Healthy Skepticism Library item: 796

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Publication type: news

Kirkey S.
Children's drugs an 'educated guess'
The Ottawa Citizen 2005 Feb 1

Full text:

Thousands of times a day, a child in Canada is given medication that hasn’t been properly tested for their age group. While two key measures are being introduced to solve the problem, that does little to help the many parents who ‘have felt the terror of losing a child,’ Sharon Kirkey reports.

In early December 2003, Gordon Mitchell was on a family vacation in Puerto Vallarta, Mexico. The 16-year-old was in his element, displaying his athletic skills as he swung his strong, young body from cables in the trees in the foothills of the Sierra Madre mountains.

At Christmas that year, Gordon was laughing and joking with his cousins and teasing his grandmother, the woman with an instinct for kids who let him smear face paint on her cheeks and eat Mr. Freezes for supper when he was little.

Four days after Christmas, his parents and little sister, Kaitlyn, left their home in Olds, Alta., for a swim at the nearby leisure centre.

Gordon Mitchell stayed home, and killed himself.

Gordon had been taking Paxil, an antidepressant his doctors prescribed for anxiety. Although he had stopped taking it about two months before he took his life, the medical examiner’s report revealed Paxil could still be detected in Gordon’s body.

The drug has since been hit with mandatory warnings of a possible increased risk of suicidal thinking and “self-harm” in children and adolescents, and a British ban on its use in anyone under 18.

His parents were not told the antidepressant has never been licensed for children in Canada, that it was being prescribed “off label” — meaning for purposes not approved by Health Canada — or that its prescribing information cautioned doctors that “safety and effectiveness in children under 18 have not been established.”

Thousands of times a day in Canada, a child is drugged with a pill, syrup or lotion that hasn’t been adequately tested on children, if at all. Drug labels frequently provide doctors with little or no information on its effectiveness, age-appropriate dose or safety in youngsters, especially for children less than two.

Now, after years of glacial progress compared with the U.S. and European countries, Canada is moving to improve drug investigation in children. Health Canada is proposing giving pharmaceutical companies an extra six months “market exclusivity,” which prevents a generic version of the drug from coming on the market. This measure is meant to encourage the drug makers to test a new drug on “pediatric age groups” — from premature babies born before the 37th week gestation to 17-year-olds — if their drug is likely to be used on children.

A similar provision adopted by U.S. drug regulators six years ago has led to safety and dosing labelling changes on at least 40 drugs. U.S. drug makers have also faced charges from the Alliance for Human Research Protection that children are being exploited for profit and exposed to pain, and potentially harmful medicines, in the name of assembling “good clinical data,” even if the drug offers them no potential benefit.

In a separate development, an $8.4-million, nationwide project partly funded by Genome Canada will be launched today that could make drug use for children safer worldwide. At least seven children’s hospitals will join to monitor and report adverse reactions to drugs in children, from rashes to drug-induced hepatitis and Stevens-Johnson Syndrome, a rare and potentially fatal blistering, burning allergic reaction. Researchers will also collect DNA and blood samples, searching for genetic markers that could explain why a drug is safe for one child, but not another.

Instead of sitting around, waiting for drug reaction reports in children, “we’re hiring people to go out and find them,” says co-principal investigator Dr. Bruce Carleton of Children’s and Women’s Health Centre of British Columbia, and the University of B.C.‘s Centre for Healthcare Innovation and Improvement.

In so doing, he says, they hope to develop a central registry, share it among hospitals and detect drug reaction patterns.

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Gordon’s parents only learned of new warnings about Paxil from media reports in 2003. It took two visits to persuade Gordon’s physician to take him off the drug. He was switched to Zyprexa, an antipsychotic that has only been studied in adults. He was also taking the acne drug Accutane, which — again, unbeknownst to his parents — has been linked with a possible increased risk of aggression and suicide.

“It’s realistic to expect full disclosure when making decisions about your family’s health,” Gordon’s mother, Joyanne, says. She believes that, while some of Gordon’s struggles were due to his generalized anxiety disorder, “in retrospect, many, if not most, were due to the medications that he was on.”

All parents, she says, should be told if a drug is being prescribed “off label” to their child, and families should sign consent forms acknowledging they’ve been advised as such.

“I didn’t even know what ‘off label’ meant until Gordon died.”

