Consider phasing out codeine: CMAJ

More study needs to be done on the dangers of codeine, according to an editorial in the Canadian Medical Association Journal.

The widely used painkiller codeine is potentially dangerous and may need to be phased out altogether until more safety research is done, an editorial in the Canadian Medical Association Journal says.

The editorial, published Monday, suggests that although codeine has been a commonly used drug for the last 200 years, it could be unpredictable in some people and even lead to death in children.

Codeine is a moderate pain reliever found in some over-the-counter medication mixtures, like adult cough syrups and some forms of Tylenol and Aspirin. When someone takes codeine, their body converts it into morphine, which relieves pain.

But depending on genetics, some people can metabolize, or process, codeine quicker than others, leading to a higher and faster dose of morphine in the body that could be potentially toxic.

A genetic test is only available in medical research labs, so patients and their doctors can never know whether they have the gene variant.

The editorial authors say that codeine never really had the rigorous safety studies that new drugs go through because it first came into use two centuries ago.

Since there is little research on codeine safety, associations and hospitals should modify guidelines and warn doctors about the potential risks until further studies are done, the editorial said.

Dr. Noni MacDonald, one of the editorial authors, said morphine is a better alternative to codeine because it is easier to predict the dose that ends up in a patient's system.

Few statistics available

"Why would we still use this drug codeine when it gets metabolized into morphine anyway?" she said. "We know a lot more about the kinetics of morphine, it doesn't have some of these other problems that codeine has in terms of the erratic metabolism, and it's cheaper."

The editorial says the genetic variant has been linked to the deaths of two children, and brain injury of another. MacDonald said the number may seem small, but that could be because there are few statistics available.

"We don't know how many times children died or had very serious events when people never even thought about it being due to the codeine being metabolized to high rates of morphine," MacDonald said.

The editorial also cites a 13-year study published last year that looked at opioid deaths in Ontario. MacDonald said the study found that codeine was the only opioid used in 20 per cent of the patients, but it is unclear whether those deaths were intentional overdoses.

"That's why we said more studies need to be done, " she said.

 Lori Montgomery, the interim director of Calgary's Chronic Pain Centre, agrees that more research needs to be done on opioid drugs in general, but says phasing out codeine entirely is "premature" because there aren't many pain relief alternatives out there.

"The (editorial authors) raise a number of concerns about codeine that are very valid but apply equally to all kinds of opioids including morphine which they're suggesting as an alternative," she said.

"Patients have few enough options for medications to manage their pain as it is, and I'd be concerned about any regulation that can limit their options even more."

Wide variability

She said there is also a wide variability in patient response to morphine, but the genetic factors are not yet known.

Montgomery said codeine and tramadol are the only weak opioids available in Canada and stronger pain relief medications include morphine, oxycodone and hydromorphone, but there aren't many more options.

In April, Toronto's Hospital for Sick Children stopped giving patients codeine after a committee raised concerns about how quickly some can metabolize it into morphine.

"Some people can have very serious side-effects, and there's no way to predict it at this point," said Dr. Shinya Ito, the chairman of the committee, who explained that a high dose could cause a patient to stop breathing.

"We don't want to put the patient at that kind of risk. That's why we decided to remove codeine."

Two years ago, Health Canada endorsed a warning from a drug manufacturer to breastfeeding mothers explaining that their milk could put babies at risk if they have the genetic variant that speeds up codeine's transition into morphine.

More research needed

The editorial suggests that young kids and breastfeeding moms are among the groups that should avoid codeine. More research needs to be done on its safety for adults and older kids, MacDonald said.

Health Canada said people of North African, Ethiopian and Arab origin are most likely to have the genetic variant in question, at between 16 and 28 per cent.

Between one and 10 per cent of Caucasians have the gene variant, while it is around three per cent for those of African origin. 

The gene variant is present in less than one per cent of people of Chinese, Japanese and Hispanic origin, Health Canada wrote in the 2008 letter.

Montgomery said research shows about 10 per cent of the population in North American can't metabolize codeine into morphine, so the drug isn't effective at all.