An update on recent guidelines on antiemetic use in gastroenteritis in children.With some references to drugs for GERD

1. DRUGS FOR
VOMITING IN CHILDREN
FROM GUIDELINES TO REAL LIFE
DR SHAILESH MEHTA
M.D.PEDIATRICS
Practicing pediatrician Chandigarh

2. ANTI EMETICS IN ACUTE GE
WHY DO WE USE THEM?
• in order to increase the success rate of oral
rehydration therapy
• increase patient comfort or to reduce concerns
of parents
• In a survey of randomly selected board-certified
emergency physicians, pediatricians and pediatric
emergency medicine specialists demonstrated
that more than 50% of clinicians report usage of
antiemetics across all three specialties despite
the acknowledgement that the use of antiemetics
remains controversial in this setting.

4. Anti-Emetic Drugs
1. ANTIHISTAMINES
Cyclizine
Promethazine
Dimenhydrinate
2. DOPAMINE RECEPTOR
ANTAGONISTS
Domperidone
Metoclopramide
Prochlorperazine
3. NEUROKININ RECEPTOR
ANTAGONISTS
Aprepitant
4. ANTIMUSCARINICS
Hyoscine
5. SHT3 RECEPTOR
ANTAGONISTS
Ondansetron
Granisteron
6. CANNABINOIDS
Nabitone

5. CHOICE OF DRUGS-
VOMITING IN ACUTE GE
• A drug once considered a wonder drug .
• Is an antihistaminic
• Also used in motion sickness
• It was the most frequently prescribed agent
(64.8%), amongst all prescriptions of
antiemetics in a 2002 survey
• No more recommended in vomiting in A.GE

6. ISSUES WITH PROMETHAZINE
• Respiratory depression; over sedation; agitation; hallucinations;
seizures; and dystonic reactions have been reported with
promethazine use in children.
A wide range of weight-based doses (0.45 to 6.4 mg per kg) were
associated with respiratory depression and cardiac arrests
• FDA in late 2004, added a “boxed warning” was added to the labeling
for promethazine hydrochloride (Phenergan), including a
contraindication for use in children less than two years of age and a
strengthened warning with regard to the use in children two years of
age or older
Starke PR, Weaver J, Chowdhury BA. Boxed warning added to
promethazine labeling for pediatric use. N Engl J Med.
2005;352(25):2653
Kwon KT, Rudkin SE, Langdorf MI: Antiemetic use in pediatric
gastroenteritis: a national survey of emergency physicians,
pediatricians, and pediatric emergency physicians. Clin.
Pediatrics41,641–652 (2002).

7. VOMITING IN ACUTE GE
• A dopamine antagonist
• Both central and peripheral acting
• Being widely used for children less than 1 year
• However , not recommended by any authority
• The side effects outweigh the benefits if any

8. METOCLOPRAMIDE WARNING

9. METOCLOPRAMIDE PRODUCT INSERT

10. METOCLOPRAMIDE
CONTRA INDICATED LESS THAN 1 YRS
OF AGE https://www.gov.uk/drug-
safety-update/metoclopramide-risk-
of-neurological-adverse-effects

11. VOMITING IN ACUTE GE
• A drug which seems to be slightly out of popularity
• FDA boxed warning 2004 –PROLONGS QTc interval
• IAP TASK FORCE 2004 deemed it to be safest of all
anti emetics in Acute GE
• Not included in any systematic review .Poor quality
of evidence to prove its efficacy.
• Dopamine D2 antagonist with less CNS side effects.
Alhashimi D, Alhashimi H, Fedorowicz Z. Antiemetics for reducing vomiting
related to acute gastroenteritis in children and adolescents.
Cochrane Database Syst Rev 2009
DeCamp LR, Byerley JS, Doshi N, Steiner MJ. Use of antiemetic
agents in acute gastroenteritis: a systematic review and meta-analysis.
Arch Pediatr Adolesc Med 2008

12. DOMPERIDONE DROPS
NO PRODUCT INSERT

13. DOMPERIDONE SYRUP

14. MOST SYSTEMATIC REVIEWS ON ANTIEMETICS USE IN
GASTROENTERITIS EXCLUDE THE FOLLOWING DRUGS
• PROMETHAZINE- FDA BLACK BOX WARNING-NOT TO BE USED UNDER 2YEARS OF
AGE
• DOMPERIDONE- , 2004, FDA issued a public warning that distributing any
INJECTABLE domperidone-containing products is illegal
Sudden Cardiac Death and Ventricular Arrhythmias Associated with Domperidone:
Evidence Supporting Health Canada’s Warning
Salmaan Kanji, Alyssa Stevenson, Brian Hutton
Can J Hosp Pharm. 2014 Jul-Aug; 67(4): 311–312
HEALTH CANADA AND NICE ADVOCATE DOMPERIDONE USE AS GALACTAGOGUE
ONLY WITH A WARNING NOTE THAT IT HAS POTENTIAL TO CAUSE ARRYTHMIA IN
INFANT AND MOTHER
• CYCLIZINE
• HYOSCINE
( ANTIHISTAMINICS AND ANTIMUSCARINICS MORE USEFUL IN LABYRYNTHINE
CAUSES OF VOMITING)

