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ORIGINAL STUDY
Prescription medicine use by one million
Canadian children
Lama Abi Khaled MBA1, Fida Ahmad MSc1, Tom Brogan BA Econ1, Joan Fearnley MSc1,
John Graham MD MSc CCFP2, Stuart MacLeod MD PhD FRCPC3, Joan McCormick MBA1
L Abi Khaled, F Ahmad, T Brogan, J Fearnley, J Graham,
S MacLeod, J McCormick. Prescription medicine use by one
million Canadian children. Paediatrics Child Health 2003;Vol
8(Suppl A):xx-xx.
Drugs are an increasing and integral part of the treatment of childhood conditions. There is widespread concern regarding the inadequacy of paediatric data from clinical trials, which results in limited
prescribing information available to support optimal pharmacotherapy for children. One explanation for the limited prescribing information in paediatrics is the perception of relatively infrequent use of
drugs in the treatment of childhood conditions. To date there have
been few population studies quantifying the extent of prescription
drug use among Canadian children.
Prescription information from administrative databases were available for over one million paediatric claimants likely representing
approximately two million eligible children. Nearly 15% of Canadian
children actually had a claim for a prescription drug recorded in this
database. Descriptive statistics were employed to describe drug utilization for those who had a drug claim.
The two largest therapeutic areas were antibiotics (76% of claimants)
and respiratory drugs (18% of claimants). Among the top 20 drugs
dispensed to paediatric claimants, 14 were antibiotics and the top
drug overall was amoxicillin. Psychotropic drugs defined as stimulants, antidepressants, antipsychotics and anticonvulsants were dispensed to 6% of all paediatric claimants. In virtually every
therapeutic area, the usage of drugs differed markedly across age
groups.
A wide range of drugs are prescribed to children, many of which are
being used outside of the age ranges approved by Health Canada.
However, most new drugs are used relatively infrequently in children.
The large numbers of Canadian children documented in this study
using prescription medicines reinforces the value of vigilance in
ensuring that physicians are equipped with adequate information to
ensure safe and effective prescribing.
The use of therapeutic drugs is widespread, and for a large number of
these drugs, safety and efficacy among children has not been established, although no conclusions can be drawn from this study about
appropriateness of drug therapy in children. Consequently, ongoing
vigilance in accurate paediatric labelling as well as future pharmacoepidemiologic studies addressing safety and efficacy are required.
Efforts must be concentrated on those specific age ranges in which
products or drug classes are used, evidence of which can be determined from actual utilization.
Key Words: Canadian population; Children; Drug utilization;
Prescription drugs; Rate of use
Un médicament sur ordonnance utilisé par un
million d’enfants canadiens
Les médicaments font partie croissante et intégrante du traitement des
pathologies infantiles. Les inquiétudes sont généralisées quant à la
médiocrité des données pédiatriques tirées d’essais cliniques, ce qui
entraîne une information posologique limitée pour soutenir la
pharmacothérapie optimale des enfants. L’un des éléments pouvant
expliquer l’information posologique limitée est la perception d’un usage
relativement peu fréquent des médicaments pour le traitement des
maladies infantiles. Jusqu’à présent, peu d’études démographiques ont
quantifié l’étendue du recours aux médicaments sur ordonnance chez les
enfants canadiens.
L’information posologique tirée d’une base de données administrative
était disponible pour plus d’un million de requérants pédiatriques, ce qui
représente probablement environ deux millions d’enfants admissibles.
Près de 15 % des enfants canadiens détenaient une réclamation de
médicament sur ordonnance enregistrée dans cette base de données. Des
statistiques descriptives ont été utilisées pour décrire le recours aux
médicaments par les enfants qui détenaient une réclamation de
médicaments.
Les deux principales zones thérapeutiques sont les antibiotiques (76 % des
requérants) et les médicaments respiratoires (18 % des requérants). Parmi
les 20 médicaments les plus dispensés aux requérants pédiatriques,
14 étaient des antibiotiques, et le plus dispensé de tous était
l’amoxicilline. Des psychotropes définis comme des stimulants, des
antidépresseurs, des antipsychotiques et des anticonvulsivants étaient
administrés à 6 % de tous les requérants pédiatriques. Dans pratiquement
toutes les zones thérapeutiques, le recours aux médicaments différait de
manière significative entre les groupes d’âge.
Une vaste gamme de médicaments sont prescrits aux enfants, et bon
nombre d’entre eux le sont à l’extérieur des plages d’âge recommandées
par Santé Canada. Cependant, la plupart des nouveaux médicaments sont
relativement peu utilisés chez les enfants. Le grand nombre d’enfants
canadiens documentés dans la présente étude comme prenant des
médicaments sur ordonnance renforce la valeur de la vigilance à s’assurer
que les médecins possèdent de l’information convenable pour garantir
une prescription sûre et efficace.
Le recours aux médicaments thérapeutiques est généralisé, et pour un
grand nombre de ces médicaments, leur innocuité et leur efficacité chez
les enfants ne sont pas établies, même si aucune conclusion ne peut être
tirée de la présente étude quant à la pertinence de la pharmacothérapie
chez les enfants. Par conséquent, une vigilance continue relativement à
un étiquetage pédiatrique précis et des études pharmacoépidémiologiques
sur l’innocuité et l’efficacité s’imposent. Les efforts doivent être axés sur
les plages d’âge dans lesquelles les produits ou les catégories de
médicaments sont utilisées, ce qui peut être obtenu à partir de l’utilisation
réelle.
1Brogan
Inc, Ottawa; 2William Osler Health Centre, Brampton, Ontario; 3British Columbia Research Institute for Children’s and Women’s
Health, Vancouver, British Columbia
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©2003 Pulsus Group Inc. All rights reserved
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Prescription medicine use in Canadian children
Myths and challenges – Drug utilization for Canadian children
Michael J Rieder MD PhD FRCPC, Doreen Matsui MD FRCPC, Stuart MacLeod MD PhD FRCPC
The fact that the vast majority of drugs lack data on indications, efficacy, dosage or safety in children has been identified
as a problem for many years. This has been a significant burden for child health care providers and has meant that therapy for children has, on average, lagged behind that available for routine use by adults. The reasons for the dearth of drug
information for children are many and include lack of regulatory requirements for studies in children, difficulties in conducting drug research in children compared to adults, and the perception that drug utilization by children is both infrequent and largely confined to a limited number of drug classes, primarily antibiotics. Consequently, drug research in
children has been hard to do and difficult to fund.
Many of these impediments have, however, been addressed over the past decade. Major advances in paediatric research
have included drug analysis using very small sample volumes, pharmacokinetic techniques such as sparse sampling, development of surrogate markers and use of novel clinical trial designs including ‘n of one’ studies and clinical trials simulations in silico. These have provided investigators with the ability to conduct sophisticated and ethically acceptable drug
studies in infants and children. The result has been an explosion of the knowledge base supporting optimal drug therapy
in paediatrics.
Nonetheless, the perception has remained that there is selective and relatively low utilization of drugs in children.
Thus, funding to fully exploit the new research modalities and new therapeutic information has not matched the potential opportunities available.
The data summarized in this report are an important early step towards demonstrating that the previous view of drug
therapy as relatively unimportant in children is in fact a medical myth. As documented in this report, drug use in children
is both common and crosses a wide variety of drug classes. In fact, many of the drugs commonly used by children are agents
for which no data on indication, dosage or safety are readily available for practitioners.
Where will this data have an impact? First, consider the impact for new therapeutic entities. Regulatory changes in
drug approval are likely to require that new drugs be evaluated in all populations in which they will be used. This report
is extremely important in demonstrating the depth and breadth of drug utilization in children and supporting regulatory
requirements for studies in children for drugs in many classes and for many indications. This places the challenge before
Health Canada and other drug regulatory agencies to apply appropriate vigilance to ensure that new therapeutic entities
seeking market access achieve that status only after appropriate studies have been conducted among all patient groups
likely to receive these agents, including infants, children and adolescents.
As well, this data demonstrates extensive use of already marketed drugs among Canadian children. As noted above,
these are the very drugs for which safety, dosage and efficacy data are largely lacking. Overall, the data provide a compelling argument for renewed investment in drug research for Canadian children to determine if these drugs are being
used appropriately and safely.
The current report also underscores the need for primary epidemiologic data in providing more detailed insights into
current drug therapy in Canadian practice. While administrative databases such as those on which this report is based provide a broad overview of prescribing practices and are a fertile source of research hypotheses, they have important limitations. The drugs prescribed cannot be linked with other clinical data and it is therefore impossible to draw conclusions
about diagnostic accuracy, therapeutic rationale or cost effectiveness. Given the current state of medical informatics, a
prospective drug utilization review undertaken in settings where community based paediatric care occurs would be very
useful. The present data make a strong case in support of the need for such a national paediatric prescribing study.
What is the next step? The report verifies a long suspected and unacceptable situation in which Canadian children
are likely to be treated with medications for which the prescribing physician lacks reliable information about dosage, efficacy or safety. How can this be addressed? This report supports a call for action around the issue of improved drug therapy for children and describes an outstanding opportunity for Canadian paediatricians, pharmacists and researchers.
Canada has a tradition of excellence in paediatric clinical pharmacology and continues to have some of the most productive researchers in the world in paediatric clinical pharmacology. There are currently active investigators in
Vancouver, Calgary, Winnipeg, London, Hamilton, Toronto, Ottawa, Montreal and Halifax. This report suggests that a
co-ordinated national effort on the part of these researchers, with the support of paediatricians across Canada and from
provincial and federal governments as well as child health foundations, must be mounted to address urgent issues in paediatric therapeutics and to train the next generation of highly skilled researchers who will continue this research as protein, cellular and molecular therapeutics increasingly enter the therapeutic arena.
It is the hope of Canadian paediatricians and the sponsors of this study, including Health Canada, that publication of
this initial report will serve as a benchmark for future surveillance initiatives. There is clearly a need for more detailed
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Abi Khaled et al
prospective surveys to determine patterns of drug use for children in hospital settings, in paediatric consulting practices
and in primary care settings. Steps have already been taken to obtain paediatric prescribing data from the British
Columbia Pharmacare program in order to explore possible distinctions between patterns of use in private and public
insurance plans. As long overdue emphasis is now being placed on aboriginal health, it would also be of great interest to
evaluate access to drug therapy in the population served by the Federal First Nations Insured Health Benefits program.
This covers drug costs in aboriginal communities, where often more than half of the residents are children.
While this report indicates a need for future epidemiologic studies, it also suggests some short terms actions that might
improve drug therapy for Canadian children. Areas of high utilization deserve careful scrutiny by those most familiar with
paediatric pharmacotherapy. The volume of use certainly justifies the compilation of a handbook of paediatric drug therapy suitable for use in community non-hospital settings in Canada, ideally suited for use on a PDA or accessible via the
Internet. While we may lack data from pivotal trials conducted in children, there is nonetheless a wealth of clinical experience and practice based evidence that may serve as interim measures to define the safe and effective use of drugs for children with appropriate dosing guidelines.
To quote Voltaire, “best is the enemy of better.” We should not be deterred from making short term improvements
while we await the more definitive identification of best practice guidelines that will emerge over the next decade.
These efforts will also need to involve partnerships that extend beyond our borders. It would be safe to assume that,
with some minor differences, the findings in this report can be extrapolated to much of the rest of the developed world.
Thus, the imperative for increased drug research in children in pursuit of the common goal of better health through optimal therapy will need to include partners in Europe, the United States and Asia. As well, the challenge of optimal drug
therapy for children will be even greater in the developing world, where children make up a large percentage of the population. Partnering with Asia, Africa and South America in defining optimal drug therapy for children should also be a
major imperative in order to work towards the goal of better health for children everywhere.
The Drug Therapy and Hazardous Substances Committee of the Canadian Paediatric Society anticipates that the publication of this report will highlight a public policy issue of extraordinary importance to children. By shedding light on the
gaps in our existing paediatric therapeutic knowledge, we hope to enlist the help of paediatricians, pharmacists, primary
care practitioners with an interest in children’s care and appropriate researchers.
Recognition of the existing problem should fuel demand for better prescribing information. The central question is not
what we can afford to do at this time, but whether or not we can afford the risk of continuing a laissez-faire approach to
paediatric therapy.
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Prescription medicine use in Canadian children
DATA AND METHODOLOGY
DATA SOURCES
The data used in this report are from administrative databases
compiled from the operation of a number of private drug payment plans. These data are from payment systems that result in
the direct transfer of the claim information to the adjudication
system and contain sufficient information to permit an analysis of drug use. Under these payment systems, there is a high
probability that each prescription filled by individuals in the
plan will be submitted and accepted as a paper claim and
hence, a record created. Data from programmes that use a payment system which require the plan member to file a claim for
compensation have not been used in this study. These were
excluded as there can be a delay of up to two years in processing these claims or claimants may not submit some prescriptions, resulting in incomplete data history for those claimants.
For the two-year period relevant to this report (1999/2000),
the aggregate private payer database includes 7 million
claimants of all ages and over 88 million prescriptions for pharmaceutical products.
Claimants from the private payer drug plan database were
included in this study if they were 17 years of age or less
throughout all of 1999 and had at least one claim during the 12
months following their birthday in 1999. Based on these criteria, there were over 1,031,000 paediatric claimants for which
records were available for analysis. All data were provided
using untraceable identifiers and under strict conditions that
protect individual confidentiality.
DATA LIMITATIONS
The data used in this study are from payment systems that capture information for billing purposes. The data reported here
are counts of claimants who actually made a claim in the study
period and have not been extrapolated to represent all
Canadians. Preliminary data indicate that 55% of eligible beneficiaries are younger than the age of 15 and 48% of
those 15 to 24 years old make a claim for an eligible benefit in
a 12-month period.
The coverage of the relevant drug plans varies by region
with the lowest rates in the western provinces. The rates of use
reported here use only actual claimants as a base and therefore
these rates overestimate true prevalence rates among this paediatric population.
Eligible benefits under the vast majority of private plans
include most prescription drugs, particularly those that may be
used for children. Most plans do not include over-the-counter
(OTC) drugs, with some exceptions, and exclude or limit some
‘lifestyle’ drugs. Limitations such as annual maximum costs or
quantity limits may apply on selected drugs (prescription and
otherwise) that are covered. The payment rules will have no
bearing on the results of this study since these provisions do
not affect the reported drug quantities or other details regarding the prescription. In other work conducted by the authors,
it was found that claimant contribution amounts had only a
minor influence on the claimant’s drug purchasing behaviour
and no measurable influence on the purchasing behaviour if
the purchase was for a child.
Paediatr Child Health Vol 8 Suppl A April 2003
The study database does not capture patient diagnosis,
hence the analysis cannot determine the reason for prescribing
a certain drug. It is possible in some cases, however, to deduce
the reason if a drug has essentially a single purpose or indication (e.g., insulin for diabetes) or if other drugs used by the
patient suggest a diagnosis. The study cannot assess if a particular therapy is appropriate or effective, or to detail the rate of
adverse events.
Finally, the children included in this study do not necessarily reflect the health status of the Canadian population at
large. The analysis includes a heavy concentration of children
of working parents; that is parents who were working or have
been in the workforce (e.g., retiree). As a result, it cannot be
concluded that the socio-economic characteristics of the children analyzed in this study represent all segments of Canadian
society.
METHODOLOGY
An advisory panel of physicians and pharmacists was formed to
provide direction for the report, medical expertise to guide the
analysis and to ensure that high standards of research were
employed. The advisory panel is not responsible for errors or
shortening of this study.
The data were organized into a single database containing
the age and sex of the study children and the drugs used over
the relevant time period. The rate of use of these drugs is calculated by dividing the number of claimants prescribed these
drugs by the total number of claimants in the study database.
In the analysis of specific drugs, the rate of use is based on the
number of claimants using drugs in the same therapeutic
class.
The 12-month period following each patient’s 1999
birthday is defined as the study period. This approach
ensures that the age of each patient is constant throughout
the study period.
The results are reported by the following age groups:
younger than one year of age, one year, ages two to six, ages
seven to 12 and 13 to 17 of the patients’ birthday in 1999. In
some analysis the first two age groups were excluded given the
very small number of claimants. In other cases, only certain
age groups were analyzed (e.g., acne therapy and contraceptives).
Claimants were classified into one of the following three
groups based on their history of drug use:
• New-to-therapy patients were not dispensed any drug in the
same therapeutic class as the target drug 180 days prior to
the first prescription for the target drug in the study (index
claim).
• Existing patients are those who had 1 or more claims for a
target drug during the 180 days, prior to the index claim.
• New-to-system patients are those who had no claim history
prior to the index claim.
A target drug is one that meets the definition relevant to
the particular analysis.
Disease analysis
In addition to an overview of drug use among the selected
claimant population, this study contains a more detailed exam9A
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TABLE 1
The eleven therapeutic areas analyzed in this study
Therapeutic areas (in alphabetical order)
Acne therapy
Analgesics, anti-inflammatory agents and DMARDs
Antibiotics
Anticonvulsants
Antidepressants
Antidiabetic agents
Antipsychotics
Contraceptive therapy
Gastrointestinal drugs
Respiratory drugs
Stimulants
ination of the use of drugs within 11 therapeutic areas (Table
1), based on the recommendation of the advisory panel. Their
recommendations were based primarily on the number of
claimants using these drug classes, on recent changes in drug
therapy and on long standing issues related to specific drugs.
The drugs are classified by therapeutic area based on the
indications provided in their respective product monographs
(uses for the drug approved by Health Canada), a brief review
of the literature, or based on the advisory panel’s expert opinion. (The list of drugs in each area is provided in the relevant
section of the study.) Since each claimant’s diagnosis and
symptoms are unknown, as is the physician’s objective in prescribing a drug product, there is a chance that some claimants
may be misclassified. Claimants can be included in more than
one therapeutic area.
Concomitant drug use
For the purpose of this study, concomitant drug use is defined
as the simultaneous use of multiple drugs to treat a single condition. A literature review was conducted to assist in selecting
the drugs for the concomitant drug use analysis. Concomitant
drugs are not necessarily in the same class or the same therapeutic area. Drugs were considered to be used concomitantly if
they were dispensed on the same day, or one drug was dispensed during a period of continuous use of another drug indicated for the condition under study.
Therapy duration
The length of time children remain on a drug (days of therapy)
or the amount of drug dispensed (course of therapy) over a
period of time is relevant for some therapeutic areas. These
measurements may become complicated or distorted if using an
inconsistent time period for the analysis, or if claimants enter
or leave the study database (e.g., the claimant’s parent changes
employer). In these types of analysis, the time period was standardized for each patient to be the 12 months following the
first claim for the drug under study (12-month index period).
To avoid distortions due to claimants leaving the database,
claimants were included in the analysis only if they had at least
one claim for any drug during the 12 months following the end
of the index period.
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PAEDIATRIC DRUG USE: AN OVERVIEW
There have long been questions about the use of pharmaceutical therapies among children, both the amount used as well as
the scope or range of products used. As anonymous data collection has evolved, it is now possible to quantify drug use among
a large segment of the Canadian population. This study takes
advantage of these developments to begin the process of understanding how medicines are used to treat children. This study
has been designed to set the groundwork for further investigation, including both analyses of usage data and clinical studies.
The power of the study, of course, is in the magnitude of the
available database, which over a 12-month period allows for
the observation of over one million active claimants younger
than the age of 18 years. It cannot claim to represent the entire
Canadian population nor can it determine the appropriateness
of therapy.
The origin of this work was of the interest from the
Canadian Paediatric Drugs and Hazardous Substances
Committee, the foresight of its former Chair, Dr. Stuart
MacLeod, and the enthusiasm of Dr. Robert Peterson (Director
General, Therapeutic Products Programme, Health Canada).
The industry sponsors of this report quickly recognized the
benefit of these ideas for the health of children and appropriate drug use, and have made this work possible through both a
financial contribution and through their knowledge of therapeutic areas.
A fundamental part of this study was the creation of the
advisory panel which proved to be invaluable in advising on
the direction the work should take and in contributing to an
understanding of the results. Experts in the paediatric field
have provided commentary that adds substantially to this study
and provides guidance for further research.
The authors remain responsible for errors of commission
and omission.
STUDY POPULATION
There were 1,031,731 claimants who met the study criteria
and whose drug use records were included in this study. The
profile of these claimants and the representativeness of the
database are discussed in this overview. The use of select common drugs, which provides a context for the detailed therapeutic analysis later in this study, is also presented.
The number of claimants by single year of age ranged from
a low of 48,690 in the 12 years of age group to a high of 63,670
in the 17 years of age group (Figure 1).
The database used for this study accounts for 15% of the seven million Canadians younger than age 18 reported by
Statistics Canada Census figures (1). The proportion of children in the study relative to the population was highest among
the one- to five-year-old children (16% to 19%), and the
16- and 17-year-olds (over 15%) (Figure 1). The lowest capture
rate relative to population was in the nine to 13 age groups,
(12% to 13%). Because just over half of the children eligible for
benefits make a claim in a year, the findings in this report represent drug utilization for about 30% of all Canadian children.
The higher representation of children one to five years of
age can be attributed to their relatively high rate of antibiotic
use compared with other age groups. For a large proportion of
this group this was the only drug used in the 12-month study
period. The higher representation among 16- and 17-year-olds
was partly due to the use of oral contraceptives among girls.
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Prescription medicine use in Canadian children
20%
70
West
16%
18%
Total claimants ('000)
16%
50
14%
12%
40
10%
30
8%
6%
20
4%
10
2%
-
Territories Atlantic
0%
12%
<1
Quebec
21%
Proportion of Canadian population
60
Ontario
51%
Percent distribution of the paediatric claimants by region
7%
14%
Territories
23%
Atlantic
8%
West
Quebec
0%
0
1
2
Male
3
4
5
6
7
Female
8
Ontario
9 10 11 12 13 14 15 16 17
% of Canadian population
Figure 1) Number of paediatric claimants by age and sex and proportion of Canadian population. The proportion of Canadian population
included in this study ranges from 18% for the one-year-olds to 12% for
the 11-year-olds
The lower rate of use for the nine- to 13-year-olds is likely
related to fewer children in this age band requiring drugs. This
conclusion is based on two facts. There are no provisions in
private drug plans that would exclude children in this age band
from receiving benefits. Secondly, this finding is consistent
with a study from the Manitoba Centre for Health Policy and
Evaluation that also showed a smaller percentage of nine- to
13-year-old children received prescription drugs compared to
other age groups (2).
The proportion of female claimants ranged from a low of
47% for children younger than one year to 58% in children 17
years old (according to Census data, about 49% of the population younger than 18 in each single year of age were girls in the
year 2000). The high proportion of 17-year-old girls is mainly
due to oral contraceptive use.
The claimant population in this study included children
from each region of the country. Approximately 50% of
claimants in the database were from Ontario, 21% were from
Quebec, 12% were from the Atlantic region, 16% were from
the West and less than 1% were from the Territories (Figure 2).
As mentioned previously, the database used for this analysis
captured the drug use data for 15% of Canadian children. The
capture rate varied by region from a low of 7% in the Territories
to a high of 23% in the Atlantic region (Figure 2).
The variation in the capture rate is mainly due to the drug
plans for which data were available.
DRUG UTILIZATION PATTERNS
Within the drug plan data accessible by the authors, children
use far fewer drugs on average than the adult population.
Children represent nearly one quarter of claimants of all ages in
the database, but account for only 12% of the total prescriptions as measured by the database used in this study (3). The
same data also showed, however, that children who have serious medical conditions have the same high drug use patterns as
adults who also have serious medical conditions. A smaller proportion of children than adults fall into the very ill category.
There were nearly 1,400 different drugs and four million prescriptions dispensed to children resulting in an average of 3.9
prescriptions per claimant in the 12-month study period (Table
1). However, the average is deceiving since the distribution of
Paediatr Child Health Vol 8 Suppl A April 2003
19%
Percentage of paediatric claimants in National population by region
Figure 2) Percentage distribution and representation of paediatric
claimants by region
TABLE 1
Distribution of claimants and prescriptions and number of
prescriptions per claimant for selected therapeutic areas
Distribution of
claimants
Therapeutic class
780,684
182,271
84,024
Share of
total
claimants
76%
18%
8%
72,504
40,512
33,882
16,731
3,873
6,409
16,267
3,583
1,031,731
Number of
Claimants
Antibiotics
Respiratory drugs
Analgesics and antiinflammatory drugs
Acne drugs
Contraceptives
Stimulants
Antidepressants
Antipsychotic agents
Anti-convulsant agents
Gastrointestinal agents
Antidiabetic drugs
All drugs (total)
Distribution of
prescriptions
Number of share of total
prescriptions prescriptions
Prescriptions
per claimant
1,740,446
522,216
116,005
43%
13%
3%
2.2
2.9
1.4
7%
4%
3%
2%
0.4%
0.6%
2%
0.3%
223,700
194,796
161,184
64,929
20,023
46,261
40,299
41,682
6%
5%
4%
2%
0.5%
1%
1%
1%
3.1
4.8
4.8
3.9
5.2
7.2
2.5
11.6
100%
4,028,502
100%
3.9
The sum of claimants by therapeutic class exceeds the total 1.03 million
claimants because some claimants were dispensed drugs from more than
one therapeutic class
high prescription use is concentrated among a relatively small
portion of patients. About 26% of children averaged more than
four prescriptions each during the 12-month study period,
accounting for 72% of the total prescriptions. A further 13%
had three prescriptions and 63% had only one or two.
Eleven therapeutic areas have been identified for analysis
(see methodology section). Approximately 89% of all children
in the study had a claim for a drug in one of these 11 therapeutic areas and some children had claims for drugs in more
than one therapeutic area. The sum of the number and share of
claimants for the 11 areas, therefore exceed the total of unique
claimants. The remaining 11% of children did not have a
claim for any drug included in the detailed analysis. Table 1
shows the distribution of patients and prescriptions, and the
number of prescriptions per claimant by therapeutic area during the 12-month study period.
Antibiotics were dispensed to 76% of the children during
the 12-month study period (Table 1). For nearly half of these
children, an antibiotic was the only drug dispensed. This study
cannot determine whether the antibiotic therapy was medically warranted and does not draw any conclusion regarding the
under or overuse of this class of drug.
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TABLE 2
Top drug used in each class based on the total claimant
count
Therapeutic area
Antibiotics
Respiratory drugs
Analgesics and antiinflammatory drugs
Total number of
Total number of
claimants in the claimats using the
therapeutic area
Drug
Drug
a
% of claimants
using the Drug in
the therapeutic
area
TABLE 3
Top drugs in database based on total claimant count
Drug
Description
Amoxicillin
Salbutamol (b)
Amoxicillin
Salbutamola
Acetaminophen/
caffeine/ codeineb
Tretinoin/
Erythromycinc
Ethinyl estradiol
/Norgestimated,e
780,684
182,271
353,814
129,094
45%
71%
84,024
25,790
31%
Fluticasone propionate
72,504
15,138
21%
40,512
12,013
30%
Stimulants
Methylphenidatea
33,882
28,947
85%
Antidepressants
Antipsychotics
Paroxetineb
Risperidonea
16,731
3,873
4,199
2,680
25%
69%
Cefaclor
Sulfamethoxazole & trimethoprim
Azithromycin dihydrate
Hydrocortisone
Cefprozil
Amoxicillin & clavulanic acid
Penicillin V potassium
Gentamicin sulfate
Betamethasone valerate
Cephalexin monohydrate
Gentamicin Sulfate &
betamethasone sodium phosphate
Pivampicillin
Sulfacetamide sodium
Methylphenidate HCl
Fluticasone propionate
Budesonide
Acne drugs
Contraceptives
Anticonvulsants
Carbamazepine
Gastrointestinal
drugs
Ranitidinea
Antidiabetics
Human insulina
b
6,409
2,509
39%
16,267
8,157
50%
3,583
3,319
93%
a) Top drug in the class and in all age groups; b) Top drug in the class but
not in all age groups; c) Top drug in the class but not in single year of age
(10-17 year olds included in the acne analysis); d) Top drug in 11-17 year
old female claimants that were included in the contraceptives analysis;
e) Includes only Tri-Cyclen®
Respiratory drugs were the next largest therapeutic area
with 18% of children having at least one prescription for a respiratory drug. Antibiotics and respiratory drugs alone accounted for 56% of the total prescriptions. However, the average
number of prescriptions per patient per year for each of these
therapeutic areas was relatively small (2.2 for antibiotics and
2.9 for respiratory drugs), suggesting a high degree of use as
acute therapy.
The third largest therapeutic area was for drugs in the analgesic and anti-inflammatory areas for which nearly 8% of
claimant had a claim with an average of 1.4 prescriptions per
claimants during the 12-month study period. This suggests that
these agents were more likely used for acute pain or for shortterm therapy.
A small proportion of children used psychotropic drugs,
including stimulants, antidepressants and antipsychotics.
Approximately 3% of the children in the study database
received a prescription for a stimulant such as
methylphenidate and 2% and less than 1% of the total children in the database used antidepressants and antipsychotics,
respectively. Among these three therapeutic areas, the average
prescriptions per patient was highest for antipsychotic drugs
(5.2) followed by stimulants (4.8) and antidepressants (3.9).
