Transcript Document

NHMRC Nausea Studies
A two-stage trial of antiemetic therapy in patients
with cancer and nausea not related to anticancer
therapy
Study 1
• A randomised open
label study of
guideline driven
targeted antiemetic
therapy versus single
agent antiemetic
therapy (haloperidol)
Study 2
• A randomised controlled
double blind study of
levomepromazine versus
placebo with rescue
antiemetics (best
supportive care (BSC)) in
patients with refractory
nausea
What is working well?
• Study 1
What is working less well?
• Study 2
Recruitment – both studies
(up to and including 01/03/2013)
Study 1
Study 2
Total
Pre-screened
539
138
677
Randomised
128
33
161
Completed
99
16
114
Needed
150
203
Study 2
Aim:
 To compare the effectiveness of parenteral levomepromazine
versus placebo and BSC rescue in improving the management of
nausea in patients with cancer and refractory nausea not related
to anticancer therapy.
Treatment schedule:
– levomepromazine 3.125mg – 9.375mg sc or iv per 24 hours
delivered in multiples of 3.125mg/2ml day-tds or
– placebo (N/Saline) given as 2ml sc or iv day-tds
with BSC rescue in all arms
Study 2 population
Inclusion criteria
Exclusion criteria
Patients who:
Patients who:






are 18 years or over
have a clinical diagnosis of cancer
have nausea with an average score
over the last 24 hours of greater than or
equal to 3 on an 11 point numerical
rating scale (NRS) anchored at 0 (no
nausea) and 10 (worst possible
nausea)
have refractory nausea despite
adequate treatment (as defined above)
are able to comply with all trial
requirements
are able to provide fully informed
consent








have nausea related to the treatment of cancer (i.e. surgery,
chemotherapy, radiotherapy) where acute treatment with
5HT3 antagonists is indicated (i.e. within 5 days of
anticancer therapy)
have nausea for which a specific antiemetic is indicated and
randomisation to study medications or placebo would not be
appropriate (e.g. dexamethasone for acutely raised ICP)
have undergone a procedure or intervention with the
potential to affect nausea within 2 days prior to the study or
are likely to undergo a procedure or intervention with the
potential to affect nausea during the 3 day study period
have received levomepromazine within the last 3 days
if on corticosteroids, the dose has changed within 48 hours
prior to study
have a definite contraindication to levomepromazine (e.g.
prior 5HT3 sensitivity, severe hepatic impairment (LFTs > 5
x upper limit of normal*), symptomatic postural hypotension)
have had a previous adverse reaction to either of the study
medications
are pregnant or breastfeeding
*this applies to AST, ALT or bilirubin but not to ALP or GGT measurements
7
Frequently asked questions
If the patient has several
possible causes of nausea,
which arm?
• try to determine which is the most
likely/dominant cause (it doesn’t matter if
you are wrong)
• it is better to define the most likely cause
than put in the cause unknown arm
• it does not matter if the true cause
becomes clear or changes
Clinical practice guidelines for the management of nausea
(Modified from the original Glare1 CPGs according to expert consensus)
3 step treatment as determined by cause
Code
Dominant cause
A
Central/ CTZ stimulation
B
CNS disease
C
Vestibular involvement
D
Gastric stasis
E
Ileus
F
Mechanical obstruction
G
Gastritis
H
Cause undetermined (or multifactorial)
1. Glare P et al. Systematic review of the efficacy of antiemetics in the treatment of nausea in patients with far advanced cancer. Support Care
Cancer 2004; 12:432-40
Study 1 – Targeted therapy treatment steps
Dominant cause
Treatment
Step 1
Treatment
Step 2
A: Central/CTZ
stimulation
Treatment
Step 3
Prochlorperazine 5mg tds po
Haloperidol 1.5mg/24hrs po or sc
or 25mg PR
Clinicalfollowed
practice
by guidelines for the management of nausea
5mg tds po
or 12.5mg bd IM/iv
B: CNS disease
Dexamethasone 8mg/24hrs
Dexamethasone 12mg/24hrs
po/sc/iv
po/sc/iv
C: Vestibular
Prochlorperazine 5mg tds po
Prochlorperazine 10mg tds po
involvement
or 25mg PR
or 25mg PR
followed by
followed by
5mg tds po
10mg tds po
or 12.5mg bd IM/iv
or 12.5mg tds IM/iv
D: Gastric stasis
Metoclopramide 10mg qid po/sc/iv Metoclopramide 10mg Q4h po/sc/iv
Haloperidol 3mg/24hrs po or sc
E: Ileus
Metoclopramide 10mg qid po/sc/iv
Metoclopramide 10mg Q4h po/sc/iv
Metoclopramide 10mg Q4h po/sc/iv
Dexamethasone 8mg/24hrs po/sc/iv
F: Mechanical
obstruction
Haloperidol 1.5mg/24hrs po/sc
Dexamethasone 8mg/24hrs
po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 8mg/24hrs po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 8mg/24hrs po/sc/iv
Hyoscine butylbromide 80mg/24hrs sc
or Ranitidine 200mg/24hrs sc
G: Gastritis
Metoclopramide 10mg qid po/sc/iv
PPI min dose
Metoclopramide 10mg qid po/sc/iv
PPI max dose
Metoclopramide 10mg Q4h po/sc/iv
PPI max dose
H: Cause
undetermined
(or multifactorial)
Metoclopramide 10mg qid po/sc/iv
Metoclopramide 10mg qid po/sc/iv
Haloperidol 1.5mg/24hrs po/sc
Metoclopramide 10mg Q4h po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 16mg/24hrs po/sc/iv
Promethazine 25 mg tds po
or 12.5mg sc
followed by
10mg tds po
Metoclopramide 10mg Q4h po/sc/iv
Dexamethasone 8mg/24hrs po/sc/iv
11
Do I have to wait for results of
investigations so I know which
arm to put the patient in?
• No, the patient has nausea that needs
treating now
• the longer you wait, the less likely it is that
the patient will start the study
• if the cause of nausea is unknown, enter it
as such
• do not change course
Study 1 population
Inclusion criteria V3.0
Exclusion criteria V3.0
Patients who:
Patients who:






