A recent CBC interview on the subject prompted me to look this up, somewhat
out of personal curiosity, since when my kids were born, moms were given
codeine - has that changed?

 

From InfantRisk  (Thomas Hale):


Codeine Problem


Codeine is one of the most commonly used analgesics in the world. But
interestingly it is not biologically active itself. Instead, it must be
metabolized by the liver to its more active form, morphine. In most
individuals, about 7% of codeine is metabolized to morphine, which provides
the relief from pain. However some individuals have excessively active drug
metabolizing enzymes (CYP2D6) that can convert codeine to much higher
levels. We call these individuals, ultra-rapid metabolizer genotypes. In one
case, it was fatal for the infant.

The case recently documented, led to the death of a 13 day old infant,
following its mothers use of 30 mg codeine twice daily. A maternal dose of
30 mg twice daily would not have bothered most breastfeeding infants, but in
this case the milk levels were much higher. Morphine levels in milk were 87
ng/mL in the above case, while they are normally reported to be 1.9 to 20.5
ng/ml in non-hyper-metabolizers, even following 60 mg doses. 

The frequency of the CYP2DG hyper-metabolizer state is not necessarily rare,
while only 1% in Finland, it occurs at a rate of 10% in Greece and Portugal,
and 29% in Ethiopia. Somnolence and poor milk intake were the classic
symptoms observed in this infant. 

The best advice is probably to avoid using codeine in most breastfeeding
mothers. Use ibuprofen or acetaminophen when they control the pain, and use
hydrocodone (Norco, Vicodin) when the pain is much greater.  

If you do choose to use codeine, watch the infant closely for signs of
opiate poisoning: blue lips, poor feeding, poor-shallow breathing,
constipation, pin-point constriction of the pupils, etc. 

Reference:

1. Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ. Pharmacogenetics of
morphine poisoning in a breastfed neonate of a codeine-prescribed mother.
Lancet. 2006 Aug 19;368(9536):704. PubMed PMID: 16920476. 


Consider phasing out codeine: CMAJ


Last Updated: Tuesday, October 5, 2010


The Canadian Press 


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.



Read more:
<http://www.cbc.ca/health/story/2010/10/05/health-codeine-cmaj-phase-out.htm
l#ixzz130PY3Pu1>
http://www.cbc.ca/health/story/2010/10/05/health-codeine-cmaj-phase-out.html
#ixzz130PY3Pu1


             ***********************************************

Archives: http://community.lsoft.com/archives/LACTNET.html
To reach list owners: [log in to unmask]
Mail all list management commands to: [log in to unmask]
COMMANDS:
1. To temporarily stop your subscription write in the body of an email: set lactnet nomail
2. To start it again: set lactnet mail
3. To unsubscribe: unsubscribe lactnet
4. To get a comprehensive list of rules and directions: get lactnet welcome