Drugs in these therapeutic areas tend to be used more as chronic therapies compared with respiratory drugs or antibiotics.
A very small proportion of children were dispensed antidiabetic drugs (less than 1%). These were likely type 1 diabetics
given the age of the study group and the fact that most of them
used insulin. These drugs were used chronically as indicated by
the high average number of prescriptions per claimant (11.6).
The average number of prescriptions per claimant for the
target drugs was calculated for the 12 months following the
claimant’s birthday.
For many therapeutic areas, one or two drugs accounted for
a very large share of usage within the class as measured by number of claimants (Table 2). For example, methylphenidate was
12A
Clarithromycin
Number of
claimants
Share of the total
claimants in the
study
Oral antibiotica
Inhaled short acting
acting B2-agonistsb
Oral antibiotica
Inhaled
corticosteroidsb
Oral antibiotica
Oral antibiotica
Oral antibiotica
Topical corticosteroidc
Oral antibiotica
Oral antibiotica
Oral antibiotica
Ophthalmic antibiotica
Topical corticosteroidc
Oral antibiotica
353,814
34%
125,201
12%
96,744
9%
81,762
8%
79,491
74,739
69,639
63,294
58,238
41,184
39,946
34,761
33,465
32,883
8%
7%
7%
6%
6%
4%
4%
3%
3%
3%
Ophthalmic antibiotica
32,059
3%
Oral antibiotica
Ophthalmic antibiotica
Oral psychostimulantd
Nasal corticosteroidc
Inhaled corticosteroidb
30,242
29,840
28,947
28,413
25,886
3%
3%
3%
3%
3%
a) Antibiotic therapeutic area; b) Respiratory therapeutic area; c) Not included in any of the target drugs used to identify the 11 therapeutic areas; d)
Stimulant therapeutic area. NOC Notice of Compliance (authority to market
in Canada granted by Health Canada). The date provided refers to the first
NOC granted for the drug, not any subsequent NOCs granted for specific
dosage forms or indications for specific conditions or for use in the paediatric
population
used by 85% of children prescribed a stimulant and salbutamol
was used by 71% of children prescribed a respiratory drug.
Most of the top drugs used by all paediatric claimants were
from one of the 11 therapeutic areas. Of the 20 drugs dispensed
to the largest number of patients, 17 were either an antibiotic
or a respiratory agent included in the detailed therapeutic area
analysis (Table 3). Thirty four per cent of claimants received a
prescription for amoxicillin, an older antibiotic. Inhaled salbutamol, used for asthma, was the second most used drug (12% of
all claimants). Another antibiotic, clarithromycin, was the
third most widely used drug, with 9% of claimants.
Corticosteroids in different formulations were also among
the top drugs. Fluticasone propionate and budesonide, both in
the inhaled formulation, were used by 8% and 3% of the total
paediatric claimants in the study database, respectively.
Hydrocortisone and betamethasone valerate, both topical corticosteroids, were dispensed to 6% and 3% of the total paediatric claimants, respectively. Finally, nasal fluticasone
propionate, for seasonal allergic rhinitis, was used by 3% of the
total paediatric claimants.
The use of a drug within the therapeutic area varies with
age so that a leading drug overall may not be the top ranked
drug in each age group (Table 4). Of the top 10 drugs for
children younger than one year of age, eight were antibiotics and one was for respiratory problems. The other was
for skin inflammation. For age groups younger than
12 years, the list of top 10 products differs little except for
ranking. The most notable difference is the appearance of a
stimulant (methylphenidate) for the seven- to 12-year-olds.
The top drugs change more substantially for the 13- to
17-year-olds with the addition of drugs for pain, acne and
contraception.
Paediatr Child Health Vol 8 Suppl A April 2003
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Prescription medicine use in Canadian children
TABLE 4
The top 10 drugs based on the total claimant count by age
group
<1 year
Amoxicillin
Hydrocortisone
Salbutamol
Nystatin
1 year
Amoxicillin
Hydrocortisone
Cefaclor
Amoxicillin
Salbutamol
Fluticasone
propionate
Sulfamethoxazole Cefaclor
/trimethoprim
Sulfamethoxazole Salbutamol
/trimethoprim
Cefprozil
Cefprozil
Cefaclor
Azithromycin
dihydrate
Gentamicin sulfate Clarithromycin
Sulfacetamide
sodium
Azithromycin
dihydrate
2-6 years
Fluticasone
propionate
Gentamicin
sulfate
7-12 years
Amoxicillin
Salbutamol
Fluticasone
propionate
Clarithromycin
13-17 years
Amoxicillin
Salbutamol
Clarithromycin
Acetaminophen/
caffeine / codeine
phosphate
Clarithromycin
Cefaclor
Fluticasone
propionate
Sulfamethoxazole Methylphenidate Penicillin V
/trimethoprim
potassium
Azithromycin
Sulfamethoxazole Minocycline
dihydrate
/ trimethoprim
Cefprozil
Azithromycin
Ethinyl estradiol /
dihydrate
levonorgestrel
Hydrocortisone
Hydrocortisone
Erythromycin
Amoxicillin &
clavulanic acid
Cefprozil
Ethinyl estradiol /
norgestimate
NEW DRUGS
New drugs can offer improvements in therapy either in terms
of safety or efficacy. However, because of the difficulties in conducting clinical trials in children, many new products are not
yet approved for children. This short analysis provides evidence of the degree to which new drugs are used in children.
This study defines new drugs as those that received approval
from the federal regulatory authority between 1997 and 1999.
Because new drugs take three years or more to reach full market potential, it can be expected that the use of these drugs will
increase and hence the results are indicative.
In total, 50 new drugs approved between 1997 to 1999
were dispensed to the paediatric claimants in this study. Only
13 of these were dispensed to more than 400 claimants during
the study period and were included in the following analysis
(Table 5).
Only two of the 13 drugs in this analysis are indicated for
children as young as three and most are not approved for use in
people less than 18 years of age based on the respective product
monographs. Most of the new drugs were used by the older age
groups (Table 5). Where there is any appreciable use in other
age groups, the indication supports its use in the age group.
The new drug prescribed to most children in the study,
montelukast sodium (asthma), was used by 5% (8,991) of all
the children dispensed an asthma drug. It is indicated for
patients six years of age and older (4). While the results
showed that 20% of its use was for those two- to six-year-olds,
only 3% of the children with asthma in this age group were dispensed montelukast sodium. Formoterol fumarate, another
asthma drug, had a higher share of its use in younger children
(28% in the two to six year age group) but this is only 0.2% of
asthma drug users in this age group.
Zanamivir, a new drug for influenza, has not been adequately studied in children younger than 12 years, according to the
product monograph (4), although there were 507 children dispensed this drug out of over one million children in the database. Three-quarters of zanamivir claimants were older than 13
years old and 21% (110 children) were seven to 12 years old.
Bupropion (depression) had 24% of its use in the seven to 12
year age group and 72% in the 13 to 17 year group. This means
that 5% of the seven- to 12-year-olds and fewer than 6% of the
older children who had a prescription for an antidepressant
were dispensed bupropion. According to the product monoPaediatr Child Health Vol 8 Suppl A April 2003
TABLE 5
Leading new drugs (NOC 1997-1999) by year of NOC
Drug
(all dosage forms
and strengths)
NOC
yeara
Age
restrictionb
Celecoxib
1999
<18
Osteoarthritis &
rheumatoid
arthritis in adults
Citalopram
1999
<18
Depression
pediatrics
Indicationb
Osteoarthritis,
pain, primary
dysmenorrhea
Total
Claimants
Percent distribution of
claimants using the drug by
age
<2
2-6
7-12
13-17
years years years
years
2,229
1%
3%
11%
84%
994
0%
1%
9%
89%
1,427
1%
2%
9%
88%
507
0%
2%
21%
77%
1%
3%
24%
72%
464
1%
22%
51%
26%
8,991
0%
20%
54%
26%
Rofecoxib
1999
Zanamivir
Children and
1999
Influenza virus
infants
Bupropion l
1998
<18
Depression
Emedastine
difumarate
1998
<3
Allergic
conjunctivitis
Montelukast sodium
1998
<6
Asthma
Zolmitriptan
1998
<18
Migraine
411
1%
2%
6%
91%
Formoterol fumarate
1997
<12
Asthma
796
7%
28%
32%
32%
Levofloxacin
1997
<18
694
1%
2%
9%
87%
Olopatadine
1997
<3
3,681
1%
19%
50%
30%
Tazarotene
1997
<12
453
1%
1%
15%
83%
Zarfirlukast
1997
<12
434
1%
1%
22%
77%
Bacterial
infections
Allergic
conjunctivitis
Plaque psoriasis
and acne vulgaris.
1,425
Asthma
a) The date provided refers to the first NOC granted for the drug, not any
subsequent NOCs granted for specific dosage forms or indications for specific conditions or for use in the paediatric population; NOC Notice of
Compliance (authority to market in Canada granted by Health Canada);
b) All indications and age restrictions were derived from Compendium of
Pharmaceuticals and Specialties 2001(4)
TABLE 6
Rate of use of the new drugs in the therapeutic area for
both paediatric and adult claimants
Drug
Celecoxib
Citalopram
Rofecoxib
Bupropion
Montelukast sodium
Formoterol fumarate
Levofloxacin
Tazarotene
Zarfirlukast
Rate per 1000 active claimants
Paediatric Claimants
Adult Claimants
27
210
59
93
17
207
85
162
49
45
4
19
1
10
6
10
2
14
graph, the safety and effectiveness of bupropion in individuals
younger than 18 years old have not been established (4).
Although the rate of use of the new drugs per 1,000
active claimants varied by drug (Table 6), the rates of use
for the paediatric claimants were lower than that for the
adult claimants, except montelukast sodium where the rate
of use was higher among children (49 per 1,000) than
adults (45 per 1,000). Since this study, the indication of
montelukast has been changed to include children older
than two years (5).
ANTIBIOTICS
Data from the National Center for Health Statistics in the
United States indicate that five conditions, otitis media, sinusitis,
bronchitis, pharyngitis and non-specific upper respiratory tract
infection, accounted for approximately 75% of all outpatient prescriptions for antimicrobial medications in children (1,2). A
study on the antibiotic prescribing for Canadian preschool children showed that 74% of preschool children who made visits for
respiratory infection were prescribed an antibiotic (3).
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Abi Khaled et al
CLAIMANT DEMOGRAPHICS
Over 780,000 of the 1.03 million paediatric claimants (76%)
in this study received at least one prescription for an antibiotic during the study period. Antibiotic prescriptions were the
only drugs recorded for 38% (383,401) of all claimants.
Slightly more than half of the children dispensed an
antibiotic were male, a figure which approximates the representation of males in this age group in the paediatric population (Figure 1). The proportion of male claimants was
slightly over half for children younger than seven and slightly under a half for children older than the age of eight.
The rate of antibiotic use was very high across all age
groups, exceeding 700 per 1,000 active claimants in the database, except in the 17-year-old age group, which was slightly
lower (690 per 1,000 active claimants) (Figure 2). The highest
rate of utilization of antibiotics was in the one to six year age
group with rates approaching 900 antibiotic claimants per
1,000 children in the database.
DRUG UTILIZATION
Utilization by dosage form
Overall, oral liquid antibiotics were used by 63% of children
while oral solids were used by 33% (Table 1). Other formulations such as topical and ophthalmic were used by 30% of
claimants. There is a substantial use of multiple medications by
patients, which accounts for the fact that the percentage figures sum to more than 100%.
The use of the different antibiotic dosage forms (tablet, liquid, ophthalmic, etc) is strongly correlated with age. Infants
and very young children cannot swallow solid dosage forms
(i.e., tablets or capsules) and are therefore more likely to be
prescribed liquid formulations. Oral solid formulations may be
used by crushing tablets or mixing with liquids, which may be
the case particularly for drugs not sold in a liquid format. An
examination of the use of antibiotic dosage forms shows that in
the younger than two year age groups, oral liquids were used by
88% and 94% of the antibiotic claimants. In the two to six
year group, over 92% had oral liquids. For the seven to 12 year
group, the use of liquids dropped dramatically with 65% of
14A
90%
50
80%
70%
40
60%
% Male
50%
30
% Female
40%
20
30%
% claimants/gender
Total claimants ('000)
TARGET DRUG LIST
The target drug list included all of the antibiotics or combination products including an antibiotic component. These
agents are used for the treatment of upper and lower respiratory tract infections, acute otitis media, skin and soft tissue infections, urogenital infections, gastrointestinal infections, bone
and joint infections, and other types of infections (7).
Antibiotics were categorized into seven classes according to
their dosage form: oral solid, oral liquid, topical,
ophthalmic/otic, injectable, vaginal, and nasal/inhaled.
100%
60
20%
10
10%
0
0%
<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age
Figure 1) Number of claimants prescribed antibiotics by age (bars) and
per cent of claimants by sex (lines). Claimants two to six years of age
constitute the highest number of those prescribed antibiotics. This is followed by claimants seven to 12 and 13 to 17 years of age respectively. A
high number of <1 and one year of age claimants were prescribed antibiotics. There is slightly more male claimants six years of age and younger
1,000
Rate of use per 1,000 active claimants
The use of antibiotics is reportedly higher among very young
children relative to the prevalence in older age groups (1-6). In
one study, 27% and 70% of infants at 100 and 200 days of life
respectively had received at least one antibiotic prescription
(6). Another study showed that children younger than four
years of age received 53% of all antibiotic prescriptions (2).
900
800
700
600
500
400
300
200
100
0
<1 1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17
Age
Figure 2) The rate of use of antibiotics per 1,000 active claimants.
The rate of use decreases slightly by age but become stable at 700 per
1,000 active claimants older than the age of 11 years
antibiotic claimants dispensed a liquid formulation. For the
oldest age group, liquids were used by only 8% of the
claimants.
Ophthalmic and otic antibiotics were prescribed to 17% of
all children using an antibiotic, but the rate was much higher
in the youngest children. About 30% of infants and 25% of
one-year-olds were dispensed a drug in this dosage form. The
rate dropped progressively with age to 11% for 13- to 17-yearolds.
Topical antibiotics were used by 13% of children but 24%
of 13- to 17-year-olds who used an antibiotic were dispensed a
topical. This is likely related to the treatment of acne (8). It
also could be that older children are more prone to skin infections and other conditions requiring topical antibiotics.
Topical antibiotics were dispensed to a relatively consistent
proportion of children younger than 13, with the rate ranging
between 8% (two- to six-year-olds) to 12% (infants). This
analysis may underestimate topical antibiotic use because
some of these products are sold without a prescription and
some private drug plans do not include over-the-counter drugs
as eligible benefits. Injectable and vaginal antibiotics were
Paediatr Child Health Vol 8 Suppl A April 2003
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Prescription medicine use in Canadian children
TABLE 1
Antibiotics claimants by dosage form and age
Dosage form
Oral solid
Oral liquid
Topical
Ophtalmic/otic
Vaginal
Injectable
Nasal inhaler
< 1 year
N = 40,791
n
427
35,735
4,706
12,042
**
34
0
%
1%
88%
12%
30%
N/A
<1%
0%
1 year
N = 54,751
n
850
51,462
5,855
13,709
**
25
0
%
2%
94%
11%
25%
N/A
<1%
0%
2-6 years
N = 261,663
n
14,355
240,466
21,510
51,059
79
68
0
7-12 years
N = 232,588
%
5%
92%
8%
20%
<1%
<1%
0%
n
85,101
150,158
22,070
35,794
72
102
**
%
37%
65%
10%
15%
<1%
<1%
0%
13-17 years
N = 190,891
n
154,701
16,090
45,660
20,197
540
221
**
%
81%
8%
24%
11%
<1%
<1%
0%
Total claimants
(<1-17 years)
N = 780,684
n
%
255,434
33%
493,911
63%
99,801
13%
132,801
17%
703
<1%
450
<1%
8
0%
400
350
300
250
200
150
100
50
0
Penicillins
Macrolides
Cephalosporins
Aminoglycosides
Sulfonamide & trimethoprim
Su
lfa
m
et
ho
x
Am
Cl
ar oxic
ith
i
ro llin
m
az
y
c
ol
e/ Ce in
tri
m facl
e
o
Az thop r
ith rim
Am
ro
ox
m
y
ic
illi Ce cin
G n/c fpr
en la
oz
il
P t a vu
Ce en mic lan
a
ic
i
G pha illin n s te
u
en
l
ta exi v p lfat
e
m n m ot
ici
a
n/ on siu
be oh m
ta
y
m d ra
et
Su
te
h
lfa
P a
ce iva son
ta
m e
m
p
id ici
l
e
so lin
di
um
Total claimants ('000)
N Total number of claimants prescribed antibiotics; n Number of claimants by dosage form; % Percentage of claimants dispensed a dosage form within the age
group (n/N). The sum of claimants and percentage by age group does not total since one claimant can be dispensed multiple dosage forms in the same year
Figure 3) Number of claimants prescribed antibiotics by drug. Drugs
prescribed to less than 4% of the total claimants on antibiotics are not
shown. Amoxicillin is dispensed to the largest number of claimants on
antibiotics
used by a very small number of children (less than 1%) most
of them were 13 to 17 years old.
Utilization by drug
Amoxicillin, an aminopenicillin, was used by 353,814 children
or 45% of all children that were prescribed an antibiotic
(Figure 3). Amoxicillin is recommended as first line therapy
for a large number of conditions including acute otitis media
and sinusitis, two conditions highly prevalent in the paediatric
population (2-4,6). It was the top antibiotic for children in all
ages (Tables 2 and 3) but the proportion of children in each
age group using this product declined with age. Over 60% of
those younger than two years were dispensed amoxicillin, 53%
of those two to six and only 28% of the claimants aged 13 to 17
years (Table 2). This may be due to the existence of more
antibiotics approved for older children than approved for the
youngest age groups. Amoxicillin is available in a number of
liquid formulations with a variety of flavourings, which make it
easier for parents to administer to the youngest children.
Clarithromycin, a macrolide antibiotic, was the second
most used drug in this therapeutic area, dispensed to over
96,000 claimants or 13% of those dispensed an antibiotic. It
is however, much less used in the youngest age groups, ranking 8th for infants and 6th for one-year-olds. Azithromycin,
Paediatr Child Health Vol 8 Suppl A April 2003
another macrolide, was used by nearly 70,000 children (9%)
and ranks fifth among the antibiotics prescribed for children
in the study population.
Cefaclor and cefprozil (2nd generation cephalosporins)
were used by 13% and 8% respectively of all children that were
prescribed an antibiotic, while cephalexin a 1st generation
cephalosporin, was used by 4% of children prescribed an
antibiotic. Cefaclor and cefprozil were highly used by the
younger age groups but used less by the older ages (Table 2).
On the other hand, cephalexin was used more by the older age
groups.
Several agents stood out for having a much higher rate of
use in the adolescent population relative to the rate for children younger than 11 years of age. Penicillin V potassium,
minocycline, erythromycin, and tretinoin/erythromycin were
ranked third, fourth, fifth and sixth among agents in the 13 to
17 year age group (Table 3), although only penicillin V potassium was one of the top 10 antibiotics overall (Table 2).
Minocycline, erythromycin, tretinoin/erythromycin and tetracycline are used for the management of acne, a condition common in adolescents and a likely explanation for their high
ranking in the older age group in this study.
Erythromycin ethylsuccinate and sulfisoxazole acetyl
(Pediazole®) was one of the top 10 antibiotics for children 6
years of age and younger and was rarely used in adolescents
(less than 1%) (Table 3). This drug is indicated for the treatment of otitis media in children (7).
Amoxicillin and clarithromycin were also the top two
antibiotics among adult claimants (Table 2). Amoxicillin and
clarithromycin were used by 23% and 5% of adults making
antibiotic claims respectively. The drug which ranked third for
adults, ciprofloxacin, was ranked 38th for children.
Ciprofloxacin was used by 9% of adult claimants but less than
1% of the paediatric antibiotic claimants. According to the
product monograph “the safety of ciprofloxacin in children has
not yet been established” (7).
Most of these drugs have no restrictions on use by age within the paediatric age groups (Table 2). There are however
exceptions. The monograph for sulfamethoxazole and
trimethoprim (Septra®) states that this drug is “contraindicated in infants less than 2 months of age” (7). The use in this
specific age group has not been analyzed in the current study.
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Abi Khaled et al
TABLE 2
Leading antibiotics (number of claimants) by drug and age
< 1 year
N = 40,791
Drug
Amoxicillin
Clarithromycina
Cefaclor
Sulfamethoxazole
& trimethoprimb
Azithromycin
Cefprozil
Amoxicillin &
clavulanic acid
Gentamicin sulfatec
Penicillin V
potassium
Cephalexin
monohydrate
1 year
N = 54,751
2-6 years
N = 261,663
7-12 years
N = 232,588
13-17 years
N = 190,891
nch
25,190
3,542
4,631
5,255
R
1
8
4
2
nch
33,073
7,303
8,945
8,795
R
1
6
2
3
nch
137,239
34,096
36,211
31,719
R
1
3
2
4
nch
104,617
29,971
22,400
17,557
R
1
2
3
4
nch
53,695
21,832
7,304
11,413
R
1
2
13
8
Total claimants
(<1-17 years)
N = 780,684
nch
R
353,814
1
96,744
2
79,491
3
74,739
4
Adult claimants
(18-65 years)
N = 5,436,018
nch
R
486,612
1
293,279
2
41,477
24
167,650
6
3,958
4,692
2,511
7
3
9
7,650
8,020
4,700
5
4
8
29,797
28,013
16,879
5
6
7
16,159
13,528
11,092
5
6
9
12,048
3,985
6,002
7
24
17
69,639
58,238
41,184
5
6
7
194,530
34,631
68,326
4
26
13
4,471
148
5
31
5,149
423
7
28
16,827
5,931
8
18
8,727
12,875
11
7
4,911
20,569
20
3
40,085
39,946
8
9
52,507
184,578
16
5
1,065
17
1,812
14
9,934
13
10,120
10
9,952
10
32,883
10
139,517
7
a) Biaxin® monograph: "Use of clarithromycin tablets in children under 12 years of age has not been studied. Use of clarithromycin granules for suspension in children under 6 months has not been studied. In pneumonia, clarithromycin granules were not studied in children younger than 3 years"; b) Septra® monograph: contraindicated "in infants less than 2 months of age"; c) Garamycin Ophtalmic/Otic® preparations monograph: "Safety and effectiveness in children below the age of
6 years have not been established". Garamycin® Topical Preparations monograph: "Gentamicin has been used successfully in infants over 1 year of age as well as
in adults and children". N Total number of claimants prescribed antibiotics; nch Number of claimants by chemical; R Rank of drugs in each age group. Indication and
age restriction from Compendium of Pharmaceuticals and Specialities, 2001.(7) The sum of claimants and percentage by age group does not total, since one
claimant can be dispensed multiple drugs in the same year
TABLE 3
Leading antibiotics by age group
1 year
Amoxicillin
Amoxicillin
Sulfamethoxazol Cefaclor
e & Trimethoprim
Cefprozil
Sulfamethoxazole
& trimethoprim
Cefaclor
Cefprozil
2-6 years
100%
7-12 years
Amoxicillin
Cefaclor
Amoxicillin
Clarithromycin
Clarithromycin
Cefaclor
80%
Amoxicillin
Clarithromycin
Penicillin V
potassium
Sulfamethoxazole Sulfamethoxazole Minocycline
& trimethoprim
& trimethoprim
Gentamicin
Azithromycin
Azithromycin
Azithromycin
Erythromycin
sulfate
dihydrate
dihydrate
dihydrate
Sulfacetamide
Clarithromycin
Cefprozil
Cefprozil
Tretinoin &
sodium
Erythromycin
Azithromycin
Gentamicin sulfate Amoxicillin &
Penicillin V
Azithromycin
dihydrate
Clavulanic acid
potassium
dihydrate
Clarithromycin
Amoxicillin &
Gentamicin sulfate Gentamicin
Sulfamethoxazole
clavulanic acid
sulfate &
& trimethoprim
betamethasone
sodium
phosphate
Amoxicillin &
Sulfacetamide
Sulfacetamide
Amoxicillin &
Tetracycline
clavulanic acid
sodium
sodium
clavulanic acid
Erythromycin
Erythromycin
Erythromycin
Cephalexin
Cephalexin
ethylsuccinate & ethylsuccinate &
ethylsuccinate & monohydrate
monohydrate
sulfisoxazole
sulfisoxazole
sulfisoxazole
acetyl
acetyl
acetyl
The monographs for clarithromycin (Biaxin®) and gentamicin
(Garamycin®) indicate that for some forms of these drugs,
study in patients younger than 12 and six years of age respectively is not available to support safety and efficacy (7).
Thousands of paediatric claimants outside these age restrictions received these agents.
Multiple antibiotic courses
Multiple courses of antibiotic therapy during a 12-month period could indicate a treatment failure of a first drug, re-infection, a new unrelated infection or an ongoing medical
condition that requires chronic antibiotic therapy. Previous
studies have found a high rate of multiple courses of therapy for
young children (4,5).
The analysis contained in this study reviews the number of
prescriptions dispensed to individuals over a 12-month period
starting with the first prescription for an antibiotic in the study
16A
90%
13-17 years
70%
% claimants
<1 year
60%
50%
40%
30%
20%
10%
0%
<1
1
2-6
7-12
13-17
Age
1 course of therapy
2 courses of therapy
4 courses of therapy
5+ courses of therapy
3 courses of therapy
Figure 4) Distribution of claimants dispensed an oral antibiotic by the
number of courses of therapy and age. Claimants aged one year represent the highest number of those prescribed five or more courses of therapy and the lowest number of those prescribed one course of therapy.
The number of claimants prescribed five or more courses of therapy
decreases by age
period. There is no evidence presented in this study explaining
the reasons for multiple prescriptions.
Of the children who were prescribed an antibiotic, 7%
received five or more courses of therapy (Figure 4). This proportion ranged from a high of 16% for the one-year-olds to a
low of 4% for children seven years of age and older. Of the
children younger than one year of age dispensed an antibiotic,
10% had five or more courses of therapy.
The results of this analysis are consistent with another
Canadian study conducted in Manitoba that reported young
children were three times more likely than adolescents to
receive five or more antibiotic prescriptions (5).
For all age groups except the one year olds, 50% to 65%
(depending on the age group) were dispensed a single antibiotic
agent, regardless of how many prescriptions for antibiotics were
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Prescription medicine use in Canadian children
A large number of different antibiotics were prescribed over
the 12-month study period. Five or more antibiotics were dispensed to 5% of infants and to 7% of one-year-olds. For the
older age groups, only 1% had five or more drugs. Younger children were more likely than older children to receive more than
one antibiotic agent with the highest proportion (57%) in the
one-year-olds. For these patients, there may have been more
than one prescription and more than one dosage form but the
same drug entity was dispensed.
100%
90%
80%
% claimants
70%
60%
50%
40%
30%
20%
10%
0%
<1
1
2-6
7-12
13-17
Age
1 drug
2 drugs
3 drugs
4 drugs
5+ drugs
Figure 5) Distribution of claimants prescribed antibiotics by the number
of drugs and age. Claimants one year of age represent the highest number of those prescribed five or more drugs and the lowest number of those
prescribed one drug. The number of claimants prescribed five or more
drugs decreases by age whereas that of claimants prescribed one course of
therapy increases by age except for the one-year-olds
received (Figure 5). Almost 65% of the seven- to 12-year-olds
and over 62% of those 13 to 17 years had a single antibiotic.
SUMMARY FINDINGS
1. 76% of claimants in the study population had at least one
prescription for antibiotics with no gender differences.
2. Amoxicillin was the leading antibiotic for all ages. The
top ten antibiotics varied with age.
3. On average 7% of the children received five or more
courses of antibiotics and young children were more
likely than adolescents to receive five or more antibiotic
prescriptions.
4. In addition, younger children were more likely to receive
more than one antibiotic agent than older children with
the highest proportion (57%) in the one-year-olds.
Expert Comment – Antibiotics
David P Speert MD, Professor and Head Division of Infectious and Immunological Diseases, Department of
Pediatrics, University of British Columbia and BC’s Children’s Hospital
Frequent infections are an expected rite of passage of early childhood, and antibiotics (for their treatment) are therefore
prescribed frequently. Children in the first few years of life experience many respiratory tract infections as they confront
common viruses to which they have not yet mounted an immunological defense. ‘Education’ of the immune system with
exposure to these varied respiratory viruses constitutes a series of ‘lessons’ that our children cannot avoid, nor should they!
The chapter on antibiotic use clearly documents the extraordinary frequency with which children are given antibiotics,
but it is not possible to determine how often this practice is appropriate. However, information from other sources can be
extrapolated to these data; one can predict that at least 50% of the antibiotic prescriptions are unnecessary and may, in
fact, do substantial harm. For instance, over half of the children or adults presenting for medical care with an upper respiratory tract infection (common cold) are given a prescription for an antibiotic. Since such infections are invariably caused
by viruses, antibiotic use is not indicated. Antibiotics should also not be given for pharyngitis, unless a bacterial etiology
(in particular Group A streptococcus) has been established. Finally, most cases of otitis media in children will resolve irrespective of antibiotic therapy, leading many experts to advise against the routine use of antimicrobial therapy for this common paediatric condition.