are 18 years or over
have a clinical diagnosis of cancer
have nausea with an average score over
the last 24 hours of greater than or equal
to 3 on an 11 point numerical rating scale
(NRS) anchored at 0 (no nausea) and 10
(worst possible nausea)
are not currently receiving antiemetics or
are already receiving antiemetics but
these are inappropriate as defined by the
antiemetic guidelines or
are at a suboptimal dose
are able to comply with all trial
requirements
are able to provide fully informed consent








have nausea related to the treatment of cancer (i.e. surgery,
chemotherapy, radiotherapy) where acute treatment with
5HT3 antagonists is indicated (i.e. within 5 days of anticancer
therapy)
have nausea for which a specific antiemetic is indicated and
randomisation to haloperidol would not be appropriate (e.g.
dexamethasone for acutely raised ICP)
if on corticosteroids, the dose has changed within 48 hours
prior to study
have undergone a procedure or intervention with the potential
to affect nausea within 2 days prior to study or are likely to
undergo a procedure or intervention with the potential to
affect nausea during the 3 day study period
if on corticosteroids, the dose has changed within 48 hours
prior to study
have a definite contraindication to any of the drugs listed in
the guidelines (e.g. Parkinson’s disease, QTc prolongation*
on most recent ECG, uncontrolled seizures)
have had a prior serious adverse event following use of any
of the drugs listed in the guidelines (e.g. dystonic reaction,
neuroleptic malignant syndrome)
are pregnant or breastfeeding
* >450msecs in men, >470msecs in women
13
If a pt has a reversible cause of
nausea, are they eligible
• Yes, in the real world, they will be given
antiemetics so it is appropriate to include
them
• Eg nausea from renal impairment that is
likely to improve following rehydration
• Note, these pts were excluded in an earlier
version
What if a specific antiemetic is
indicated?
• Eg raised ICP for which dexamethasone is
indicated
• No, not eligible, as they may be
randomised to haloperido,l not the
targeted treatment (arm B)
• a clinical decision may have been made
for “no increase in dex dose”. The pt is still
ineligible as they might be randomised to
an increase in dex rather than haloperidol
Study 1 population
Inclusion criteria V3.0
Exclusion criteria V3.0
Patients who:
Patients who:






are 18 years or over
have a clinical diagnosis of cancer
have nausea with an average score over
the last 24 hours of greater than or equal
to 3 on an 11 point numerical rating scale
(NRS) anchored at 0 (no nausea) and 10
(worst possible nausea)
are not currently receiving antiemetics or
are already receiving antiemetics but
these are inappropriate as defined by the
antiemetic guidelines or
are at a suboptimal dose
are able to comply with all trial
requirements
are able to provide fully informed consent








