1. “I am Sick of Feeling Sick”
Managing Nausea and Vomiting in the Palliative Patient
Paul Daeninck
WRHA Palliative Care Program
Greg Harochaw
Taché Pharmacy

2. Declaration Advisor or Paid Speaker for the following:
Valeant Pharmaceuticals
Bayer
Wyeth Pharmaceuticals

3. Objectives
At the end of this session, the attendee will be able to:
Identify the numerous GI issues causing nausea and vomiting in the palliative patient
Discuss the principles in determining the therapies for specific situations of nausea and vomiting
Recognize the complex physiology and potential for use of alternative routes in treating nausea and vomiting

4. GI Issues Causing Nausea/Vomiting
Medications
Radiation
Constipation
Bowel obstruction
Diarrhea
Ascites
Hemorrhage
Viscus perforation
Esophageal/gastric/ biliary duct obstruction
Liver failure
Pancreatic failure
Absorption syndromes
Infections
Electrolytes

5. Approach To Symptom Control
Thorough assessment
history; physical examination
Discussion
goals of care, hopes, expectations, anticipated course of illness (impact on investigations & interventions)
Investigations
blood tests, X-Ray, CT, MRI, etc
Treatments
pharmacological and non-pharmacological; interventions
Ongoing reassessment/review
Options, goals, expectations, etc.

6. Symptom Prevalence Pain Fatigue/Asthenia Constipation Dyspnea Nausea
Vomiting
Delirium
Depression/suffering % %
70%
60+% %
30% % %

7. Mechanisms of Nausea & Vomiting
vomiting centre: medulla
activated by stimuli from:
Chemoreceptor Trigger Zone (CTZ)
area postrema, floor of 4th ventricle
outside BBB (fenestrated venules)
Upper GI tract & pharynx
Vestibular apparatus/Cerebellum
Higher cortical centres

8. Integrative Vomiting Centre (IVC) Chemoreceptor Trigger Zone
Cerebral
High CNS
Chemoreceptor
Trigger Zone
Sights, Smells
Memories
Toxic
Cancer
Infection
Radiation
Drugs
Chemotherapy
Opioids
Digoxin, etc
Biochemical
Uremia
Hypercalcemia
Vestibular
Cerebellar
Integrative
Vomiting
Centre (IVC)
Opioids
Cerebellar Tumor
GI Tract
Vagal
Increased
Intracranial Press
Distension
Over-eating
Gastric Stasis
Ext. Pressure
Obstruction
High, mid, low
Constipation
Chemical Irritants
Blood, drugs
Primary or
Metastatic Tumor
G. Michael Downing

9. Pathogenesis of chemo- & RT-induced emesis (CIE, RIE)
3rd vent
Area postrema

10. N/V Related Problems Medical Decreased QoL Psychological distress
dehydration / electrolyte abnormalities
esophageal tears / GI bleed
aspiration pneumonia
Decreased QoL
weight loss / anorexia
weakness / lethargy
Psychological distress
Refusal of beneficial therapy

11. Principles of Therapy Treat the underlying cause
Environmental measures
Antiemetic use:
anticipate need
use adequate, regular doses
aim at receptor involved
combinations if necessary
anticipate need for alternate routes

12. Environmental Measures
Limit exposure to food smells
open food trays prior to presentation
Bland foods (BRAT)
Small, frequent snacks/meals
Good oral hygene
Fresh air, calming environment
Sitting upright post meal
Avoid alcohol

13. Acupuncture/pressure
Not as well studied
Safe in trained hands
Often used in conjunction with meds
Some evidence in CINV, delayed NV
Theory behind wrist/pressure bands
Dibble et al. Oncol Nurs Forum :813-20
Weightman et al. BMJ :1379

14. Anti-Emetic Agents Transdermal scopolamine Benzodiazepines
Antihistamines
Cannabinoids
Metoclopramide, Domperidone
Neuroleptics / Anti-psychotics
Corticosteroids
5-HT3 Antagonists
NK1 Antagonists (aprepitant)