It is clear that many courses of antibiotic therapy could be avoided without causing harm, but there is also reason to be
concerned about the actual danger of injudicious use of these therapies. Children who receive a course of oral antibiotics
are at higher risk for colonization in the upper respiratory tract with a penicillin resistant strain of pneumococcus, rendering them susceptible to invasive disease with organisms which are challenging to treat. Each course of antibiotics carries
a risk of adverse events such as diarrhea, rash, or even anaphylaxis. Efforts should therefore be directed at enhancing discretion in dispensing these powerful drugs. Should overuse continue to be the norm, many of the most effective drugs
could lose their place in our anti-infective armamentarium.
Strategies to decrease the injudicious use of antibiotics should be multipronged, targeting prescribing physicians as well
as consumers. Misperceptions abound regarding why these drugs are over-prescribed: patients often feel that their physicians wish to dispense antibiotics and physicians often believe that their patients will be disappointed if an antibiotic is
not given. Informed decision making demands continuing education about the indications for antibiotic therapy in children and the risks associated with their overuse. Such programs have been introduced with success in British Columbia
and elsewhere in Canada, but sustained success requires ongoing education.
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Abi Khaled et al
Respiratory drugs are used for a number of respiratory diseases
or infections such as asthma and chronic obstructive pulmonary disorder (COPD). Asthma is a chronic lung condition that is most common in childhood and occurs in
approximately 7% to 10% of the paediatric population (1).
Statistics showed that twice the number of boys than girls
had asthma in young children and about the equal proportion
in adolescents (1,2).
Some other respiratory diseases or infections include bronchopulmonary dysplasia (BPD), which occurs in premature
infants during the first days of life (1,3), croup, which is most
common in children between six months and three years of age
especially during the winter season (4), and respiratory syncytial virus (RSV), which can cause serious respiratory tract
infections in very young children (1). Chronic obstructive pulmonary disorder (COPD), which includes chronic bronchitis
and emphysema, is more prevalent among adults and is usually
associated with long term smoking (1).
Since asthma is the most prevalent chronic respiratory condition in children (1,3), it constituted the focus of this analysis
and this label is used throughout this section as a matter of
convenience. Since diagnosis is not available, some of the
patients in this section may be suffering from diseases other
than asthma.
TARGET DRUG LIST
The target drug list includes medications that are indicated for
the treatment of asthma and asthma-like symptoms as listed in
Table 1 (Note that this analysis is based on retail prescriptions
and did not include medication dispensed in hospital).
Epinephrine and oral corticosteroids were excluded because
they are used in other conditions and the purpose of the target
drug list is to keep the focus as narrow as possible.
If a drug has more than one formulation, only the form that
is generally used for the treatment of asthma was included in
the target drug list. Forms like nasal spray or topical solutions
that are used for conditions other than asthma were excluded.
Medications used for the treatment of asthma are generally
divided into two main categories: relievers and controllers.
Reliever medications are best represented by inhaled short-acting-β2-agonists (SABA). These quick acting bronchodilators
are used to relieve acute intercurrent asthma symptoms. They
are intended for use only when needed rather than for prophylaxis (5).
The controllers include anti-inflammatory medications such
as inhaled and oral corticosteroids (although oral corticosteroids were not included as target drugs), leukotriene receptor
antagonists (LTRA), and nonsteroidal inhaled anti-inflammatory agents. Controllers are taken regularly to control asthma
and prevent exacerbation (5). The controller group also
includes some bronchodilators that are taken regularly in addition to inhaled corticosteroids (IS) to help achieve and maintain asthma control. These include the long acting β2-agonists
(LABAs), xanthines and ipratropium bromide. Prednisone and
prednisolone (oral corticosteroids) are commonly used in combination with other agents for the treatment of asthma exacerbation; therefore they were included in a special analysis
examining their use in combination with the target drugs.
The drugs included in this analysis were grouped into six
classes based on their mechanism of action.
CLAIMANT DEMOGRAPHICS
There were 182,271 claimants (18% of the 1.03 million paediatric claimants) who had at least one prescription for a target
respiratory drug.
A higher proportion of claimants were boys (about 60%)
than girls for ages younger than 12 (Figure 1). However, the
rate of use of these drugs among girls begins to rise and surpasses the rate for boys older than age 15.
The rate of respiratory drug use per 1,000 active claimants
was over 100 for children in each single year of age. In terms of
the rate of use between the ages of four and 12, the rate ranges
between 192 and 204 per 1,000 active claimants (Figure 2).
The rate is lowest (120 per 1,000 active claimants) for 17-yearolds. There was a large number of infants one year of age and
14
TABLE 1
Respiratory target drugs
Relievers
Short-acting E2-agonists (SABAa)
Drug
Fenoterol HBr, pirbuterol acetate, procaterol HCl
hemihydrate, salbutamol sulfate, salbutamol,
terbutaline sulfate
Ipratropium bromide, ipratropium bromide &
salbutamol sulphate.
Controllers
Long-acting E2-agonists (LABA)
Inhaled corticosteroids (IS)
Leukotriene Receptor
Antagonists (LTRA)
Xanthines
Nonsteroidal inhaled antiinflammatory agents
Formoterol fumarate, salmeterol xinafoate
Beclomethasone dipropionate, budesonide,
flunisolide, fluticasone propionate, triamcinolone
acetonide
Montelukast, zafirlukast
80%
10
70%
% Male
60%
8
50%
6
4
40%
% Female
30%
20%
2
10%
0
0%
<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age
Aminophylline, guaiacol & pot.iodide & theophylline
& pyrilamine maleate, oxtriphylline, theophylline &
ephedrine & phenobarbital, theophylline &
pot.iodide, theophylline & potassium, theophylline
calcium glycinate, theophylline
Ketotifen, nedocromil sodium, sodium
cromoglycate
The target drugs were determined by literature review and advice from the
advisory panel. Indication and age restriction from Compendium of
Pharmaceuticals and Specialities, 2001
18A
90%
12
Total claimants ('000)
Class
100%
% claimants/gender
RESPIRATORY DRUGS
Figure 1) Number of claimants prescribed respiratory drugs by age
(bars) and percent of claimants by sex (lines). Claimants aged two to six
and seven to 12 constitute the highest number of claimants. There is a
significant number of claimants up to and including one-year-olds dispensed respiratory drugs. The number of male claimants is higher than
that of female claimants in the younger than 12 years age groups. The
sex numbers equal out in the 13 to 17 years age group
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Prescription medicine use in Canadian children
TABLE 2
Distribution of claimants by class and age
< 1 year
N = 8,142
Class
SABA
HDS
LDS
LTRA
Nonsteroidal inhaled antiinflammatory agents
LABA
Xanthines
Oral corticosteroids
1 year
N = 10,819
2-6 years
N = 57,825
7-12 years
N = 64,085
Total claimants
(<1-17 years)
N = 182,271
n
%
146,259
80%
70,729
39%
61,368
34%
9,386
5%
6,746
4%
13-17 years
N = 41,400
n
7,164
1,174
4,153
**
195
%
88%
14%
51%
N/A
2%
n
8,930
2,431
5,712
23
381
%
83%
22%
53%
0%
4%
n
44,713
19,754
27,163
1,806
2,480
%
77%
34%
47%
3%
4%
n
50,300
28,414
19,222
4,958
2,518
%
78%
44%
30%
8%
4%
n
35,152
18,956
5,118
2,596
1,172
%
85%
46%
12%
6%
3%
**
66
149
N/A
1%
2%
21
62
285
0%
1%
3%
247
308
1,658
0%
1%
3%
924
337
3,376
1%
<1%
5%
1,193
428
2,624
3%
1%
6%
2,388
1,201
8,092
1%
1%
4%
N Total number of claimants prescribed respiratory drugs; n Number of claimants by class; % Percentage of claimants dispensed a class within the age group (n/N).
**fewer than six claimants. SABA Short-acting β2-agonists (includes ipratropium bromide); HDS High-dose steroids; LDS Low-dose steroids; LTRA Leukotriene
receptor antagonists; LABA Long-acting β2-agonists. The sum of claimants and percentage by age group does not total, because one claimant can be dispensed
multiple classes of respiratory drugs in the same year.
150
200
Total claimants ('000)
180
160
140
120
100
80
80%
120
90
39%
60
37%
30
5%
1%
4%
1%
4%
y
nh
a
le
d
an
tiin
fla
m
m
te
r
at
or
oi
ds
in
es
lC
or
ti c
os
BA
LA
R
A
LT
O
ra
20
Xa
nt
h
40
LD
S
60
H
D
S
0
SA
BA
Rate of use per 1,000 active claimants
220
4
5
6
7
8
9 10 11 12 13 14 15 16 17
Age
Figure 2) The rate of use of respiratory drugs per 1,000 active
claimants. The rate of use increases slightly by age until 11 years and
start decreasing after the age of 12. The rate of use of respiratory drugs
ranges between 115 and 205 claimants per 1,000 active claimants
younger who were dispensed respiratory drugs (154 per 1,000
active claimants). These results are consistent with the fact
that most children with asthma develop symptoms before five
years of age (6) and that the prevalence of asthma decreases
with age (7,8).
DRUG UTILIZATION
Utilization by class
Short-acting inhaled β2-agonists (SABA) were dispensed to
80% of claimants prescribed target respiratory drugs (Figure
3). SABAs are reportedly the drugs of choice in both children
and adults for the relief of acute asthmatic symptoms and the
short term prevention of exercise-induced bronchospasm
(3,5,9). The rate of use of SABA was relatively low for the
two- to six-year-olds (77% of the respiratory claimants) and
seven- to 12-year-olds (79%), and exceeded 80% for all other
age groups (Table 2).
The next largest class was high dose inhaled steroids
(HDS), controllers that were used by 39% of respiratory drug
claimants, followed by low dose steroids (LDS), which were
prescribed to 34%. Inhaled corticosteroids are used as the primary long term treatment for controlling childhood asthma
(1,3,5,9). For high dose inhaled steroids, the rate of use was
Paediatr Child Health Vol 8 Suppl A April 2003
ro
id
3
st
e
2
N
on
<1 1
al
i
0
Figure 3) Number of claimants prescribed respiratory drugs by class.
The different classes include the reliever SABA and controllers such as
HDS, LDS, LTRA, LABA, Xanthines, oral corticosteroids (prednisone and prednisolone) prescribed to claimants with asthma exacerbation and nonsteroidal inhaled anti-inflammatory drugs. There were more
claimants dispensed SABA than the controllers. Among the controllers,
HDS and LDS were the two prescribed to the most claimants. SABA
Short-acting β2-agonists (includes ipratropium bromide), HDS Highdose steroids; LDS Low-dose steroids; LTRA Leukotriene receptor
antagonists; LABA Long-acting β2-agonists
higher in older age groups than the younger ones.
Approximately 14% of the younger than one year group had
an HDS, while 46% of those 13 to 17 years fell into this group.
The pattern of use by age for low dose steroids is opposite that
for high dose steroids. Half of the infants were dispensed an
LDS compared with only 12% for those in the oldest age
group.
Leukotriene receptor antagonists and long acting β2-agonists, both relatively new classes of drugs, account for a small
proportion (5%) of claimants prescribed target respiratory
drugs. Xanthines were prescribed to only 1% of the respiratory
drug claimants. Xanthines have both bronchodilator and antiinflammatory effects and may be used as an adjunctive therapy
with inhaled corticosteroids (5,9). In Canada, xanthines are
used most often in severe asthmatic cases in addition to treatment with other drugs (3).
In order to estimate the amount of oral corticosteroid use
in asthma, the number of target drug claimants who were also
prescribed prednisone or prednisolone (which were not on the
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Abi Khaled et al
TABLE 3
The top 10 respiratory drugs (by claimant count) by drug and age
Drug
Salbutamol a
Fluticasone propionate b
Budesonide
Beclomethasone
diproprionate
Terbutaline c
Montelukast d
Salbutamol sulfate e
Sodium cromoglycate
Ketotifen
Ipratropium bromide f
nch
6,729
3,562
1,211
618
R
1
2
3
4
nch
8,489
5,595
1,437
1,211
R
1
2
3
4
nch
42,358
32,469
5,839
8,888
R
1
2
4
3
nch
42,807
27,420
10,550
9,359
R
1
2
3
4
nch
28,711
12,716
6,849
4,635
R
1
2
3
5
nch
129,094
81,762
25,886
24,711
R
1
2
3
4
Adult
claimants (1865 years)
N = 418,531
nch
R
262,412
1
162,599
2
70,069
3
26,155
5
**
**
613
92
107
139
N/A
N/A
5
8
7
6
**
22
637
132
255
154
N/A
11
5
8
6
7
1,028
1,803
2,173
981
1,505
671
8
6
5
9
7
10
7,045
4,869
1,634
1,398
980
537
5
6
7
8
9
11
5,972
2,295
1,142
734
234
391
4
6
7
9
15
12
14,054
8,992
6,199
3,337
3,081
1,892
5
6
7
8
9
10
40,940
18,868
8,148
2,464
1,398
13,968
< 1 year
N = 8,142
1 year
N = 10,819
2-6 years
N = 57,825
7-12 years
N = 64,085
13-17 years
N = 41,400
Total claimants
(<1-17 years)
N = 182,271
4
6
11
18
20
10
a) Ventolin Respirator® Solution and Ventolin Nebules® monographs: "Experience is insufficient for recommending the treatment of children under 5 years of
age". Ventolin Diskus monograph: "Safety and efficacy in children below 4 years of age have not been established". Ventodisk blisters/Diskhaler® and Ventolin
Rotacaps/Rotahaler® monograph: "Experience is insufficient for recommending the treatment of children under 6 years of age"; b) Flovent® monograph:
"Fluticasone is not presently recommended for children younger than 4 years of age due to limited clinical data in this age group"; c) Bricanyl® Tablets and
Turbuhaler monographs: "Terbutaline is not presently recommended for children below 6 years of age due to limited clinical data in this paediatric group"; d)
Singulair® monograph: "Safety and effectiveness in paediatric patients younger than 6 years of age have not been studied"; e) Airomir® monograph: "Safety and
effectiveness in children below the age of 6 years have not been established", Salbutamol Nebuamp monograph: "Use of salbutamol in children under 5 years
of age has not been established"; f) Atrovent® Inhalation Aerosol monograph: "Efficacy and safety in children younger than 12 years have not been established".
Atrovent Inhalation Solution monograph: "The efficacy and safety in children younger than 5 years have not been established". N Total number of claimants prescribed respiratory drugs; nch Number of claimants by chemical; R Rank of drug in each age group. **fewer than six claimants. Indication and age restriction from
Compendium of Pharmaceuticals and Specialities, 2001.(11) The sum of claimants and percentage by age group does not total, since one claimant can be dispensed multiple drugs in the same year
20A
Total claimants ('000)
120
IS
LTRA
Oral Corticosteroids
100
Nonsteroidal inhaled
anti-inflammatory
80
60
40
20
0
Sa
lb
ut
on
am
e
ol
pr
Be
o
cl
pi
om
on
at
et
Bu
e
ha
de
so
so
ne
n
id
di
e
pr
Te
op
rb
i
o
ut
na
al
te
M
in
on
e
su
te
lfa
lu
ka
te
st
so
di
um
Pr
Sa
ed
ni
lb
so
ut
am
So
ne
di
ol
um
su
lfa
cr
te
om
og
ly
ca
te
Ip
Ke
ra
t ro
to
tif
pi
en
um
br
om
id
e
Utilization by drug
Salbutamol, a short-acting β2-agonist, was the leading respiratory drug that was used by more than 125,000 claimants
(approximately 71% of all children dispensed respiratory
drugs) (Figure 4). This finding is consistent with several studies in Canada, which showed that salbutamol is the most commonly used SABA (3,5,10).
Fluticasone (81,700 claimants), budesonide (25,900
claimants) and beclomethasone dipropionate (24,700
claimants), all of which are inhaled steroids, were ranked second, third and fourth, respectively.
Terbutaline, a short-acting β2-agonist, was fifth in the list
of respiratory drugs prescribed to children in the database
(14,000 claimants). Fewer than 9,000 claimants used each of
the other top 10 respiratory drugs.
Salbutamol, fluticasone propionate and budesonide were
the top three drugs for all paediatric age groups with the exception of the two to six year age group (Table 3).
Beclomethasone dipropionate is third for this age group and
fourth or fifth for all other age groups. Terbutaline was fourth
in the 13 to 17 year group.
The greatest difference in the rankings of use was for terbutaline and montelukast, which were rarely used among the
youngest two age groups. Terbutaline is available in both oral
solid and turbuhaler formats, and montelukast is only available
SABA
140
Fl
ut
ic
as
list of target drugs used to identify respiratory claimants) was
assessed. These oral corticosteroids were prescribed to 4% of
the respiratory claimants (Figure 3). Short courses of oral corticosteroids can be added to therapy for children with severe
asthma exacerbations unresponsive to other drugs (5,9). Oral
corticosteroids had the highest rate in the 7 to 12 and 13 to 17
age groups (5% and 6% respectively).
Figure 4) Number of claimants prescribed respiratory drugs by drug.
Drugs prescribed to less than 1% of the total claimants in the study are
not shown. Salbutamol, a short-acting β2-agonist, is the top drug.
Fluticasone and budesonide are ranked second and third, respectively,
both being high dose steroids. Beclomethasone diproprionate, a low dose
steroid, is ranked fourth, whereas terbutaline a short-acting β2-agonist is
ranked fifth in the list of target respiratory drugs
in an oral solid format. In general, oral solids are less commonly used in younger children.
Age restrictions for the top 10 respiratory agents are
included in Table 3. Most of these drugs are not recommended for children younger than four, five or six years (some
forms of salbutamol, salbutamol sulfate, and ipratropium bromide, fluticasone, terbulatine, and montelukast) because
there is either insufficient experience or clinical data recommending their use or the safety and efficacy in children have
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Prescription medicine use in Canadian children
TABLE 4
Distribution of claimants younger than six years by
delivery system
Drug
Beclomethasone
Budesonide
Fluticasone propionate
Fenoterol HBR
Ipratropium bromide
Ipratropium bromide &
salbutamol sulfate
Salbutamol
Salbutamol sulfate
Terbutaline sulfate
MDI
100%
N/A
99%
77%
28%
89%
85%
24%
N/A
Inhaled
Nebulizer Dry powder
N/A
0%
90%
12%
N/A
1%
23%
N/A
74%
N/A
11%
13%
76%
N/A
SABA+LTRA
+
PRED
1%
Total claimants
(under 6 years)
8,827
7,181
35,363
132
849
N/A
0%
0%
100%
SABA+IS+
CONTR+
PRED
7%
C
SABA &
Multiple
controllers
A
Other drug
combination
SABA Only
SABA+IS+
CONTR
57%
SABA+IS+
PRED
35%
7%
5%
27%
45%
Total SABA & multiple controller claimants:12,705
16%
167
49,483
3,090
509
SABA+PRED
1%
SABA+LTRA
1%
SABA+NSIA
1%
SABA+(XAN or
LABA)
0%
B
N/A The formulation does not exist
not been established (11). There is, however, use of these
drugs in children below the recommended age.
SABA & one
controller
IS Only
Total respiratory claimants:182,271
SABA+IS
97%
Total SABA & one controller claimants:82,910
Asthma drug use among children younger than six years
Over the past few years the recommended inhalation delivery
method for treating young asthmatic children has changed
from the nebulizer to metered dose inhalers combined with a
device called a spacer (12,13). The purpose of this analysis is
to quantify the extent to which children five years of age and
younger were prescribed inhaled asthma medication in a
metered dose, dry powder or nebulizer form during the
1999/2000 study period.
According to the data used in this study, the proportion of
use of the nebulizer form exceeded the use of other inhaled formats in children younger than six for three agents (Table 4):
budesonide (90% of inhaled use was in the nebulizer format),
salbutamol sulfate (76%) and ipratropium bromide (74%).
However, each of these products have fewer claimants in the
five years and younger age group compared to the other drugs
in the class, accounting for only 11%, 5% and 1% of the respiratory drug claimants respectively.
Of the most widely used drugs among the children younger
than six years, salbutamol (49,500 claimants) had 13% of its
use from the nebulizer format and fluticasone propionate
(35,363 claimants) is not sold in a nebulizer format.
Salbutamol sulfate/ipratropium bromide and fenoterol HBr
were mostly used as metered dose inhalers rather than nebulizers but were each used by less than 1% of claimants in the five
years and younger age group.
This brief analysis demonstrates that in the paediatric population under review, nebulizers were less important in terms of
the numbers of patients treated relative to metered dose
inhalers. Metered dose inhalers were used far more frequently,
possibly with the aid of a spacer device.
Multiple Drug Therapy
Asthma is a disease for which the symptoms vary from person
to person, and even the same person’s condition may fluctuate
throughout the year. According to the 1999 Canadian asthma
consensus report, more than one medication may be prescribed
to maintain control (5). Most of the combinations include a
SABA and an inhaled steroid. The drugs added to the regimen
include leukotriene receptor antagonists, LABA, xanthines, or
in the case of severe asthma, oral prednisone or prednisolone
may be required for short term treatment (3,5,9,12).
Paediatr Child Health Vol 8 Suppl A April 2003
Figure 5) Distribution of claimants prescribed respiratory drugs by drug
therapy. Approximately 27% of claimants are prescribed short-acting
β2-agonists (SABA) monotherapy and 16% are prescribed inhaled
steroids (IS) monotherapy. Claimants prescribed SABA with one controller represent 45% of all respiratory claimants and of those 97% are
prescribed IS as the controller. Prednisone is used alone with a SABA in
1% of the respiratory claimants and in 43% of claimants prescribed
SABA with multiple controllers. IS Inhaled steroids; LTRA Leukotriene
receptor antagonists; LABA Long-acting β2-agonists; NSIA
Nonsteroidal inhaled anti-inflammatory; XAN Xanthines; PRED
Prednisone; CONT Any controller other than IS
The current study found that 52% of respiratory claimants
were using a SABA and at least one other drug in the therapeutic area during the study period (Figure 5A). Forty three
per cent of respiratory claimants were dispensed either a short
acting β2-agonist or an inhaled steroid (IS) alone. The
remaining 5% of children were dispensed one or more of the
other drugs indicated for asthma but neither a SABA nor an
IS. However, given the possible use of these other drugs in
diseases other than asthma, the remainder of this analysis will
concentrate on those claimants who received a short-acting
β2-agonist or an inhaled steroid and another drug in the
therapeutic area.
Among the asthma drug claimants, 45% were using a SABA
and one controller and 7% were using a SABA and two or more
controllers over the course of the 12-month study period (Figure
5A). Of the 45% using one controller, almost all (97%) were
using the SABA with an inhaled steroid (Figure 5B). The
remaining 3% were split roughly equally among leukotriene
receptor antagonists, oral prednisone or nonsteroidal inhaled
anti-inflammatory drugs. SABA used in addition to either xanthines or a LABA alone was used by less than 1% of children.
Of the 7% of the respiratory claimants dispensed a SABA
and multiple controllers during the study period, 57% were
using inhaled steroids and one or more of the additional
therapies (LTRA, LABA, xanthines or nonsteroidal inhaled
anti-inflammatory agents) (Figure 5C). There were 35%
who were dispensed prednisone along with the SABA and
an inhaled steroid. Prednisone, as mentioned previously, is
added to the treatment regime in severe asthma that does
not respond to other drugs (5,9). Another 7% of multiple
controller patients were dispensed prednisone and another
controller in addition to a SABA and an inhaled steroid.
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Abi Khaled et al
The remaining 1% were dispensed a SABA, a leukotriene
receptor antagonist and prednisone during the 12-month
study period (Figure 5C).
Approximately 27% of asthma drug claimants (48,445)
were dispensed an inhaled SABA alone, with no other target
drug during the 12-month study period (Figure 5A). Inhaled
short-acting β2-agonist monotherapy can be used to relieve
the symptoms in very mild asthma (5) or to prevent bronchospasm induced by exercise or another trigger (3).
Claimants that received only inhaled steroids (low or high
dose) during the 12-month study period represented 16%
(nearly 29,000) of the respiratory claimants.
TABLE 1
Analgesics, anti-inflammatory and DMARDs target drugs
SUMMARY FINDING
1. 18% of claimants in the study population had at least one
prescription for respiratory drugs. Boys were more likely
to receive respiratory drugs than girls in the younger
age groups, while for adolescents the proportion of
girls that received respiratory drugs exceed that of boys.
2. SABA was the leading class of respiratory drugs followed
by inhaled steroids. Salbutamol, fluticasone propionate
and budesonide were the top three respiratory drugs.
3. Most of the respiratory claimants were using SABA and
inhaled steroids during the 12-month study period.
Metered dose inhalers were used far more frequently,
possibly with the aid of a spacer device for children five
years of age and younger.
The target drugs were determined by literature review and advice of advisory
panel
NSAIDs
(Non-narcotic analgesics)
Total claimants ('000)
Disease modifying drugs
(DMARDs)
Products
Alfentanil HCl, butorphanol tartrate, codeine phospatea,
fentanyl citrate, hydromorphone HCl, meperidine HCl
(pethidine), methadone, morphine HCl, morphine sulfate,
nalbuphine HCl, oxycodone HCl, oxymorphone HCl,
pentazocine HCl, pentazocine lactate, propoxyphene
HCl, propoxyphene napsylate, sufentanil citrate
Celecoxib, choline magnesium trisalicylate, diclofenac
potassium, diclofenac sodium, diflunisal etodolac,
fenoprofen calcium, floctafenine, flurbiprofen, ibuprofenb,
indomethacin, ketoprofen, ketorolac tromethamine,
mefenamic acid, meloxicam, nabumetone, naproxen
sodium, naproxen, oxaprozin, piroxicam - B-cyclodextrin,
piroxicam, rofecoxib, sulindac, tenoxicam, tiaprofenic
acid, tolmetin sodium
Aurothioglucose, azathioprine, hydroxychloroquine
sulfate, leflunomide, methotrexate sodium penicillamine,
sodium aurothiomalate, sulfasalazine
18
100%
16
90%
14
80%
12
70%
% Male
60%
10
50%
8
6
40%
% Female
30%
4
20%
2
10%
0
ANALGESICS, ANTI-INFLAMMATORIES
AND DMARDS DRUGS
Analgesics and anti-inflammatory drugs are both used to
control acute and chronic pain, while disease modifying
drugs (DMARDs) are used for the treatment of rheumatic
diseases.
Acute pain in children includes sport or playground
injuries, post operation pain, trauma, burns, menstrual pain,
acute episode of sickle cell anemia and cancer (1). Chronic
pain in children is poorly understood and remains an area that
requires more research, particularly in comparison to the
extensive literature on adult chronic pain (2). Chronic pain in
children includes headache, musculoskeletal pain and abdominal pain. Several studies reported that the prevalence rates of
headache, abdominal pain and back pain are higher in girls
than boys, particularly in older girls (approximately 10 years or
older) (3-5).
Musculoskeletal pain is the most common type of chronic
pain in children. It affects 10% to 20% of school aged children
(6). A recent school based survey of adolescents in British
Columbia showed that musculoskeletal pain was the second
most common medical problem (after acne) (6). Over 5% of
these adolescents had a limb pain of such severity that they
believed that they had arthritis (6). Some of the common musculoskeletal pains in children include growing pains, strains
and sprains, juvenile rheumatoid arthritis (JRA), and OsgoodSchlatter disease (6).
Of the above conditions, JRA is a serious long term condition which affects one in 1,000 Canadian children younger
than the age of 16 (7). It causes pain, stiffness and swelling in
one or more of the joints (inflammation). Its symptom is an
22A
% claimants/gender
Class
Opioids
(Narcotic analgesics)
0%
<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age
Figure 1) Number of claimants prescribed analgesics, anti-inflammatory drugs and DMARDs by age (bars) and percentage of claimants by sex
(lines). Most claimants dispensed these medications are between the ages
of 13 and 17 years. There are more male than female claimants aged 11
years and younger
inflammation lasting longer than six weeks that is not caused
by an injury or other illness (7).
Osgood-Schlatter disease is another condition that causes
knee pain in older children and teenagers, especially those
who are active in sports. It appears during the growth spurt
(ages nine to 13), when bones are growing rapidly (8).
TARGET DRUG LIST
The target drug list included opioids, DMARDs and nonsteroidal anti-inflammatory drugs (NSAIDs) except salicylic
acid derivatives (Table 1). Drugs specifically indicated for
migraine were not included in the target drug list.
Only those formulations available as a prescription medication were included in the target drug list. Not all private drug
plans cover over-the-counter drugs so their inclusion would
lead to an incomplete picture of actual utilization. For codeine
phosphate in combination with other chemicals, only prescription products indicated in analgesia are included. Those medications indicated for cough and common cold were excluded.
Although oral corticosteroids are used for the treatment of
JRA (7,9-11), they were not included in the target drug list.
