring MB, Len January 1994
Combined Harvey,
ndansetron FR4CP,
and Haloperidol in Karen
a Patient with Trethowan,
advance MB, and
Cancer Veronica
Murdoch,
Agnes Noble; Palliative Care CNS; Clatterbridge Cancer Centre

Dexamethasone
Dexamethasone
Corticosteroid
Mechanism of action unclear
Dose 8mg-16mg
Extensive side-effect profile
‘Add-on’ anti-emetic when all else fails
2 Randomised controlled trials
Article title Authors Journal Year Type of study Level of Key points
evidence
Dexamethasone for the Kirkbride P., Bezjak A., Journal of Clinical 2000 Randomised Level 2 Dexamethasone 2mg
prophylaxis of radiation- Pater J., Zee B., Oncology, May 2000, controlled trial tds seems to be an
induced emesis: A Palmer M.J., Wong R., vol./is. 18/9(1960- effective prophylactic
National Cancer Institute Cross P., Gulavita S., 1966), 0732-183X anti-emetic for radiation
of Canada clinical trials Blood P., Sun A., (May 2000) induced emesis.
group phase III study Dundas G., Ganguly
P.K., Lim J.,
Chowdhury A.D.,
Kumar S.E., Dar A.R.

Dexamethasone in Bruera E., Moyano Journal of Pain and 2004 Randomised Level 1- Dexamethasone was not
addition to J.R., Sala R., Rico M.A., Symptom controlled trial superior to placebo in
metoclopramide for Bosnjak S., Bertolino Management, the management of
chronic nausea in patients M., Willey J., Strasser October 2004, vol./is. chronic nausea in
with advanced cancer: A F., Palmer J.L. 28/4(381-388), 0885- patients with advanced
randomized controlled 3924 (October 2004) cancer also taking
trial Metoclopramide.
Agnes Noble; Palliative Care CNS; Clatterbridge Cancer Centre

Haloperidol
Haloperidol
Antipsychotic D2 antagonist
Precise mechanism of action unknown
Extrapyramidal side-effects
Dose: 1.5mg-5mg orally; 1.5mg-3mg SC (PCF/BNF dose)
4 studies
Article title Authors Journal Year Type of study Level of Key points
evidence
The efficacy of Hardy J.R., Journal of Pain 2010 Open label Level 4 Haloperidol has some
haloperidol in the O'Shea A., and Symptom uncontrolled study efficacy in the
management of White C., Management, 3 metropolitan treatment of nausea
nausea and Gilshenan K., 2010, vol./is. hospitals in and vomiting in the
vomiting in Welch L., 40/1(111-116), Australia patient study group.
patients with Douglas C. 0885-3924 (2010)
cancer.

Haloperidol for Cole DR, Duffy New York State 1974 Double blind study Level 2 Haloperidol was
radiation sickness: DF Journal of superior to placebo for
Control of Medicine, August nausea and vomiting in
associated nausea, 1974, vol./is. patients receiving
vomiting, and 74/9(1558-62), radiation therapy.
anorexia. 0028-7628;0028-
7628 (1974 Aug)
Haloperidol for the Perkins P, Cochrane 2009 Cochrane review Level 1 There is not enough
treatment of Dorman S Database of evidence to be able to
nausea and Systematic recommend
vomiting in Reviews, 2009, Haloperidol for the
palliative care vol./is. treatment of nausea
patients. /2(CD006271), and vomiting in adult
1361-6137;1469- patients suffering from
493X (2009) incurable progressive
medical conditions.

Systematic review Glare P, Supportive Care in 2004 Systematic review Level 2 3 Level 1 studies
of the efficacy of Pereira G, Cancer, June reviewed.
antiemetics in the Kristjanson LJ, 2004, vol./is. Very few good quality
treatment of Stockler M, 12/6(432-40), data available.
nausea in patients Tattersall M 0941-4355;0941- Result is uncertain.
with far-advanced 4355 (2004 Jun)
cancer.
Agnes Noble; Palliative Care CNS; Clatterbridge Cancer Centre

