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It's time to phase out codeine, doctors urge

Doctors are warning codeine may be dangerous for some kids who have rare genetic anomalies that make them 'ultrarapid metabolizer' of the drug.
Doctors are warning codeine may be dangerous for some kids who have rare genetic anomalies that make them 'ultrarapid metabolizer' of the drug.

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Date: Monday Oct. 4, 2010 2:05 PM ET

Codeine might be a widely used painkiller, but it's also a risky medication that should be phased out until more research can be done, argues an editorial in the Canadian Medical Association Journal.

Pediatricians Dr. Noni MacDonald and Dr. Stuart MacLeod write in the editorial that codeine is simply not effective enough as a pain reliever to justify its risks, which include unpredictable reactions and even death.

Codeine is found in a number of medication mixtures, including in some forms of Tylenol and Aspirin that are available without a prescription.

The drug is converted in the body into its active metabolite, morphine, which relieves pain. The problem is that some people have genetic variations that cause them to become ultra-rapid metabolizers of codeine

These people convert standard doses of codeine into morphine much faster than others, leading to higher-than-expected morphine levels in their blood. This can lead to toxicity symptoms such as extreme sleepiness, shallow breathing and in some cases, death.

Infants and children are particularly vulnerable to morphine overdose, and reports are emerging of infants who died after breastfeeding from their mothers who turned out to be rapid metabollizers.

People of North African, Ethiopian and Arab origin are most likely to have the genetic variant that makes them rapid metabolizers, but people of Caucasian and Asian background can also have the gene variant.

The only way to know who will over-metabolize the drug and who won't is to test for the variant through a medical research lab.

The authors note that genetic testing prior to prescribing codeine is impractical, since the testing is expensive.

"Perhaps a more direct approach is now needed: to stop using the prodrug codeine altogether and instead use its active metabolite, morphine," they write.

"Not only is the metabolism of morphine more predictable than that of codeine, but also it is cheaper."

The authors note that although codeine can been prescribed for decades, there is really very little research on its safety.

"Because codeine has been in common use for over 200 years, it was never subjected to the regulatory requirement for the rigorous safety studies that are now mandatory for new drugs," the authors note.

Given the risks of codeine, it's time to reevaluate the drug and how to lessen its risks, they write. Restricting access to codeine for infants and young children is one option, they note, but because not a lot of research has been done on codeine, it is unclear at what age the risks of the drug start to fall.

The authors say that until more research has been done, doctors should be warned about the potential risks of codeine, especially for newborns and children.

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