have nausea related to the treatment of cancer (i.e. surgery,
chemotherapy, radiotherapy) where acute treatment with
5HT3 antagonists is indicated (i.e. within 5 days of anticancer
therapy)
have nausea for which a specific antiemetic is indicated and
randomisation to haloperidol would not be appropriate (e.g.
dexamethasone for acutely raised ICP)
if on corticosteroids, the dose has changed within 48 hours
prior to study
have undergone a procedure or intervention with the potential
to affect nausea within 2 days prior to study or are likely to
undergo a procedure or intervention with the potential to
affect nausea during the 3 day study period
if on corticosteroids, the dose has changed within 48 hours
prior to study
have a definite contraindication to any of the drugs listed in
the guidelines (e.g. Parkinson’s disease, QTc prolongation*
on most recent ECG, uncontrolled seizures)
have had a prior serious adverse event following use of any
of the drugs listed in the guidelines (e.g. dystonic reaction,
neuroleptic malignant syndrome)
are pregnant or breastfeeding
* >450msecs in men, >470msecs in women
16
What constitutes an inappropriate
antiemetic?
• any antiemetic not PBS listed for the
treatment of nausea eg cyclizine,
levomepromazine, ondansetron (outside
specific indications)
• also remember inappropriate dosing eg
maxolon 10mg tds, stemetil prn,
haloperidol 0.5 mg prn*
* If pt has had 2 doses within a 24 hour period, they are
not eligible as GPG dose
Study 1
Definition of appropriate antiemetics
• If there is a clear aetiology, an appropriate antiemetic is
any drug listed in the guidelines for that particular
indication at the doses listed, or haloperidol 1-3mg/24hrs
• The use of agents not listed in the guidelines (e.g.
cyclizine, 5HT3 antagonists, levomepromazine) is
considered inappropriate when considering study 1
• Any antiemetic that is not licensed for the treatment of
nausea in this setting must be considered inappropriate
Study 1 – Targeted therapy treatment steps
Dominant cause
Treatment
Step 1
Treatment
Step 2
A: Central/CTZ
stimulation
Treatment
Step 3
Prochlorperazine 5mg tds po
Haloperidol 1.5mg/24hrs po or sc
or 25mg PR
Clinicalfollowed
practice
by guidelines for the management of nausea
5mg tds po
or 12.5mg bd IM/iv
B: CNS disease
Dexamethasone 8mg/24hrs
Dexamethasone 12mg/24hrs
po/sc/iv
po/sc/iv
C: Vestibular
Prochlorperazine 5mg tds po
Prochlorperazine 10mg tds po
involvement
or 25mg PR
or 25mg PR
followed by
followed by
5mg tds po
10mg tds po
or 12.5mg bd IM/iv
or 12.5mg tds IM/iv
D: Gastric stasis
Metoclopramide 10mg qid po/sc/iv Metoclopramide 10mg Q4h po/sc/iv
Haloperidol 3mg/24hrs po or sc
E: Ileus
Metoclopramide 10mg qid po/sc/iv
Metoclopramide 10mg Q4h po/sc/iv
Metoclopramide 10mg Q4h po/sc/iv
Dexamethasone 8mg/24hrs po/sc/iv
F: Mechanical
obstruction
Haloperidol 1.5mg/24hrs po/sc
Dexamethasone 8mg/24hrs
po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 8mg/24hrs po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 8mg/24hrs po/sc/iv
Hyoscine butylbromide 80mg/24hrs sc
or Ranitidine 200mg/24hrs sc
G: Gastritis
Metoclopramide 10mg qid po/sc/iv
PPI min dose
Metoclopramide 10mg qid po/sc/iv
PPI max dose
Metoclopramide 10mg Q4h po/sc/iv
PPI max dose
H: Cause
undetermined
(or multifactorial)
Metoclopramide 10mg qid po/sc/iv
Metoclopramide 10mg qid po/sc/iv
Haloperidol 1.5mg/24hrs po/sc
Metoclopramide 10mg Q4h po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 16mg/24hrs po/sc/iv
Promethazine 25 mg tds po
or 12.5mg sc
followed by
10mg tds po
Metoclopramide 10mg Q4h po/sc/iv
Dexamethasone 8mg/24hrs po/sc/iv
19
Potential participant with a nausea score <3
on prn antiemetics plus 1.5mg haloperidol
nocte for delirium. Is she eligible for study 1?
• No, score <3 and already on 1.5mg
haloperidol (>step1 dose)
• Also, is she able to consent of delirious?
• What about study 2? Assuming
competence and higher score, only if she
has had 3mg haloperidol/24 hrs (or any of
the other drugs listed in section 3.1)
My patient is already on dexamethasone,
are they eligible?
• Pts must be on a stable dose for 48 hours or
have discontinued steroids 48 hours prior
• if randomised to Arm F and already on dex, this
can get complicated (think about it….)
• important to have a degree of flexibility with this
issue
• suggest call to discuss, write a file note
• study is meant to reflect real world practice
Study 1 population
Inclusion criteria V3.0
Exclusion criteria V3.0
Patients who:
Patients who:



