Transcript Effectiveness of child-resistant packaging in preventing

Toxicological criteria
for
child-resistant
packaging for
pharmaceuticals
Part 1
Accident Case Data
Dr Glyn Volans
Child poisoning study
Project Team
Guy’s & St Thomas’
NHS Foundation Trust, London, UK
Medical Toxicology Unit
Bara V, Bates N, Edwards N,
Volans G, Wiseman H.
Pharmacy
Tomlin S
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
Child poisoning study
Aims

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
Child poisoning study
Aims

To assess the hazard to
children from maximum 8
dose units

To suggest how to use
toxicity data as criterion for
deciding appropriate childresistant packaging for drugs
Child poisoning study
Methods (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
Child poisoning study
Methods (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
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
2.
spontaneously
Moderate, pronounced prolonged
symptoms
Severe, life threatening symptoms
3.
4. Death
Persson et al 1966
Child poisoning study
Drugs reviewed
Cause serious toxicity
dothiepin
imipramine
amoxapine
dapsone
methadone
nifedipine
quinine
lomotil ®
atropine,
diphenoxylate
Frequently ingested
temazepam hyoscine HBr
for travel sickness
atenolol
propranolol carbamazepine
(cbz)
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
Child poisoning study
Drugs reviewed
temazepam
hyoscine
atenolol
amoxapine
propranolol
dapsone
nifedipine
methadone
cbz
quinine
dothiepin
imipramine
Lomotil
severe toxicity
or death
moderate
toxicity
minor toxicity
0
10
20
30
40
Number of cases
50
60
Toxic doses in children
numbers of highest dose units
highest dose
Unit
(mg)
Moderate
Severe
Fatal
no. of highest dose
units
3-30
8-50
5-50
imipramine
25
quinine
300
-
7-20
5-40
methadone
dothiepin
cbz
nifedipine
Lomotil®
amoxapine
propranolol
5
75
400
60
2.5
100
160
2-12
1-10
1.5-7
0.5-8
2-100
1-2
0.5-3
2-3
2-14
2-12
2-15
0.5
4-16
2
4
1-20
6
1
0.5
atenolol
100
-
1
-
Hyoscine HBr
Dapsone
0.3
100
1.5-16
1-32
15
(6)
(50)
Child poisoning study
Severe toxicity from doses
equivalent to < 8 units
methadone
cbz
nifedipine
dothiepin
Lomotil®
imipramine
Quinine
propranolol
amoxapine
atenolol
Total
cases due to
< 8 highestdose units or
equivalent
6
8
4
8
9
4
2
2
2
2
47
total
%
6
9
6
13
20
20
13
2
2
2
93
100
89
66
62
45
20
15
50
Child poisoning study
Conclusions

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
Child poisoning study
Part 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
Child poisoning study
Conclusions

Packaging allowing access
to 8 dose units will not
always protect children from
severe poisoning.
Child poisoning study
Discussion

Need to compare case data
with evidence from clinical
trials and therapeutic data
– Steve Tomlin’s presentation

Can more be done to
improve the quality of
childhood accident data for
pharmaceuticals?
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 ADR’s
to WHO Uppsala

Improve staff training, audit
and research
Acknowledgement
This study was
commissioned by
ANEC
European Association for
Coordination of Consumer
Representation in
Standardisation
ANEC Project Advisor
Dr Franz Fiala