Toxicological criteria for child-resistant packaging for pharmaceuticals Part 1 Accident Case Data Dr Glyn Volans

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Toxicological criteria for child-resistant
packaging for pharmaceuticals Part 1 Accident
Case DataDr Glyn Volans
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Child poisoning study Project Team

• Guys St Thomas
• NHS Foundation Trust, London, UK
• Medical Toxicology Unit
• Bara V, Bates N, Edwards N, Volans G, Wiseman H.
• Pharmacy
• Tomlin S

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Non-reclosable child-resistant packaging for
pharmaceuticals

• European Standard
• For unit, strip or blister packages
• limits access to no more than
• 8 dose units
• does not take toxicity into account

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Child poisoning studyAims

• To use accident data to identify
  selected pharmaceuticals that are particularly
  hazardous to children
• To review quality and quantity of toxicity data
  in case reports from
• publications
• surveillance systems

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Child poisoning studyAims

• To assess the hazard to children from maximum 8
  dose units
• To suggest how to use toxicity data as criterion
  for deciding appropriate child-resistant
  packaging for drugs

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Child poisoning studyMethods (1)

• For 13 drugs
• Accidental ingestions
• Age 0-5 years
• Dose, clinical effects, outcome
• Not
• multiple ingestions or liquids or drugs given by
  someone else
• Sources
• Literature
• Poisons centre case reports
• London
• AAPCC 1983-2000

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Child poisoning studyMethods (2)

• For each case we graded toxicity using the
  Poisons Severity Score
• (Persson et al. 1998,
• Clin Toxicol, 36,205-213 )
• For each drug we reviewed doses associated with
  each grade of severity

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Poisoning Severity Score(EAPCC / IPCS / EC)

• Facilitates comparison of cases
• Lists symptoms and signs associated with each
  grade
• Grades of severity of poisoning
• 0 No signs of poisoning
• 1 minor symptoms, resolving spontaneously
• 2. Moderate, pronounced prolonged symptoms
• 3. Severe, life threatening symptoms
• 4. Death
• Persson et al 1966

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Child poisoning study Drugs reviewed
Cause serious toxicity Cause serious toxicity
dothiepin imipramine amoxapine dapsone methadone nifedipine quinine lomotil atropine, diphenoxylate
Frequently ingested Frequently ingested
temazepam atenolol propranolol hyoscine HBr for travel sickness carbamazepine (cbz)

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Child poisoning study Results

• Few cases fulfilled the case criteria
• Severe or fatal cases
• Only 10-20 were found for each of
• impramine, dothiepin, Lomotil, quinine
• Less than 10 each for the other drugs
• a wide dose range for each grade of poisoning

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Child poisoning studyDrugs reviewed
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Toxic doses in childrennumbers of highest dose
units
highest dose Unit highest dose Unit Mod-erate Severe Severe Fatal
(mg) no. of highest dose units no. of highest dose units no. of highest dose units no. of highest dose units
imipramine 25 3-30 8-50 5-50 5-50
quinine 300 - 7-20 5-40 5-40
methadone 5 2-12 2-3 4-16 4-16
dothiepin 75 1-10 2-14 2 2
cbz 400 1.5-7 2-12 4 4
nifedipine 60 0.5-8 - 1-20 1-20
Lomotil 2.5 2-100 2-15 6 6
amoxapine 100 1-2 - 1 1
propranolol 160 0.5-3 0.5 0.5 0.5
atenolol 100 - 1 - -
Hyoscine HBr 0.3 1.5-16 - (6) (6)
Dapsone 100 1-32 15 (50) (50)
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Child poisoning studySevere toxicity from doses
equivalent to lt 8 units
cases due to lt 8 highest-dose units or equivalent total
methadone 6 6 100
cbz 8 9 89
nifedipine 4 6 66
dothiepin 8 13 62
Lomotil 9 20 45
imipramine 4 20 20
Quinine 2 13 15
propranolol amoxapine atenolol 2 2 2 2 2 2
Total 47 93 50
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Child poisoning studyConclusions

• Case reports
• dose estimates often missing or unreliable
• child age and weight often missing or unreliable
  
• toxic dose data
• few serious cases
• few cases for children of same age and weight

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Child poisoning studyPart 1 Conclusions

• From a survey of case reports of poisoning with
  selected drugs
• Estimating toxic dose is difficult
• Nevertheless evidence shows
• Pharmaceuticals may cause severe toxicity to
  children in doses equivalent to less than 8 units

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Child poisoning study Conclusions

• Packaging allowing access to 8 dose units will
  not always protect children from severe poisoning.

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Child poisoning study Discussion

• Need to compare case data with evidence from
  clinical trials and therapeutic data
• Steve Tomlins presentation
• Can more be done to improve the quality of
  childhood accident data for pharmaceuticals?

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Proposals for improvements developments

• Collect targeted case data
• new molecules
• non prescription switches
• generics
• paediatric formulations
• all severe toxic exposures
• Improve/standardise European data
• Report centrally as for ADRs to WHO Uppsala
• Improve staff training, audit and research

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Acknowledgement

• This study was commissioned by
• ANEC
• European Association for Coordination of Consumer
  Representation in Standardisation
• ANEC Project Advisor
• Dr Franz Fiala