15. Integrative Vomiting Centre (IVC) Chemoreceptor Trigger Zone Cerebral
High CNS
Chemoreceptor
Trigger Zone
D2 Antagonist
Prochlorperazine
Haloperidol
Methotrimeprazine
Gastrokinetics
Metoclopromide
5HT3 Antagonist
Ondansetron
Granisetron
Olanzepine?
Benzodiazepines
Cannabinoids
Relaxation
Vestibular
Cerebellar
Integrative
Vomiting
Centre (IVC)
H1 Antagonist
Dimenhydrinate
Methotrimeprazine
Anticholinergic
Scopolamine
Atropine
Cannabinoids
GI Tract
Vagal
D2 Antagonist
Gastrokinetics
Metoclopromide
Domeperidone Phenothiazines
Methotrimeprazine
5HT4 Agonist
5HT3 Antagonist
Ondansetron
Octreotide
Dexamethasone
Cannabinoids
Anticholinergic
Scopolamine
Atropine
H1 Antagonist
Dimenhydrinate
Cyclizine
Methotrimeprazine
5HT2 Antagonist
5HT3 Antagonist
Ondansetron
Increased
Intracranial Press
Dexamethasone
? VP Shunt
G. Michael Downing

16. Antiemetics and Dosing
Haloperidol mg po/sq/iv q4-12h
MTMZ mg po/sl/sq q4-8h
Prochlorperazine mg po/pr/iv
CPZ mg po/pr/iv
Scopolamine patch (Transderm-V)
Metoclopramide mg po/sq/pr q4-8h
Domperidone 10 mg po q4-8h
DOPAMINE
ANTAGONISTS
ANTIMUSCARINIC
PROKINETIC

17. Antiemetics and Dosing
Dimenhydrinate mg po/pr q4-8h
Promethazine 25 mg po/iv q4-6h (Not sq)
Meclizine 25 mg po q6-12h
Ondansetron mg q 12 h po/sq/iv
Granisetron 1- 2 mg q 12 h po/sq
Dexamethasone 4-16 mg po/sq/iv daily
Lorazepam mg po/sl q4-12h
Nabilone mg po/sl q8-12h
Olanzepine mg OD H1
ANTAGONISTS
SEROTONIN
ANTAGONISTS
MISCELLANEOUS

18. Olanzepine Atypical antipsychotic agent
Used in schizophrenia, delirium
Blocks multiple receptors
D1-4, 5-HT2/3/6, α1adrenergic, H1, M1-4
High affinity for serotonin vs dopaminergic
Well tolerated
Few drug interactions

19. Olanzepine Has been used in several case studies
Recently used in CINV and delayed NV
Good results with few problems
May also have some appetite benefits
Less expensive than 5-HT3 antagonists
Navari et al. Support Care Cancer 2007 Mar 21
Navari et al. Support Care Cancer :529-34
Passik et al. Cancer Invest :383-8
Passik et al. JPSM :485-89
Srivastava et al. JPSM :578-82
Jackson et al. J Pall Med :251-55

20. Cannabinoids & Nausea

21. Dorsal Vagal Complex—NTS
The Nucleus of the Solitary Tract (NTS) receives information about:
Blood-borne emetics via the brainstem (BS) CTZ
Abdominal irritants via vagal afferents
NTS neurons, in turn, project to a BS central pattern generator, which coordinates emesis behavior
Higher cortical and limbic regions (governing taste, smell, sight, pain, memory and emotion) can suppress or stimulate nausea and vomiting through descending connections to the BS emetic circuitry
Cannabinoids are thought to exert their antiemetic effects primarily via action on CB1 receptors in the NTS and higher cortical and limbic regions
Indirect, partial actions on 5-HT and DA signaling via 5-HT3 and D2 receptors are implicated
Cortex Limbic System
Brainstem Emetic Circuitry
Dorsal Vagal Complex—NTS
Stomach Wall

22. Cannabinoids in CINV 20 pts, RCT, P vs THC, X-over
10 or 15 mg/m2 po q4h x 3, various tumours
Chemotherapy not specified
Anti-emetic effect seen in 14/20 THC vs 0/22 P (p<0.001)
No patients vomited while “high”
Sallan et al, NEJM :

23. Cannabinoids in CINV 30 RCTs systematically reviewed
N=1366 pts; 25 trials X-over design
Nabilone, dronabinol, levonantradol (IM)
Stemitil, domperidone, metoclopramide
Variety of tumours
Low to highly emetogenic chemotherapies
Studied first 24 h (acute efficacy)
Tramer et al, BMJ :16-23