Corticosteroids are indicated for a large number of inflammatory diseases and the purpose of the target drug list is to keep the
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Prescription medicine use in Canadian children
TABLE 2
Distribution of claimants by class
Total claimants
(<1-17 years)
N =84,024
n
%
n
%
n
%
n
%
n
%
n
%
DMARDs
**
N/A
**
N/A
57
1%
192
1%
392
1%
646
1%
NSAIDs
72
12%
146
10%
1,018
11%
4,786
32%
35,965
62%
41,987
50%
Opioids
522
88%
1,284
90%
8,578
90%
10,440
70%
28,026
49%
48,850
58%
N Total number of claimants prescribed analgesics, anti-inflammatory drugs and DMARDs; n Number of claimants by class; % Percentage of claimants dispensed
a class within the age group (n/N). ** Fewer than six claimants. The sum of claimants and percentage by age group does not total, since one claimant can be dispensed multiple drugs in the same year.
< 1 year
N = 593
Class
1 year
N = 1,427
2-6 years
N = 9,545
7-12 years
N = 14,914
52
48
250
44
40
200
Total claimants ('000)
150
100
50
36
32
28
24
20
16
12
8
0
4
5
6
7
8
9 10 11 12 13 14 15 16 17
4
Age
CLAIMANT DEMOGRAPHICS
Claimants prescribed an analgesic, an anti-inflammatory or
a DMARD in the study database accounted for 84,024 or
approximately 8% of all paediatric claimants selected for
the study. Over 68% of these claimants were 13 years of age
and younger with more girls than boys prescribed an agent
from this therapeutic area in this age range. Claimants 12
Paediatr Child Health Vol 8 Suppl A April 2003
DMARDs
NSAIDs
Opioids
Figure 3) Number of claimants dispensed analgesics, anti-inflammatory drugs and DMARDs by class. Very few claimants were dispensed
DMARDs whereas opioids and NSAIDs were dispensed to about
48,000 and 42,000 respectively. NSAIDs Nonsteroidal anti-inflammatory drugs; DMARDs Disease-modifying anti-rheumatic medications
Total claimants ('000)
28
24
NSAIDs
20
Opioids
16
12
8
4
e/ c
ode
ine
0
ino
phe
n/c
affe
in
focus as narrow as possible. Analysis of oral corticosteroids
usage among children is shown separately.
Medications used to relieve pain are generally divided into
narcotic (opioids) and non-narcotic (NSAIDs) analgesics (9).
Opioids can be used for the treatment of moderate to severe
pain (9,10). However, they share common side effects including constipation, nausea, sedation, respiratory depression,
dependence and withdrawal symptoms (if used for a long period of time) (9-11).
NSAIDs are a group of medications characterised by having analgesic, antipyretic and anti-inflammatory action that
can be used for the treatment of mild to moderate pain
(9-12). NSAIDs share many common properties, especially
in their use as analgesics. They lack addictive potential and
do not result in sedation or respiratory depression, which are
associated with opioids (12). However chronic use of
NSAIDs can irritate the stomach and produce ulcer or
bleeding (9-11).
DMARDs are slow acting agents used for the treatment of
active inflammatory disease such as JRA (11). NSAIDs are
used in conjunction with DMARDs to control pain and local
inflammatory reaction (7,9,10).
0
Ace
tam
Figure 2) The rate of use of analgesics, anti-inflammatory drugs and
DMARDs per 1,000 active claimants. The rate of use increases by
age and reaches its highest at 265 claimants per 1,000 active
claimants aged 17
Ro f
eco
xib
3
Ce le
cox
ib
Dic
lofe
nac
sod
ium
2
Ibu
pro
fen
Na p
ro x
en
sod
ium
Me
fe n
am
ic a
Ket
cid
oro
la c
trom
eth
am
ine
<1 1
Na p
ro x
en
Co d
eine
pho
s
p ha
Ace
te
tam
ino
phe
n/c
ode
in e
Rate of use per 1,000 active claimants
300
13-17 years
N = 57,545
Figure 4) Number of claimants dispensed analgesics, anti-inflammatory drugs and DMARDs by drug. Drugs dispensed to less than 1% of the
total claimants on analgesics, anti-inflammatory drugs and DMARDs
are not shown. Acetaminophen/caffeine/codeine phosphate, an opioid,
was dispensed to the largest number of claimants in the study
years of age and younger accounted for the remaining 32%,
of which approximately 18% were 7 to 12 years of age, 11%
were two to six years of age, and 2% were younger than two
years. Male claimants dominated the younger age groups
(younger than 10 years) (Figure 1).
The rate of drug use per 1,000 active claimants for the
target drugs demonstrated a similar pattern as that for the
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Abi Khaled et al
TABLE 3
Rate of use of analgesics, anti-inflammatory drugs and DMARDS per 1,000 active claimants for the top 10 products by age
<1 year
N = 593
Drug
nch
Rate per
1,000
0.7
1 year
N = 1,427
nch
Rate per
1,000
0.9
2-6 years
N = 9,545
nch
7-12 years
N = 14,914
Rate per
1,000
1.6
nch
Rate per
1,000
11.5
13-17 years
N = 57,545
nch
Rate per
1,000
74.3
Total claimants
(<1-17 years)
N = 84,024
nch
Rate per
1,000
25,790
25.0
Acetaminophen &
39
60
502
3,695
21,494
Caffeine & Codeine a
Naproxen b
26
0.5
54
0.9
531
1.7
1,963
6.1
10,569
36.5
13,143
12.7
Codeine phosphate c
379
7.2
885
14.0
5,415
17.7
4,210
13.1
2,067
7.1
12,956
12.6
Acetaminophen &
93
1.8
333
5.3
2,612
8.5
2,521
7.8
3,778
13.0
9,337
9.0
Codeine Phosphate a
Ibuprofen
8
0.1
18
0.3
90
0.3
1,063
3.3
8,137
28.1
9,316
9.0
Naproxen Sodium d
9
0.2
14
0.2
117
0.7
597
1.9
7,309
25.3
8,046
7.8
Mefenamic aid e
**
N/A
**
N/A
12
0
231
0.7
3,155
10.9
3,402
3.3
Ketorolac
**
N/A
15
0.2
54
0.2
184
0.6
2,832
9.8
3,089
3.0
Tromethamine f
Celecoxib g
8
0.1
13
0
73
0
256
0
1,879
0.6
2,229
2.2
Diclofenac sodium h
**
N/A
8
0
44
0
236
0
1,813
0.6
2,105
2.0
a) Tylenol with codeine® preparations monograph: "These products containing codeine phosphate should not be administered to children except on the advice of a
physician. Tablets and caplets should not be administered to children below the age of 12 years. Safe dosage of the elixir has not been established in infants below
the age of two years"; b) Naprosyn® monograph: "Naproxen is contraindicated in children under two years of age since safety in this age group has not been established". "Naproxen suppositories are contraindicated in children under 12 years of age"; c) Codeine phosphate general monograph: "The safety and effectiveness
has not been adequately evaluated for these drugs. Children up to two years of age may be more prone to their adverse pharmacological effects"; d) Anaprox®
monograph: "The safety and efficacy of this drug in children has not been established and its use in children is therefore not recommended"; e) Ponstan® monograph: "Safety and effectiveness in children below the age of 14 have not been established"; f) Acular® and Toradol® monographs: "Safety and efficacy in children
have not been established"; g) Celebrex® monograph: "Safety and effectiveness in paediatric patients below the age of 18 years have not been evaluated"; h)
Voltaren® and voltaren® ophtha monographs: "The safety and dosage ranges of diclofenac have not been established in children under 16 years of age; therefore,
it is not recommended for paediatric use". N Total number of claimants prescribed analgesics, anti-inflammatory and DMARDS; nch Number of claimants by chemical; Rate per 10,000 Rate of use of each drug in each age group per 10,000 active claimants; ** fewer than 6 claimants. Indication and age restriction from
Compendium of Pharmaceuticals and Specialities, 2001(11)
claimant demographics. The rate of drug use was fairly constant for children one to eight years at approximately 30 per
1,000 active claimants. From the age of nine to 17, the rate
of use increased steadily up to 266 claimants per 1,000
active claimants prescribed the target drugs (Figure 2).
DRUG UTILIZATION
Utilization by class
Relatively more claimants were dispensed opioids than any
other class in this therapeutic area (Figure 3). Overall, opioids,
mainly drugs containing codeine, were used by 58% (48,800)
of children prescribed the target drugs. This ranged from 48%
of children 13 to 17 years of age to approximately 90% of those
younger than six years of age (Table 2).
NSAIDs were the second largest class prescribed to children among all other classes. Just fewer than 42,000 claimants
(50%) were prescribed NSAIDs; most of them (86%) were 13
to 17 years of age (Table 2).
More girls were prescribed NSAIDs than boys particularly
in the older age groups (data not shown). Similar findings were
reported by Manitoba Center for Health Policy and Evaluation
(13). NSAIDs have analgesic properties at lower doses and
anti-inflammatory at higher doses. NSAIDs are reportedly the
drug of choice for the treatment of menstrual pain as well as
pain and inflammation brought on by physical activity (e.g.,
sports injuries) (12).
Disease modifying drugs (DMARDs) were used by a very
small number of children. Less than 1% of the target drug children were prescribed these agents and this is consistent across
all ages.
24A
Utilization by chemical
Codeine phosphate with acetaminophen and caffeine was
the top product prescribed to the target drug claimants during the study period (Figure 4). Over 30% (25,790
claimants) of all claimants prescribed a target drug were dispensed acetaminophen/caffeine/codeine phosphate, making
it the top drug in this therapeutic area. Overall, the rate of
use of this combination product was 25 per 1,000 active
claimants. For children 13 to 17 years of age, the rate of use
of this product was 74 per 1,000 active claimants (Table 3).
Codeine phosphate and codeine phosphate with acetaminophen were used by about 13,000 (15%) and 9,000 (11%) of
the target drug claimants, respectively. For codeine phosphate alone, the rate of use per 1,000 active claimants
increased with age until the age of six and then decreased in
the older age groups. Codeine phosphate alone or in combination with other drugs is not recommended for to children
younger than two years of age (11).
Naproxen, an NSAID, was dispensed to more than
13,000 claimants or 16% of the target drug claimants. In
addition, more than 30% of all claimants dispensed NSAIDs
were dispensed naproxen. Naproxen could be used for
chronic pain such as JRA as well as minor aches and pains
(11). The rate of use of naproxen increased with age ranging
from less than one to 36.5 claimants per 1,000 active
claimants (Table 3). Naproxen is contraindicated in children younger than two years and the suppositories are contraindicated in children younger than 12 years (11).
Ibuprofen and naproxen sodium were used by 11% and 10%
respectively of the children dispensed drugs in this area.
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Prescription medicine use in Canadian children
TABLE 4
Utilization of oral corticosteroids by drug and age group
Drug
Prednisone
Dexamethasone
Triamcinolone acetonide
Methylprednisolone acetate
Hydrocortisone
Cortisone acetate
<1 year
N = 541
nch
210
309
**
**
**
**
%
39%
57%
N/A
N/A
N/A
N/A
1 year
N = 982
nch
404
541
**
**
**
**
%
41%
55%
N/A
N/A
N/A
N/A
2-6 years
N = 3,723
nch
2,386
1,219
**
9
31
27
%
64%
33%
N/A
0%
1%
1%
7-12 years
N = 6,014
nch
5,405
377
39
27
44
36
%
90%
6%
1%
0%
1%
1%
13-17 years
N = 7,230
nch
5,550
1,260
138
118
55
38
%
77%
17%
2%
2%
1%
1%
Total claimants
(<1-17 years)
N = 18,490
nch
%
13,955
75%
3,706
20%
187
1%
157
1%
138
1%
107
1%
For all oral corticosteroids: "Prolonged therapy with corticosteroids in infants and children should be avoided if possible since corticosteroids may suppress growth".
N Total number of claimants prescribed oral corticosteroids; nch Number of claimants by chemical; % Percentage of claimants prescribed a drug in each age group.
** Fewer than six claimants. Drugs prescribed to less than 1% of claimants is not shown
There is no age restriction for ibuprofen; however, the use of
naproxen sodium is not recommended for children because
its safety and efficacy have not been established (11).
Of the 42,000 claimants who were prescribed an NSAID,
more than 2,200 (5%) and 1,400 (3%) were prescribed celecoxib and rofecoxib respectively (Figure 4). Celecoxib and
rofecoxib are both cyclooxygenase-2 (COX-2) selective
inhibitors and are recent entrants as a new generation of
NSAIDs (introduced in 1999, partway through the study period). Celecoxib is indicated for osteoarthritis and rheumatoid
arthritis in adults while rofecoxib is indicated for osteoarthritis, relief of pain in adults as well as the treatment of primary
dysmenorrhea (11). For both of these products, safety and
effectiveness in paediatric claimants younger the age of 18
years have not been evaluated, according to their respective
product monographs (11).
Utilization of corticosteroids
Oral corticosteroids were used by more than 18,000 children
(approximately 2% of paediatric claimants). Of those, prednisone was dispensed to 75% of claimants using an oral corticosteroid (Table 4). This ranges from approximately 40% in
the youngest age groups (one year and younger) to 77% in
the 13 to 17 years of age group. Prednisone was dispensed to
about 8,000 claimants who were also prescribed respiratory
drugs. This use represents over 50% of the total prescriptions
of prednisone. The second most common corticosteroid overall, was dexamethasone, prescribed to 20% of all children
using oral corticosteroids. Triamcinolone acetonide, methylprednisolone acetate, hydrocortisone and cortisone acetate
were each used by 1% of the children prescribed oral corticosteroids.
ORAL CORTICOSTEROIDS
Corticosteroids are used in the treatment of inflammatory diseases of the intestine, bronchioles, nose, eyes, ears, skin and
joints (11). Their use in the treatment of asthma is included in
the analysis of respiratory drugs previously in the report. In
juvenile rheumatoid arthritis, corticosteroids are used at relatively low doses and for short periods of time until the second
line drugs (DMARDs) start to work (7,10).
SUMMARY FINDING
1. 8% of the claimants in the study population had at least
one prescription for an analgesic, anti-inflammatory or a
DMARD.
2. Over 68% of these claimants were 13 years of age and
over with more females than males.
3. Opioids were used by 58% of the target children.
NSAIDs were used by 50% and DMARDs were used by
only 1% of the children.
4. Codeine phosphate with acetaminophen and caffeine
was the top product prescribed to the target claimants
during the study period followed by naproxen.
5. Oral corticosteroids were used by 2% of the total
paediatric claimants in the study database. Prednisone
was the leading oral corticosteroid followed by
dexamethazone.
Target drug list
The target drug list includes only systemic oral corticosteroids:
betamethasone sodium phosphate, cortisone acetate, dexamethasone, dexamethasone sodium phosphate, hydrocortisone,
methylprednisolone acetate, prednisolone, prednisone, triamcinolone and triamcinolone diacetate.
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Expert Comment – Analgesics, anti-inflammatories and DMARD drugs
Stuart MacLeod MD PhD FRCPC, Executive Director, BCRI, VP, Academic Development, PHSA
The condition of pain has been in many ways a true therapeutic orphan in paediatrics. Counterintuitively, paediatrics acted until recently as if pain were a different entity in children from the familiar noxious sensations experienced by adults.
Understanding of pain in paediatrics has advanced in the past decade to a recognition that analgesic treatment may be
indicated at any time after birth or even in utero.
The mechanisms involved in nociception are extremely complicated and pharmcotherapy is correspondingly diverse.
Pain pathways include neuropeptides, amino acids, nitric oxide, and arachadonic acid metabolites as potential targets.
Naturally occurring opioids, adenosine, and monoamines (e.g., serotonin and norepinephrine) may all influence the symptomatology of pain.
The management of paediatric nociceptive pain most commonly involves the use of NSAIDs or acetaminophen plus
codeine as illustrated in the present results. It is perhaps unexpected that NSAIDs are not more heavily used in children.
Their ability to effectively reduce the inflammation associated with injury and thereby reduce pain is an important attribute. The relatively limited prescribing of these drugs in spite of an anticipated 10% to 20% prevalence of chronic musculoskeletal pain is somewhat surprising, but prescribing for children over 13 is seen to approach expected levels.
Although ibuprofen has been assessed as an antipyretic, NSAIDs as a class, especially some of the most recently introduced members (celecoxib and rofecoxib) have not yet been extensively studied in children, so considerable caution in
their prescribing for pain is commendable. Use of better known NSAIDs, such as naproxen and ibuprofen, as shown here,
is to be expected. It is highly unlikely that the selective COX2 inhibitors, (e.g., celecoxib and rofecoxib), will be found to
possess any significant therapeutic or safety advantage in children.
The data available in this study do not permit the assessment of management techniques for complex regional pain disorders or neuropathic pain. Such syndromes are unresponsive to conventional analgesics, including opiates. Mainstays of
therapy not shown in the study include anticonvulsants (gabapentin and carbamazepine), antidepressants, antiarrhythmics and local anesthetics.
The most dramatic observation is the degree of reliance placed by prescribers on combination products containing
acetaminophen and codeine. This is especially notable in the treatment of older children. Such combinations have long
since gained a leading place in analgesic therapy in Canada despite limited evidence of therapeutic advantage over the
same agents taken singly. In paediatrics it appears that the market for combination analgesic products has been maintained
in spite of the introduction of many competing opioid agents. This may again reflect a lack of evidence concerning the
place of newer opioids in paediatric therapy. Alternatively, the observation suggests that the pain requiring treatment in
children is more likely to be acute or considered short term. The common prescription of codeine phosphate as a single
agent in younger children is almost certainly for relief of chronic non-productive cough.
The data presented on disease modifying drugs and oral corticosteroids is too limited for interpretation. Inflammatory
arthritis remains a rare disease among children and treatment requires highly specialized knowledge.
Altogether these results underscore the need for more detailed study of nociceptive pain and its pharmacotherapy in
children. If acetaminophen-codeine combinations are to remain the cornerstones of therapy, appropriate clinical trials in
common paediatric conditions are indicated.
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Prescription medicine use in Canadian children
ACNE PRESCRIPTION DRUGS
Acne generally starts early in adolescence (between the ages of
10 and 13), with hormonal changes associated with puberty,
and lasts into the twenties (1,2). It has been reported that
more than 40% of adolescents will require a physician’s treatment for acne. (2).
Females and males are equally susceptible to acne.
Paradoxically, women are more likely to seek treatment but
men are more prone to severe forms of acne (2). Depending on
the severity and the factors causing acne, topical and systemic
agents such as benzoyl peroxide, retinoids, antibiotics or hormonal therapy are all recommended treatments.
TARGET DRUG LIST
The target drug list included medications that are indicated for
the treatment of acne as listed in Table 1. If the drug has more
than one formulation, only those forms used for the treatment
of acne were included in the target drug list.
Oral antibiotics used for the treatment of acne were excluded because they are indicated for the treatment of a large number of conditions and the purpose of the target drug list is to
keep the focus as narrow as possible. However, the concomitant
use of these antibiotics for the selected target drug claimants
was analysed separately. Also, over-the-counter drugs (OTCs)
such as low strength benzoyl peroxide (5% or less), which may
be used by a wide number of adolescents for the treatment of
mild, acne were not included in the list. These products are not
consistently reported in the claims database.
Acne target drugs were grouped into four classes according
to the form and the route of administration: topical antibiotics,
‘topical other’, oral retinoid and hormonal therapy. The class
of ‘topical other’ included non-antibiotics as well as combinations of antibiotics with other agents. Hormonal therapy
included only two drugs: Tri-Cyclen® and Diane-35®. TriCyclen® is the only oral contraceptive also approved by
Health Canada for acne treatment (3). Although Diane-35®
(antiandrogen/estrogen combination) is indicated for treatment of severe acne in females unresponsive to other treatment, it provides reliable contraception when taken as
recommended (3). Finally, the class oral retinoid included only
isotretinoin, which is also available in a topical form that was
included in the ‘topical other’ class.
CLAIMANT DEMOGRAPHICS
Acne is associated with adolescence; therefore, the following
analysis describes the use of acne therapy among adolescents
aged 10 to 17 years.
More than 71,000 adolescent claimants (10 to 17 years
old) had at least one claim for the target drugs, including hormonal therapy. This represented 16% of all claimants in this
age group in the study population. Data showed more girls
than boys were using the target drugs at each age. The difference was much larger for ages younger than 14 where girls represented 70% of claimants. This may be partly due to the fact
that acne is a problem of puberty and, in general, girls reach
puberty earlier than boys. After age 14, about 60% of
claimants were girls (Figure 1).
Two hormonal therapies, which are prescribed exclusively to girls, were included in the target drug list. Their incluPaediatr Child Health Vol 8 Suppl A April 2003
TABLE 1
Acne therapy target drugs
Class
Topical antibiotic
Topical other
Oral retinoid
Hormonal therapy
Drug
Clindamycin phosphate
Erythromycin
Benzoyl peroxide
Benzoyl peroxide & erythromycin
Adapalene
Neomycin & methylprednisolone
Trade name
Dalacin T® topical solution
Erysol®, Sans-Acne®, Staticin®, T-stat®
Acetoxyl®, Desquam-x®, Benzoxyl®, other
Benzamycin®
Differin®
Neo-Medrol Acne® solution
Isotretinoin (topical)
Tretinoin
Tretinoin & erythromycin
Tazarotene
Sulfacetamide sodium & sulfur
Isotretinoin (oral)
Norgestimate & ethinyl estradiol
Cyproterone acetate & ethinyl
estradiol
Isotrex®
Retin-A®, StieVa-A®, Vitamin A® acid, other
Stievamycin®
Tazorac® gel
Sulfacet-R®
Accutane®
Tri-Cyclen®
Diane-35®
The target drugs were determined by literature review and advice from the
advisory panel
Figure 1) Number of claimants prescribed acne therapy by age (bars)
and percentage of claimants by sex (lines). The top chart includes
claimants prescribed hormonal therapy whereas the chart below excludes
those claimants. There were more female than male claimants aged 14
years and over where hormonal therapy was included as part of the acne
therapy
sion in the study skews the break down by sex of the population. When hormonal therapy was excluded, the number
of claimants was 59,600 and the sex difference observed in
the 13- to 17-year-olds disappeared; girls remained dominant in younger ages (Figure 1, lower panel). The use of
hormonal therapy may be intended as contraception rather
than acne.
DRUG UTILIZATION
The class of ‘topical other’ was used by 52% of children 10 to
17 years of age who were prescribed acne therapy, approximately half of them were girls (Figure 2). This class is commonly prescribed for almost all types of mild to moderate acne
(3) and includes nine different drugs or combinations of drugs
that come in a variety of products and in several delivery systems, such as creams, washes, gels, and cleansing pads.
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Abi Khaled et al
F:M
1,1 :1
45
40
30
25
F:M
1,2:1
20
F:M
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8
6
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15
/e
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EE thr
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nz
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EE
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al
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e/
su
lfu
r
Tr
et
in
oi
n
5
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Topical antibiotics
Topical other
Oral retinoid
Hormonal therapy
Class of acne therapy
Figure 2) Number of claimants prescribed acne therapy by class and
sex. ‘Topical other’ was the class dispensed to the largest number of
claimants with slightly more females than males. Oral retinoid
(Accutane®) was dispensed to twice as many males as females
Figure 3) Number of claimants prescribed acne therapy by drug.
Tretinoin and erythromycin (Stievamycin®) was dispensed to the
largest number of claimants. Ethinyl estradiol and norgestimate and
tretinoin followed as distant second and third drugs dispensed to
claimants on acne therapy. EE Ethinyl Estradiol
100%
8
Females
Males
Total claimants ('000)
7
4
80%
3.5
6
70%
% claimants
5
4
3
2
3
60%
2.5
50%
2
40%
1.5
1
10%
0.5
e/
e
ox
id
Er
yt
hr
ha
t
os
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et
in
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m
yc
in
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om
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oy
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ot
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N
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n
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ap
et
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al
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en
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e
m
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id
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ac
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om
yc
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C
lin
da
ry
/e
oi
n
et
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Tr
4.5
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0%
Prescription/claimant
Total claimants ('000)
35
Topical antibiotics
Topical other
Oral retinoid
Hormonal therapy
16
14
12
Total claimants ('000)
50
0
10
11
12
13
14
15
16
17
Age
1 drug
2 drugs
3 drugs
4+drugs
Figure 4) Number of males and females claimants prescribed acne
therapy by drug. Overall, there were more females than males prescribed drugs for acne therapy except for isotretinoin (Accutane®),
benzoyl peroxide and tretinoin and erythromycin. Hormonal therapy
was not included in this graph since it is prescribed to females only
Figure 5) Distribution of claimants by the number of drug products
(trade names) used for the treatment of acne (bars) and the number
of prescription per patient (blue line) during the 12-month period by
single year of age. A multiple ingredient product is considered as one
drug product and drugs of different trade names but similar chemical
structure are considered as different products
The combination of tretinoin and erythromycin
(Stievamycin® topical gel) was the top acne product used by
21% of children prescribed acne therapy (Figure 3). Another
topical antibiotic combination, benzoyl peroxide and erythromycin (Benzamycin®), was used by 12% of the10 to 17 year
olds prescribed acne therapy.
Tretinoin, benzoyl peroxide, adapalene, and tazarotene, all
classed under ‘topical other’, were used by 16%, 12%, 9% and
1% of claimants respectively. For benzoyl peroxide, the data
included only benzoyl peroxide products available by prescription (greater than 5% concentration). The data therefore underestimate the use of benzoyl peroxide because, no
doubt there is considerable use of the OTC formulation of
this product.
Topical antibiotics were used by 25% of children aged 10 to
17 years who were prescribed acne therapy. This class included
two medications: clindamycin phosphate and erythromycin.
16% and 13% of acne claimants in this age group used clindamycin phosphate and erythromycin respectively. Slightly more
females than males received this class of acne therapy. Similar to
‘topical other’, topical antibiotics are recommended for use in the
treatment of mild to moderate acne (3). In general, topical
antibiotics are not recommended for use alone due to the risk of
bacterial resistance. Instead combinations with benzoyl peroxide
or another topical medication are recommended (4).
A third class, hormonal therapy (Tri-Cyclen® and
Diane-35®), was used by 20% of children 10 to 17 years old
who were prescribed acne therapy. All of these claimants were
female. This equates to 34% of female claimants who received
acne therapy in this age group. As noted earlier, some of this
usage may be for contraception. Ethinyl estradiol and norgestimate (Tri-Cyclen®) was used by 16% of children. Cyproterone
acetate and ethinyl estradiol (Diane-35®) was used by 5% of
claimants prescribed acne therapy.
The oral retinoid class included only one drug, isotretinoin
(Accutane®). This drug was used by 11% of children 10 to 17
years old who were prescribed acne therapy with twice as many
males as females. Accutane® is a derivative of vitamin A recommended for use in severe scarring, cystic acne. However,
Accutane® is teratogenic and should not be used in females at
risk of pregnancy unless hormonal contraceptives are used concomitantly (3).
The data show that the sex differences in the utilization of
acne medications varied among drugs (Figure 4). A major sex
difference was observed in oral isotretinoin (Accutane®) utiliza-
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Prescription medicine use in Canadian children
TABLE 2
Distribution of claimants by class of acne therapy
prescribed oral antibiotics concomitantly
TABLE 3
Distribution of claimants by class of acne therapy and by
sex prescribed oral antibiotics concomitantly
Hormonal therapy
Oral retinoid
N= 14,396
N=7,740
Claimants
%
Claimants
%
Minocycline 50mg
215
1%
19
<1%
Minocycline 100mg
247
2%
45
<1%
Tetracycline 250mg
145
1%
20
<1%
Doxycycline 100mg
65
0%
10
<1%
Erythromycin 250mg
99
1%
46
<1%
Erythromycin 333mg
118
1%
29
<1%
Erythromycin 500mg
**
N/A
**
N/A
Topical
Topical other
antibiotic
N=42,648
N=17,054
%F
%M
%F
%M
%F
%M
Minocycline 50mg
21%
79%
45%
55%
48% 52%
Minocycline 100mg
18%
82%
40%
60%
38% 62%
Tetracycline 250mg
32%
68%
43%
57%
41% 59%
Doxycycline 100mg
50%
50%
47%
53%
43% 57%
Erythromycin 250mg 41%
59%
49%
51%
47% 53%
Erythromycin 333mg 39%
61%
42%
58%
48% 52%
N Total number of claimants in each class of acne therapy; %F Percentage of
female claimants concomitantly prescribed antibiotics in each class of acne
therapy. N excludes the claims of some private payers thus the number of
claimants by class of acne therapy is not equal to that presented previously.
