Except for drugs specifically
targeted towards childhood diseases, clinical trials rarely
include kids for some very good reasons, including issues
of informed consent, fear of litigation and bad publicity
in the case of serious adverse events — just to name
a few.
PUT
AWAY THE WEIGH SCALE
Approximately 75% of drugs approved for use have never
been tested in kids yet many of these meds make their
way into pediatrics.
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Pediatric prescribing points
to remember
• Children
are prone to drug toxicity
• Dosing strictly according
to weight can result in over-dosing
• Be especially wary of preparations
such as long-acting meds, extensively metabolized
drugs, and both inhaled and intravenous meds
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Physicians who prescribe them for
their young patients often find that there are no published
dosing guidelines to follow. They may mistakenly just
reduce the dose according to weight. This isn't appropriate
because kids metabolize and excrete drugs less rapidly
as their livers and kidneys aren't mature yet. They
also tend to have greater peripheral tissue blood flow
due to a quicker heart rate. As a result, drugs are
more rapidly disseminated and concentrated in tissues.
Teens are also at risk. Physiologic differences between
child and adult persist well into the teenage years
— even an adult-size teen may suffer toxicity when
dosed according to body weight.
CAREFUL
WHAT YOU WISH FOR
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Don't kid around with these
meds
Rest - in peace? Meds
with longer half-lives are especially dangerous
— sedatives and opioids in particular because
of their respiratory depressant effects. In one
study of young patients in ICU, the sedative propofol
resulted in a two- to threefold rise in mortality
vs other sedatives — the drug is no longer
recommended for kids. Even drugs felt to be minimally
sedating in adults, such as local anesthetics,
may cause serious over-sedation or toxicity in
small children. Opioids used chronically may also
increase the risk of addiction — though this
has never been definitely studied in kids.
Can't breathe easy The
rapid dissemination of drugs to tissues in kids
may cause serious side effects particularly in
meds for acute asthma exacerbation. Inhalants,
such as beta-receptor agonists, are generally
absorbed much more quickly into the bloodstream
than oral preparations. Intravenous drugs like
steroids have virtually immediate systemic access.
To date, there are almost no pediatric clinical
trials testing drugs for acute asthma, either
for efficacy or safety.
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There are no easy solutions to
the problem. Pharmaceutical companies understandably
are reluctant to include children in clinical trials,
except for drugs specifically targeted to childhood
disease. Attempts to legislate for more trials involving
children have been half-hearted, largely because enforcing
such laws could open the clinical trial door to other
vulnerable groups such as pregnant females, the infirm
elderly and significantly immuno-compromised patients.
Increasing access to clinical trials for these groups
almost certainly would cause company insurance premiums
to skyrocket, which in turn could slow down the development
of new and innovative drugs or limit production to meds
that solely target the young to middle-aged adult.
HOW
TO DEAL
It has been suggested that an international formulary
be created to establish guidelines for the rational
use of drugs in kids. Another strategy is to implement
a system of post-marketing pharmacovigilance specifically
for children. However, neither project has gained momentum.
The former proposal mistakenly implies that there are
adequate data available on which a formulary could bebased.
The latter proposal would be very costly and poses many
logistical difficulties. So, what's a practicing physician
to do? These inadequacies definitely leave us with relatively
little guidance when prescribing meds to children. The
points below may be of help.
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