General considerations

It is important to complete an individual risk assessment for your patient and to apply the principles of prescribing in breastfeeding when looking at the available information and making treatment decisions.

Recommendation

Codeine should not be used during breastfeeding.

Use of dihydrocodeine or tramadol while breastfeeding should be at the lowest effective dose for the shortest duration.

Regular use of any opioid in a breastfeeding mother beyond 3 days should be under close medical supervision.

A non-opioid analgesic, such as paracetamol or ibuprofen, should be used wherever possible.

Codeine

Recommendation

The Medicines and Healthcare products Regulatory Agency (MHRA) advises that codeine should not be used during breastfeeding.

The risks of using codeine during breastfeeding cannot be easily managed.

Evidence against its use

Codeine used to be taken by many breastfeeding mothers for pain management. However, this changed due to a case report of an infant death whose mother was taking codeine and was breastfeeding her infant. 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 recent 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.

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 adverse effects.

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.

Dihydrocodeine

Recommendation

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

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 during breastfeeding. A mother was using dihydrocodeine as a cough suppressant (5.28mg/24 hours) and was breastfeeding her 2 day old infant. The day after the cough suppressant was used, the infant became difficult to arouse and was not feeding well. 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 of these also 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. Further studies are needed to confirm this.

Tramadol

Recommendation

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

Milk levels are low

Most evidence for the use of tramadol, in maternal doses up to 400mg, report very small amounts in breastmilk of 2.2–2.24% of the weight-adjusted maternal dose. The active metabolite is reported as 0.64% of the weight-adjusted maternal dose.

In another study, detectable levels (>12 micrograms/L) of tramadol were found in samples of breastmilk collected 10 hours after a 50 mg maternal dose of intravenous or oral tramadol.

A further study where the mother was taking tramadol 50mg at an unknown frequency also showed variable amounts of tramadol in the breast milk ranging from 0.3– 9.1% of the weight-adjusted maternal dose. The mother may have had reduced clearance or metabolism.

With usual maternal dosage, the amount excreted into breastmilk is much less than the dose that has been given to newborn infants for analgesia.

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 a very potent and active metabolite (M1). This conversion can also be affected by ultrarapid metabolism. However, the activity and conversion of tramadol is complex and also involves other pathways. Therefore the effect of ultrarapid metabolism is not as profound compared to codeine.

Evidence suggests that these differences in metabolism do not have a significant impact on milk levels.

Monitoring the infant

If dihydrocodeine or tramadol are used during breastfeeding, infants should be monitored for sedation, breathing difficulties, constipation, difficulty feeding, and adequate weight gain. This advice also applies if codeine is taken accidentally.

Infants exposed to opioids during pregnancy or for longer periods while breastfeeding should be observed for withdrawal symptoms if the mother suddenly stops taking the medication or breastfeeding suddenly stops.

If side effects occur

If side effects develop in either the infant or the mother, medical advice should be sought immediately.

Dihydrocodeine or tramadol should be replaced by an alternative non-opioid analgesic. Depending on the severity of the side-effects, breastfeeding may also be advised to temporarily discontinue until a cause has been confirmed; although this would be rare.

Significant side-effects in the mother could suggest she is an ultrarapid metaboliser, which also increases the risk of side-effects in the infant.

Infants at most risk

Neonates and infants less than 2 months are at the most risk from the side-effects of dihydrocodeine and tramadol because they have underdeveloped livers, which means they cannot metabolise the medicines as effectively.

Extra caution should be taken when breastfeeding younger infants and neonates.

Patient Information

The NHS website provides advice for patients on the use of specific medicines in breastfeeding.

Contact us

Get in touch with the UK Drugs In Lactation Advisory Service (UKDILAS), our specialist breastfeeding medicines advice service, if you need support in the following situations:

• you need further advice
• the infant is unwell or premature
• multiple medicines are being taken

About our recommendations

Recommendations are based on published evidence where available. However, evidence is generally very poor and limited, and can require professional interpretation. Assessments are often based on reviewing case reports which can be conflicting and lack detail.

If there is no published clinical evidence, assessments are based on: pharmacodynamic and pharmacokinetic principles, extrapolation from similar drugs, risk assessment of normal clinical use, expert advice, and unpublished data. Simulated data is now increasingly being used due to the ethical difficulties around gathering good quality evidence in this area.

Bibliography

Full referencing is available on request.

Update history