The strength selected for each antibiotic is based on the recommended daily
dose for the treatment of acne. The class of hormonal therapy was excluded
because it is prescribed exclusively to girls
Concomitant
antibiotics
Topical antibiotic
N=17,054
Claimants
%
850
5%
1,025
6%
904
5%
80
0%
284
2%
100
1%
**
N/A
Topical other
N=42,648
Claimants
%
3,245
8%
4,391
10%
3,342
8%
286
1%
827
2%
331
1%
30
0%
N Total number of claimants in each class of acne therapy; % Percentage of
claimant concomitantly prescribed antibiotics in each class of acne therapy;
N excludes the claims of some private payers thus the number of claimants by
class of acne therapy is not equal to that presented previously. ** Fewer than
six claimants. The strength selected for each antibiotic is based on the recommended daily dose for the treatment of acne
tion. Among claimants who had at least one claim for
Accutane®, 66% were male. The strong warnings about the
drug’s teratogenic effects likely result in the much lower use
among females.
Both benzoyl peroxide and tretinoin/erythromycin combinations were also used by relatively more males. All other
drugs were used by more females than males (Figure 4).
Claimants by number of drugs
On average, 68% of acne claimants 10 to 17 years old used
only one of the target acne products and approximately 3%
were dispensed four or more of the products during the 12month study period (Figure 5). A multiple ingredient combination product is considered to be a single product for this
analysis. The percentage of claimants using two or more drug
products increased with age up to age 15 then declined after
that age. Those adolescents, who were using more than one
product for acne, could have been using it concomitantly or at
different times during the 12-month study index period which
commenced with the first claim for a target drug.
Although most claimants obtained only a single drug product
in the 12-month period, the average number of prescriptions per
patient increased with age from 1.5 prescriptions/claimant in the
10-year-olds to 3.8 prescriptions/claimant in the 17-year-olds.
Use of oral antibiotics as acne therapies
Oral antibiotics such as minocycline, tetracycline, doxycycline
and erythromycin are used for the treatment of inflammatory
acne (1,2,5).
Minocycline, tetracycline and doxycycline are members of
the tetracycline family with similar spectra of activity and are
the most recommended oral antibiotics for the treatment of
acne (4,5). However, each is associated with restrictions and the
risk of adverse reactions which may limit their use in children.
In total, oral minocycline, erythromycin, tetracycline and
doxycycline were each used by 4%, 3%, 2% and less than 1%
of all children aged 10 to 17 years respectively in the study
population. This includes use alone or in combination with
other drugs. Table 2 presents the distribution of claimants who
were using oral antibiotics concomitantly with each class of
acne medication during the study period.
The class, ‘topical other’, had the highest share of claimants
with concomitant oral antibiotic use at 10% for minocycline
100mg, 8% for each of minocycline 50mg and tetracycline
250mg, and 1% for doxycycline. Topical antibiotics had the
Paediatr Child Health Vol 8 Suppl A April 2003
Concomitant
antibiotics
Oral retinoid
N=7,740
second highest rate of concomitant oral antibiotic use, with as
many as 6% of claimants receiving both a topical and one of
the selected oral antibiotics. Claimants using hormonal therapy had a much lower rate of concomitant oral antibiotic use
with 1% to 2% of claimants using both products. Oral
isotretinoin had the lowest percentage of claimants using concomitant oral antibiotics at less than 1% for all of the four
selected antibiotics.
Regardless of the class of acne therapy prescribed, minocycline 100mg was the most prevalent concomitant antibiotic
(Table 2). The use of concomitant minocycline 100mg ranged
from 0.6% of the target drug claimants taking oral isotretinoin
to 10% of those taking medicines in the ‘topical other’ class.
Tetracycline 250mg was ranked second among concomitant
antibiotics for all classes of acne therapy except ‘oral retinoids.’
Oral erythromycin was ranked third.
Boys were more likely than girls to be prescribed oral antibiotics concomitantly with acne therapy (Table 3). This is the
case regardless of the class of acne therapy or the concomitant
antibiotic used.
SUMMARY FINDINGS
1. 16% of the study claimants aged 10 to 17 year olds had at
least one claim for acne therapy with more females than
males in the children younger than 14 years.
2. Topical other was the leading acne class used by 52% of
the target children, and tretinoin/erythromycin
(Stievamycin® topical gel) was the top acne product over
all and for male claimants. On the other hand, TriCyclen® was the top product for female claimants. TriCyclen® was also the leading contraceptive product for
female adolescents. Oral isotretinoin (Accutane®)
seems to be one of the least common treatment for acne
in females, probably because of its teratogenic effect.
3. Most of the claimants were using one acne product
during the 12-month study period.
4. Minocycline was the most prevalent concomitant
antibiotic used with all classes of acne therapy followed
by tetracycline. The class, ‘topical other’, had the
highest share of claimants with concomitant oral
antibiotic use while the lowest share was for oral
isotretinoin.
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Expert Comment – Acne prescription drugs
Sari Kives MD, Adolescent and Paediatric Gynecologist, Department of Obstetrics and Gynecology,
Saint Michael’s Hospital, Toronto, Ontario
Topical medications, antibiotics, oral contraceptive pills and Accutane® are the drugs of choice for treating acne in both
adults and adolescents. This therapeutic class typically has a large therapeutic index with the exception of Accutane® in
females.
This study demonstrates that most physicians use a stepwise approach when selecting an acne medication for adolescents 10 to 17 years of age.
‘Topical other’ and topical antibiotics are the classes of drugs most frequently prescribed to this population (62% and
25% respectively) as they are both safe and effective and have minimal side effects. Frequently ‘topical other’ and topical
antibiotics are combined with oral antibiotics to treat inflammatory acne in up to 10% of adolescents. Unfortunately topical treatments alone are less effective if treating more severe acne.
Hormonal therapy in the form of the oral contraceptive pill (OCP), is frequently prescribed as second line for girls, as
this subclass is both curative and preventative for acne and/or contraception. It is reassuring to see that a large number of
physicians are prescribing the OCP in this young population. The OCP has many other benefits that should be emphasized to improve compliance in this often difficult population. The beneficial effect on acne provided by the OCP is not
exclusive to Tri-Cyclen® and Diane-35®. In fact all OCP formulations impact favorably on acne by lowering circulating
androgens. In this study 34% of girls were prescribed the OCP. Often this medication is prescribed to prevent pregnancy
first and acne second. As this database only allows for drug identification it is uncertain if in fact the OCP was prescribed
solely for acne. Many physicians do not realize that it is safe to initiate the OCP shortly after menarche exclusively to help
treat dysmenorrhea, menorrhagia, hirsutism as well as acne without a full pelvic exam. In conjunction with an oral antibiotic this medication can be extremely effective and is a safe alternative to Accutane® in the female population with severe
acne. Surprisingly in this study, very few patients (less then 1%) were treated with this effective combination.
Accutane® is still an excellent option for the treatment and prevention of acne but is unfortunately teratogenic. It is
therefore comforting that only 7% of the females in this study are on Accutane®. Even if the OCP is prescribed in conjunction with Accutane® one should be wary. Previous literature suggests that only 50% to 75% of women who begin taking oral contraceptives and do not want to be pregnant are still using them after one year (1). Compliance is often worse
in the adolescent population. Accutane® should therefore be restricted to the most severe cases of acne in girls who are
older and can understand the potential danger. In the male population this teratogenic risk is obviously not a concern and
Accutane® is therefore a good option for adolescent boys who have failed topical treatments, oral antibiotics or a combination of both.
Although most patients were using one medication, the average number of prescriptions increased with age. This is not
surprising as often adolescents are not compliant with treatment and switch medications if there is no immediate significant improvement. In addition, adolescents are more self-conscious and are looking for quicker and better results. Future
studies should focus on the effectiveness of acne treatment in this difficult population. At present, prescribing practices in
adolescents are very similar to those of the adult population in this therapeutic category. One might consider adjusting this
pattern if we find that certain medications are less effective than others for the treatment of acne in adolescents.
REFERENCE
1. Rosenberg MJ, Waugh MS, Burnhill MS. Compliance, counseling and satisfaction with oral contraceptives: A prospective evaluation.
Fam Plann Perspect 1998;30:89-92
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TARGET DRUG LIST
The target drug list included all forms of hormonal contraceptives (oral, injectable, implant and emergency contraceptives)
as listed in Table 1.
In addition to conception control, some of these drugs are
also prescribed for the treatment of acne, menorrhagia, dysmenorrhea, hirsutism and other androgen-mediated disorders
(5). This report cannot distinguish the reasons for use.
CLAIMANT DEMOGRAPHICS
Contraceptives are prescribed exclusively to women and their
use is started in adolescence, therefore the following analysis
describes the use of these products among 11- to 17-year-old
girls. More than 38,000 girls 11 to 17 years of age had at least
one prescription for a contraceptive. This represents 19% of all
female claimants older than the age of 10 year in the study
population. Ninety per cent of girls prescribed contraceptives
were 15 years of age and older (Figure 1).
16
Total female claimants ('000)
500
14
400
12
10
300
8
200
6
4
100
2
0
0
11
12
13
Composition
Drug
50)g
Estrogen
Monophasic
EE/ ethynodiol diacetate
EE/ norgestrel
mestranol/ norethindrone
< 50)g
Estrogen
Monophasic
EE/ norethindrone
EE/ norgestimate
EE/desogestrel
EE/ ethynodiol diacetate
EE/ levonorgestrel
EE/ norethindrone acetate
Biphasic
Triphasic
Injectable
Implant
Emergency
Progestin-only
antiandrogenestrogen
Progestogen
Progestin
EE/ norethindrone
EE/ norethindrone
EE/ levonorgestrel
EE/ norgestimate
Norethindrone
EE/Cyproterone Acetate
Medroxyprogesterone
acetate
levonorgestrel
EE/ levonorgestrel
levonorgestrel
16
17
40
94%
35
30
25
20
15
10
9%
0
TABLE 1
Contraceptive therapy target-drugs
Form
15
Figure 1) Number of female claimants 11 years of age and older dispensed contraceptive therapy by age (bars) and rate of use of contraceptive therapy per 1,000 female active claimants (line). Female
claimants 17 years of age represent the highest proportion of those dispensed contraceptives and this proportion decreases by age. The rate
of use of contraceptive therapy among active claimants increases with
age from four claimants per 1,000 female active claimants aged 11
years to 460 per 1,000 claimants aged 17 years
5
Oral
14
Age
Total claimants ('000)
Hormonal contraception for women is the most common form
of birth control, used by approximately 80% of women in
North America at some time during their reproductive lives
(1). These hormones may be administered in tablet forms,
through skin implants or by injection. Each type is available
only by prescription. Oral contraceptives (OC) are the method
of choice for most young women, especially teens (2,3).
Injectable contraceptives and implants both provide longterm conception control; three months and five years, respectively. Emergency contraceptives, commonly called ‘morning
after’ pills contain a higher dose of hormones (4).
600
18
Rate of use per 1,000 active female
claimants
HORMONAL CONTRACEPTIVES
Oral
Trade name
Demulen 50®
Ovral®
Norinyl1/50®,
Ortho-Novum1/50®
Brevicon 1/35®, 0.5/35
Ortho 1/35®, o.5/35
Select 1/35®
Cyclen®
Marvelon®, Ortho-Cept®
Demulen 30®
Mini-Oval®, Alesse®
Loestrin 1.5/30®,
Minestrin 1/20®
Ortho 10/11®, Synphasic®
Ortho 7/7/7®
Triphasil®, Triquilar®
Tri-Cyclen®
Micronor®
Diane-35® a
Depo-Provera®, Alti-MPA®,
Gen-Medroxy®,
Novo-Medrone®,
Penta-Medroxyprogesterone®
Norplant®
Preven® b
Plan B® c
EE Ethinyl estradiol. a) Diane-35® is indicated for the treatment of women with
severe acne vulgaris and should not be prescribed solely for its contraceptive
properties (5); b) Preven® was introduced to the Canadian market in July
1999 and discontinued in August 2001; c) Plan B® was introduced to the
Canadian market in February 2000. The target-drugs were determined by literature review and advice of advisory panel.
Paediatr Child Health Vol 8 Suppl A April 2003
Injectable
Figure 2) Number of female claimants 11 years of age and older
dispensed contraceptive therapy by contraceptive method. Female
claimants are dispensed more oral than injectable contraceptives. A
very small number of female claimants had a claim for emergency
postcoital contraception and implants (data not shown). Oral contraceptives include estrogens, progestin, estrogen mono/biphasics
and triphasics. Injectable contraceptives include medroxyprogesterone
acetate
The rate of contraceptive use increased dramatically by age
from four per 1,000 active female claimants for the 11-yearolds to 450 for the 17-year-olds (Figure 1).
DRUG UTILIZATION
Utilization by contraceptive class
Oral contraceptives accounted for the largest proportion
(94%) of usage in this study (Figure 2). The injectable contraceptive, medroxyprogesterone acetate, was used by 9% of the
target drug claimants. In addition to conception control;
medroxyprogesterone acetate is also indicated for the treatment of endometriosis, and adjunctive and/or palliative treatment of recurrent and/or metastatic endometrial or renal cell
carcinoma (4). A very small proportion of contraceptive
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TABLE 2
Female (F) claimants aged 11 to 17 years prescribed oral contraceptives by number of prescriptions and single year of age
Prescriptions
1-3
4-6
7-9
10+
11 F
N = 61
n
21
6
8
26
%
34%
10%
13%
43%
12 F
N = 151
n
36
26
18
71
%
24%
17%
12%
47%
13 F
N = 593
n
94
68
88
343
%
16%
11%
15%
58%
14 F
N = 2,057
n
229
241
260
1,327
15 F
N = 5,234
%
11%
12%
13%
65%
n
458
509
639
3,628
16 F
N = 9,024
%
9%
10%
12%
69%
n
671
777
1,009
6,567
%
7%
9%
11%
73%
17 F
N = 12,075
Total claimants
N = 29,195
n
899
1,034
1,417
8,725
n
2,408
2,661
3,439
20,687
%
7%
9%
12%
72%
%
8%
9%
12%
71%
N Total number of claimants prescribed contraceptives; n Number of claimants by number of prescription; % Percentage of claimants by number of prescriptions (n/N)
Claimants by number of oral contraceptive cycles
According to the Committee on Adolescent Health Care of
American College of Obstetricians and Gynecologists, adolescents are more likely to miss taking OC tablets than adults
and may not take OC consistently depending on their pattern of sexuality (3). The purpose of the following analysis is
to show the extent to which teenage girls remain on oral contraceptives during a 12-month period. To ensure a consistent
year of analysis, the study period commenced with the first
claim for an OC and only female claimants who were present
in the study database after the 12-month study period were
included.
32A
Triphasic Oral Contraceptives
Injectable Contraceptives
Total claimants ('000)
Utilization by drug product (trade name)
Tri-Cyclen® was the top oral contraceptive, prescribed to 30%
of female contraceptive users aged 11 to 17 years. Tri-Cyclen®
is a triphasic oral contraceptive that is indicated for the treatment of moderate acne in addition to conception control.
Triphasil 28 and 21 and Triquilar 28, all triphasic contraceptives, were used by 8%, 2% and 4%, respectively.
Alesse®, a more recently introduced monophasic oral contraceptive, was ranked second among oral contraceptives (21%
of target drug claimants). Another monophasic contraceptive,
Marvelon® was used by 14%, other monophasic OCs were
each used by less than 5% of the female contraceptive
claimants older than 10 years of age. Diane-35® was used by
8% of women prescribed contraceptives. This product is an
effective contraceptive, although it is indicated for the treatment of severe acne (5).
Tri-Cyclen®, Marvelon® and Alesse®, top three drugs for
adolescents, were also the top three drugs used by adult women
in the study database. The individual drug products do not
appear to be prescribed differentially based on patient age.
Depo-Provera (medroxprogesterone), an injectable contraceptive, was the only non-oral contraceptive included among
the top 10 products (Figure 3). Depo-Provera®, which ranked
sixth, was used by 7% of girls aged 11 to 17 years who had a
claim for a contraceptive.
12
10
8
Monophasic Oral Contraceptives
Hormonal Therapy for Acne
Biphasic Oral Contaceptives
6
4
2
0
Tr
i-C
yc
le
Al n
es
M
ar se
ve
D lon
ia
Tr ne
ip -3
D ha 5
e p si
o- l 2
8
P
T r ro v
iq era
ui
la
r2
C 8
y
M cl e
in
n
Tr -Ov
ip
r
a
ha
l
s
D il 21
em
ul
en
Sy O v r
Lo n
a
es ph l
tri as
i
n
1. c
5/
30
claimants (less than 1%) had a claim for an emergency contraceptive (data not shown). None of the girls in the study were
dispensed an implant.
Figure 3) Number of female claimants 11 years of age and older dispensed contraceptive therapy by drug product (trade names). Drugs
dispensed to less than 2% of the total claimants on contraceptive therapy are not shown. Tri-Cyclen® was prescribed to the largest number
of female claimants aged 11 years and older. Alesse®, Marvelon®,
Diane-35® and Triphasil 28® are ranked second, third, fourth and
fifth in the list of drugs dispensed to the largest number of female
claimants. The only injectable contraceptive in the study is DepoProvera® and is ranked sixth among all contraceptives dispensed to
girls aged 11 years and older
Most of the girls on oral contraceptives were dispensed 10
or more cycles over the 12-month study period (Table 2). The
proportion of female claimants with 10 or more prescriptions
for oral contraceptives increased by age ranging from 43% of
the 11-year-olds to 72% of the 17- year-olds. This is a high rate
of continuation relative to many other therapeutic areas.
SUMMARY FINDINGS
1. 19% of all female claimants aged 11 to 17 years had at
least one prescription for hormonal contraceptives. Most
of these girls were 15 years of age and older.
2. Oral contraceptives were the preferred method of
hormonal birth control used by girls in the study
(94%). Tri-Cyclen® was the top oral contraceptive
followed by Alesse® and Marvelon®.
3. Most of the girls taking contraceptives were dispensed
10 or more cycles during the 12-month period.
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Prescription medicine use in Canadian children
Expert Comment – Hormonal Contraceptives
Sari Kives MD, Adolescent and Paediatric Gynecologist, Department of Obstetrics and Gynecology,
Saint Michael's Hospital, Toronto, Ontario
The oral contraceptive pill (OCP) is the most frequently used contraceptive among Canadian women aged 15 to
44 years according to the most recent Canadian consensus on contraception (1998) (1). It is therefore not surprising that
the OCP was also the most frequently used contraceptive among this population of Canadian paediatric drug claimants in
this database evaluation (1999/2000).
Oral contraceptive pills accounted for the largest proportion of females (94%) between the ages of 11 and 17 years
claiming one of the contraceptive target drugs. Overall, the rate of use of contraceptive therapy among female subjects 11
to 17 years of age in the study database was 19%. A much smaller percentage of females less than 12 years of age were on
contraceptive therapy (less than 1% of the total female claimants in the study database).
Often adolescents are initiated on contraceptive therapy for its non-contraceptive benefits. The use of contraceptives
in this younger age group likely reflects adolescents on the OCP or DMPA to help control dysmenorrhea and menorrhagia rather then to prevent pregnancy. It is safe to consider the OCP or DMPA for the adolescent who is menstruating
regardless of age to help regulate menses. Often parents with children with special needs seek control of their menses prior to the onset of puberty in anticipation of difficulties. It is advisable however, to wait until menarche occurs prior to initiating a contraceptive therapy.
Tri-Cyclen®, Marvelon®, and Alesse® were the three most frequently used OCP in adolescents in this study. We must
not forget however, that all OCPs provide contraception as well as non-contraceptive benefits regardless of formulation.
DMPA was prescribed much less frequently as compared to the OCP in this paediatric study. This finding is consistent
with the Canadian consensus where in fact only 1% of women aged 15 to 44 years of age selected an injectable form of
contraceptive therapy (1). Unlike the Canadian consensus study, in this population DMPA accounted for 9% of the target drugs prescribed to females between the ages of 11 and 17 years. This notable difference in DMPA use between the two
study groups may reflect a prescription bias, as DMPA is often prescribed to improve compliance in this difficult adolescent population. Furthermore, DMPA is often selected as the primary method of controlling menses in the younger mentally disabled patient, as a frequent side effect is amenorrhea. Emergency contraception was prescribed very infrequently
in this study group. This may reflect either poor awareness of this effective method of pregnancy prevention or more likely the frequent use of sample packs of OCPs as a method of dispensing emergency contraception.
Finally OCP compliance as suggested by the number of female patients claiming 10 or more prescriptions of oral contraceptives increased with age from 58% at 13 years to 72% at 17 years. This presumed compliance was based on prescriptions filled and is greater than the literature reports. In fact in a recent retrospective study by Zibners et al (2), the
continuation rate at one year was only 12% for the OCP and 45% for DMPA. This large discrepancy in contraceptive
compliance between this study and Zibners’s retrospective study demonstrates the inaccuracy of relying on prescriptions
filled as a measure of compliance. At present, prescribing practices in adolescents are very similar to the adult population
in this therapeutic category. Adolescents are notoriously non-compliant and we as providers must continuously look for
new methods to improve their compliance.
REFERENCES
1. The Canadian Consensus Conference on Contraception. SOGC May 1998;20(5), May (2) 1998;20(6), June 1998;20(7), June
1998;20(8).
2. Zibners A, Cromer B, Hayes J. Comparison of continuation rates for hormonal contraception among adolescents. J Pediatric Adolesc
Gynecol 1999;12:90-4.
Paediatr Child Health Vol 8 Suppl A April 2003
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Abi Khaled et al
4.4
100%
4.0
TARGET DRUG LIST
The target drug list included all stimulants that are indicated
for the treatment of ADHD (1) as listed in Table 1.
CLAIMANT DEMOGRAPHICS
There were 33,882 children in the study database who were
dispensed methylphenidate or dextroamphetamine (3% of the
TABLE 1
Stimulant target drugs
Drug
Methylphenidate
Dextroamphetamine
Pemolinea
Primary
indication
ADHD
Age restriction
Ritalin® monograph: “Methylphenidate should not be
used in children under 6 years of age, since safety and
efficacy in this age group have not been established”.
Dexedrine® monograph: “Amphetamines are not
recommended for use in Attention-Deficit Hyperactivity
Disorder in children under 6 years of age”.
a) Withdrawn from market September 1999 due to reports of fatal liver disease, however was in use during study period. The target-drugs were
determined by literature review and advice of advisory panel. Indication
and age restriction from Compendium of Pharmaceuticals and Specialities,
2001 (1)
34A
90%
Total claimants ('000)
3.6
80%
3.2
70%
2.8
60%
2.4
50%
2.0
40%
1.6
% Female
1.2
30%
0.8
20%
0.4
10%
0.0
0%
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17
Age
Figure 1) Number of claimants prescribed stimulants by age (bars)
and percent age of claimants by sex (lines). Most claimants prescribed
stimulants were between the ages of seven and 15 years. The number
of claimants on stimulants reaches a peak at age nine and then
decreases. There were very few claimants aged one year and less prescribed stimulants (not shown). The number of male claimants
exceeded that of female claimants for each age group
80
Rate of use per 1,000 active claimants
Stimulants are a class of psychotropic medication indicated for
the treatment of attention deficit hyperactivity disorder
(ADHD) and narcolepsy (1).
ADHD is a cognitive-behavioural syndrome characterized
by developmentally inappropriate hyperactivity, inattention,
impulsivity and distractibility (2,3). ADHD affects 3% to 5%
of children aged 18 years and younger (2,4,5). The condition
becomes evident in preschool or early elementary school years
and generally persists into adolescence (4). It is, however, usually diagnosed between the ages of eight and 10 and found
more frequently in boys, with two to three times more boys
than girls being diagnosed with ADHD (2,4-6).
Methylphenidate and dextroamphetamine are the recommended first line treatments for ADHD (3,7-9) and are effective in more than 70% of ADHD patients in improving the
core symptoms of inattention, impulsivity and hyperactivity
(7-9). Pemoline, a third stimulant, was available but was
removed from the Canadian market in September 1999
because of hepatotoxicity associated with its use (10). A number of other new drugs to treat ADHD are also reportedly in
development or have applied for Health Canada approval.
Methylphenidate is much more widely prescribed than dextroamphetamine, and according to Health Canada data, annual consumption of methylphenidate increased by 500%
between 1990 and 1997 (11). Another study showed an
increase in methylphenidate prescriptions to children younger
than 20 years in British Columbia from 0.2% in 1990 to 1.1%
in 1996 (12).
The marked increases in the use of stimulants for children
during the 1990s has resulted in public health concerns about
the frequency and appropriateness with which these medications
are prescribed to children (12). However, children with ADHD
who are not treated appropriately may suffer long term effects
and may develop other emotional or mental health problems.
Other drugs such as antidepressants and antipsychotics
have reportedly been used to treat ADHD (13-16). An anlysis
of specific psychotropic drugs in combination with stimulants
is also presented.
% Male
% claimants/gender
STIMULANTS
70
60
50
40
30
20
10
0
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17
Age
Figure 2) The rate of use of stimulants per 1,000 active claimants.
The rate of use increases by age and reaches a peak at ages 10 and
11 years with more than 75 claimants per 1,000 active claimants
prescribed these drugs. The rate of use for claimants aged one year
and younger is very small (not shown)
1.03 million claimants in the study). Nearly 7% of these were
two to six years of age, over 62% were seven to 12 years and
31% were 13 to 17. Stimulants are not recommended for use in
children younger than six years of age.
Among children dispensed stimulants, 80% were boys
(Figure 1). A similar age-sex pattern was reported by a study of
children in Manitoba (6).
The rate of stimulant use per 1,000 active claimants
increased with age, from 0.4 per 1,000 active claimants for the
two-year-olds to a peak of 80 per 1,000 active claimants at ages
10 and 11 years, then declined to 17 for the 17-year-olds
(Figure 2).
DRUG UTILIZATION
Utilization by drug
Methylphenidate was dispensed to 28,900 children or approximately 85% of all children dispensed a stimulant (Table 2).
Other studies reported that methylphenidate was much more
widely prescribed than dextroamphetamine (5,9,16,17), a
finding that is borne out in the current study.
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Prescription medicine use in Canadian children
TABLE 2
Distribution of claimants by drug and age
Methylphenidate
Dextroamphetamine
nch
1,921
372
7-12 years
N = 21,405
%
88%
17%
nch
19,029
3,331
13-17 years
N = 10,289
%
89%
16%
nch
7,991
2,699
%
78%
26%
Total claimants
(<1-17 years)
N = 33,882
Adult claimants
(18-65 years)
N = 10,684
nch
28,947
6,404
nch
7,565
3,507
%
85%
19%
35%
30%
%
71%
33%
N Total number of claimants prescribed stimulants; nch Number of claimants by
chemical; % Percentage of claimants by drug within age group (nch/N). The
sum of claimants and percentage by age group does not total, because one
claimant can be dispensed multiple drugs in the same year
25%
% claimants
2-6 years
N = 2,180
Drug
20%
15%
10%
5%
2.2
0%
2.0
0-30
Total claimants ('000)
1.8
31-90
91-182
183-272
272-365
Days of therapy
1.6
1.4
Existing
New to Therapy
1.2
1.0
0.8
0.6
0.4
0.2
0.0
2
3
4
5
6
7
8
9
10 11 12 13
14 15 16 17
Figure 4) Percentage of claimants prescribed stimulants by the number
of days they remain on therapy based on their drug use history (existing,
new-to-therapy). Existing claimants had more days of therapy during
the index period compared with new-to-therapy claimants. Because no
history on the new-to-system claimants exists, these were excluded from
this analysis
Age
Existing
New to therapy
New to system
Figure 3) Number of claimants prescribed stimulants by age based on
their drug use history (existing, new-to-therapy and new-to-system).
Claimants counted are only those with the field “days supplied” available
in their claim records and thus the sum of these claimants does not total
the number of claimants dispensed a target stimulant. New-to-therapy
and new-to-system are largest share for claimants younge than seven
years. Claimants continuing therapy are greater for eight years and older
On average, dextroamphetamine was used by 19% of the
children dispensed a stimulant. However, a relatively higher
proportion of children 13 to 17 used dextroamphetamine than
observed for the younger age groups. Approximately 26% of
the 13- to 17-year-olds receiving a stimulant were dispensed
dextroamphetamine compared with 16% for those younger
than age of 13 years.
Only 0.4% of stimulant claimants received pemoline, a
drug that was withdrawn from the Canadian market on
September 30, 1999 (near the start of the study period).
Depending on the age group, between 4% and 5% of children were dispensed both methylphenidate and dextroamphetamine during the 12-month study period, likely a result of
claimants switching drugs rather than using both drugs simultaneously (data not shown).
Pattern of Use
Claimants can be split into those commencing therapy in the
study year versus those who are continuing therapy underway
in the previous year. (See Methodology section for details).
The number of children in both the new-to-therapy and newto-system classes (i.e., likely initiating therapy) were larger
than the number of claimants who were continuing therapy for
children younger than eight years of age. The number of existing claimants was the largest proportion of children for each
age older than eight. Although there were claimants initiating
therapy in every age group, the number reaches a maximum by
age eight, then declined with age. This is expected because
ADHD is frequently diagnosed early in life and requires treatment for several years (2-5).
Paediatr Child Health Vol 8 Suppl A April 2003
Experts recommend that drug therapy for ADHD be interrupted once symptoms are controlled or when the child is
under less stress (1). The number of days of therapy covered by
dispensed prescriptions was analyzed for the 12-months following the index claim for each claimant during the study period.