are 18 years or over
have a clinical diagnosis of cancer
have nausea with an average score over
the last 24 hours of greater than or equal
to 3 on an 11 point numerical rating scale
(NRS) anchored at 0 (no nausea) and 10
(worst possible nausea)

are not currently receiving antiemetics or
are already receiving antiemetics but
these are inappropriate as defined by the
antiemetic guidelines or
are at a suboptimal dose

are able to comply with all trial
requirements
are able to provide fully informed consent

 have nausea related to the treatment of cancer (i.e.
surgery, chemotherapy, radiotherapy) where acute
treatment with 5HT3 antagonists is indicated (i.e.
within 5 days of anticancer therapy)
 have nausea for which a specific antiemetic is
indicated and randomisation to haloperidol would not
be appropriate (e.g. dexamethasone for acutely
raised ICP)
 if on corticosteroids, the dose has changed within
48 hours prior to study
 have undergone a procedure or intervention with the
potential to affect nausea within 2 days prior to study
or are likely to undergo a procedure or intervention
with the potential to affect nausea during the 3 day
study period
 have a definite contraindication to any of the drugs
listed in the guidelines (e.g. Parkinson’s disease,
QTc prolongation* on most recent ECG,
uncontrolled seizures)
 have had a prior serious adverse event following use
of any of the drugs listed in the guidelines (e.g.
dystonic reaction, neuroleptic malignant syndrome)
 are pregnant or breastfeeding
22
* >450msecs in men, >470msecs in women
What prn medications can I give in
study 1
• if randomised to haloperidol – maxalon
10mg q4h
• if randomised to targeted therapy –
haloperidol 0.5mg q6h (exc. Arm F)
• REMEMBER to stop all other regular
antiemetics
• put note in chart to stop out of study
prescriptions
The first dose was given at 2.30pm.
What time do I give the drug if he
goes up to a bd dose tomorrow?
• the first assessment is due 24 hours post
the od dose ie at 2.30pm
• bd doses do not have to be given at 0800
and 2000hrs but whenever is convenient
for patient and staff
The first dose was given at 2.30pm.
What time to I give the drug if he
goes up to a bd dose tomorrow?
• the last dose in a bd or tds regimen must
be given at least 6 hours prior to the
assessment time (in this case 08.30am)
• there can be flexibility in dosing times
• best to chart the daily dose each day
following the 24 hour assessment, as the
dose may change
What is the definition of
response?
• A two point improvement on an 11
point nausea NRS for average
nausea and score <3/10
• In the absence of above, a dose
increase is indicated
Response assessment
See table below (protocol section 11.2)
Initial score
3
4
5
6
7
8
9
10
Maximum score for
response
1
2
2
2
2
2
2
2
Do I have to do an ECG on all pts
to check for QTc prolongation?
• No, it is not standard practice to do ECGs
before starting patients on any of the
guideline medications
• If there is an ECG in the notes showing
QTc prolongation, suggest repeat if
possible, as will then often be within
normal limits
• ?need to refer to cardiology
Study 1 population
Exclusion criteria V3.0
Patients who:
Inclusion criteria V3.0