24. Cannabinoids in CINV Oral nabilone (16) Oral dronabinol (13)
IM levonantradol (1)
Prochlorperazine (7)
metoclopramide, alizapride
domperidone (2)
chlorpromazine, placebo (4)
prochlorperazine (6)
metoclopramide (2)
haloperidol, placebo (6)
chlorpromazine
Tramer et al, BMJ :16-23

25. Control of N/V with Cannabinoids: Systematic Review
Control (Placebo or Active)
Event rate (%)
vs. Placebo vs. Active
70%
57%
59%
43%
Nausea
66%
34%
57%
45%
Vomiting
vs. Placebo vs. Active
30 randomized, comparative studies of cannabinoids with placebo or other antiemetics (oral nabilone, 16 studies; oral dronabinol, 11 studies; intramuscular levonatrodol, 1 study)
Active control= prochlorperazine, metoclopramide, chlorpromazine, haloperidol, domperidone, and alizapride
active control= prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, alzapride
Tramèr MR, et al. BMJ. 2001;323:1-8.

26. Complete Control of N/V with Cannabinoids
Nausea
NNT (95% CI)
Versus placebo (4 studies)
8.0 ( )
Versus active control (7 studies)
6.4 (4.0-16)
Vomiting
Versus placebo (4 studies)
3.3 ( )
Versus active control (6 studies)
8.0 (4.5-38)
Relative risk (95% CI) Favors cannabinoids
NNT= number needed to treat; active control= prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, alzapride.
Tramèr MR, et al. BMJ. 2001;323:1-8

27. Patients’ Preference for Cannabinoids
Relative risk (95% CI) Favors cannabinoids
Versus placebo (4 studies)
Versus active control (14 studies)
1.6 ( )
2.8 ( )
Preference for cannabinoids
NNT (95% CI)
NNT = number needed to treat; active control= prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, alzapride
Tramèr MR, et al. BMJ. 2001;323:1-8.

28. Cannabinoids in CINV
Cannabinoids may be superior to conventional therapies in low-moderate emetogenic setting
Patient preference for cannabinoids ranged from 38-90% (placebo 4-20%)
Cannabinoids produced significantly more side effects (good & bad), more pt withdrawals
“In selected patients, cannabinoids may be useful as mood enhancing adjuvants for the control of chemotherapy related sickness”
Tramer et al, BMJ :16-23

29. Cannabinoids in CINV 8-THC less psychotropic, less $, stable
Less psychomimetic effects in children
Phase II trial, 8 pts (3-13 yrs)
Variety of cancers, chemotherapy
Starting dose of 5 mg/m2
Nausea and vomiting eliminated
No psychotropic effects seen
Abrahamov et al, Life Sci :2097

30. Experimental Emesis Linda Parker et al, Wilfred Laurier U.
Series of studies with rats/shrews
Model for anticipatory nausea
THC or CBD >> ondansetron
THC/CBD maybe most effective
Limebeer and Parker Neuroreport 1999
Parker et al Neuroreport 2002
Parker et al Psychopharm 2004
Limebeer et al Physiol Behav 2006

31. Cannabinoids in CINV
Several RCTs in chemotherapy-induced emesis (CINV)
Pre 5-HT3 antagonist era (ondansetron)
Oral or IM meds vs best treatment
No comparison with 5-HT3 antagonist
No controlled trials of inhaled marijuana

32. Inhaled Marijuana
Cross-over CINV study, placebo control, marijuana vs dronabinol
n= 20 (15 men), 14 NSCLC
25% no vomiting, 15% no nausea
35% hallucinations or time perception changes
Preference:
20% marijuana, 35% dronabinol, 45% no pref
THC > marijuana therapeutic potency
Levitt et al, JCO 1984 abstract C-354

33. Inhaled Marijuana CINV, open trial, no control
n=74, chronic users, 25% dropped out
Preference:
18 (34%) v effective, 26 (44%) mod effective 12 (22%) no benefit
Side Effects:
sedation 88%, dry mouth 77%, dizziness 39% 13% no A/E
Vinciguerra et al, N Y State J Med 1988, 88:525

34. Special Situations
Constipation
Obstruction

35. Symptom Prevalence Pain Fatigue/Asthenia Constipation Dyspnea Nausea
Vomiting
Delirium
Depression/suffering
80 – 90+% %
70%
60+% %
30% % %