15. VOMITING IN ACUTE GE
• Another wonder drug
• Scores over any other anti emetic in many systematic
reviews
• Superior to metoclopramide in its anti emetic effect
• Used 1 month onwards for certain indications
(http://www.accessdata.fda.gov/drugsatfda_docs/label
/2012/020007s043lbl.pdf)
• 5HT3 receptor antagonist
• Not recommended so far for use in acute
gastroenteritis
• No serious side effects except increase diarrhoea

16. RESULT OF LARGEST SYSTEMATIC
REVIEW –
COMPARISON BETWEEN VARIOUS
LICENSED ANTI EMETICS
• ONDENSETRON VS METOCLOPRAMIDE VS DIMENHYDRINATE VS
DEXAMETHASONE
• The Cochrane Central Register of Controlled Trials, MEDLINE and
EMBASE searched from 1980 to March 2011
• 1479 PARTICIPANTS , 7 RCT , Age 1yr-18yr
• Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing
vomiting related to acute gastroenteritis in children and
adolescents.
• Cochrane Database Syst Rev2011;(9):CD005506

17. CONCLUSIONS
• Oral ondansetron increased the proportion of
patients who had ceased vomiting and reduced
the number needing intravenous rehydration and
immediate hospital admission.
• Proportion of patients with cessation of vomiting
in 24 hours was (58%) with IV ondansetron, (17%)
placebo and (33%) in the metoclopramide group
(P value = 0.039).
• LOW or limited evidence to support the role of
Dimenhydrinate or Dexamethasone in
gastroenteritis induced vomiting in children and
adolescents

18. METOCLOPROMIDE VS
ONDANSETRON
SYSTEMATIC LITERATURE REVIEW TILL
2012
• metoclopramide appears to be less efficacious in the
treatment of gastroenteritis induced vomiting and are
associated with more adverse events than
ondansetron.
• BMC Public Health. 2013; 13(Suppl 3): S9.
• The effect of antiemetics in childhood gastroenteritis
• Jai K Das, Rohail Kumar,Rehana A Salam, Stephen
Freedman, and Zulfiqar A Bhutta

19. SOME ISSUES WITH ONDANSETRON
• RECOMMENDATIONS ARE THAT IT SHOULD BE USED ONLY IN
POST SURGERY OR POST CHEMOTHERAPY EMESIS
HOWEVER , IN SOME STUDIES , WHERE ONDANSETRON WAS
USED TO CONTROL VOMITING DUE TO GASTROENTERITIS,
FOLLOWING WERE THE CONCLUSIONS
Ondansetron to be used as a single dose( if at all to be used)
in gastroenteritis as an indication
• TILL DATE IT IS AN OFF LABEL PRESCRIPTION
• THE READMISSION RATES AFTER 72HRS ARE SAME IN
PLACEBO VS ONDANSETRON
• ONDANSETRON REDUCES THE IMMEDIATE NEED FOR IV
FLUIDS HOWEVER IT INCREASES EPISODES OF DIARRHOEA
Roslund G, Hepps TS, McQuillen KK: The role of oral ondansetron in children with vomiting
as a result of acute gastritis/gastroenteritis who have failed oral rehydration therapy: a
randomized controlled trial. Ann. Emerg. Med.52,22–29 (2008).
DeCamp LR, Byerley JS, Doshi N, Steiner MJ.
Clin Exp Gastroenterol. 2010; 3: 97–112.
Arch Pediatr Adolesc Med. 2008 Sep;162(9):858-65

20. DILEMMAS
VOMITING DUE TO ACUTE GASTROENTERITIS
• STUDIES INDICATE DOMPERIDONE AND
METOCLOPROMIDE ARE NEITHER SAFE NOR
EFFECTIVE NOR RECOMMENDED IN
GASTROENTERITIS INDUCED VOMITING IN
CHILDREN
• STUDIES INDICATE ONDENSETRON TO BE
MOST EFFECTIVE FOR VOMITING IN ACUTE GE
BUT NOT APPROVED FOR THIS INDICATION