In fact, less than 30 per cent of drugs used in children — from inhaled steroids for asthma to medications for epilepsy, high blood pressure, nausea and attention deficit disorder, and anesthetics to sedate children before surgery — have been properly tested in children, or tested in the specific age groups for which they’re used.According to an article published last year in the Canadian Medical Association Journal, much of pediatric prescribing boils down to “educated guesses” about doses and safety.

It’s a potentially dangerous situation, experts say, that can do two things: make physicians reluctant or afraid to use promising new drugs that may help a sick child, or expose children to needless risks because of overdosing or under dosing.

According to Health Canada data provided to CanWest News Service, between Jan. 1, 2001 and Oct. 31, 2004, 96 children in Canada died after a suspected adverse drug reaction. In all cases, the death was recorded as “drug may be contributory” or “died due to adverse drug reaction.”

Overall, the department received 33,340 reports of suspected drug reactions over that period, 2,244 of them in patients aged 18 or less.

The reports are based on suspicion only and no cause-and-effect link has been established. But doctors say it’s almost certain the true number of deaths and serious injuries involving a drug side effect is much higher.

A 2003 study published in the journal Pediatrics concluded adverse reactions to drugs are a “significant” cause of death and injury in children under two.

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Many drug reactions are due to error: With so little information on prescribing for children, doctors calculate doses based on weight, and pharmacists have to dilute drugs for children. That can lead to huge calculation mistakes, mixing up milligrams for micrograms, or misplacing a decimal.

The errors can go unnoticed because the amounts sound so small.

“If you say, ‘this baby needs a teaspoon of medicine,’ that sounds right. But what if what they really needed was one-10th — .5 ml, instead of 5 ml?” says Dr. Michael Rieder, a pediatrician at the Children’s Hospital of Western Ontario in London, who works in an adverse drug reaction clinic that treats about 600 children a year.

The extra half-year market protection for drug companies that test new medicines on children is a start, he and others say. But it does nothing to improve testing of older drugs that have been on the market for years.

“Most drugs we use in children are in that category, from digoxin to morphine,” says Dr. Gideon Koren, senior scientist in the Hospital for Sick Children Research Institute in Toronto and professor of pediatrics, pharmacology, pharmacy and medicine at the University of Toronto.

“Morphine is now the No. 1, or close to it, drug for causing serious adverse events in children. It’s used by thousands of kids every day after surgery, but if you open the product monograph, it says not recommended for young children because there is not enough (safety) data. The reality is that, for forever, drug companies were not interested in children.”

The U.S. consumer watchdog group Public Citizen says the extra patent extensions have led drug companies to do pediatric tests on their most “lucrative” drugs, such as medicines for heartburn and high cholesterol, just to stretch out their market monopoly. A feature article titled “The Pediatric Gap” by Jerome Groopman in the Jan. 10 issue of the New Yorker says companies are satisfying the requirements “without generating meaningful data on how to prescribe its drug for children,” according to an expert in pediatric drug trials.

Mrs. Mitchell and her husband, Jim, are preparing to launch a website to encourage parents to report adverse drug reactions and force changes to Canada’s voluntary reporting system.

“We were very involved and asked the right questions. Even when we phoned the hospital to ask for advice on symptoms (of a drug reaction) they couldn’t, or didn’t, advise us his nightmares, increased anxiety and other symptoms could be an adverse reaction,” Mrs. Mitchell says.

“Drug companies do not feel the terror of losing a child.”

In Need of Testing

In 2003, The U.S. Department of Health and Human Services named the following 12 commonly prescribed drugs as the “highest-priority” drugs needing testing in children:

Azithromycin: an antibiotic used to treat many different infections

Baclofen: a muscle relaxant that relieves cramping and spasms caused by multiple sclerosis, spinal cord injury and other muscle disorders

Bumetanide: a diuretic that causes the kidneys to get rid of excess water and salt from the body

Dobutamine: stimulates the heart and is used in critically sick children

Dopamine: used to treat shock in critically ill patients

Furosemide: a diuretic

Heparin: used for the prevention and treatment of harmful clots in the blood vessels

Lithium: used for the treatment of bipolar disorder

Lorazepam: often prescribed for anxiety and sleep problems in adults, used in children for the treatment of acute seizures and long-term sedation in the intensive care unit;

Rifampin: used in combination with other drugs to treat tuberculosis, and to treat carriers of certain meningitis-causing bacteria

Sodium Nitroprusside: used to reduce blood pressure in critically sick children

Spironolactone: used to prevent loss of potassium