Most prescription drugs kids take not approved for their use

Most prescription drugs kids take not approved for their use
Here's what you should know
BY HEATHER NEWMAN • FREE PRESS STAFF WRITER • September 21, 2008


All of the prescription drugs your kids are taking probably aren't approved for them.
If you didn't know that, you've got company.

The majority of parents surveyed in a recent poll think whatever their pediatrician prescribes is safe.

But according to doctors and researchers at the University of Michigan, 70% of available drugs -- including those being used to treat kids for everything from respiratory illnesses to weight issues -- have not been approved by the Food and Drug Administration for use by children.

The FDA is reviewing the use of cold medicines in children ages 2 to 11. The drugs were pulled off store shelves for kids under 2 earlier this year after several kids died from accidental overdoses.

The two FDA committees overseeing the review are to meet in October.

The statistics used to be worse. About a decade ago, 80% to 90% of drugs were not approved for kids.

And while the numbers are improving, pediatricians and researchers say they're not comfortable.

"It's business as usual, but it's not business the way you want it to be done," said Dr. Richard Gorman, a pediatrician and chairman of the American Academy of Pediatrics Section on Clinical Pharmacology and Therapeutics. The gap is a huge concern for doctors, who must use educated guesses about which medicines might be effective and what dosages to prescribe.

The academy's official position is that it's up to the pediatrician to prescribe off-label drugs to children if there's a scientific reason to expect they'll be helpful and when there is a lack of realistic alternatives -- the situation those doctors and parents are faced with every day, he said.

Finding child test subjects can be difficult.

For Mike and Connie Wall of Plymouth, the decision to put their 11-year-old daughter Christine into a study for a cancer vaccine last October was a hard one. She had a rare type of cancer -- a malignant peripheral nerve sheath tumor -- with a high return rate; the vaccine, if successful, would help.

"We prayed and agonized over it a lot," Mike Wall said. "We don't know if it could be a lifesaver or harmful. We may not know forever."

He said that if her condition hadn't been life-threatening, they wouldn't have participated in the research. Christine now appears to be in remission.

Researchers say traditionally there has not been much financial incentive for drug companies to test children, who may represent a tiny portion of the market for a particular drug, and finding parents willing to have drugs tested on their children can be difficult.

"That leaves parents and doctors in a tough situation," said Dr. Matthew Davis, U-M associate professor of pediatrics, a pediatrician at C.S. Mott Children's Hospital in Ann Arbor and coauthor of the National Poll on Children's Health that was released in May. The study surveyed more than 2,000 parents and found that 83% believe that their child's last prescription was FDA-approved.

Test subjects
While about 30% of medicines have been approved for kids, some drugs, like those to treat Alzheimer's, truly are useful only for adult conditions. The percentage of drugs that children are prescribed off-label hasn't been specifically nailed down.

But parents often end up effectively testing drugs on their children without knowing it.

Children are not just small adults, said Dr. Esther Yoon a lecturer in the U-M division of pediatrics, a practicing pediatrician in Canton and the poll's coauthor. "They metabolize substances differently."

Beth Hurley, 42, of Canton said she made the tough decision to turn down Elidel skin cream for her son Aiden's eczema after reading that it hadn't been approved for children. The condition left him with cracking and bleeding skin behind his knees as a toddler. Nothing helped. One doctor suggested the new cream.

"It had not been approved for children 2 years and younger," Hurley said. On a TV commercial, she noted that the side effects included possible cancer or death. "I said, 'Are you kidding me?' "

A few years later in 2005, the drug was given a "black box" warning, the most serious the FDA can add, because of its role as a possible cause of skin cancer.

"I really felt, thank God we made that decision," said Hurley, who was a paid discussion leader for the Free Press' former MotorCityMoms.com site. "We have always erred on the side of caution. Cracking, bleeding skin -- that's horrible, but I'm not willing to risk death for it."

That said, the family decided to allow their son, who has allergies, to use Zyrtec, which had not been approved for children his age. That was after reading up on potential side effects and quizzing their doctor. "It's been because we were desperate, and there were no dire warnings," Hurley said. "When your child can't breathe..."