21. NOT ALL THAT NICE
Both the American Academy of Pediatrics and NICE guidelines
indicate that there is a consensus of opinion that
“antiemetics are not needed for the management of
vomiting due to gastroenteritis in children.”
If at all they are used , they are deemed as “off label
prescriptions” , and therefore need to be prescribed after an
“informed consent”
American Academy of Pediatrics (AAP). Practice parameter: the management of acute gastroenteritis in young
children. American academy of Pediatics, Provisional committee on Quality Improvement, Subcommittee on
Acute Gastroenteritis. Pediatrics 1996;97:424e35.
National Collaborating Centre for Women’s and Children’s Health. Diarrhoea and Vomiting Diagnosis,
Assessment and Management in Children Younger than 5 years. London: RCOG Press, 2009
Khanna R, Lakhanpaul M, Burman-Roy S,et al. BMJ2009;25:1009e12

22. SUNNY 6MONTHS CHILD
Informant mother
Recurrent vomits since 2weeks, not sleeping well,
accepting feeds but cries during or after feeds.
No fever or loose stools
WT 7KG
NO DEHYDRATION, AF not depressed nor bulging
PLAYFUL
ON COMPLEMENTARY FEEDS AND BREASTFEEDS

23. GERD
They may “ VOMIT” OR “REGURGITATE” OR “SPIT
up” throughout the day. In fact, more than half of
all infants under 3 months old have GERD.
The most common symptoms of GERD in
children are:
- Frequent or recurrent vomiting
- Frequent or persistent cough/wheezy chest
- Refusing to eat or difficulty eating (choking or
gagging with feeding)
- Crying with feeding
- Heartburn, or abdominal pain
- Inadequate weight gain

24. CHOICE OF DRUGS
• DOMPERIDONE ?
• METOCLOPRAMIDE?
• PPI?
• H2RA?
• CISAPRIDE?
• ONDENSETRON?
• PROMETHAZINE?

25. DOMPERIDONE – POOR EVIDENCE
SUPPORTING ITS ROLE IN GERD
• Evidence for the efficacy of domperidone in GER is
very poor in older children, infants and neonates as
the result of limitations in study design and length of
follow-up, and this evidence is too weak to permit
recommendations
Tighe M, Afzal NA, Bevan A, Hayen A, Munro A, Beattie
RM. Pharmacological treatment of children with
gastro-oesophageal reflux. Cochrane Database of
Systematic Reviews 2014, Issue 11. Art. No.: CD008550.
DOI: 10.1002/14651858.CD008550.pub2

26. METOCLOPRAMIDE FOR GERD
7RCT – FOUND REDUCTION IN DAILY
SYMPTOMS
• A meta-analysis of 7 RCTs of metoclopramide in developmentally healthy children
1 month to 2 years of age with symptoms of GER found that metoclopramide
reduced daily symptoms and the RI but was associated with significant side effects.
• Metoclopramide commonly produces adverse side effects in infants
and children, particularly lethargy, irritability, gynecomastia,
galacctorhea, and extrapyramidal reactions and has caused
permanent tardive dyskinesia
Craig WR, Hanlon-Dearman A, Sinclair C, Taback S, Moffatt M.
Metoclopramide, thickened feedings, and positioning for gastro-oesophageal reflux in children
under two years.
Cochrane Database Syst Rev. 2004:CD003502

27. GERD GUIDELINES ESPGHAN 2009
• PROKINETICS- CISAPRIDE, DOMPERIDONE,
METOCLOPRAMIDE NOT RECOMMENDED
DUE TO INSUFFICIENT EVIDENCE OF THEIR
EFFICACY
• ADVERSE EFFECTS OF PROKINETIC AGENTS
OUTWEIGH THE BENEFITS IF ANY

28. GERD GUIDELINES ESPGHAN 2009
• HISTAMINE 2 RECEPTOR ANTAGONISTS (H2RA)
• PROTON PUMP INHIBITORS
BOTH DEEMED SAFE AND EFFECTIVE FOR
GERD
HOWEVER PPI APPROVAL IS BEYOND 1 YEAR
OF AGE

29. FDA ON RANITIDINE
The safety and effectiveness of ZANTAC have
been established in the age-group of 1 month
to 16 years
http://www.accessdata.fda.gov/drugsatfda_d
ocs/label/2009/018703s067,019675s034,0202
51s018lbl.pdf

30. INTROSPECTION
• AM I HAVING COMPLETE KNOWLEDGE
ABOUT THE ANTI EMETIC AND ITS SIDE
EFFECTS ?
• IS THE DRUG APPROVED FOR USE FOR THE
INDICATION I AM USING ?
• AM I DOING JUSTICE TO MY PATIENT ?

31. SOMETIMES
DOING NOTHING IS THE BEST
THING
A BIG BIG THANK YOU