36. Malignancy Direct effects obstruction by tumor in wall
external compression by tumor
neural damage
L/S spinal cord
cauda equina/pelvic plexus
hypercalcemia

37. Malignancy Secondary effects poor po intake dehydration
weakness/inactivity
confusion
depression
unfamiliar toilet arrangements

38. Medications Opioids  Ileocecal & anal sphincter tone
 Peristaltic activity (SI & C)
Impaired defecation reflex
 sensitivity to distension
 internal anal sphincter tone
 Water, electrolyte absorption (SI & C)

39. Concurrent Disease Diabetes Hypothyroidism Hypokalemia Hernia
Anal fissure/stenosis
Hemorrhoids
Autonomic neuropathy
diabetes
spinal cord disease
chemotherapy
Parkinson’s disease
ALS/MS
Dementia

40. Treatment Prophylaxis good symptom control activity adequate hydration
recognize drug effect
create a favorable environment

41. Treatment: Laxatives >80% pts on opioids need laxatives
Little research to guide choice
Softener and stimulant best first choice
May require oral/rectal routes
Enemas useful in impaction
Bulk forming agents worsen situation

42. Treatment: Laxatives Surfactants: docusate
Contact cathartics: senna, bisacodyl
Osmotic laxatives: lactulose
Saline osmotics: MgOH, Phosphasoda
Enemas: oil, saline, soap suds, Fleet

43. Other Approaches Prokinetic agents: domperidone, metoclopramide
Antibiotics: erythromycin
Herbal preparations: mulberry, rhubarb, licorice, prune juice

44. New Agents Selective opioid antagonists Active in periphery, esp. gut
Methylnaltrexone, Alvimopan
Studies used IV and oral application
S/E
abd cramping, flatulence, nausea, dizziness

46. Bowel Obstruction Common problem Associated with advanced cancers
GI, ovarian, lymphoma
Relapse / local spread of intrabdominal tumour
Diffuse peritoneal carcinomatosis, encasement by tumour
Multiple partial bowel occlusions
(delaying or preventing propulsion of intestinal contents)
Symptoms of nausea/vomiting
abdominal pain, distention
The management of intestinal obstruction in advanced cancer patients remains a controversial topic.
Surgical intervention is considered after weighing up the risks of further morbidity form surgery.
Pandha et al. Anti-Cancer Drugs, 1996; 7:5-10

47. Bowel Obstruction: Etiology
Mechanical obstruction causes:
 secretions, gas proximal to the obstruction
distention from gas, ingested fluids, digestive secretions in turn causes  secretions
secretion
distention
Mercadante et al. JPSM 1997

48. Bowel Obstruction Standard Therapy NG tube/IV fluids (“drip & suck”)
Bowel rest
Pain control (opioids)
Radiological assessment
Surgical intervention

49. Bowel Obstruction Palliative Therapy Opioid analgesics, dexamethasone
Promotility agents
metoclopramide/domperidone
Octreotide (Sandostatin)
Hyoscine butylbromide (Buscopan)

50. Somatostatin Analogues
Octreotide, vapreotide, lanreotide
Receptor activity
brain, pituitary, pancreas, GI tract, immune cells
Used in many conditions
Prolongs GI transit time
 fluid secretion in jejunum
 water/electrolyte absorption
decreases peristasis
reduces GI blood flow
Inhibits exocrine pancreatic secretion

51. Bowel Obstruction in Ovarian Cancer
13 pts, advanced ovarian cancer, inoperable GI obstruction
Octreotide dose of µg/day
Octreotide controlled vomiting in all cases
Vomiting stopped in 2-3 days of starting tx
Mangili et al., Gynecologic Oncology 1996

52. Bowel Obstruction in Ovarian Cancer
NG drainage  from 2000 to <100 ml/day
Complete relief of symptoms within 3 days (range 1-6 days)
8/13 pts D/C from hospital, continued treatment at home
Mangili et al., Gynecologic Oncology 1996

53. Delivery Routes for Medications
Standard
Oral
Intravenous
Inhalation (nebulized)
Subcutaneous
Alternative
Sublingual
transmucosal
mouthwashes
Intranasal
Transdermal (topical)
Rectal
Vaginal
Intraosseus GH

