by Amy Spangler
June 12, 2007

The safety of drugs during pregnancy and lactation has been a topic of debate for many years. Currently, the safety of codeine is the focus of a class action suit filed in Toronto, Canada. The suit was triggered by the death of Tariq Jamieson, a healthy, full-term, exclusively breastfed baby boy who died at 13 days of age from morphine poisoning.

Tariq’s mother was experiencing pain after birth and was given a prescription for Tylenol 3. Ms. Jamieson took two tablets every six hours on day 1. The dose was reduced to one tablet every six hours on day 2 after Ms. Jamieson complained of constipation and sleepiness. Ms. Jamieson continued taking Tylenol 3 for two weeks.

According to Ms. Jamieson, Tariq had difficulty breastfeeding and appeared lethargic on day 7, and on day 11 was taken to a pediatrician due to concerns over poor skin color and poor feeding. An examination by the pediatrician showed that Tariq had regained his birth weight, so he was sent home. Two days later, the family was unable to awaken Tariq and called for emergency medical care. Attempts at resuscitation failed, and the newborn was pronounced dead.

Postmortem examination revealed a blood level of 70 ng/mL of morphine. Additionally, breast milk collected and stored on day 9 by Ms. Jamieson had a morphine level of 87 ng/mL. Typically, breastfed newborns of mothers receiving morphine would have a level of 0-2.2 ng/mL.

Tylenol 3 contains 500 mg of acetaminophen and 30 mg of codeine. In the body, codeine is metabolized to morphine. The rate at which codeine is metabolized varies with genotype. Individuals are classified as normal metabolizers, extensive metabolizers, or ultra-rapid metabolizers.

Genotyping revealed that Ms. Jamieson carries three CYP2D6 genes known to cause enhanced formation of morphine from codeine. Ms. Jamieson classification as an ultra-metabolizer would explain the high level of morphine in her breast milk. Genotyping also revealed that the father and baby each carried two CYP2D6 genes classifying them as extensive metabolizers. Only 1 percent of Caucasians are classified as ultra-rapid metabolizers, but up to 30 percent of Asians and Africans-Americans fall into this category.

Rare but real tragedy
This is the first documented death of a baby from morphine poisoning as a result of a breastfeeding mother taking codeine. What makes this case exceptional is the fact that the mother, father, and infant all carried two or more CYP2D6 genes.

Given the recent tragedy, parents and health professionals now face a dilemma.

Not surprisingly, Ms. Jamieson believes that codeine should never be used by breastfeeding mothers, regardless of the situation. However, experts from the Motherisk Program at The Hospital for Sick Children in Toronto feel a more comprehensive approach is appropriate and have identified the following strategies:

1. Avoid codeine while breastfeeding. This will decrease the baby’s risk for morphine poisoning but increase the potential for uncontrolled maternal pain.
2. Limit the use of high dose codeine (240 mg/d) to 2-3 days. This will decrease the baby’s risk for morphine poisoning but may still be too high a dose for ultra-rapid metabolizers. 
3. Avoid breastfeeding while taking codeine. This will decrease the baby’s risk of morphine poisoning but deny the baby the benefits of breastfeeding. 
4. Genotype all breastfeeding mothers. This is extremely expensive and not widely available.
5. Inform and monitor mother and baby for signs of morphine poisoning. This would facilitate maternal pain control and allow for early intervention should symptoms of toxicity appear in the baby.

Motherisk is currently recruiting patients for a study that will further examine the safety of codeine in breastfeeding mothers and babies.

Editor’s Note—August 17, 2007
On August 17, 2007, the Food and Drug Administration (FDA) issued a public health advisory on the use of codeine in breastfeeding mothers. This action comes in response to the rare occurrence detailed above.

Use of codeine products to manage pain after birth is common, and reports of serious side effects in breastfeeding infants are rare. However, the FDA has asked the makers of prescription codeine-containing products to include information about differences in codeine metabolism and concerns with breastfeeding in the drug label. Doctors who prescribe codeine need to be aware of the potential for the increased risks to breastfeeding babies of mothers who are ultra-rapid metabolizers of codeine.