This was used to estimate the extent to which interruptions in
therapy occur in practice. This analysis was conducted separately for existing and new-to-therapy claimants. (See
Methodology section).
Data showed that a large proportion of children do not
receive a drug supply sufficient to meet a full year of therapy,
even considering breaks in therapy (Figure 4).
For example, 30% of existing claimants had 272 to 365 days
of therapy compared with 20% of those who had initiated therapy in the year. About the same proportions of new and existing patients (roughly 55%) had between 91 and 272 days of
therapy. Only 12% of existing claimants had 90 days or less
while 23% of new-to-therapy claimants had only a short duration of treatment. It appears that newly started children are
more likely to take long breaks or stop therapy than those who
have been receiving treatment for a longer period of time.
Concomitant psychotropic drug use
Stimulants (methylphenidate and dextroamphetamine) have
been shown to be effective in approximately 70% of children
in controlled, short term studies (9). Some children are less
responsive or have comorbid conditions with ADHD such as
depression, anxiety, obsessive compulsive disorder, conduct
disorder and bipolar disorder (7,13-16). Other psychotropic
drugs, although not approved for ADHD by Health Canada in
1999/2000, are reportedly used in conjunction or in place of
stimulants in the treatment of ADHD and related symptoms
(7,13-16).
The extent to which selected psychotropic drugs are used in
conjunction with stimulants is analyzed in this section. For the
purposes of this analysis, concomitant psychotropic drugs are
defined as antipsychotics, antidepressants, anticonvulsants and
clonidine.
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Methylphenidate
concomitant
psychotropic
10%
Methylphenidate
non-concomitant
psychotropic
3%
Dextroamphetamine
concomitant psychotropic
TABLE 4
Distribution of claimants prescribed psychotropic drugs
concomitantly by age
Dextroamphetami
ne nonconcomitant
psychotropic
7%
22%
Methylphenidate
2-12 years
N=1,956
Concomitant drug
Methylphenidate
no psychotropic
87%
Dextroamphetamine no psychotropic
71%
Total methylphenidate claimants: 28,366
Stimulant
Concomitant
psychotropic
12%
Total dextroamphetamine claimants: 6,105
Stimulant nonconcomitant
psychotropic
3%
Stimulant no
psychotropic
85%
Total stimulant claimants: 33,041
Figure 5) Distribution of claimants prescribed stimulants by drug therapy. Of all claimants dispensed a stimulant, 85% were not prescribed
target psychotropic drugs, 12% were prescribed a target psychotropic
drug concomitantly and 3% were prescribed a target psychotropic drug
but not concomitantly. Of methylphenidate claimants, 87% were not
prescribed target psychotropic drugs and 10% were prescribed concomitantly a target psychotropic drug. For dextroamphetamine, 71% were
not prescribed target psychotropic drugs and 22% used target psychotropic drugs concomitantly
TABLE 3
Distribution of claimants prescribed stimulants and other
psychotropic drugs concomitantly
Concomitant drug
Typical antipsychotics
Atypical antipsychotics
Anticonvulsants
SSRI
TCA
SNRI
Other antidepressants
Clonidine
Methylphenidate
N = 2,852
Claimants
133
665
324
653
287
43
160
1,087
%
5%
23%
11%
23%
10%
2%
6%
38%
Dextroamphetamine
N = 1,355
Claimants
55
375
130
383
106
20
126
444
%
4%
28%
10%
28%
8%
1%
9%
33%
N Total number of claimants prescribed stimulants; nch Number of claimants by
chemical, % Percentage of claimants by drug within age group (nch/N). The
sum of claimants and percentage by age group does not total, because one
claimant can be dispensed multiple drugs in the same year
On average, 12% of children dispensed a stimulant used a
concomitant psychotropic drug. However, this rate differed
dramatically depending on the stimulant used (Figure 5).
Almost 10% of methylphenidate users where dispensed concomitant drugs compared with 22% of dextroamphetamine
claimants. Note that 85% of stimulant claimants did not
receive any other concomitant drugs (as defined above) during
the study period.
Among all the concomitant psychotropic drugs, clonidine was the most frequently used with 38% and 33% of
claimants dispensed concomitant clonidine with
methylphenidate or dextroamphetamine, respectively (Table
3). Clonidine has reportedly been used in combination with
methylphenidate to manage ADHD and stimulant-induced
insomnia (13,14). The next most common combinations
were with either an atypical antipsychotic or an SSRI.
Typical antipsychotics are recommended for either comorbid
tics or aggression (14-16), while SSRIs are recommended if a
child with ADHD also has comorbid major depression disorder or anxiety (15,16).
36A
Claimants
Typical antipsychotics
99
Atypical antipsychotics
453
Anticonvulsants
217
SSRI
345
TCA
218
SNRI
16
Other antidepressants
81
Clonidine
867
%
5%
23%
11%
18%
11%
1%
4%
44%
Dextroamphetamine
13-17 years
N=896
Claimants
32
197
107
308
69
27
79
220
%
4%
22%
12%
34%
8%
3%
9%
25%
2-12 years
N=780
Claimants
35
227
70
163
81
12
49
307
13-17 years
N=575
% Claimants
4%
21
29%
148
9%
60
21%
220
10%
26
2%
10
6%
77
39%
137
%
4%
26%
10%
38%
5%
2%
13%
24%
N Total number of claimants prescribed the stimulant concomitantly with any
psychotropic drug and by age; claimants Number of claimants prescribed stimulants with the concomitant drug by age; % Percentage of claimants prescribed
a stimulant with a concomitant drug; SSRI Selective serotonin reuptake
inhibitors; TCA Tricyclic antidepressants; SNRI Selective norepinephrine reuptake inhibitors
TABLE 5
Distribution of claimants prescribed psychotropic drugs
concomitantly by sex
Methylphenidate
N= 2,786a
Concomitant drug
Typical antipsychotics
Atypical antipsychotics
Anticonvulsants
SSRI
TCA
SNRI
Other antidepressants
Clonidine
M
n=2,219
Claimants
%
103
5%
556
25%
247
11%
455
21%
218
10%
30
1%
130
6%
903
41%
F
n=567
Claimants
30
97
75
173
62
12
12
164
Dextroamphetamine
N= 1,321a
%
5%
17%
13%
31%
11%
2%
2%
29%
M
n=1,063
Claimants
%
42
4%
329
31%
102
10%
283
27%
76
7%
12
1%
97
9%
352
33%
F
n=258
Claimants
%
11
4%
38
15%
27
10%
91
35%
29
11%
8
3%
8
3%
78
30%
a) the number of claimants excludes claimants with an ‘unknown’ reported sex
N Total number of claimants prescribed the stimulant concomitantly with any
psychotropic drug; claimants Number of claimants prescribed stimulants with
the concomitant drug; % Percentage of claimants prescribed a stimulant with a
concomitant drug; SSRI Selective serotonin reuptake inhibitors; TCA Tricyclic
antidepressants; SNRI Selective norepinephrine reuptake inhibitors
Atypical antipsychotics were prescribed in combination
with a stimulant to 23% and 28% of the total claimants receiving concomitant psychotropic drugs with methylphenidate
and dextroamphetamine, respectively, compared with less than
5% for typical antipsychotics.
In general, the use of concomitant therapies was relatively
constant across age groups. Just over 9% of claimants younger
than 12 years of age who received methylphenidate had concomitant psychotropic therapy compared with about 11% for
13- to 17-year-olds. For dextroamphetamine, there was no difference with about 21% of each age group receiving concomitant therapy.
The same three concomitant drug groups were most used
regardless of age (Table 4). Clonidine was most frequently used
for those younger than 12 years while SSRIs were used most frequently in older children (13 to 17 years of age) with both
methylphenidate and dextroamphetamine. Atypical antipsychotics were the second most frequently used concomitant therapy for the younger than 12 year age group followed by SSRIs.
Although the rate of use of concomitant medications did
not vary between sexes, the class used did differ. Clonidine and
atypical antipsychotics were the top two concomitant medications for boys, possibly due to the need to treat aggression and
hyperactivity in these children (Table 5). For girls, SSRIs were
the most commonly used concomitant medication.
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Prescription medicine use in Canadian children
SUMMARY FINDING
1. 3% of claimants in the study population received at least
one prescription for a stimulant. Most stimulant
claimants were boys seven to 12 years of age.
2. Methylphenidate was the leading stimulant, used by
approximately 85% of children in all age groups.
3. Data in this study showed that children were more likely
to start stimulant therapy before the age of eight.
4. Most children were using stimulant therapy alone with
no other psychotropic medications. Only 12% of
children dispensed a stimulant used a concomitant
psychotropic drug. Clonidine was the most used
concomitant medication followed by SSRIs and
antipsychotics. The ranking of these concomitant classes
varied with both age and sex.
Expert Comment – Stimulants
Anton R Miller MB ChB FRCPC, Clinical Associate Professor, Department of Pediatrics, (Division of
Developmental Pediatrics), University of BC; The Centre for Community Child Health Research,
Children's and Women's Health Centre of BC
The main issue of concern in relation to the prescription of stimulants to children revolves around the extent and appropriateness of their prescription. This includes concerns about the extent of prescription of methylphenidate (MPH) to
children younger than 6 years, which represents ‘off label’ prescribing. Other issues include lack of evidence of safety, and
to a lesser extent, efficacy, for these drugs when used over the long-term. There are also questions of safety when stimulants are used in combination with other psychotropic drugs. Finally, there is some consternation in Canada at a lack of
availability of certain once-daily preparations, such as Adderall®.
In terms of the results presented, the one year prevalence figures presented (3% for children less than 18 years, and
7.5% for children between 9 and 10 years of age) are higher than one might expect from published and in-progress population-based studies from British Columbia and Manitoba. This likely results from the fact that the current study is not
population-based. The rate of use data in the present study may overestimate the prevalence in the general population.
Furthermore, dextroamphetamine (DEX) prescription has increased at the expense of MPH in certain provinces, such
as British Columbia. It would be interesting to examine in more detail provincial trends in relative utilization of the major
drugs, and in overall utilization prevalence.
The age distribution of children on stimulants is not news, but it should make us pause and think about the 8 -12 year
peak for a condition that is by definition present prior to age 7 and increasingly described as persisting into adolescence
and adulthood. What is happening in children’s lives to necessitate medication treatment at these ages, and what happens
when they no longer continue to take it? The tendency of newly-prescribed patients to spend fewer days on medication
than existing patients, also raises questions about the circumstances surrounding initiation of stimulant medications.
The relatively high rate of concomitant use of MPH with clonidine does raise some concerns, given sporadic reports of
adverse effects from this combination.
Comforting findings are that the data presented are not markedly different from other jurisdictions, and that rates of
concomitant drug use is no higher than 13% of cases.
Future research should look at the issues highlighted above, as well as the following: (1) What kind of clinical assessment do children receive prior to starting stimulant medication? (2) are management plans drawn up that look at overall
needs and other kinds of interventions? (3) what is the safety and effectiveness profile of multiple drug regimens? and (4)
what are the reasons for DEX’s relatively higher use among older children and youth, compared with MPH, and among
those on more than one psychotropic agent?
My understanding of the formal indications for use of the stimulant drugs in children are: (1) attention-deficit/hyperactivity disorder (ADHD); and (2) narcolepsy (rarely). However the stimulants are also quite commonly prescribed in
management of (3) non-specific disruptive and/or aggressive behavior problems; (4) disruptive and/or aggressive behavior that is part of conduct disorder or oppositional-defiant disorder; (5) learning difficulties of various kinds; and (6) as an
enhancer of academic performance in presence of attentional difficulties (sometimes).
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Abi Khaled et al
TARGET DRUG LIST
The target drug list included all the antidepressant medications listed in Table 1. These agents were classified based on
their respective mechanisms of action into four therapeutic
classes.
4.0
100%
3.5
90%
% Male
60%
2.0
50%
TABLE 1
Antidepressant target drugs
Class
Selective Serotonin Reuptake
Inhibitors (SSRI)
Selective Norepinephrine Reuptake
Inhibitors (SNRI)
Tricyclic antidepressants (TCA)
Monoamine Oxidase Inhibitors
(MAOIs)
Other
Drug
Citalopram HBr, fluoxetine HCl, fluvoxamine
maleate, paroxetine HCl, sertraline HCl
Venlafaxine
Amitriptyline HCl, amitriptyline HCl, amitriptyline
pamoate, clomipramine HCl, desipramine HCl,
doxepin HCl, imipramine, maprotiline HCl,
perphenazine protriptyline HCl, trimipramine
maleate, trimipramine
Isocarboxazid, moclobemide, phenelzine
sulfate, phenelzine, tranylcypromine sulphate
Amoxapine, bupropion, nefazodone HCl,
trazodone HCl
The target drugs were determined by literature review and advice of advisory
panel. Indication and age restriction from Compendium of Pharmaceuticals
and Specialities, 2001(1)
38A
40%
% Female
1.5
30%
1.0
20%
0.5
10%
0.0
0%
2
3
5
6
7
8
9 10 11 12 13 14 15 16 17
Age
Figure 1) Number of claimants prescribed antidepressants by age
(bars) and percentage of claimants by sex (lines). Most claimants
prescribed antidepressants were between the ages of 13 and 17 years.
There were too few claimants aged one year and younger for analysis.
The share of male claimants aged 13 years and younger is much higher than that of female claimants of the same ages. After age 13, girls
are a much greater share than boys
52
48
44
40
36
32
28
24
20
16
12
8
4
0
2
CLAIMANT DEMOGRAPHICS
Claimants prescribed antidepressants in the study database
accounted for 16,731 or less than 2% of the total 1.03 million
claimants in the study population. Approximately 70% were
13 to 17 years of age, 25% were 7 to 12 years and 5% were two
to six years of age (Figure 1). Claimants aged one year and
younger have been excluded from this analysis given their
small number (56 claimants).
Male claimants dominated the younger than 14 years age
groups while females were more prevalent in each single year
of age older than 14 years. A similar age-sex pattern was
reported by a study of children in Manitoba (11).
70%
2.5
% claimants/gender
80%
3.0
Rate of use per 1,000 active claimants
Antidepressants are psychotropic medications indicated for use
in the treatment of a variety of depressive illnesses. These may
also be indicated for a number of other conditions including
obsessive compulsive disorder (OCD), panic disorder, eating
disorders, bedwetting and chronic pain (1). Although not indicated in the product monographs, antidepressants are reportedly used in the treatment of ADHD (2-4).
According to the product monographs approved by Health
Canada, the efficacy and safety of the majority of antidepressants has not been established in children younger than 18
years of age. The use of imipramine in children five years and
older for enuresis is a notable exception (1).
Depression among children and adolescents reportedly
affects 2% of prepubertal children and 5% to 8% of adolescents. The sex ratio is equivalent in prepubertal children and
affects twice a many girls as boys in adolescence (5,6).
In addition to depression, OCD and ADHD are reportedly
being treated with antidepressants. OCD can start any time
from preschool age to adulthood (7,8), while ADHD affects
children between the ages of five and 12 years and is more
common in boys than girls (9). Enuresis, which can be treated
with imipramine, is another condition that is more prevalent
in young boys (10).
Total claimants ('000)
ANTIDEPRESSANTS
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17
Age
Figure 2) The rate of use of antidepressants per 1,000 active
claimants. The rate of use increases by age and reaches its highest at
52 per 1,000 active claimants aged 17 years. The rate of use for
claimants aged one year and younger is not shown
The rate of use of antidepressants per 1,000 active
claimants consistently increased with age, from approximately
0.5 per 1,000 active claimants for the two-year-olds to 52 for
the 17-year-olds (Figure 2).
DRUG UTILIZATION
The largest proportion of claimants dispensed antidepressants
(62%) were dispensed a selective serotonin reuptake inhibitor
(SSRI) (Table 2). The rate increased sharply with age with
36% of the two- to six-year-olds dispensed an SSRI, 49% for
the seven- to 12-year-olds and 68% for those 13 to 17 years.
The top three antidepressants, paroxetine (dispensed to
25% of antidepressant claimants), sertraline (18%) and fluoxetine (13%) are SSRIs (Figure 3). Two other SSRIs, citalopram
hydrobromide and fluvoxamine maleate were each used by 6%
of claimants dispensed antidepressants. These top three medicines overall were also the top three antidepressants for the 13
to 17 years age group (Table 3). These agents are indicated for
depression and OCD and none of them has been approved in
Canada for use in children (1). However these drugs “have
been used and continue to be studied in this age group. Further
Paediatr Child Health Vol 8 Suppl A April 2003
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Prescription medicine use in Canadian children
TABLE 2
Distribution of claimants by drug class and age
2-6 years
N = 673
Class
SSRI
SNRI
TCA
MAO
Other
n
239
15
377
0
57
%
36%
2%
56%
0%
8%
7-12 years
N = 4,291
n
2,102
120
1,889
**
408
%
49%
3%
44%
0%
10%
13-17 years
N = 11,730
n
7,961
836
2,325
41
1,818
%
68%
7%
20%
0%
15%
Total claimants
(<1-17 years)
N = 16,731
n
%
10,322
62%
972
6%
4,600
27%
45
0%
2,290
14%
N Total number of claimants prescribed antidepressants; n Number of
claimants by class; % Percent of claimants within the age group (n/N). **fewer than 6 claimants. SSRI Selective serotonin reuptake inhibitors; SNRI
Selective norepinephrine reuptake inhibitors; TCA Tricyclic antidepressants,
MAOI Monoamine oxidase inhibitors. The sum of claimants and percentage
by age group does not total, since one claimant can be dispensed multiple
drugs in the same year
Total claimants ('000)
SSRI
4.4
TCA
4.0
SNRI
3.6
Other
3.2
2.8
2.4
2.0
1.6
TABLE 3
The top 10 antidepressants (by claimant count) by drug
and age
Drug
Paroxetine a
Sertraline a
Fluoxetine a
Amitriptyline b
Imipramine c
Bupropion a
Citalopram HBr a
Fluvoxamine a
Venlafaxine a
Trazodone a
2-6 years
N = 673
nch
87
60
76
83
258
37
14
16
15
14
7-12 years
N = 4,291
R
2
5
4
3
1
6
9/10
7
8
9/10
nch
705
612
534
529
1092
255
93
314
120
110
R
2
3
4
5
1
7
12
6
10
11
13-17 years
N = 11,730
nch
3,398
2,373
1,506
1,417
482
1,128
883
656
836
497
R
1
2
3
4
10
5
6
8
7
9
Total claimants
(<1–17 years)
N = 16,731
nch
4,199
3,049
2,118
2,034
1,834
1,425
994
986
972
621
R
1
2
3
4
5
6
7
8
9
10
Adult claimants
(18-65 years)
N = 560,013
nch
136,000
72,470
58,137
99,578
7,202
90,559
51,923
15,880
57,740
35,752
R
1
4
5
2
13
3
7
10
6
8
a) Paxil®, Zoloft®, Prozac®, Wellbutrin® SR, Celexa®, Effexor®, and
Desyrel®monographs: "Safety and effectiveness in children below the age of
18 have not been established"; b) Elavil monograph: "In view of the lack of
experience with the use of this drug in the treatment of depression in children,
amitriptyline is not recommended for depressed patients younger than 12
years of age"; c) Tofranil® monograph: "Effectiveness of imipramine in children for conditions other than nocturnal enuresis has not been established.
The safety and effectiveness of the drug as temporary adjunctive therapy for
nocturnal enuresis in children younger than five years of age has not been
established". N Total number of claimants prescribed antidepressant drugs;
nch Number of claimants by chemical; R Rank in each age group by number
of claimants. Indication and age restriction from Compendium of
Pharmaceuticals and Specialities, 2001 (1)
1.2
0.8
0.4
Pa
r
ox
et
Se ine
rtr
al
in
Fl
uo e
x
Am eti
itr ne
ip
Im tylin
e
ip
ra
m
Bu ine
C
pr
it
op
Fl
uv alo
i
ox pra on
am m
HB
in
e
r
m
a
Ve lea
t
nl
af e
a
Tr xin
e
a
C zod
lo
m one
ip
r
N am
ef
i
az ne
D odo
es
ne
ip
ra
m
N
in
or
e
tri
pt
yli
ne
0.0
Figure 3) Number of claimants prescribed antidepressants by drug.
Drugs prescribed to less than 1% of the total claimants on antidepressants are not shown. The top three antidepressants dispensed to
the largest number of claimants are paroxetine, sertraline and fluoxetine, all three selective serotonin reuptake inhibitors (SSRIs).
SNRI Selective norepinephrine reuptake inhibitors; TCA Tricyclic
antidepressants; MAOI Monoamine oxidase inhibitor
experience with these agents in children is expected to result
in specific guidelines for their use in this group” (1).
The class of tricyclic antidepressants (TCAs) was used by
27% of claimants prescribed antidepressants but were more likely to be used for claimants two to six years of age (56%). Only
20% of 13- to 17-year-olds were dispensed a TCA (Table 2).
The TCAs with the largest number of claimants, amitriptyline and imipramine, were used by 12% and 11% of the antidepressant claimants, respectively. Amitriptyline was ranked
fifth among all antidepressants for claimants between seven
and 12 years of age and ranked third for those in the two to six
years age group (Table 3). Amitriptyline is not recommended
for children younger than 12 years (1). Imipramine, however,
was the top antidepressant dispensed to children 12 years of
age and younger (Table 3). Of the children dispensed
imipramine, 74% were two to 12 years of age. Imipramine is
the only antidepressant indicated for nocturnal enuresis (1);
however, “the safety and effectiveness of this drug in children
younger than 5 years of age have not been established” (1).
Desmopressin acetate (DDAVP), an antidiuretic, is another
drug used for the management of nocturnal enuresis (1).
Results using the same paediatric database showed that the
age-sex distribution of children using DDVAP was similar to
that for imipramine. Both of these drugs were mostly used by
boys seven to 12 years of age.
Paediatr Child Health Vol 8 Suppl A April 2003
The ‘other’ antidepressants, bupropion, trazodone and nefazodone were used by 9%, 4% and 2% of all antidepressant
claimants, respectively. Bupropion has reportedly been used in
ADHD in addition to its use for the symptomatic relief of
depressive illness (2-4).
Venlafaxine, the only SNRI, was used by 6% of antidepressant claimants, the majority of them were in the 13 to 17 year
age group.
Very few children in the study (less than 100) received an
antidepressant belonging to the monoamine oxidase inhibitor
class.
SUMMARY FINDINGS
1. 2% of claimants in the study population had at least one
claim for antidepressant drugs. Most antidepressant
claimants in the study population were 13 years of age and
older with more girls than boys. For children 12 years of
age and younger, there were more boys than girls
prescribed antidepressants
2. The use of different classes of antidepressants varied with
age. SSRIs were more likely to be prescribed to the
13- to 17-year-olds, while the use of TCAs was more
prevalent in the younger age groups, with imipramine as
the agent used by the single largest number of claimants
ANTIPSYCHOTICS
Antipsychotic drugs are indicated for the treatment of schizophrenia and related psychiatric symptoms including agitation,
hyperactivity and aggression (1-4). In children, both typical
and atypical antipsychotic medications are used in the treatment of tics, behavioural problems in autism and ADHD, psychotic illness including childhood schizophrenia, and conduct
disorder (2-4).
Both schizophrenia and conduct disorder usually develop in
late childhood or early adolescence (5,6). In contrast, autism is
generally detectable by the age of three years and affects as
many as one child per 286 births in Canada (7). These conditions are much more common in boys than girls (5-7).
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Abi Khaled et al
Typical Antipsychotics
Atypical Antipsychotic
Chlorpromazine, enanthate, flupenthixol,
fluphenazine, fuphenazine decanoate haloperidol,
loxapine succinate, mesoridazine besylate,
methotrimprazine palmitate, pericyazine,
perphenazine, pimozide, pipotiazine,
prochlorperazine, thioridazine, thiothixene,
trifluoperazine, zuclopenthixol acetate, zuclopenthixol
decanoate, zuclopenthixol dihydrochloride
Clozapine, olanzapine, quetiapine fumerate,
risperidone
The target drugs were determined by literature review and advice of advisory
panel
Class
n
238
201
Atypical antipsychotics
Typical antipsychotics
%
57%
48%
7-12 years
N = 1,671
n
1,371
411
%
82%
25%
13-17 years
N = 1,774
n
1,467
458
%
83%
26%
Total
claimants
(<1-17 years)
N = 3,873
n
3,080
1,077
%
80%
28%
N Total number of claimants prescribed antipsychotics; n Number of claimants
by class; % Percentage of claimants within the age group (n/N). **fewer than
6 claimants. The sum of claimants and percentage by age group does not
total, because one claimant can be dispensed multiple classes of antipsychotics in the same year
TABLE 3
The top 10 antipsychotics (by claimant count) by drug and
age group
Drug
Risperidone a
Olanzapine a
Thioridazine HCl b
Pimozide c
Haloperidol d
Quetiapine fumarate a
Methotrimeprazine
Chlorpromazine HCl e
Pericyazine f
Loxapine succinate g
2-6 years
N = 417
nch
229
10
145
**
7
**
24
8
12
**
R
1
5
2
N/A
7
N/A
3
6
4
N/A
7-12 years
N = 1,671
nch
1,282
112
161
79
46
32
33
30
62
**
R
1
3
2
4
6
8
7
9
5
N/A
13-17 years
N = 1,774
nch
1,166
329
76
58
88
83
59
77
32
33
R
1
2
6
8
3
4
7
5
10
9
Total
claimants
(<1-17 years)
N = 3,873
Adult claimants
(18-65 years)
N = 32,008
nch
2680
452
386
142
141
118
117
116
106
41
nch
8,946
8,643
896
660
2,353
2,462
4,175
2,024
60
1,562
R
1
2
3
4
5
6
7
8
9
10
R
1
2
11
12
5
4
3
6
21
10
a) Risperdal® tablets, Zyprexa®, and Seroquel® monographs: "The safety and
efficacy in children younger than the age of 18 years have not been established"; b) Mellaril® monograph: "Thioridazine should not be given to children
under 2 years of age"; c) Orap® monograph: "Safety and effectiveness in children have not been established; therefore, this drug is not recommended for
use in the paediatric age group"; d) Haldol® monograph: "Safety and effectiveness in young children have not been established; therefore, haloperidol is
contraindicated in this age group"; e) Chlorpromazine HCl general monograph: "The safety and efficacy of chlorpromazine in children less than 6
months of age has not been established"; f) Neuleptil® monograph:
"Pericyazine is not recommended in children under 5 years of age, since limited clinical experience is available"; g) Loxapac® monograph: "Studies have
not been performed in children; therefore, this drug is not recommended for
use in children below the age of 16". N Total number of claimants prescribed
antipsychotic drugs; nch Number of claimants by chemical; R Rank of drug in
each age group by number of claimants. **fewer than six claimants. Indication
and age restriction from Compendium of Pharmaceuticals and Specialities,
2001 (1). The order of drugs used in the table is based on the ranking of these
drugs depending on the total claimants
Aggression in children is a major public health concern
and a significant cause of morbidity and mortality (8,9).
Several diagnoses are associated with aggression such as conduct disorder, substance abuse, autism and other pervasive
developmental disorders (8-14). Several studies have reported
that aggression was the main target symptom for treatment
with antipsychotic drugs, especially risperidone and clozapine
(8,10-13).
40A
4.0
100%
3.5
90%
80%
% Male
3.0
70%
2.5
60%
2.0
50%
% Female
1.5
40%
30%
1.0
20%
0.5
10%
0.0
0%
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age
TABLE 2
Distribution of claimants prescribed antipsychotics by
drug class and age
2-6 years
N = 417
Total claimants ('000)
Drug
Figure 1) Number of claimants prescribed antipsychotic drugs by age
(bars) and percentage of claimants by sex (lines). Most claimants
prescribed antipsychotics were between the ages of 13 and 17 years.
There were very few claimants aged one year and younger prescribed
antipsychotics (not shown). The share of male claimants exceeded
that of females claimants across all ages
7
Rate of use per 1,000 active claimants
Class
% claimants/gender
TABLE 1
Antipsychotic target drugs
6
5
4
3
2
1
0
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17
Age
Figure 2) The rate of use of antipsychotic drugs per 1,000 active
claimants. The rate of use increases with age and reaches its peak at
age 13 with seven claimants per 1,000 active claimants prescribed a
target antipsychotic drug. The rate of use for claimants aged one year
and younger is very small (not shown)
TARGET DRUG LIST
The agents identified for this analysis fall into the two classes:
atypical and typical antipsychotics as listed in Table 1.
CLAIMANT DEMOGRAPHICS
There were a total of 4,013 (0.4%) children in the database
who were dispensed an antipsychotic. Approximately 46% of
the antipsychotic claimants were 13 to 17 years of age, 43%
were seven to 12 years and 11% were two to six years (Figure 1).
The number of claimants aged one year and younger was too
small to evaluate (11 claimants).
In all age groups, there were more male than female
claimants (Figure 1). A similar finding was reported by a study
based on Manitoba children in which all age groups, except
the younger than four years age group, had more antipsychotic
use in boys than girls (15).