Patients who:






are 18 years or over
have a clinical diagnosis of cancer
have nausea with an average score over
the last 24 hours of greater than or equal
to 3 on an 11 point numerical rating scale
(NRS) anchored at 0 (no nausea) and 10
(worst possible nausea)
are not currently receiving antiemetics or
are already receiving antiemetics but
these are inappropriate as defined by the
antiemetic guidelines or
are at a suboptimal dose
are able to comply with all trial
requirements
are able to provide fully informed consent







have nausea related to the treatment of cancer (i.e. surgery,
chemotherapy, radiotherapy) where acute treatment with
5HT3 antagonists is indicated (i.e. within 5 days of anticancer
therapy)
have nausea for which a specific antiemetic is indicated and
randomisation to haloperidol would not be appropriate (e.g.
dexamethasone for acutely raised ICP)
if on corticosteroids, the dose has changed within 48 hours
prior to study
have undergone a procedure or intervention with the potential
to affect nausea within 2 days prior to study or are likely to
undergo a procedure or intervention with the potential to
affect nausea during the 3 day study period
if on corticosteroids, the dose has changed within 48 hours
prior to study
have a definite contraindication to any of the drugs listed in
the guidelines (e.g. Parkinson’s disease, QTc prolongation*
on most recent ECG, uncontrolled seizures)
have had a prior serious adverse event following use of any
of the drugs listed in the guidelines (e.g. dystonic reaction,
neuroleptic malignant syndrome)
are pregnant or breastfeeding
* >450msecs in men, >470msecs in
women
29
If a pt is on chemotherapy, are
they ever eligible?
• Study 1, yes. Ondansetron is only indicated for
acute N/V ie within the first 5 days. If they have
delayed N/V after that time they are eligible as
long as they haven’t been given any of the GPG
antiemetics at doses listed
• Note, ondansetron is not indicated for all
chemotherapy eg targeted Rx or low dose
continuous
If a pt is on chemotherapy, are
they ever eligible?
• Study 2, yes, even more so, as they will
almost certainly have had ≥8mg
ondansetron
• the study would have to be completed
before the next course of chemo is due
however, if they get dex with the chemo
A pt on ondansetron 8mg is now
eligible for study1 and study 2?
• correct, they would be eligible for study 1
because this is an inappropriate antiemetic
• and they would be eligible for study 2 if
they still have N/V >3/10 despite 8mg
ondansetron
• please prioritise study 1 however
Study 2 population
Inclusion criteria
Exclusion criteria
Patients who:
Patients who:






are 18 years or over
have a clinical diagnosis of cancer
have nausea with an average score
over the last 24 hours of greater than or
equal to 3 on an 11 point numerical
rating scale (NRS) anchored at 0 (no
nausea) and 10 (worst possible
nausea)
have refractory nausea despite
adequate treatment (as defined above)
are able to comply with all trial
requirements
are able to provide fully informed
consent








