Dose
of Reality
As More Drugs Are Tested in Kids, Labels Are
Changing
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By Francesca Lunzer Kritz
Special to The Washington Post
Tuesday, September 10, 2002; Page HE05
Wendy Goldberg of Bethesda wonders each day if some of the many drugs her
11-year-old daughter, Abby, has taken for severe asthma since she was 8
weeks old may have done more harm than good.
While all the drugs were approved by the Food and Drug Administration
(FDA) as safe and effective, most of their testing was done in adults, not
kids. Of the seven drugs Abby now takes, only four have dosing information,
relatively new to their labels, that addresses children in Abby's age group.
Three of the four, however, don't have information for children under 6,
though asthma is common in very young children.
What prompted the label changes are recent findings that resulted from a
series of federal directives that new drugs (as well as some older ones)
that may be taken by children be tested in the age groups that use them.
Previously, say experts, dose recommendations for children were based
largely on guesswork.
New information about dosing for children is beginning to appear on drug
labels only now, says Mark Schreiner, head of pediatric clinical trials at
the Children's Hospital of Philadelphia and a leading expert on drug use in
children, because clinical trials take several years to complete and be
evaluated by the FDA. William Rodriguez, an expert on pediatric testing at
the FDA, says label changes have now been made for nearly 60 drugs, with
additional changes expected for 100 more within the next few years. (See
chart on Page F5.)
In the case of Flonase, one of the allergy and asthma drugs taken by Abby
Goldberg, research showed that the drug could be taken safely and
effectively in children as young as 4.
The rationale for not studying children's dosing of drugs until now has
been, ironically enough, child protection. Because of ethics and liability
concerns prompted by the drugs' potential for side effects, researchers have
traditionally been reluctant to test drugs on children or women of
childbearing age. In recent years, however, patient advocates have argued
that such considerations may put members of these and other groups at
heightened risk if it stymies research.
"At times, children have been harmed and maybe even killed because of a
lack of knowledge of how drugs would affect them," says Robert Ward, a
former chairman of the American Academy of Pediatrics (AAP) Committee on
Drugs. He cites as an example the deaths in the 1950s of several newborns
after they were given an antibiotic called chloramphenicol. Because the
babies' livers were unable to break down the drug, toxic levels of it built
up, leading to their deaths.
Other drugs that have caused side effects -- some serious -- in children,
according to the FDA, include sulfa drugs (antibacterials that caused
jaundice in some newborns), the painkiller fentany (which caused withdrawal
symptoms for some patients after long-term use) and the antibiotic
tetracycline (which stained teeth in some children)
Richard Gorman, chairman of the AAP committee, calls the requirement to
test drugs in children one of the most important developments in pediatric
medicine. Until now, he says, no more than a third of all drugs used in
children were actually studied in kids. Vaccines widely used in children
were among those drugs previously tested.
For other drugs, doctors have done their best to extrapolate the best
children's dose based on body weight and some understanding of how
particular drugs work, says Schreiner, "but what we have discovered through
the clinical trials is that sometimes we overdosed, risking serious side
effects, and sometimes we underdosed and therefore gave drugs [in doses]
that weren't sufficiently effective."
Course
Corrections
One example of a misjudgment prior to expanded child testing is the
epilepsy drug Neurontin, for which dosing was increased after tests showed
that higher doses controlled seizures better in children without causing
more severe side effects.
In some cases, clinical trials have shown that a drug should not be used
at all in children below certain ages. That has been the case with the
eczema drug Elidel, which poses a risk of infections and diarrhea in
children younger than 2. Testing on Diprolene, which is used to treat
certain rashes, found that the drug could cause endocrine problems in
younger children. Its label now recommends that the cream not be used in
children 12 and younger.
Conditions for which much more pediatric drug information is still
needed, according to the FDA, include depression, epilepsy, severe pain,
gastrointestinal problems, allergic reactions and high blood pressure.
Safety and efficacy information is especially sparse on many drugs used in
children under 2, according to the agency.
Recent congressional moves, as well as pending action, suggest that
testing in children will continue. The Best Pharmaceuticals for Children
Act, which gives a financial incentive -- a six-month patent extension -- to
pharmaceutical companies that test drugs in kids, was signed into law
earlier this year and applies through 2007. An attempt by some Democratic
senators to cut the benefit to three months failed. Drugs that owe their
expanded information to this law include children's pain and fever relievers
Advil and Motrin. Both drug labels now carry information on dosing for
babies 6 months to 2 years.
The Senate Appropriations Committee is also expected this year to
consider a funding request that would allow the National Institutes of
Health to conduct pediatric testing of some drugs whose patents have
expired, since the drug companies often have no incentive to do so. Also
pending is congressional legislation to codify an FDA rule empowering the
agency to force companies to test certain drugs. After the FDA considered
shelving the rule earlier this year, an outcry from groups such as the AAP
led Secretary of Health and Human Services Tommy Thompson to promise to
retain it. Not satisfied, three Democratic senators have written legislation
to make the rule federal law.
A tight legislative calendar could keep the bill from becoming law this
year, but Sen. Christopher Dodd (D-Conn.), chairman of a Senate subcommittee
on children and families and one of the bill's authors, says he will
reintroduce the measure early next year if Congress does not pass it before
the current session concludes.
Francesca Lunzer Kritz is a regular contributor to the Health section.
© 2002 The Washington Post Company
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