Using codeine, dihydrocodeine or tramadol during breastfeeding

Avoid use

Codeine is not recommended. The Medicines and Healthcare products Regulatory Agency (MHRA) advises that it should not be used during breastfeeding.

The risks of using codeine during breastfeeding cannot be easily managed and there have been reports of serious side effects in breastfed infants.

Infant monitoring if codeine is taken accidentally

If a few doses of codeine are accidently used during breastfeeding, the mother should be advised to stop taking codeine and the infant monitored for side effects such as sedation, slowed breathing rate/apnoea, irritability, looking pale, dry mouth, gastro-intestinal disturbances, and difficulty feeding.

If significant side effects develop in either the infant or the mother, medical advice should be sought immediately. Significant side-effects in the mother could suggest she is an ultrarapid metaboliser, which also increases the risk of side effects in the infant.

Since codeine has a short half-life, the mother can consider abstaining from feeding for a short period of time (at least 4 hours) to allow a reduction in her milk levels before feeding again. However, this is not always necessary or practical.

Evidence of harm

Codeine used to be taken by many breastfeeding mothers for pain management. However, this changed due to a case report of an infant death. The mother was reported to be an ultrarapid metaboliser, having additional copies of the CYP2D6 enzyme involved in codeine metabolism. Ultrarapid metabolisers convert codeine to its active metabolite morphine to a greater and much quicker extent than normal. In the case report, there were increased levels of morphine in the breastmilk which led to fatal morphine toxicity in the infant.

Although re-examination of this data has questioned codeine-containing breast milk being the cause of this fatality, codeine use during breastfeeding is still not recommended.

At present it is not practical to identify who might be an ultrarapid metaboliser. It is more likely in some ethnic origins, but cannot be predicted by ethnic origin alone. Identification needs to be done by genotyping, which is not readily available.

Effects in infants

Following maternal use of codeine, there have been several reports of serious side-effects. These include bradycardia, respiratory depression, sedation, apnoea, cyanosis. Lethargy, drowsiness and poor feeding have also been reported.

Use with caution

Dihydrocodeine can be used short-term during breastfeeding with caution and infant monitoring.

Infant monitoring

As a precaution, monitor for potential side effects including sedation, breathing difficulties, gastro-intestinal disturbances, irritability, looking pale, dry mouth, difficulty feeding, and adequate weight gain.

Milk levels are likely to be low

There is extensive experience of the safe use of dihydrocodeine during breastfeeding. However, there is no published evidence to confirm its safety or the amount present in milk. Based on the drugs properties, it would be expected to pass into milk, but in small amounts.

Effects in infants

There is only one case report of the use of dihydrocodeine whilst breastfeeding a 2 day old infant. A mother was using dihydrocodeine as a cough suppressant (5.28mg/24 hours). The day after the cough suppressant was used, the infant was admitted to hospital and found to be bradycardic, hypoglycaemic, and had low oxygen saturation. However, 24 hours after admission, all symptoms resolved. It has been proposed that the mother was an ultra-rapid metaboliser.

Metabolism of dihydrocodeine

Dihydrocodeine is metabolised by a number of different pathways. One involves the CYP2D6 enzyme that converts dihydrocodeine to dihydromorphine, which also has potent analgesic activity. There is no data to confirm whether additional copies of the CYP2D6 enzyme have implications on dihydrocodeine metabolism and its potential to cause side effects.

Use with caution

Tramadol (both oral and intravenous) can be used short-term during breastfeeding with caution and infant monitoring.

Infant monitoring

As a precaution, monitor for potential side effects including sedation, breathing difficulties, gastro-intestinal disturbances, irritability, looking pale, dry mouth, difficulty feeding, and adequate weight gain.

Milk levels are low

Tramadol usually passes into breast milk in very small amounts. Most evidence shows that a breastfed infant would receive maternal weight-adjusted dosages of around 2.2% of tramadol and 0.64% of its active metabolite. Some other studies, including intravenous use of tramadol, have reported higher levels, but these are still defined as clinically insignificant.

In other countries, tramadol is given directly to neonates and infants for analgesia. The amounts of tramadol excreted into breast milk are much less than these doses.

Effects in infants

Limited evidence shows that infant serum levels are very low when exposed to tramadol via breast milk. Studies in over 220 women who breastfed their infants have not found any adverse effects attributable to tramadol.

In contrast, there is a case of a breastfed 8-month-old infant of a woman addicted to tramadol who suffered fatal poisoning. However, it could not be established that the cause of the infant death was exposure to tramadol through breast milk.

Metabolism of tramadol

Tramadol is converted into an active metabolite (M1), which has weak opioid activity. This conversion can also be affected by ultrarapid metabolism. However, the activity and conversion of tramadol is complex and involves other pathways. Evidence suggests that these differences in metabolism do not have a significant impact on milk levels.