have nausea related to the treatment of cancer (i.e. surgery,
chemotherapy, radiotherapy) where acute treatment with
5HT3 antagonists is indicated (i.e. within 5 days of
anticancer therapy)
have nausea for which a specific antiemetic is indicated and
randomisation to study medications or placebo would not be
appropriate (e.g. dexamethasone for acutely raised ICP)
have undergone a procedure or intervention with the
potential to affect nausea within 2 days prior to the study or
are likely to undergo a procedure or intervention with the
potential to affect nausea during the 3 day study period
have received levomepromazine within the last 3 days
if on corticosteroids, the dose has changed within 48 hours
prior to study
have a definite contraindication to levomepromazine (e.g.
prior 5HT3 sensitivity, severe hepatic impairment (LFTs > 5
x upper limit of normal*), symptomatic postural hypotension)
have had a previous adverse reaction to either of the study
medications
are pregnant or breastfeeding
*this applies to AST, ALT or bilirubin but not to ALP or GGT measurements
33
Study 2
Refractory nausea is defined as:
• nausea rated as ≥3/10 on a NRS for average nausea after completion of study 1; OR
• nausea rated as ≥3/10 at baseline despite the use of:
– appropriate antiemetics at sufficient dose (step 3) as specified in the study 1
targeted guideline category (see Appendix 15.1.2) or
– haloperidol 3mg/24hrs or
– promethazine 25mg po tds (25mg sc 24 hrly) or
– metoclopramide 60mg/24hrs or
– domperidone 20mg qid or
– cyclizine 100mg/24hrs (75mg/24hrs in the elderly) or
– ondansetron 8mg/day
OR
• nausea rated as ≥3/10 at baseline if appropriate antiemetics, or any of those listed
above, have not been tolerated because of side-effects.
If patients have been on antiemetic combinations, at least one of the agents must have been
given at doses as specified above.
What about the other 5HT3
antagonists?
• the rules that apply to ondansetron apply
also to the other drugs in this class eg
granisetron and tropisetron
• dose equivalents are :
- ondansetron 8mg
- tropisetron 5mg/day for 6 days
- granisetron 3mg
Can out-patients do this study?
• Study 1 yes, we need detailed daily record
keeping however for the purposes of
monitoring
• Study 2, yes, if there is the facility for
visiting pts at home to give the injections
We have a patient on maxalon 10mg qid
who still has nausea. Can he go straight to
step 2 in study 1
• No, he is not eligible as already on a GPG
dose
Can he go straight to study 2?
• No, because he needs to have had 60mg
maxolon/24 hours (10mg q4h as per step
3) or as per section 3.1
• Suggest increase the dose to 10mg q4h or
20mg qid
• If he still has nausea, he can go to study 2
• Remember to count b’thru doses into the
total daily dose
Study 2
Refractory nausea is defined as:
• nausea rated as ≥3/10 on a NRS for average nausea after completion of study 1; OR
• nausea rated as ≥3/10 at baseline despite the use of:
– appropriate antiemetics at sufficient dose (step 3) as specified in the study 1
targeted guideline category (see Appendix 15.1.2) or
– haloperidol 3mg/24hrs or
– promethazine 25mg po tds (25mg sc 24 hrly) or
– metoclopramide 60mg/24hrs or
– domperidone 20mg qid or
– cyclizine 100mg/24hrs (75mg/24hrs in the elderly) or
– ondansetron 8mg/day
OR
• nausea rated as ≥3/10 at baseline if appropriate antiemetics, or any of those listed
above, have not been tolerated because of side-effects.
If patients have been on antiemetic combinations, at least one of the agents must have been
given at doses as specified above.
What prn meds can I give pts on
study 2?
•
•
•
•
•
•
maxalon
prochlorperazine
haloperidol
promethazine
no dose or time restriction stated
NOT ondansetron, cyclizine,
levomepromazine
• this is best supportive care
Study 1 – Targeted therapy treatment steps
Dominant cause
Treatment
Step 1
Treatment
Step 2
A: Central/CTZ
stimulation
Treatment
Step 3
Prochlorperazine 5mg tds po
Haloperidol 1.5mg/24hrs po or sc
or 25mg PR
Clinicalfollowed
practice
by guidelines for the management of nausea
5mg tds po
or 12.5mg bd IM/iv
B: CNS disease
Dexamethasone 8mg/24hrs
Dexamethasone 12mg/24hrs
po/sc/iv
po/sc/iv
C: Vestibular
Prochlorperazine 5mg tds po
Prochlorperazine 10mg tds po
involvement
or 25mg PR
or 25mg PR
followed by
followed by
5mg tds po
10mg tds po
or 12.5mg bd IM/iv
or 12.5mg tds IM/iv
D: Gastric stasis
Metoclopramide 10mg qid po/sc/iv Metoclopramide 10mg Q4h po/sc/iv
Haloperidol 3mg/24hrs po or sc
E: Ileus
Metoclopramide 10mg qid po/sc/iv
Metoclopramide 10mg Q4h po/sc/iv
Metoclopramide 10mg Q4h po/sc/iv
Dexamethasone 8mg/24hrs po/sc/iv
F: Mechanical
obstruction
Haloperidol 1.5mg/24hrs po/sc
Dexamethasone 8mg/24hrs
po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 8mg/24hrs po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 8mg/24hrs po/sc/iv
Hyoscine butylbromide 80mg/24hrs sc
or Ranitidine 200mg/24hrs sc
G: Gastritis
Metoclopramide 10mg qid po/sc/iv
PPI min dose
Metoclopramide 10mg qid po/sc/iv
PPI max dose
Metoclopramide 10mg Q4h po/sc/iv
PPI max dose
H: Cause
undetermined
(or multifactorial)
Metoclopramide 10mg qid po/sc/iv
Metoclopramide 10mg qid po/sc/iv
Haloperidol 1.5mg/24hrs po/sc
Metoclopramide 10mg Q4h po/sc/iv
Haloperidol 3mg/24hrs po/sc
Dexamethasone 16mg/24hrs po/sc/iv
Promethazine 25 mg tds po
or 12.5mg sc
followed by
10mg tds po
Metoclopramide 10mg Q4h po/sc/iv
Dexamethasone 8mg/24hrs po/sc/iv
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