54. Think “Outside the Box”
More to indications/ Routes admin. Than “CPS”

55. Alternative Routes of Drug Administration
Alternative delivery routes
transmucosal
transdermal (topical)
rectal
Review of the science

56. Oral Mucosal Delivery Advantages: High vascular permeability
Avoids “first pass” hepatic elimination
High potency of drug (small volumes)
Less intimidating/ “low-tech” administration
easier in home, PCH, LTC
Alternate administration route
pt NPO, difficulty swallowing, SBO, etc.
(immediate absorption to systemic circulation)

57. Oral Mucosal Delivery Barriers:
Lipophilic Rx: needs intact mucosal cell membrane
Hydrophilic Rx: poor absorption
Volume of dose
Ideally  0.5 ml; > 1-2 ml  swallowed
Excessive salvation  swallowing of dose
Acceptable delivery vehicle/taste

58. Highly lipophilic  better than oral absorption??
Oral Mucosal Delivery
Oral transmucosal drugs
Lorazepam
Olanzapine wafers (Zyprexa Zydis®)
Proclorperazine buccal tabs (Stemetil®)
Mirtazapine (Remeron® RD)
Highly lipophilic  better than oral absorption??

59. Oral Mucosal Delivery Haloperidol (Haldol®)
Protect from light & freezing
Store below 40ºC  discoloration & grayish-red precipitate
Methotrimeprazine (Nozinan®)
25 mg/ml injectable
(store room temp, protect from light)

60. Topical Route Oral route not desirable More localized action Mucositis
Inability to swallow
Nausea/vomiting
Obstruction
Poor taste of product
Dry mouth
More localized action

61. Topical Route: Advantages
Avoids the GI tract and hepatic first-pass metabolism
Delivers to a specific site
Controls absorption rate
Provides constant dosing  depot effect with anhydrous gels
Reduces systemic side effects
Heir, Gary DMD, et al. IJPC 2004; 8:

62. Topical Route: Advantages
Improves compliance
Allows ↑ concentration of Rx at site of application
Plasma concentrations of <10% compared to oral route
Heir, Gary DMD, et al. IJPC 2004; 8:

63. Topical Route: Drawbacks
Variations in the stratum corneum barrier
Delivery dosing may require adjustment
Rate of absorption may vary
Rash most common SE
Heir, Gary DMD, et al. IJPC 2004; 8:

64. Topical Route Mouthwash/rinses Transdermal Route Buccal spray
Misoprostol, Diphenhydramine, Lidocaine, Triamcinolone,
Sucralfate, Dry Mouth Formulations
Transdermal Route
Fentanyl, Oxybutinin, Estrogen, Nitrate patches
Transdermal gels
Buccal spray
Morphine, Fentanyl, Triamcinolone, Lidocaine
Medicated lollipops
Fentanyl, Nicotine, Tetracaine, Dextromethorphan, Diphenyhydramine, Nystatin

65. Topical Anti-Nauseant Gels
Scopolamine 0.25mg/0.1ml
Transderm V patch releases ~1mg over 72 hr
~0.1mg Q8H vs 0.25mg
Apply 0.1 – 0.2ml Q8H
Expiry date about 6 months

66. Topical Anti-Nauseant Gels
ABHR
Ativan/Benadryl/Haldol/Reglan
Lorazepam 2- 4 mg higher brain (cortex)
Diphenhydramine mg  vestibular
Haloperidol 2-4 mg  CTZ
Metoclopramide mg/ml  afferent impulses from periphery
Dose 0.25ml inner wrist QID
Moon RB Intl J Pharm Compound :95-8

68. Subcut Antiemetics Haloperidol 0.5 - 1 mg po/sq/iv q4-12h
MTMZ mg po/sl/sq q4-8h
Metoclopramide mg po/sq/pr q4-8h
Ondansetron mg q 12 h po/sq/iv
Granisetron 1- 2 mg q 12 h po/sq
Dexamethasone 4-16 mg po/sq/iv daily
Dimenhydrinate mg po/pr/sq q4-8h
Scopolamine mg sq
Promethazine (Not sq)

69. Case: Maria de J. 35 y o, mother of 3, works in textiles
Lower abdominal pain, nausea
Investigations reveal ovarian mass, resection: adenocarcinoma
Chemo with platinum/paclitaxel, nausea with first 2 cycles, N/V subsequently
Admitted for IV hydration, pt wants to stop tx gh