Domperidone
Domperidone
D2 receptor antagonist
Acts on gastro-oesophageal and gastro-duodenal junctions – Pro-kinetic
Acts on dopamine receptors in CTZ
Less likely to cause central effects
Increased risk of serious cardiac side-effects: MHRA guidance
No relevant evidence within audit criteria
Agnes Noble; Palliative Care CNS; Clatterbridge Cancer Centre

Hyoscine Butylbromide
Hyoscine Butlybromide
Antimuscarinic
Doesn’t cross blood-brain barrier –
No central anti-emetic effects
No drowsiness
No relevant evidence within audit criteria
Dr Jamie Barfield; Palliative Medicine ST3; Aintree Hospital

Granisetron
Granisetron

• A serotonin 5-HT3 receptor antagonist


• Main effect is to reduce the activity of the
vagus nerve, which activates the vomiting
centre in the medulla oblongata
• metabolized slowly by the liver, giving it a
longer than average half-life. One doses
usually lasts 4 to 9 hours and is usually
administered once or twice daily
• Excreted by the liver and kidneys
Granisetron
• 3 open label trials, 2 RCT, 1 review
• Good control of radiation induced nausea with
between 3-6mg IV over 24 hours or 2mg PO,
• Also used in bowel obstruction at 3mg IV daily
with dexamethasone
Article title Authors Journal Year Type of study Level of Key points
evidence

Double-blind, randomized, Spitzer TR, Bone Marrow 2000 Double blind Level 1+ 1. N=34
parallel-group study on the Friedman CJ, Transplant. RCT 2. Granisetron vs
efficacy and safety of oral Bushnell W, Ondansetron for
granisetron and oral Frankel SR, Total Body
ondansetron in the prophylaxis Raschko J. Irradiation priori to
of nausea and vomiting in BMT
patients receiving 3. During first 24hrs
hyperfractionated total body Grnaisetron 61.1%
irradiation vs Ondansetron
46.7% had no
emesis vs control
6.7%
4. Graniseton 33% and
Ondansetron 26.7%
had no vomiting
over 4 days
5. Complete response
in 15/22 patients
(68%)

The antiemetic effect of Logue JP, Clin Oncol 1991 Open Label Level 2+ 1. 9/13 patients had a
granisetron in lower hemibody Magee B, Cohort study complete response
radiotherapy Hunter RD, to 20mcg/kg
Murdoch RD 2. 6/9 patietns had a
complete response
to 40 mcg/kg
Intractable nausea and Buchanan & Pallitive Medicine 2007 Case reports Level 3 2 patients with intractable
vomiting successfully treated Muirhead N&V who responded when
with granisetron 5- other anti-emetics
hydroxytryptamine type 3 including ondansetron
receptor antagonists in failed
Palliative medicine
Granisetron transdermal system Simmons & Dig Dis Sci 2014 Open label Cohort Level 2+ 1. Non-palliative patients
improves refractory nausea and Parkman study with gastroparesis
vomiting in gastroparesis 2. N=36
3. 18 improved
4. 15 same
5. 2 worse
Total body irradiation prior to bone Belkacemi et al Int J Radiatio 1996 Open Label Cohort Level 2+ 1. Comppared 3mg IV
marrow transplantation: efficacy Oncology Biol Phys Study oever 5 min (Tx A) +
and safety of granisetron in the 3mg Granisetron over
prophylaxis and control of 24hrs IV (Tx B) for TBI
radiation-induced emesis 2. TxA n=15 TxB n=21
3. TxA 67% complete
control at 12 hrs vs TxB
81%
The efficacy and safety of once Lanciano et al Cancer 2001 Double blind RCT Level 1++ 1. Granisetron (n=134) vs
daily Kytril (granisetron Investigations placebo (n=126) post
hydrochloride) tablets in ht 10-30# XRT
eprophylaxis of nausea and emesis 2. Median time to 1st
following fractionated upper nausea 11 vs 1 day
abdominal radiotherapy 3. Median time to 1st
emesis 35 vs 9 days
Granisetron, a selective 5-HT3 Hunter et al Bone Marrow 1991 Open Label Level 2+ 1. n=32
receptor antagonist, for the Transplantation Cohort Study 2. 18 (56.3%) got total
prevention of radiation induced (ABSTRACT ONLY) To test efficacy for protection
emesis during total body highly emetogenic 3. 13 (40.6%) major
irradiation irraiation protection
4.
Granisetron in the prevention of Grant Prentice Bone Marrow 1995 RCT Level 1+ 1. Granisetron vs
irradiation-induced emesis et al Transplantation Double blind Metoclopramide /
(ABSTRACT ONLY) N=30 Dexamethasone/ Lorazepam
2. Granisetron significantly
better at 24hr and 7day
3. At 24hr 53% complete
response to Granisetron vs
13%
Dr Jamie Barfield; Palliative Medicine ST3; Aintree Hospital

