Syrup of Ipecac OTC or not OTC?

1. Syrup of IpecacOTC or not OTC? Milton Tenenbein, MD Nonprescription Drug Advisory Committee Bethesda MD; June 12, 2003

2. Syrup of IpecacOTC or not OTC? That is the question.

3. Objectives • to discuss the need for OTC status of syrup of ipecac • to discuss four specific questions posed by the committee

4. Committee Questions 1. Role of gut decontamination? 2. Role of ipecac in gut decontamination? 2a. Benefits and risks of ipecac? 2b. Literature assessment of benefits/risk? 2c. Remote populations? 3. Abuse potential of syrup of ipecac? 4. What are alternatives to ipecac?

5. Disease Burden • poison centers reported 1.2x106 exposures in children < 6 in 2001 • poisoning death is unusual in children < 6 • 500 per annum in the 1940s • 25 in 1997 • poison prevention is a success story

6. Reasons for Success I • child resistant closures • constituent reformulations • anticipatory guidance • public education • legislation

7. Reasons for Success II • poison control centers • product formulation/poison treatment databases • sophisticated medical treatment resources • new antidotes • safer medications

8. Two Most Important Reasons 1. Child resistant closures 2. Safer medications

9. Poison Treatment Gastrointestinal decontamination is cardinal principle in the management of the overdose patient.

10. Traditional Hospital Management Gastric Emptying • syrup of ipecac, or • gastric lavage Toxin Adsorption • activated charcoal + a cathartic

11. Poison Treatment in the Home • ipecac became an “obvious” intervention • FDA OTC status since 1965 • a policy of the AAP (Pediatrics 1994;94:566-7) • TIPP • other injury prevention publications • poison prevention brochures • a policy of the AAPCC

12. Support for Ipecac in the Home • AAP & AAPCC are reviewing this policy • its rescinding is anticipated

13. AACT/EAPCCT Position PapersJ ToxicolClin Toxicol 1997;35:695-762 • 5 position papers - hospital treatment • ipecac; gastric lavage; charcoal; cathartics; whole bowel irrigation • “retired” ipecac, lavage and cathartics • advocates charcoal as first line therapy • emphasis upon first hour after ingestion

14. AACT/EAPCCT Position PaperJ ToxicolClin Toxicol 1997;35:699-799 • specific ipecac statement • “its routine administration in the emergency department should be abandoned” • no definitive statement on ipecac in the home • this statement generated considerable thought, discussion and debate regarding ipecac in the home

15. “Ipecac in the HomeA Health Hazard?” Clin Toxicol 1981;18:969-972 “The ipecac story is but another example of a seemingly sensible preventive health strategy being universally recommended and widely accepted before its efficacy and validity has been established.”

16. Ipecac - Efficacy There are no data that support benefit for the patient from ipecac in the home. There are data that support lack of benefit for the patient treated with ipecac in the hospital.

17. Ipecac - Performance Children • 28% of dose removed (range: 0-78%) • (immediately after ingestion) • thus - poor and unreliable performance Adults • 5 min: 51-83% removal • 30 min: 2-59% removal

18. Ipecac - Adverse Effects • emesis is unpleasant • persistent vomiting: 13-17% • diarrhea: 8-13% • lethargy: 12-21% • inability to tolerate subsequent therapies • activated charcoal • N-acetylcysteine • whole bowel irrigation

19. Ipecac - Inappropriate Use • frequently used when not indicated • occasionally used when contraindicated

20. Ipecac - Misuse • eating disorders • Munchausen Syndrome by Proxy

21. AAPCC Data% Ipecac Use 1985: 15% 2001: 0.7%

22. Decreased Hospital Visits • an assumed benefit of ipecac in the home  decreased hospital visits

23. Decreased Hospital Visits “Home use of ipecac was very weakly associated with increased, not decreased referral to the ED.” * * Bond GR. Home syrup of ipecac use after pediatric pharmaceutical exposure does not reduce emergency department use or improve outcome. Pediatrics, in press.

24. Alternative Charcoal in the Home

25. Charcoal in the Home Shortcomings • poorly accepted by young children • in E.D. - frequently given by nasogastric tube • sedimentation during storage • messy - caretaker acceptance?

26. Charcoal in the HomePublished Experience • 3 articles and 3 abstracts • therapeutic dose not given >50% • home vs E.D. administration • 35 vs 65 minutes • potential benefit of this 30 minutes?

27. Charcoal in the Home Clin Pediatr Emerg Med 2000;1:191-194 • premature to recommend this intervention

28. Conclusions • discontinue use of ipecac in the home • premature to use charcoal in the home

29. FDA NDAC Questions

30. Question 1 Role of gut decontamination? • limited • serious poisonings presenting to the hospital within one hour

31. Question 2 Role of ipecac in gut decontamination? • no role

32. Question 2a Benefits and risks of ipecac? • speculated benefit - removal of poison • risks - • persistent vomiting: 13-17% • diarrhea: 8-13% • lethargy: 12-21% • poor tolerance of subsequent oral therapies • inappropriate use and frank misuse

33. Question 2b Literature assessment of benefits/risk? • no literature demonstrating benefit • literature describing risks • adverse effects - quantified • misuse - anecdotal • abuse - anecdotal • complications - anecdotal

34. Question 2c Remote populations? • no evidence for efficacy of ipecac • efficacy does not improve with distance from care

35. Question 3 Abuse potential of syrup of ipecac? • Eating Disorders • occasional • Munchausen Syndrome by Proxy • rare

36. Question 4 What are alternatives to ipecac? • Hospital - activated charcoal • Home - call the Poison Centre

37. Summary and Conclusion Since the use of ipecac in the home will no longer be recommended and since there is a potential for its misuse and abuse, it makes no sense for it to remain as an OTC drug.