Compared with stimulant and antidepressant use, the rate
of antipsychotic use was low in all age groups, ranging from 0.6
per 1,000 active claimants in the two-year-olds to a high of
seven per 1,000 active claimants in the 13-year-olds (Figure 2).
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Prescription medicine use in Canadian children
DRUG UTILIZATION
The majority of children prescribed an antipsychotic were
dispensed an atypical antipsychotic (80%) while 28% were
dispensed a typical antipsychotic (Table 2). However, for the
two- to six-year-olds, the difference in the rate of use of these
two classes was much smaller, with 57% using atypical agents
and 48% using typical antipsychotics. Eight per cent of
antipsychotic claimants were dispensed both typical and atypical antipsychotics during the 12-month study period.
Risperidone was the leading antipsychotic agent for all age
groups (Table 3). Over 70% of the children receiving an
antipsychotic were dispensed risperidone. The second antipsychotic agent, overall, was olanzapine, which was dispensed to
12% of the antipsychotic claimants. Both of these agents are
atypical antipsychotics and the respective monographs state
that: “the safety and efficacy in children younger than the age
of 18 have not been established” (1).
Thioridazine was the leading typical antipsychotic agent
used by 10% of antipsychotic claimants in this study. This
agent was ranked second among children two to six years old
and seven- to 12-year olds; however, it was ranked sixth in the
13 to 17 years of age. “Thioridazine should not be given to
children under 2 years of age” (1).
Other antipsychotics in the top 10 drugs are not recommended for use in children. These include pimozide, loxapine
succinate and haloperidol (1). Chlorpromazine and pericyazine are not recommended for children younger than six
months of age and five years of age, respectively (Table 3).
Comparing the adult use of antipsychotics with that reported in the current study of paediatric claimants confirms the
dominance of risperidone within this therapeutic area (Table
3). However, olanzapine and methotrimeprazine appear to be
relatively more commonly used in adults than in children.
Note that the latter agent has a broad range of indications, in
addition to psychotic disturbances, including analgesia and
anesthesia (1).
SUMMARY FINDINGS
1. 0.4% of claimants in the study population had at least
one claim for antipsychotics. Approximately half of the
antipsychotic claimants were 13- to 17-year-olds with
more boys than girls.
2. Risperidone was by far the leading antipsychotic agent
for all age groups. Typical antipsychotics such as
thioridazine were more likely prescribed to younger
children than adolescents.
Expert Comment – Antidepressants and antipsychotics
Atilla Turgay MD FRCPD, Professor, University of Toronto, Chief of Medical Staff, The Scarborough Hospital
Both antipsychotics and antidepressants are large spectrum psychoactive medications with many beneficial effects on a
wide range of clinical symptoms. Their multiple positive effects allow physicians to use these medications in the treatment
of a variety of mental disorders. Paediatric medication studies have indicated that Canadian physicians were not limited
in using antidepressants and antipsychotics in children and adolescents, even in the absence of strong evidence-based published research on their effectiveness and safety.
The use of antidepressant and antipsychotic medications in the treatment of mental disorders in children seems to be
a common practice in Canada, often before the formal approval of the use of these medications in children. These medications are used across age groups and for both sexes. Studies indicate that the rates of psychosis and depression increase
with age; hence, the use of antipsychotic and antidepressant medications in the treatment of these disorders also increases with age. However, most of these medications have not received formal governmental approval for use in treating children and adolescents. Hence, the package inserts do not indicate the use for individuals who are younger than the age of
18 years and practice guidelines for prescribing have not been well established. This important issue of ‘off label’ use of the
new generation antipsychotics and antidepressants in the absence of well established and replicated research studies on
the safety and efficacy of these medications needs to be addressed carefully by professional associations for general practitioners and specialists.
Because most of the medications used in children are approved for adult use, we must endeavour to develop thorough
guidelines for ‘off label’ use and increase our knowledge through research studies and publications, which may lead to the
formal approval of these drugs in the treatment of childhood mental disorders. Because there are no published, placebo
controlled multiple site studies and no formal approval for these drugs in the treatment of child and adolescent psychiatric
disorders, one would expect a less common use of these medications in children.
The study of Prescription medicine use by one million Canadian children indicated that there is a general tendency to
prescribe the newer generation antipsychotics (atypical) as opposed to the older generation antipsychotics (typical) and a
preference to use SSRIs and SNRIs over tricyclic antidepressants. Studies have indicated that SSRIs are more effective
than tricyclics in the treatment of mood disorders in children and adolescents. There are similar trends in drug preferences
and use for adult patients versus child and adolescent patients. In the absence of evidence-based information, it appears
that physicians are generalizing the scientific knowledge and evidence that has been gained from adult studies and translating it for use in children and adolescents.
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Physicians often struggle in the treatment of children and adolescents whose psychopathologies can be as severe as
those in adults and tend to be more treatment resistant. Many child and adolescent psychiatric disorders may not respond
only to educational and psychosocial interventions and may require psychoactive medication as part of the treatment. The
use of medication in child and adolescent psychiatric disorders is still not as common practice as it is in adults. This will
improve with the presence of more research in child and adolescent psychiatry and an increased knowledge and understanding regarding the effectiveness of these treatments for children and adolescents. Generally, smaller doses are administered to children and adolescents, but this should be reviewed carefully on a case by case basis.
Thus far, there have been relatively few complaints/concerns raised about the use of psychoactive medications, such as
atypical antipsychotics and the newer generation antidepressants, despite their wide spread use in the treatment of
child/adolescent mental disorders. During the present study period, published research data were not yet available regarding the use of atypical antipsychotics in children. However, recent publications (within the past two years) have demonstrated the safety and efficacy of the new generation antipsychotics and antidepressants in children and adolescents.
Canadian and American studies about the medication use in children in North America have demonstrated the multiple uses of antidepressants and antipsychotics in children and adolescents. For example, antidepressants are used for
major depression, dysthymic disorder and anxiety disorders (including obsessive compulsive disorders). Tricyclic antidepressants (imipramine, desipramine) are used to treat ADHD and Tourette’s disorder. Typical and atypical antipsychotics
are used for the treatment of schizophrenia and other psychotic episodes, conduct disorder, tic and Tourette’s disorder,
aggressive behaviour, bipolar disorder, Autism and other pervasive developmental disorders. There are many systemic
studies with large sample sizes and case reports about the large spectrum effectiveness of these products. In summary, the
Canadian physicians did well with the use of new generation antipsychotics and antidepressants with their clinical discretion and knowledge based on adult experiences.
Hopefully in the future, more research will be done to help physicians with their prescribing. For instance, children,
adolescents and geriatric patients should be well represented in clinical trials. After the efficacy and safety of the psychoactive drugs are demonstrated with adult patients, studies with these particular populations should be completed as
soon as possible.
In addition, ‘head to head comparison studies’ of the new products will provide information about the differential use
of these medications.
Most child and adolescent psychiatric disorders are not single disorders and are commonly associated with other disorders. For example, many patients with ADHD also have oppositional defiant disorder and many depressed adolescents also
suffer from anxiety disorders. We need to increase our knowledge through psychopharmacological research to determine
the most effective medication(s) in the treatment of various clusterings of comorbid disorders.
Finally, although there is some limited information regarding the effectiveness of different classes of medications in
child and adolescent psychiatric disorders, the safety of combination medications needs to be studied formally.
‘Polypharmacy’ without strong research support does not represent safe and ethical practice.
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Prescription medicine use in Canadian children
ANTICONVULSANTS
0.7
CLAIMANT DEMOGRAPHICS
There were a total of 6,409 children who had at least one claim
for an anticonvulsant or about 1% of the total 1.03 million
claimants in the study population. Of the claimants prescribed
anticonvulsants, 40% were 13- to 17-year-olds, 35% were seven
to 12 years and 19% were two to six years (Figure 1). Those
children younger than two years made up 5% of claimants prescribed an anticonvulsant.
There was a slightly higher proportion of boys than girls in
each single year of age younger than 15 years dispensed an
anticonvulsant, however, after the age of 15, the difference
reversed (Figure 1).
The rate of use of anticonvulsant drugs per 1,000 active
claimants in the study database increased with age, from 2.7
per 1,000 active claimants for the two-year-olds and younger to
9.8 per thousand claimants for the 17-year-olds (Figure 2). The
increase in the rate per 1,000 active claimants is related to age
although there are peaks at ages eight and 13 years. This variation could be an artefact resulting from the relatively small
numbers of claimants prescribed drugs in this category.
90%
70%
% Male
0.4
60%
50%
0.3
40%
% Female
30%
0.2
% claimants/gender
Total claimants ('000)
80%
0.5
20%
0.1
10%
0.0
0%
<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age
Figure 1) Number of claimants prescribed anticonvulsant drugs by
age (bars) and percentage of claimants by sex (lines). Most claimants
prescribed anticonvulsants were between the ages of 13 and 17 years.
The number of male claimants prescribed anticonvulsants is greater
than that of female claimants except for those 15 years and older
10
Rate of use per 1,000 active claimants
TARGET DRUG LIST
The target drug list included all the anticonvulsant medications that are indicated for the treatment of epilepsy. This list
included all commonly prescribed anticonvulsants.
100%
0.6
9
8
7
6
5
4
3
2
1
0
<1 1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17
Age
Figure 2) The rate of use of anticonvulsants per 1,000 active
claimants. The rate of use per 1,000 active claimants increases by
age and reaches its highest at age 17 with about 10 claimants per
1,000 active claimants prescribed these drugs
2.8
Total claimants ('000)
Anticonvulsant drugs are commonly used in the treatment of
epilepsy (1). Epilepsy is a condition that affects an average of
14,000 Canadians each year, of which 3,200 are children
younger than the age of 10 years (2). Epilepsy can develop at
any age in children or adults. Thirty per cent of new cases every
year begin in childhood, particularly in early childhood and
around the time of adolescence. In approximately 50% of the
cases of childhood epilepsy, children outgrow their seizures (2).
Anticonvulsants can be divided into first and secondgeneration anticonvulsants. First-generation anticonvulsants
are indicated for adjunctive use as well as monotherapy for
epilepsy while second-generation anticonvulsants are usually
used as adjunctive therapy, ‘add-on’, for the treatment of
epilepsy. Some anticonvulsant drugs such as carbamazepine
(1), gabapentin and phenytoin (3) are also used in neuropathic pain; others such as carbamazepine, valproate and divalproex sodium have been approved to treat acute manic
episodes in bipolar disorder (1,4).
2.4
2.0
1.6
1.2
0.8
0.4
DRUG UTILIZATION
The top four anticonvulsants were carbamazepine (39% of anticonvulsant claimants), divalproex sodium (24%), clobazam and
valporoate sodium (13%) (Figure 3). However, the ranking of
TABLE 1
Anticonvulsant target drugs
Class
Drug
First generation
anticonvulsants
Carbamazepine, clobazam, divalproex
sodium, ethosuximide, phenobarbital,
phenytoin, phenytoin, primidone,
valproic acid
Second generation
Gabapentin, lamotrigine, topiramate,
anticonvulsants
vigabatrin
The target drugs were determined by literature review and advice of advisory
panel
Paediatr Child Health Vol 8 Suppl A April 2003
C
ar
D bam
iv
al
az
pr
oe epi
n
x
so e
di
um
Va C
lp lob
ro
az
at
e am
so
La diu
m
m
Ph otr
en igi
ob ne
ar
Ph bita
en l
y
G
ab toin
ap
To ent
in
p
Et iram
ho
su ate
Va xim
i
lp
ro d e
ic
Vi acid
ga
ba
t ri
n
0.0
Figure 3) Number of claimants prescribed anticonvulsant drugs by
chemical. Chemicals prescribed to less than 1% of the total claimants
on anticonvulsants in the study are not shown. Carbamazepine,
divalproex sodium, clobazam, valproate sodium and lamotrigine are
the top five drugs prescribed to claimants in the study
these products differs dramatically across age groups (Table 2).
Carbamazepine ranked first for children two years and older
while it ranked second for the one-year-olds and fifth for those
younger than one year. Carbamazepine is one of the cornerstones of anticonvulsant therapy in the paediatric population,
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TABLE 2
The top 10 anticonvulsants (by claimant count) by drug and age
Drug name
Carbamazepine
Divalproex sodiuma
Clobazam
Valproate sodiuma
Lamotrigineb
Phenobarbital
Phenytoin
Gabapentinc
Topiramated
Ethosuximidee
<1 year
N = 145
nch
10
**
14
9
**
99
18
**
**
**
R
5
N/A
4
6
N/A
1
3
N/A
N/A
N/A
1 year
N = 168
2-6 years
N = 1,241
7-12 years
N = 2,264
nch
37
**
36
30
16
69
21
**
12
**
nch
455
101
242
391
110
136
71
51
48
47
nch
979
513
330
300
200
96
115
81
62
129
R
2
N/A
3
4
7
1
6
N/A
8
N/A
R
1
6
3
2
5
4
7
8
9
10
R
1
2
3
4
5
8
7
9
10
6
13-17 years
N = 2,591
nch
1,028
935
221
91
196
66
222
151
103
49
R
1
2
4
9
5
10
3
6
8
11
Total claimants
(<1-17 years)
N = 6,409
nch
2,509
1,551
843
821
527
466
447
285
230
226
R
1
2
3
4
5
6
7
8
9
10
Adult claimants
(18-65 years)
N = 59,419
nch
18,043
15,064
1,882
147
2,078
2,906
12,225
12,631
2,444
221
R
1
2
9
13
8
5
4
3
6
11
a) Epival®, Depakene®, and Epiject IV® monographs: "Experience has indicated that children under the age of 2 years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by
mental retardation, and those with organic brain disease."; b) Lamictal® monograph: "Safety and efficacy in patients below the age of 16 years, other than those with
Lennox-Gastaut Syndrome, have not been established"; c) Neurontin® monograph: "Systematic studies to establish safety and efficacy in children have not been performed"; d) Topomax® monograph: "Safety and effectiveness in children under 2 years of age have not been established"; e) Zarontin® monograph: "Safety and effectiveness in paediatric patients below the age of 3 years have not been established". N Total number of claimants prescribed anticonvulsant drugs; nch Number of
claimants by chemical; R Rank of drug in each age group by number of claimants. ** Fewer than six claimants. Indication and age restriction from Compendium of
Pharmaceuticals and Specialities, 2001 (1)
where it is used in almost all type of seizures (5-7) and is a preferred medication for students because it seldom causes sedation
or learning problems (7). Divalproex sodium and valproate
sodium are not recommended for use in children younger than
two years of age since there is an increased risk of developing
fatal hepatotoxicity from using these drugs, especially in children with medical conditions (1).
Phenobarbital ranked first for claimants one year of age and
younger, fourth for claimants two to six years while it ranked
eighth and 10th for claimants seven to 12 years and 13 to
17 years, respectively. There is no age restriction for this drug.
Among the newer anticonvulsants, lamotrigine was dispensed to 8% of the anticonvulsant claimants. Gabapentin
and topiramate were each prescribed to approximately 4%.
These three drugs were mainly prescribed to older children
(Table 2). Lamotrigine and gabapentin are not indicated for
children because safety and efficacy have not been established
(1). Topiramate was only approved early in 2000 (part way
through the study period) for use with other medications as an
adjunct treatment for seizures in children (1). The safety and
effectiveness of this drug have not been established in children
younger than two years of age (1).
The use of drugs in this class for children differed markedly
from the use among adults except for the leading two products
in the class. The top two drugs in both populations were carbamazepine and divalproex sodium (Table 2). Clobazam,
which ranked third for paediatric claimants, was ranked ninth
for adults. On the other hand, gabapentin ranked third for
adults but was ranked between 6th and 10th for paediatric
claimants.
‘OFF LABEL’ USE
Many anticonvulsants are effective in the treatment of a variety of neurological disorders. For instance, topiramate, lamotrigine and divalproex sodium are used to treat mood disorders
(4) and gabapentin is used for the treatment of neuralgia (3).
44A
Carbamazepine has some use in treating comorbid ADHD
and bipolar disorders (8). Valporic acid, carbamazepine and
topimarate are used in the management of frequent migraine
(9). Confirmation that there is substantial use of these drugs
for conditions other than epilepsy is apparent from the fact
that there is an estimated 14,000 Canadians with epilepsy
(2), yet this study recorded over 65,000 people (all ages) dispensed a drug in this class. As noted earlier, the data used in
this study are from a subset of Canadians. That means the
number of people using anticonvulsants found in this study
underestimates the true number of Canadians using these
drugs.
The patient’s diagnosis is not recorded on the claim record;
therefore, the apparent reason for use can only be inferred by
examining the patient’s history of drug use. The following
pharmacological markers have been used to draw inferences
about the use of these agents among the paediatric population.
a – an antipsychotic (including lithium) followed by the use
of an anticonvulsant concomitantly, the patient is deemed to
be using the anticonvulsant for mood stabilization;
b – an antiviral indicated for herpes; a diabetes medicine
either insulin or an oral agent; or chronic use of a muscle relaxant, or a narcotic analgesic, the patient is deemed to be prescribed the anticonvulsant to treat postherpetic neuralgia,
diabetic neuropathy or another form of neuralgia;
c – a migraine medicine (triptans, ergotamine, fiorinal,
etc), the patient is deemed to use the anticonvulsant for
migraine prophylaxis;
d – a weight loss drug and the use of topiramate, the deemed
indication is obesity (weight loss is a common side effect of
topiramate [1]); and
e – any patient who fits none of these profiles is assumed to
be prescribed the drug for epilepsy.
Based on the exclusion criteria listed above, an analysis of
the data showed that 85% of children in the study population
were prescribed an anticonvulsant for epilepsy treatment
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Prescription medicine use in Canadian children
100%
Paediatric population
General population
90%
80%
Migraine
prophylaxis
2%
Epilepsy
85%
Mono
57%
70%
% claimants
Add-on
28%
Mood stabilization
9%
60%
50%
40%
30%
20%
10%
Figure 4) Distribution of paediatric claimants prescribed anticonvulsants by derived indications. Claimants are mostly prescribed anticonvulsants for epilepsy treatment, some as monotherapy and some as
add-on. Mood stabilization, neuropathic pain and postherpatic neuralgia
and migraine prophylaxis are other possible indications for anticonvulsant use
(Figure 4). In the adult population, the use of the anticonvulsant drugs for reasons other than epilepsy was much more common with 44% of the adult population meeting one of the
above criteria (Figure 5).
The rate of use by indication differs substantially by drug.
77% of all gabapentin paediatric claimants appear to be prescribed anticonvulsants to control epilepsy compared with
only 31% of gabapentin users in the adult population.
Similarly, 84% of all paediatric claimants prescribed some form
of valproic acid or divalproex sodium appear to be epileptic
compared with just 37% in the general population.
Paediatr Child Health Vol 8 Suppl A April 2003
0%
To
pi
ra
m
at
G
e
ab
ap
en
tin
La
m
ot
Ca
rig
in
rb
e
am
az
ep
in
e
Ph
en
yt
oi
n
C
lo
ba
za
m
Pr
im
id
D
on
iv
e
al
pr
oi
c
ac
id
Vi
ga
ba
t ri
n
Al
ld
ru
gs
Neuropathic Pain
& Post Herpatic
Neuralgia
4%
Figure 5) Proportion of anticonvulsant claimants, whose derived indication is epilepsy, by drug: paediatrics versus adult population. Overall,
claimants in the paediatric population are more likely to take anticonvulsants for epilepsy as opposed to the general population. The rate varies
depending on the drug, particularly among adult users
SUMMARY FINDINGS
1. Approximately 1% of children in the study database
were prescribed an anticonvulsant during the 12-month
study period. Three quarters of these children were older
than the age of seven.
2. The use of anticonvulsants varied with age. The top
products were carbamazepine for the two years of age and
older age groups, and phenobarbital for the one year of
age and younger age groups.
3. The majority of paediatric claimants (85%) prescribed
anticonvulsant drugs appear to be prescribed the drugs to
treat epilepsy, whereas in the adult population nearly
half of all claimants prescribed an anticonvulsant were
prescribed the medicines to treat conditions other than
epilepsy.
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Expert Comment – Anticonvulsants
J Dooley MB BCh FRCP(C), Professor of Pediatrics and Head, Division of Pediatric Neurology,
Dalhousie University and IWK Health Centre, Halifax, Nova Scotia
Epilepsy is a disabling condition for many affected children. Achieving seizure control allows children and their families
to regain a normal life style. Antiepilectic drugs (AEDs) are currently our best hope of achieving this goal for the majority of children with epilepsy, although alternate therapies such as surgery, the ketogenic diet and vagal nerve stimulation
have a role for some children. The use of AEDs may however be associated with significant adverse effects. The major
issue for paediatric epileptologists is to achieve complete seizure control without cognitive or systemic adverse effects.
Tracking the use of AEDs is important for evaluating trends in the treatment of paediatric epilepsy. Most data on AED
use is based on the treatment of children with refractory epilepsy within tertiary care clinics. The present study allows a
view of the use of AEDs by Canadian children in a less restricted setting.
The study is, however, restricted to those who had private insurance coverage and may therefore under represent some
of the generic preparations and older (cheaper) AEDs. Furthermore, the present study does not permit definitive analysis
of the specific indication being treated. Efforts should be made to determine the indications for AED use in future analyses.
The number of children taking AEDs in the population studied (6,409 of 1,030,000) is in keeping with estimated
epilepsy prevalence rates of 0.5%.
The data show that carbamazepine was used by 39% of the children and that valproate, divalproex sodium and valproic
acid accounted for 40% of use. Clobazam was used by 13%, which is higher than the rate of use in other countries. This
may reflect the study by Canadian paediatric epileptologists that showed clobazam to be as effective as carbamazepine or
phenytoin, while being associated with fewer potential serious adverse events. Among the newer AEDs, lamotrigine was
used by 8%, and both gabapentin and topiramate were used by approximately 4%. Phenobarbital and phenytoin were each
used by approximately 7%. Phenobarbital, the oldest available AED, was used almost exclusively in young children. This
pattern of use reflects the absence of data on newer AEDs in very young children and the availability of phenobarbital in
liquid formulation. Phenytoin is used less frequently in children than in adults. It is metabolized by zero order kinetics and
attaining therapeutic levels can be difficult in children. Ethosuximide was rarely used because it is limited for children
with absence epilepsy. Finally vigabatrin and primidone were the least frequently prescribed AEDs. Vigabatrin has been
associated with retinal damage and is now limited for the treatment of infantile spasms. Primidone is metabolized to phenobarbital and phenylethylmalonic acid and is rarely used in children.
The data on prescriptions by age accurately reflect prescribing practices. As noted above, phenobarbital was used in
younger children but rarely in school-aged children because of its potential to interfere with learning. In contrast, divalproex sodium was primarily used by older children who were able to swallow the medication. Somewhat surprisingly, valproate sodium or divalproex sodium were used by more than 1/3 of the population aged two to six years and by almost 20%
of one-year-olds. There has been concern about higher potential for serious valproate-related hepatic adverse events in
younger children.
The study is a major contribution to our understanding of how AEDs are used in Canadian children. The data reflect
use in a large population but is very similar to AED use in specialized clinics. The sponsors of the study are to be congratulated for this undertaking. Hopefully, repeating the study will provide longitudinal data, which will allow further insights
into the evolution of AED use in Canada.
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Prescription medicine use in Canadian children
TARGET DRUG LIST
Gastrointestinal drugs that were used to select the claimants
for this analysis have been divided into four classes: Histamine
H2 receptor antagonists (H2RAs), proton pump inhibitors
(PPIs), prokinetic agents, and miscellaneous gastrointestinal
drugs (Table 1).
Over-the-counter GI drugs such as ranitidine (oral solid
75 mg and under), famotidine (oral solid 10 mg and under) and
cimetidine (oral solid 100 mg and under) are not captured consistently in this database of private payer drug claims therefore
underestimating the use of histamine H2 receptor antagonists.
Other over-the-counter drugs, which may be used by a wide
number of claimants for minor gastrointestinal complaints
(diarrhea, heartburn, etc), were also excluded.
Cisapride monohydrate was withdrawn from the Canadian
market August 7, 2000 (6), part way through the time period
of this analysis.
Although antibiotics and corticosteroids are part of the recommended treatment regimens for ulcer and Crohn’s disease,
these drugs are used for several other conditions and thus were
not included in the target drug list.
CLAIMANT DEMOGRAPHICS
There were 16,267 children in the study database who had at
least one claim for a gastrointestinal target drug (2% of all paediatric claimants).
Nearly 9,000 (55%) of the children prescribed gastrointestinal drugs were 13 to 17 years of age, 2,600 were seven to 12
years, only 400 (3%) were one year of age. However, there
were 1,200 GI claimants in the database younger than one year
Paediatr Child Health Vol 8 Suppl A April 2003
Class
Drug
Histamine H2 Receptor
Antagonist (H2RA)
Cimetidine, famotidine & calcium carbonate &
magnesium hydroxide, famotidine, nizatidine,
ranitidine bismuth citrate, ranitidine HCl
Lansoprazole & amoxicillin & clarithromycin,
lansoprazole, omeprazole magnesium, pantoprazole
Cisapride monohydratea, domperidone maleate,
metoclopramide HCl
5-aminosalicylic acid (5-ASA), misoprostol,
olsalazine sodium, pinaverium bromide, sucralfate,
trimebutine maleate
Proton Pump Inhibitors
(PPI)
Prokinetic agents
Gastrointestinal drugs:
Miscellaneous
The target drugs were determined by literature review and advice of advisory
panel. a) Cisapride monohydrate was withdrawn from the market in
August 2000
100%
2.8
90%
2.4
2.0
70%
% Male
1.6
60%
50%
1.2
40%
% Female
30%
0.8
% claimants/gender
80%
Total claimants ('000)
Several gastrointestinal (GI) conditions that affect young children are treatable with prescription medications. These
include gastroesophageal reflux disease (GERD), peptic ulcer
disease (PUD), recurrent abdominal pain (RAP) and inflammatory bowel disease (IBD) (1).
In infants, the prevalence of gastroesophageal reflux (GER)
varies by age peaking at 67% for four month olds and dropping
to approximately 5% by the age of one year (2). However, only
10% of these infants with GER develop the clinical condition
known as GERD and require medical attention (2). GERD
could also affect older children, adolescents and adults, and is
usually associated with esophagitis (2).
PUD is uncommon among children, although the prevalence of this condition increases with age (3).
RAP is defined as having at least three episodes of abdominal pain for a period of three months or more (4). RAP usually occurs before puberty with two distinct peaks of frequency.
The first peak occurs between five and seven years of age, with
equal frequency in boys and girls, and in 5% to 8% of children.
The second peak occurs between eight and 12 years of age,
with a prevalence approaching 25%, and is far more prevalent
in girls (4).
IBD describes a group of illnesses in which there is inflammation in a part of the gastrointestinal tract. The two most
prevalent forms of IBD are Crohn’s disease and ulcerative colitis. IBD most commonly begins during adolescence and early
adulthood (5).
TABLE 1
Gastrointestinal target drugs
20%
0.4
10%
0.0
0%
<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age
Figure 1) Number of claimants prescribed gastrointestinal drugs by age
(bars) and percent of claimants by sex (lines). Of the claimants prescribed gastrointestinal drugs, 13 to 17 years of age claimants represented the highest percentage and claimants younger than one year of age
also accounted for a significant number. The number of male claimants
is higher than that of female claimants six years of age and younger
40
Rate of use per 1,000 active claimants
GASTROINTESTINAL DRUGS
35
30
25
20
15
10
5
0
<1 1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17
Age
Figure 2) The rate of use of gastrointestinal drugs per 1,000 active
claimants. The rate of use increases by age to a high of 40 claimants per
1,000 active claimants aged 17 years. Approximately 23 per 1,000 active
claimants aged younger than one year of age had a claim for a GI drug
of age. For age groups younger than four years, there were more
boys than girls. The proportions were approximately equal
among the four-year-olds and a slightly higher share of girls
from age five to 11 years. At age 12 years and older, the proportion of girls increases for each single year of age to about
63% for the 17-year-olds (Figure 1).
Claimants younger than one year of age prescribed target
GI drugs had a rate of drug use of 23 claimants for every 1,000
active claimants. This is likely higher than the rate in other
young age groups because GER is reportedly more common in
children younger than one year of age (7). The rate of use of
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Abi Khaled et al
TABLE 2
Distribution of claimants by class and age
Histamine H2 receptor
antagonist
Proton pump inhibitors
Prokinetic agents
Gastrointestinal drugs:
miscellaneous
< 1 year
N = 1,227
1 year
N = 407
2-6 years
N = 1,681
7-12 years
N = 3,958
13-17 years
N = 8,994
n
851
%
69%
n
219
%
54%
n
1,015
%
60%
n
2,609
%
66%
n
5,264
%
59%
n
9,958
%
61%
45
901
10
4%
73%
1%
52
234
19
13%
57%
5%
257
564
125
15%
34%
7%
731
751
410
18%
19%
10%
2,545
1,180
1,420
28%
13%
16%
3,630
3,630
1,984
22%
22%
12%
N Total number of claimants prescribed gastrointestinal drugs; n Number of
claimants by class; % Percentage of claimants dispensed a class within the age
group (n/N). The sum of claimants and percentage by age group does not total
because one claimant can be dispensed multiple classes of gastrointestinal
drugs in the same year
8
Total claimants ('000)
Class
10
Total
claimants
(<1-17 years)
N = 16,267
6
4
2
0
H2RA
48A
Gastrointestinal
drugs:
miscellaneous
Figure 3) Number of claimants prescribed gastrointestinal drugs by
class. More claimants were prescribed H2-receptor antagonists
(H2RA) drugs compared with proton pump inhibitors (PPI) or other
gastrointestinal agents
Total claimants ('000)
DRUG UTILIZATION
The histamine H2 receptor antagonist (H2RA) class had the
largest proportion of GI claimants compared with other GI
classes (Figure 3). Nearly two-thirds (61%) of the GI population had at least one claim for a drug in the H2RA class.