Levomepromazine
Levomepromazine

• Phenothiazine
• Low potency antipsychotic
– (approximately half as potent as chlorpromazine)
• Exerts its effects by blocking a variety of receptors
– Adrenergic, dopamine, histamine, muscarinic,
acetylcholine and serotonin
• Serious side effects
– tardive dyskinesia, akathisia, arrhythmias,
hypotension and neuroleptic malignant syndrome
Levomepromazine
• 1 case report of a man with carcinoid treated
with high dose levomepromazine that found
25mg TDS to be effective
• 1 open label study of 70 patients given
levomepromazine at doses from 3.12mg to
25mg subcut daily. No association between
dose and efficacy or sedation
Article title Authors Journal Year Type of study Level of Key points
evidence

1. Low-dose Eisenchlas J.H.; Palliative Medicine 2005 Open Label Level 2+ 1. n=70
levomepromazine in Garrigue N.; 2. Median distress
refractory emesis in Junin M.; De Use of from 8/10 to 1/10 in
advanced cancer
Simone G.G. Levomepromazine to 2/7
patients: An open-
label study control N&V in 3. Vomiting ceased in
advanced cancer 92% cases
4. S/E sedation 2/10
irrespective of dose
used
High dose Amesbury et al J Palliative Care 2004 Case report Level 3 Outline of 1 successful case
levomepromazine to
control nausea in
carcinoid syndrome
Dr Paula Powell; Community Consultant in Palliative Medicine

Olanzapine
Olanzapine
• Second – generation antipsychotic
• D1, D2, D3, D4, 5HT2A, 5HT2C, 5HT3 and 5HT6 antagonist
• Binds to α1 adrenergic, H1 and muscarinic receptors
• Phase 1 and 2 trials for chemotherapy induced N+V have shown
effectiveness as a broad spectrum anti-emetic.
• Excretion 60% renal, 30% faecal – variable between patients
• DI – Omeprazole, carbamazepine, rifampicin reduce plasma
concentration. Fluvoxamine increases. Potentiates effect of other CNS
depressants e.g. benzodiazepines
• SE – Drowsiness, constipation, dry mouth, hypotension, paradoxical
agitation, extra – pyramidal. Lowers seizure threshold.
Olanzapine
• Incidence of drug induced movement disorders are less than with
haloperidol
• In use reported as less sedating than levomepromazine
• Dose – 1.25mg - 2.5mg oral or SC 2 hourly PRN and nocte. Can be
increased to 5mg bd.
• Available as tablet, Oro-dispersible and injection IM or SC
• No site reactions reported with SC use
• If giving IM for the first time it is advised to monitor HR, RR, BP and
conscious level for 4 hours.
Full text articles reviewed for Olanzapine Medication
Article title Authors Journal Year Type of study Level of Key points
evidence
Olanzapine for W. Clay Jackson Journal of Palliative 2003 Case Series 3 6 patients with N+V not responding to usual
Intractable Nausea in Laura Tavernier Medicine Volume 6, anti-emetics. All resolved with oral
palliative Care patients Number 2, 2003 olanzapine.
Similar to levomepromazine
May be less sedating. SE profile better than
haloperidol.

Olanzapine as an Manish Srivastava Journal of Pain & 2003 Case series 3 2 cases. Patients not responded to multiple
Antiemetic in Refractory Norman Brito-Dellan Symptom anti-emetics.
Nausea and vomiting in Mellar P Davies Management Vol 25 Note – fewer interactions, lowers seizure
Advanced Cancer No 6 June 2003 threshold, ok in renal and liver dysfunction

A Pilot Exploration of the Steven D Passik Journal of Pain & 2002 Open label 2+ Well conducted.
Antiemetic Activity of Jeremy Lundberg Symptom pilot study. Small pilot 15 patients
Olanzapine for the Relief Kenneth L Kirsh Management Vol 23 Significant reduction in nausea in patients
of Nausea in patients Dale Theobald No 6 June 2002 taking opioids, no impact on cognition, no
with Advanced Cancer reported extra – pyramidal SE
and Pain.