If not this, what?
Because of legislation passed in the past 10 years, pediatric assessments -- how likely it is that a drug will be prescribed to kids -- are now required as part of the approval process. The FDA also has the power to require companies to conduct pediatric tests.

Dr. Lisa Mathis, associate director for maternal and pediatric health staff in the office for new drugs at the FDA, said much has been learned in recent years. But, she said, "We're still in a position that there are still more drugs that aren't labeled than are. But the whole environment has changed. We now have the opportunity to intervene. That said, we're not satisfied that we're where we need to be."In June, the American Academy of Pediatrics recommended that doctors use some statin cholesterol-lowering drugs in children as young as 8. Pravastatin, commonly sold as Pravachol or Selektine, was approved by the FDA for children after studies that included a two-year trial on 214 children. The drug had side effects including heartburn and muscle pain.

"That's the only one that is approved for children of that age," said Nicolas Stettler, assistant professor of pediatrics at the Children's Hospital of Philadelphia and a member of the committee that approved the new recommendations. The group had been waiting for something to help younger kids with cholesterol issues.

"The major benefit of having FDA approval is that approval indicates significant information about safety and dosing," U-M's Davis said.

Other, more common drugs for kids, such as Amoxicillin, are tested and approved for kids. But if the child has an allergy to penicillin, making amoxicillin an unsafe choice, doctors find themselves in a bind, especially for infants.

Most doctors would reach for azithromycin (sold under the brand name Zithromax), which is an excellent drug, said Yoon. The problem: It's only approved for babies over six months.

Another example is albuterol, a drug that increases air flow to the lungs, which is commonly prescribed to children with bronchiolitis, a common illness of the respiratory tract that makes it difficult for kids to breathe. Babies and toddlers are susceptible to the condition, especially in winter, Yoon said, but albuterol isn't approved for children under age 2.

"As a physician, would I use this medication? Of course. I have no other real alternatives that are FDA-approved," she said.

No one size fits all
The FDA approves about 95% of all adult medications. But getting drug approval for children involves hurdles:

• There isn't one blanket approval. A drug can be approved for children over 6 months, 2, 6 or even 12 years of age.

"There's a whole range of pediatric patients and they all present different issues in terms of drug development," said Alan Goldhammer, deputy vice president of regulatory affairs for Pharmaceutical Research and Manufacturers of America, the industry trade association for drug makers. "You can't do a study on teenagers and extrapolate it down to a baby."

• There often aren't many incentives for drug companies to get older medicines approved. If the drug is already off-patent (available in generic form), there's almost no financial advantage to do the tests.

• Finally, there's the problem of finding enough kids to do studies. About 60% of those parents polled say they would not let their children participate in tests.

Lipitor, a cholesterol-lowering medication approved for kids ages 10 and up, was tested on children ranging from 2 to 16 before it was approved, said Dr. Halit Bander, executive director, Pfizer's Cardiovascular Medical Team, Lipitor lead. There just weren't enough patients in the study younger than 10 to allow for that kind of labeling.

A followup test focused on children ages 10-17 and the drug was labeled for children that age in 2002, six years after it was approved for adults.

Testing incentives
The Food and Drug Administration has taken several steps over the past six years to encourage more manufacturers to test their drugs for children. A study released early this year by the FDA showed that drugs tested for kids at the FDA's request generally ended up getting critical changes in dosages as a result.

The Best Pharmaceuticals for Children Act, passed in 2002, gives drug companies an extra six months of exclusivity on the market if they test their medicine for children at the FDA's request. The Pediatric Research Equity Act went into effect in 2003, requiring drug companies to put new medicines through pediatric testing unless they successfully won a waiver for their products.

Potential grounds for waivers include drugs where the population of kids would be too small -- typically 50,000 or fewer nationwide -- to reasonably allow testing; or drugs that are unlikely to be used in children and offer no substantial benefit over existing drugs for them.

Since last year, 100 applications for waivers have been filed by drug companies. Another 50 requested a deferral to do pediatric research after the drug hit the market. And 50 new drugs were actually tested for kids.

"I think the best policy is for doctors to hold an open discussion with parents," Davis said. "I explain to parents the situation if I'm faced with an illness with a child where only non-FDA-approved drugs are available."

Contact HEATHER NEWMAN at 313-223-3336 or hnewman@freepress.com.