Among infants, 69% had a drug in this class, 54% of the oneyear-olds, 60% for those two to six years, 66% for the seven to
12 years and 59% for those older than 13 years (Table 2).
Ranitidine, which was the leading drug in the H2RA class,
had by far the largest proportion of GI claimants with one-half
of the GI claimants having at least one claim for the drug during the study period (Figure 4). Ranitidine was the top gastrointestinal drug for all age groups of the paediatric claimants
as well as for the adult claimants (Table 3). Ranitidine has been
successfully used in children aged eight and older, however,
“the experience with ranitidine in children is very limited” (8).
Proton pump inhibitors and prokinetics were each used by
22% on the total GI claimants.
Although both prokinetics and PPIs were used by the same
proportion of GI claimants in the study (Figure 3), the distribution of these two classes varied with age (Table 2).
The percentage of GI claimants who had a claim from the
PPI class tended to increase by age, rising from only 4% of the
younger than one year of age to 28% among the 13- to 17-yearolds. In contrast, prokinetics were the most used GI class
among children one year old and younger (73%). However,
the proportion of the GI patients using prokinetics dropped
sharply with age as only 13% of the GI patients aged 13 to 17
had a prescription for a drug from this class.
Omeprazole (a PPI) and cisapride (a prokinetic agent) were
ranked a distant second and third behind ranitidine with 15%
and 14% of the GI claimants prescribed these drugs, respectively (Figure 4). However, the ranking of these two drugs varied with age. Omeprazole ranked second for claimants seven
years of age and older and fourth and fifth for claimants
younger than seven years, while cisapride ranked second for
those six years of age and younger, third for the seven- to 12year-olds and sixth for the 13- to 17-year-olds (Table 3). The
cisapride usage will have been affected by the withdrawal of
the product during the study period and the rates of use shown
Prokinetic
agents
9
8
7
6
5
4
3
2
1
0
H2RA
PPI
Prokinetic agents
Gastrointestinal drugs: miscellaneous
Ci
R
a
sa
pr O nitid
id m
ep ine
e
m
on raz
oh ole
yd
M Cim rat
e
et
e
oc tid
lo
pr ine
5L
Am an am
in so ide
os pr
al az
i
o
D
om P cyli le
a
pe n c a
to c
Pi rido pr id
ne n az
va e m ole
riu a
m lea
br te
Fa o m
m ide
ot
Su idin
Tr
cr e
a
im
eb Ni lfat
ut za e
in tid
e
m ine
al
ea
te
the target GI drugs was consistently low for ages one through
six (about five claimants per 1,000) and increased with age
thereafter reaching a peak of 40 claimants per 1,000 for the
17-year-olds.
PPI
Figure 4) Number of claimants prescribed gastrointestinal drugs by
drug. Drugs prescribed to less than 1% of the total GI claimants are
not shown. Ranitidine, an H2-receptor antagonist, is the chemical
prescribed to the most claimants. Omeprazole and cisapride monohydrate ranked second and third with approximately 2,000 claimants
prescribed these drugs. The latter drug has since been removed from
the Canadian market
here cannot be used as an indicator of current or future patterns of use.
Metoclopramide, another prokinetic agent, ranked third for
children aged six years and younger and fifth overall (Table 3).
Prokinetic pharmacotherapy is recommended as the first line
therapy in young children (younger than two years old) for the
treatment of GERD because this condition is primarily a problem of motility in this age group (2). Domperidone maleate
was used by a small number of children compared with the
other prokinetic agents. Domperidone maleate is the only prokinetic not indicated for use in children (8).
Pantoprazole and lansoprazole, other PPIs, were prescribed
to a lower number of children than omeprazole; most of them
were 13- to 17-year-olds. The monographs for all drugs belonging to the PPI class state that their “safety and effectiveness
have not been established in children” (8).
The miscellaneous gastrointestinal drugs were dispensed to
12% of all GI claimants. The proportion of claimants dispensed drugs from this class ranged from 1% for the younger
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Prescription medicine use in Canadian children
TABLE 3
The top 10 gastrointestinal drugs (by claimant count) by drug and age
Drug
< 1 year
N = 1,227
1 year
N = 407
2-6 years
N = 1,681
7-12 years
N = 3,958
13-17 years
N = 8,994
Total claimants
(<1-17 years)
N = 16,267
Adult claimants
(18-65 years)
N = 521,697
nch
R
nch
R
nch
R
nch
R
nch
R
nch
R
nch
R
Ranitidine HCl a
840
1
205
1
846
1
2,058
1
4,208
1
8,157
1
167,618
1
Omeprazole b
35
4
30
4
155
5
546
2
1,627
2
2,393
2
164,996
2
Cisapride monohydrate c
807
2
180
2
363
2
454
3
526
6
2,330
3
20,376
9
Cimetidine
12
6
12
8
166
4
452
4
567
3
1,209
4
22,249
8
Metoclopramide HCl
115
3
53
3
194
3
249
5
455
7
1,066
5
17,447
10
Lansoprazole b
10
7
17
5
88
6
136
7
530
5
781
6
56,034
4
5 Aminosalicylic acid d
**
N/A
**
N/A
18
9
160
6
556
4
740
7
22,990
7
Pantoprazole b
**
N/A
**
N/A
17
10
56
11
427
8
508
8
56,954
3
Domperidone maleate e
24
5
14
7
36
8
96
10
270
12
440
9
30,267
5
Pinaverium bromide
**
N/A
12
11
54
12
353
9
422
10
16,391
11
a) Zantac® monograph: "Experience with ranitidine in children is limited. It has however been used successfully in children aged 8 to 18"; b) Losec®, Prevacid®,
Pantoloc® monographs: "The safety and efficacy in children have not yet been established"; c) Cisapride monohydrate® withdrawn from the market by Health
Canada, effective August 7, 2000; d) Asacol®, Mesasa®, Pentasa®, Quintasa®, and Salofalk® monographs: "Safety and efficacy of 5-ASA in children have not been
established. The potential benefits of its use should be weighed against the possible risks"; e) Motilium® monograph: "Safety and efficacy in children have not been
established; therefore, domperidone should not be used in children". N Total number of claimants prescribed gastrointestinal drugs; nch Number of claimants by
chemical; R Rank of drug in each age group. **fewer than six claimants. Indication and age restriction from Compendium of Pharmaceuticals and Specialities, 2001
(8). The sum of claimants and percentage by age group does not total, because one claimant can be dispensed multiple classes of gastrointestinal drugs in the
same year
than one year of age group to approximately 16% of the 13- to
17-year-olds (Table 2).
5-amino salicylic acid (5-ASA), which is indicated for the
treatment of IBD, and pinaverium bromide, which could be
used for the treatment and relief of abdominal pain (8), were
used by a small number of children; the majority of them were
13- to 17-year-olds. These two products were classified under
“Gastrointestinal drugs: miscellaneous”. The safety and effectiveness of 5-ASA have not been established in children (8).
SUMMARY FINDINGS
1. Two per cent of all paediatric claimants had at least one
claim for a gastrointestinal target drug. More than 50%
of the GI drug claimants were 13- to 17-year-olds with
more girls than boys. Gastrointestinal drugs were
prescribed to 1,200 infants younger than one year old,
which represent 3% of all claimants younger than one
year old in the study database.
2. The histamine H2 receptor antagonist class had the
largest proportion of GI claimants (61%) followed by
PPIs and prokinetics (22% each). Unlike PPIs, which
were more likely prescribed to older children, prokinetics
were more likely prescribed to younger children.
3. Ranitidine was the leading gastrointestinal drug for all
age groups ranging from 47% of the 13- to
17-year-old GI claimants to 68% of the younger than one
year olds. The drug that ranked second varied with age.
Omeprazole ranked second among GI drugs for children
older than seven years old while cisapride ranked second
for those six years of age and younger, with the highest
proportion in the younger than one year old group.
Expert Comment – Gastrointestinal drugs
Kevan Jacobson MB BCh FRCPC FACP, Assistant Professor and Director of Endoscopy, Department of Pediatrics,
Division of Gastroenterology, British Columbia's Children's Hospital
The present study provides the reader with a snap shot view of the spectrum of filled and claimed gastrointestinal drug prescriptions for paediatric patients younger than 18 years of age. The data were extracted from a private payer drug plan
database that included claims to private drug plans over a two-year period from 1999 to 2000. Acid suppressant and prokinetic drugs were the most commonly prescribed classes of drugs.
As one might predict, H2RAs were shown to be prescribed to the largest number of claimants (61% of patients having
at least one claim). Prokinetic agents were most commonly used in children younger than one year of age (73%), reflecting a standard of practice that was advocated for the infant with physiological reflux unresponsive to lifestyle modifications. At the time of data extraction, cisapride was still available and used as the primary prokinetic agent, however, in a
recent study, Shaoul et al (1), demonstrated that despite the common use of cisapride, the knowledge of both paediatricians and family practitioners in the use of cisapride in children was suboptimal. The authors using a standardized questionnaire sent to 80 paediatricians and 60 family practitioners in Northern Israel with approximately a 50% response rate
Paediatr Child Health Vol 8 Suppl A April 2003
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Abi Khaled et al
demonstrated that 40% of paediatricians and 65% of family practitioners failed to prescribe the recommended dose, 6% of
paediatricians and 42% of family practitioners prescribed cisapride for infantile colic, only 50% of paediatricians and 22%
of family practitioners were aware of possible interactions with macrolides, and only 31% of paediatricians and 54% of
family practitioners were aware of the association between cisapride and prolongation of the QT interval. The Shaoul
study, taken together with other studies assessing physician drug knowledge (2,3), emphasizes the need to improve physician education and to ensure appropriate prescribing practice for all age groups.
From the present study one cannot determine who prescribed the drug, whether the appropriate drug was used, whether
the physician was knowledgeable about the drug, or whether the patient was compliant or responded to the therapeutic
intervention. Although the largest proportion of claimants prescribed PPIs were the adolescent patients followed by the
seven- to 12-year-olds and then the two- to six-year-olds where efficacy, safety, dosing and pharmacokinetic and data do
exist (4,5), 45 claimants were in the age group younger than one year, where very little of such data are available. It is possible that the PPIs were prescribed by gastroenterologists following a lack of, or inadequate response to H2RAs together
with endoscopic evidence of GERD, however this is speculative and cannot be determined from the database. It has also
become evident that in the United States PPIs are being prescribed in infants younger than one year of age, for even minor
GI complaints and given the few indications for use of PPIs for those younger than one year of age, and the absence of safety, dosing and pharmacokinetic data, this is a practice of concern.
The number of paediatric claimants that filled and claimed a prescription for a gastrointestinal drug totaled 16,267 out
of 1.03 million total claimants in the study database accounting for 2% of the total claimants. Although this number is
small it likely under represents the true number of paediatric prescriptions. Over-the-counter medications were not captured and it is evident that prescribed medications such as 5-ASA compounds, where only 740 claimants were recorded
were under-represented. Despite the small number of paediatric claimants compared with adult claimants it is essential to
keep in mind the importance of the paediatric patient and the need to ensure that this population is appropriately supported, the prescribing physician is well educated with regard to indications, dosing schedules and side effects and that
there is ongoing research and development of new and effective therapies for this population. In the United States, a
strongly positive outcome has followed the Food and Drug Administration Modernization Act, which mandated the study
of drugs in children, and offered incentives to pharmaceutical firms to underwrite the studies, resulting in an increase in
paediatric drug study activity. With new data, there is the potential to make paediatric prescribing practice safer and more
appropriate.
In a recent study by Chen and Chang (6), socioeconomic characteristics such as family income level, race and insurance status were shown to influence prescription drug expenditure significantly in children. Therefore, policy makers must
be mindful of the vulnerabilities when implementing new policies and/or cost-containment measures.
Creation of such databases with surveillance of prescription patterns should become an essential part of health care.
The present database has provided valuable information regarding prescribing trends, however, as noted above additional
information is required and effective capturing of representative data is necessary to determine effective drug prescribing
practice. Moreover, such databases can be used to assess the need for and the effectiveness of educational support for
physicians.
REFERENCES
1. Shaoul R, Shahory R, Tamir A, Jaffe M. Comparison between pediatricians and family practitioners in the use of the prokinetic cisapride
for gastroesophageal reflux disease in children. Pediatrics 2002;109:1118-23.
2. Ayanian JZ, Hauptman PJ, Gaudagnoli E, Antman EM, Pashos CL, McNeil BJ. Knowledge and practices of generalist and specialist
physicians regarding drug therapy for acute myocardial infarction. N Engl J Med 1994;331:1136-42.
3. Straand J, Rokstad K. Are prescribing patterns of diuretics in general practice good enough? A report from the More and Romsdal
Prescription Study. Scand J Prim Health Care 1997;15:101-15.
4. Andersson T, Hassall E, Lundborg P, and the International Pediatric Omeprazole Pharmacokinetic Study Group. Pharmacokinetics of
orally administered omeprazole in children. Am J Gastroenterol 2000;95:3101-6.
5. Hassall E, Israel DM, Shepherd R, Radke M, Dalväg A, Sköld B, Junghard O, Lundborg P, and the International Pediatric Omeprazole
Study Group. Omeprazole for treatment of chronic erosive esophagitis in children: A multicenter study of efficacy, safety, tolerability and
dose requirements. J Pediatr 2000;137:800-7.
6. Chen AY, Chang RKR. Factors associated with prescription drug expenditures among children: An analysis of the medical expenditure
panel survey. Pediatrics 2002;109:728-32.
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Prescription medicine use in Canadian children
Diabetes mellitus (DM) is a chronic metabolic disorder caused
by a complete or relative deficiency of insulin, an ineffective
use of insulin or both (1). Two types of diabetes could affect
children: type 1 and type 2.
In type 1 diabetes endogenous insulin is not produced,
which leads to an absolute deficiency of insulin. Most children
with diabetes have type 1 and depend on insulin injections for
maintaining health (1,2). American statistics indicate that
approximately one in every 400 to 500 children and adolescents have type 1 diabetes (3).
Type 2 diabetes, or non-insulin-dependent diabetes, occurs
when the body does not produce enough insulin, or when
insulin receptor resistance occurs. Although type 2 diabetes
previously was uncommon in children, recent clinic-based
reports and regional studies consistently highlight the increasing prevalence of type 2 diabetes (4). Recent figures reveal that
20% of children and adolescents diagnosed with diabetes have
type 2, which is usually associated with obesity (3,4). The peak
age of diagnosis of type 2 diabetes in youths is between 12 and
16 years (4). Because type 2 diabetes may remain asymptomatic for a prolonged period, this type of diabetes is more likely to be misclassified, undiagnosed or under-reported than type
1 diabetes (4).
TARGET DRUG LIST
The target drug list of medication for this analysis included
all drugs used for the management of diabetes. These drugs
TABLE 1
Hypoglycemic target drugs
Class
Alpha-glucosidase inhibitors
Biguanides
Carbamoyl benzoic acid derivates
Sulfonylureas
Thiazolidinediones
Drug
Acarbose
Metformin HCl
Repaglinide
Chlorpropamide, gliclazide, glyburide, tolbutamide
Pioglitazone HCl, rosiglitazone
The target drugs were determined by literature review and advice of advisory
panel
100%
0.5
90%
Total claimants ('000)
70%
% Male
60%
0.3
50%
0.2
40%
% Female
30%
% claimants/gender
80%
0.4
TABLE 2
Distribution of claimants prescribed antidiabetic agents by
class and age
2-6 years
N = 447
Class
n
436
12
Insulin
Oral hypoglycemic
7-12 years
N = 1,305
%
98%
3%
n
1,276
31
13-17 years
N = 1,805
%
98%
2%
n
1,703
117
%
94%
6%
Total claimants
(<1-17 years)
N = 3,583
n
%
3,437
96%
164
5%
N Total number of claimants prescribed antidiabetic agents; n Number of
claimants by class; % Percentage of claimants dispensed a class within the age
group (n/N). The sum of claimants and percentage by age group does not total
because one claimant can be dispensed multiple classes in the same year
7
Rate of use per 1,000 active claimants
DIABETES THERAPY
6
5
4
3
2
1
0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17
Age
Figure 2) The rate of use of antidiabetic agents per 1,000 active
claimants. The rate of use increases by age except in the 14 years of age
group where there is a slight dip of one claimant per 1,000 active
claimants
were grouped into two main classes: insulins (human, animal and analogue forms) and oral hypoglycemic agents (5)
(Table 1).
CLAIMANT DEMOGRAPHICS
Fewer than 3,600 claimants (0.3% of all claimants in the study
population) were prescribed antidiabetic agents.
The sex distribution revealed that there were relatively
more male claimants prescribed antidiabetic agents than
female claimants (Figure 1). This is consistent across most of
the age groups except for the three-year-olds and those
between the ages of eight and 10 years. However, given the
small numbers, this should not be viewed as conclusive.
The rate of use of antidiabetic agents per 1,000 active
claimants increased with age, from approximately 0.3 per
1,000 active claimants to a peak of six per 1,000 active
claimants for the 12 to 17-year-olds.
20%
0.1
10%
0.0
DRUG UTILIZATION
0%
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age
Figure 1) Number of claimants prescribed antidiabetic agents by age
(bars) and percentage of claimants by sex (lines). Most claimants prescribed antidiabetic agents fall in the 13 to 17 years of age group. There
were very few claimants aged younger than one year prescribed antidiabetic agents (not shown). The number of male claimants exceeded
that of female claimants aged between four and seven years and those
11 years of age and older
Paediatr Child Health Vol 8 Suppl A April 2003
Utilization of antidiabetic agents by class
Most of the diabetic claimants in all age groups were prescribed
insulin (94% to 98%) (Table 2). Only 5% of the diabetic
claimants were prescribed oral hypoglycemic agents; the
majority of them were 13 to 17 years old.
Because oral antidiabetic agents were dispensed to few
claimants in the study database, no additional analyses were
conducted on the utilization of these medications.
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Abi Khaled et al
TABLE 3
Distribution of claimants prescribed insulin by type of
insulin and age
1 year
N=18
Types of
insulin
Basal
Short
Mix
n
%
18 100%
16 89%
0
0%
2-6 years
N=436
n
424
405
**
7-12 years 13-17 years
N=1,276
N=1,703
%
n
%
n
%
97% 1,244 97% 1,630 96%
93% 1,202 94% 1,619 95%
N/A
22
2%
72
4%
Total claimants
(<1-17 years)
N=3,437
n
3,319
3,245
99
%
97%
94%
3%
N Total number of claimants prescribed insulin; n Number of claimants by type
of insulin; % Percentage of claimants dispensed a type of insulin within the age
group (n/N). The sum of claimants and percentage by age group does not total,
because one claimant can be dispensed multiple types of insulin in the same
year. **fewer than six claimants
TABLE 4
Distribution of claimants prescribed basal insulin by type
of insulin regimen and age
Age group
1 year
2-6 years
7-12 years
13-17 years
Total claimants
(1-7 years)
Basal claimants
% Intermediate-acting
% Long-acting
18
424
1,244
1,630
100%
99%
99%
96%
0%
1%
3%
6%
3,319
97%
4%
The sum of claimants and percentage by age group does not total, because
one claimant can be dispensed more than one type of insulin regimen in the
same year
TABLE 5
Distribution of short acting insulin claimants by source of
insulin and age
Age group
1 year
2-6 years
7-12 years
13-17 years
Total claimants
(1-7 years)
Short acting claimants % Analogue
% Animal
% Human
16
405
1,202
1,619
69%
58%
55%
54%
0%
0%
0%
0%
44%
62%
65%
64%
3,245
55%
0%
64%
The sum of claimants and percentage by age group does not total, because one
claimant can be dispensed more than one source of insulin in the same year
Utilization by type and source of insulin
Insulins fall into one of three categories: long acting (ultralente), short acting (regular, lispro and aspart) or intermediate
acting (NPH and lente) (1,2,6). The long and intermediate
acting insulins are used to maintain a basal insulin level at all
times (1,2). Short acting or prandial insulins are administered
to counteract glucose challenges in the form of meals or snacks
(2,6). Several premixed insulins are available that contain
both prandial and basal insulins. In general, insulin-dependent
claimants will require both prandial and basal insulin for opti-
52A
mal glucose management (2). Insulin pumps administer short
acting insulin throughout the day in a pattern that mimics
endogenous insulin secretion (6).
Most claimants in all age groups were dispensed both basal
and short acting insulins (97% and 94%, on average, respectively). Premixed insulin was used by a very small number of
insulin claimants (3%); most of them were in the 13 to 17 year
age group (Table 3).
A closer look at the basal component of insulin regimens
(long and intermediate acting) reveals that these children
were primarily using intermediate acting insulins (97%); long
acting insulins were only used by 4% of children using basal
insulin (Table 4). The majority of use of long acting insulins
was in the 13 to 17 year old group.
Short acting insulins are available in human, animal and
analogue forms. However, animal insulins were virtually nonexistent in this study. No intermediate or long acting analogue
was introduced to the Canadian market in the 1999/2000
study period.
Slightly more claimants were dispensed human short acting insulins (64% of claimants prescribed short acting
insulin) compared with the 55% dispensed short acting analogues (Table 5). A very small number of claimants used
short acting animal insulins (less than 0.3%). Nineteen per
cent of claimants using short acting insulin used insulin from
both of these categories during the course of the 12-month
study period. In general, the findings are consistent across all
age groups, with some variation in the youngest age groups
possibly due to the very small numbers of claimants.
SUMMARY FINDINGS
1. Approximately 0.3% of children in the study database
had received at least one prescription for insulin or
hypogylcemic drugs.
2. Most of the children had claims for insulin (96%). Those
children were more likely to have type 1 diabetes. Only
5% of children had claims for hypoglycaemic agents;
most of them were 13- to 17-year-olds.
3. Most insulin claimants were using basal and short
acting insulins (97% and 94% respectively). On average
97% of the use of basal insulin was in the form of
intermediate acting insulin and 64% of the use of short
acting insulin was in the form of human short acting insulin.
4. Nineteen per cent of those claimants using short acting
inslulin received both human and analogue insulin products
during the 12-month study period.
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Prescription medicine use in Canadian children
Expert Comment – Diabetes therapy
Jack Holland MD FRCP, Department of Pediatrics, McMaster University, Past President,
Canadian Paediatric Society
The treatment of type 1 diabetes in childhood has remained essentially unchanged since the first use of insulin therapy by
Banting and Best in Toronto 80 years ago. Only the insulin formats have changed, with a general trend towards the use of
shorter acting analogs of insulin to achieve ‘tighter’ control. The results of the long term Diabetes Control and
Complications Trial provide strong evidence that the better the control, the better the long term outcome.
Some major concerns around the world relate to the increasing prevalence of both type 1 and type 2 diabetes, with current prevalence rates of type 1 disease between 0.1% to 0.2% of at-risk populations. Large-scale epidemiological studies are
underway to explore a variety of potentially preventive strategies.
The second concern relates to optimization of glycemic control, while minimizing the risk for harmful episodes of
hypoglycemia. In general, this is best achieved in centres offering dedicated diabetic care, continuing education, and with
patient access 24 h a day. The widespread use of accurate and affordable glucometers, the increasing use of short acting
insulin analogues and an understanding that optimal care may require several insulin adjustments throughout the day, may
have a significant impact on long term morbidity, mortality, quality of life and health care expenditures.
The data in this study were completely in keeping with current epidemiological trends and treatment strategy across
the paediatric age groups. For instance, insulin is prescribed exclusively for type 1 diabetes and oral hypoglycemic agents
are prescribed for type 2 diabetes. However, it is likely that a proportion of adolescents may be prescribed oral hypoglycemic agents for ‘metabolic syndrome’, polycystic ovarian syndrome and hirsutism, or for hyperinsulinism without overt
glucose intolerance.
In my experience, the treatment of children and adolescents with type 1 diabetes requires intense moment-to-moment
assessment to ensure optimal care throughout the critical stages of childhood development. Parents or other caregivers are
key ingredients to success. Education in the nature of diabetes and its management are very important factors in determining successful outcomes. These ideals are best achieved by a team dedicated to childhood diabetes, or by paediatricians
experienced in diabetic care.
Future research related to diabetes should capture the following:
• Trends in the use of short acting insulin/insulin analogues
• Correlation between the use of insulin and the concomitant use of monitoring devices (glucometers)
• Site-specific or physician-specific prescribing patterns. This should identify the proportion of children and
adolescents receiving care from dedicated treatment centres, physician-led ‘teams’, group or single-person practice,
family doctor or paediatrician
• If possible, the number of pumps or automated delivery systems being used for insulin delivery in type 1 diabetes
Paediatr Child Health Vol 8 Suppl A April 2003
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Abi Khaled et al
CONCLUSION
The data used in this study are from the operation of a large
number of private drug reimbursement plans, which represents
roughly 30% of Canadian children, approximately half of whom
received drug therapy during the study period. The data contain
records for over one million children across Canada who received
drug therapy during a 12-month period. The patient totals represent an absolute minimum number of Canadian children.
In total, this study captured use on almost 1,400 different
drugs (single or multiple ingredient agents) dispensed to children. In other words, while the use of drugs in children is concentrated in several specific areas, there is a broad spectrum of
agents being used, with or without appropriate research and
regulatory supervision/assistance.
In all therapeutic areas, the drugs used and the rates of use
are highly dependent on age. Decisions about clinical trials or
further database research must consider age groupings very carefully and would likely be more powerful with narrow age bands.
Aproximately 75% of children receiving a claim required
an antibiotic during the year and roughly half used no other
class of drug. Approximately 50,000 children received five or
more antibiotic claims during the study period and 67% of
these children were six years of age and younger. Among the
one-year-old children in the study, over half of them received
two or more different antibiotics during the course of the 12month study period.
The use of therapeutic drugs is widespread and for a large
number of these drugs, safety and efficacy among children has
not been established. Physicians are required to make therapeutic judgements with limited or no evidence. Consequently,
ongoing vigilance in accurate paediatric labelling as well as
future clinical and pharmacoepidemiological studies addressing safety and efficacy are required. The large numbers of
Canadian children documented in this study using prescription
medicines reinforces the importance of ensuring that physicians are equipped with adequate information to ensure safe
and effective prescribing. Efforts must be concentrated in those
specific age ranges in which products or drug classes are used,
evidence of which can be determined from actual use.
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56A
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GLOSSARY
Active claimants: individuals who were dispensed a prescription that
was recorded as a claim in the database during the study period.
Adult claimants: claimants aged 18 to 65 years who had a claim for a
target drug paid for by the same private drug payment plans as those
included in the study.
Claim: a single prescription for a drug product paid by the private drug
payment plan. The terms ‘claim’ and ‘prescription’ are used
synonymously.
Claimant: the individual for whom the drug was dispensed. In this
analysis, claimants are children of a plan member. The terms
‘claimants’ and ‘children’ are used synonymously in many cases.
Course of therapy: term used with acute therapies and signifies a
prescription filled for a target drug and dispensed to paediatric
claimants over a 12-month index period.
Concomitant drugs: drugs used simultaneously with the target drugs
during the same time period. Concomitant definition is in
methodology.
Eligible claimants: Individuals covered under a particular drug plan
including those who have and who have not made a claim during
the study period.
Index period: a 12-month period following the first claim (index
claim) for a target drug in the study period. The index period
generally goes beyond the time frame of the study period.
Private drug payment plans: privately sponsored drug plan, which is
financed wholly or in part by the employer or by contributions from
the employees. This plan states which people are covered under
what plan, what drugs are paid for, and how these drugs are paid for.
Study database: the database of drug claims reported between January
1, 1999 and December 31, 2000.
Study period: the 12-month period between each paediatric study
claimant’s 1999 and 2000 birthdays.
Study population: Claimants 17 years of age and under who filled a
prescription during the study period.
Therapeutic area: category of drugs that share a common anatomical
and clinical target that have been grouped together for analysis.
Therapeutic class: subclassification of the drugs in a therapeutic area,
generally based on mechanism of action.
Target drug(s): specific drugs within a therapeutic area used to select
target drug claimants for analysis.
Target drug claimants: individuals who claimed a prescription for a
target drug.
Paediatr Child Health Vol 8 Suppl A April 2003