Just weeks after his research sent shockwaves across the paediatric community, one Western researcher hopes the use of codeine-based medicine for toddlers may soon be a thing of the past, avoiding the deadly consequences some children have faced already.
Dr. Gideon Koren, Ivey Chair in Molecular Toxicology at Western’s Schulich School of Medicine & Dentistry, said The Hospital for Sick Children in Toronto has already stopped using codeine and McMaster University is soon to follow.
The Paediatric Medication Committee and Drug and Therapeutics Committee of London Health Sciences Centre are currently assessing whether or not to remove codeine from their formulary.
“And if you ask me, within the year, most academic institutions will do the same. Whether every physician in the country will do it, it’s hard to know,” Koren said. Since publishing his eye-opening findings on the death of four infants from codeine in the May issue of Pediatrics, more and more voices have come forward questioning the drug’s use. And discussions are already underway about a culture change in the industry.
Codeine, Koren said, has become a ‘household’ product in hospitals over the last two generations. Therefore, it may take quite a bit of awareness to realize a change with physicians.
“Clearly, the penultimate solution is either not to use it at all, or to have genetic testing done,” he said. “There is no question in my mind that in the next 10 years, each one of us will bear a small credit card that will have this and information on other genes that are affecting by drug therapy.”
As often happens, Koren’s research findings started with a tragedy.
In 2005, the Ontario Coroner’s Office came to him following the death of a baby from an unknown cause. A post-mortem found no reason for the death, other than high levels of morphine in the infant. It was determined the mother, who was breastfeeding the baby, had taken a Tylenol 3 – which contains codeine – to deal with pain after birth.
“We found that the mother was an ultra-rapid metabolizer and had produced much more morphine and passed it along,” Gideon said. “That opened our mind that genetic variability may be very important.”
A few years later, three additional cases involving the death of toddlers following an adenotonsillectomy for obstructive sleep apnea syndrome (OSAS), revealed the same ultra-rapid metabolism genotype.
When the standard patient is given codeine, their body converts 10 per cent into morphine to relieve pain. However, in the cases where a person has the ultra-rapid metabolism genotype, the conversion is closer to 40-50 per cent. In effect, doctors are poisoning people with the proper dose.
“That opened a whole Pandora’s Box because it became apparent that, although these operations are done on thousands of people, no one took the time to see what it does to the respiratory system,” Koren said. “These very troubling cases strongly suggest that many more are occurring and go undiagnosed. We cannot go on assuming that codeine is safe for all young children after tonsillectomy.”
He also stressed examining the practice of sending a young patient home right after surgery while receiving codeine. Studies have found a one-night follow-up in hospital may not be able to detect all the children at increased risk of severe respiratory complications.
Between 600,000-1.8 million children in North America under 15 are affected by OSAS, which disrupts ventilation and breathing patterns during sleep. The primary treatment is surgical intervention, generally adenotonsillectomy.
“Obstructive sleep apnea is a prevalent condition; currently, there aren’t any agreed upon standards in North America for treating paediatric post-tonsillectomy pain,” said Lauren Kelly, a PhD candidate at Western and the study’s lead author. “Many children are treated with codeine for a wide range of indications and it appears some children are at an increased risk for morbidity/mortality despite receiving standard doses.
“More research is required to help physicians identify these risk factors and be able to safely manage these children. Hopefully, these cases will serve to prevent future such tragedies by alerting physicians to these high-risk children and encouraging them to carefully monitor respiratory status following codeine use post-tonsillectomy.”
Currently not covered by OHIP, testing for the gene mutation is available at a cost of approximately $150-200.
“That’s the whole concept of individualized medicine,” he added. “You cannot assume the same dose of a particular drug will be the same for everybody. We are now in the dawn of the individualized medicine and that’s one of the big issues right now. It’s not an easy situation, and it will take work, but at least now we know that there is something here that we should look at.”
Koren said one issue is medicine changes all the time as new information is discovered. In fact, approximately 40 drugs have been identified by the United States Food and Drug Administration where genetic variability has resulted in serious incidents or lack of efficacy. For those drugs, the organization recommends genetic testing prior to use.
“It’s always a puzzle,” Koren said.