70. Case: Maria de J. 4th cycle delayed x 1 week, P & S clinic
Full assessment reveals anticipatory nausea, constipation on AXR
Oral and PR laxatives given, BZD prechemo
No vomiting, still nauseated, avoids po route
Refuses hospital stay gh

71. Case: Maria de J.
Use of triple suppository advised (tid – qid) dexamethasone 2 mg
metoclopramide 10 mg
diphenhydramine 25 mg
Nausea controlled for final 2 cycles, no hydration necessary

72. Rectal Route Drug absorption Limiting factors
Conditions/methods of administration
Care Beyond Cure: A Pharmacotherapeutic Guide to Palliative Care; Andree Neron Editor, 2000

73. Rectal Drug Absorption
First 6-8cm of rectum drain directly into systemic circulation
Drugs admin by this route: no hepatic first-pass effect
Rx high hepatic extraction may  in bioavailability; variable due to:
Patient
Absorption site
Drug formulation, penetration of mucosa
Care Beyond Cure, 2000

74. Rectal Drug Absorption
Rectum vs upper GI tract:
Absorption area
rectal mucosa: cm² (no villi in rectum)
small intestine: 2,000,000 cm² pH
Fluid content
Absorption mechanisms same (passive diffusion)
Formulation of drug is critical factor
May have to increase dosage interval i.e. Q8H vs Q12H
Care Beyond Cure, 2000

75. Rectal Limiting Factors
Drug insertion level
6-8cm (lower rectum)  systemic circulation
15-20cm (upper rectum)  portal vein  hepatic first-pass effect
Solutions:
Aqueous & alcohol solutions are the best and most rapidly absorbed
Fecal matter in rectum
Defecation reflex, involuntary expulsion
Care Beyond Cure, 2000

76. Rectal Administration
Use liquid formulations whenever possible
Use volumes <10-25 ml
>80 ml ↑ risk of spontaneous expulsion
Administer liquids with a small lubricated syringe
Rectal canula or catheter tip syringes beneficial
Cut a NG tube (#14) to 5 cm; attach to prefilled syringe
reduces chance of portal vein absorption
Care Beyond Cure, 2000

77. Rectal Administration
Administer capsules and tablets directly into the rectum
Compounding pharmacy: “designer” rectal suppositories
Administration a lot easier
Hepatic absorption usually not a problem with the use of suppositories
Care Beyond Cure, 2000

78. Rectal Administration
Lorazepam
Use parenteral preps or tablets
Bioavailability of injection > 80%
Serum concentrations < ½ of IV route
Metoclopramide
Tablets or suspensions
Phenobarbital
Excellent bioavailability  %
Peaks at ~ 4 hours
Baines, MJ BMJ 1997;315:

79. Rectal Administration
For refractory cases, use combinations that act at different receptor sites
Cerebral cortex
CTZ
GI tract
Severe or refractory nausea may benefit from corticosteroid
Care Beyond Cure, 2000

80. Triple Suppository Metoclopramide 10 - 20mg Dimenhydrinate 25 - 75mg
Prochloperazine mg
Use a formulation with a single medication or combinations of up to 3 medications

81. Other Antinauseant Suppositories
Dimenhydrinate 75mg/Metoclopramide 15mg/Prochloperazine 10mg
Dimenhydrinate 25mg/Metoclopramide 10mg/ Prochloperazine 15mg
Metoclopramide 10mg/Haloperidol 1mg
Dimenhydrinate 25mg/ Metoclopramide 20mg/ Prochloperazine 10mg/ Dexamethasone 2mg

82. Summary GI symptoms in palliative care varied Assessment important
Tailor therapy to meet pt needs
Research in area lacking
Help is available
WRHA Pall Care pgm:
Physician on call: (24 hrs)

83. Case example Young woman, chronic pain
Compression of C6 root, migraine, constant, rated 8/10
Attempted pain control using methadone, not tolerated
Lost to F/U until Jan 07, returned on meperidine (Demerol®)

84. Case example GP requested IV anti-nauseants Good effect but cumbersome
Topical compound (/ml, in PLO):
metoclopramide 20 mg
dimenhydrinate 25 mg
Benefit, but required adjustment to (/ml):
dimenhydrinate 100 mg
haloperidol 4 mg
metoclopramide 80 mg