Ref BNF 68, Palliative Care Formulary Fourth Edition 2012


Dr Paula Powell; Community Consultant in Palliative Medicine

Prochlorperazine
Prochlorperazine
• Phenothiazine antipsychotic and anti-emetic
• D2, 5HT2, H1, α1 and ACHm antagonist
• Most effective at chemoreceptor trigger zone.
• Oral bio-availability is low due to high first pass metabolism
• Buccal preparation is 2.5 X more bio-available
• Clinically important DI are unlikely but advised to monitor phenytoin
levels. More likely extra-pyramidal SE if given with lithium
• Extra-pyramidal SE are infrequent, paradoxical agitation can occur.
• Available as oral, buccal and injection IV or IM. SC irritant.
• 3-6mg bd buccal, 5-10mg tds-qds, 5-10mg IM 3-4 hrly, 2.5-10mg IV 3-
4 hrly. Max 40mg in 24 hrs
Article title Authors Journal Year Type of study Level of evidence Key points

Antiemetic in the ED: a Darren Braude The American 2006 RCT 1+ RCT comparison
randomized controlled Tricia Soliz Journal of of 3 and placebo
trial comparing 3 Cameron Crabndell Emergency anti-emetics used
common agents. Greg Hendey Medicine 2006 IV in emergency
24,177-182 dept. PCP no
better than
placebo.
Relevance limited
by population
studied, route of
administration
and single use
only.

A Prospective T J Priestman Clinical Oncology 1993 RCT – multicentre 1+++ Comparator


Randomized Double- J T Roberts (1993) 5:358-363 double blind. study.
Blind Trial Comparing B K Upadhyaya The Royal College of Ondansetron
Ondansetron Versus Radiologists more effective
Prochlorperazine for than PCP.
the Prevention of Relevant group.
Nausea and Vomiting in
Patients undergoing
Fractionated
Radiotherapy.
Prochlorperazine Versus Amy A Ernst Annals of 2000 RCT double blind 1+ Comparator
Promethazine for Steven J Weiss Emergency study. Emergency
Uncomplicated Nausea Sun Park Medicine - August Dept. IV single
and Vomiting in the Kevin Takakuwa 2000 36:2 dose. PCP more
Emergency Department: effective than
A Randomized, Double- promethazine
Blind Clinical Trial. and faster onset
of relief of
symptoms

Ref: BNF 68. Palliative Care Formulary Forth Edition 2012


Systematic Reviews – Dr Richard Latten, Consultant Palliative Medicine

• A Systemic Review of the Treatment of Nausea and/or Vomiting in


Cancer Unrelated to Chemotherapy or Radiation (2010)

• Systemic review of the efficacy of antiemetics in the treatment of


nausea in patients with far advanced cancer (2004)
Dr Richard Latten

CURRENT STANDARDS
Current Standards
1. Any patient with a history of nausea and vomiting should
have a full assessment including a history, clinical
examination and appropriate investigations to try and
identify a cause for the symptoms. (Grade D)

2. Appropriate anti emetics should be prescribed on a


regular and as required basis. (Grade D)

3. If a patient is vomiting or nauseated for more than 24


hours, anti emetics should be given via the parenteral
route. (Grade D)
4. If combinations of anti emetics are required, drugs with
different but complementary actions should be used.
(Grade D)

5. Metoclopramide should not be prescribed if the vomiting


is caused by complete intestinal obstruction. (Grade D)

6. Symptoms of nausea and vomiting should be controlled


within 72 hours. (Grade D)
Questions to consider

• Cyclizine & heart failure


• Max dose cyclizine
• Rationale for antiemetic choice incl
combinations
– E.g. Why not Prochlorperazine / Olanzapine /
Granisetron
– Especially given available evidence level
• Process of deciding choice – patient centred
approach