Using oral anticoagulants in breastfeeding women

Laura Kearney, Regional Principal Medicines Information Pharmacist, Midlands and East Medicines Advice Service (Midlands site) & UK Drugs in Lactation Advisory ServicePublished

Thromboembolic disease management whilst breastfeeding is challenging. Warfarin is the preferred choice. Guidance on using DOACs is also provided.

Recommendations apply to full-term and healthy infants. If the infant was born prematurely, is unwell, or the mother is taking multiple medicines, contact the UK Drugs in Lactation Advisory Service.

Warfarin

Warfarin is the oral anticoagulant of choice in breastfeeding women. However, choice should always be made based on the woman’s clinical condition first, with suitability in breastfeeding being considered next.

Evidence to support use

There is some published evidence to support the use of warfarin during breastfeeding. This comes from 2 studies which included 15 breastfeeding women.

Negligible amounts in milk

Warfarin is very highly protein bound, which means there is less ‘free’ warfarin to pass across into breast milk. In studies, undetectable amounts of warfarin have been found in breast milk from women taking doses of 2–12mg daily.

No effects reported in infants

No adverse effects have been reported in breastfed infants who have been exposed. Seven infants had their serum levels checked and no warfarin could be detected. Even in a case of accidental overdose, the infant did not have any adverse effects reported and all coagulation tests were normal.

Direct Oral Anticoagulants (DOACs)

There is very limited information available on the use of DOACs during breastfeeding.

All DOACs may pass into breast milk. Preference is based on the amount likely to pass into breast milk and the availability of published evidence.

Appropriate choice should always be made based on the woman’s clinical condition first, with suitability in breastfeeding being considered next.

Dabigatran etexilate

This is one of the preferred choice DOACs

Milk levels are likely to be low

Dabigatran etexilate is one of the largest of the DOAC molecules and has a large volume of distribution, therefore it would be expected to pass into breast milk in low amounts.

Milk levels were tested from two breastfeeding women who took dabigatran etexilate 220mg as a single dose. The relative infant dose was calculated to be between 0.01 and 0.07%. The infants did not receive any breast milk during this time.

Infant absorption is likely to be low

Dabigatran etexilate also has very low oral bioavailability, so the infant is unlikely to absorb clinically significant amounts from the breast milk. It is therefore very unlikely that the infant would get any side-effects.

Rivaroxaban

This is one of the preferred choice DOACs

Milk levels are low

Although rivaroxaban has a high oral bioavailability, very low levels are expected in milk due to its other pharmacokinetic properties, so infant exposure should still be minimal.

Limited evidence from 6 women taking doses between 15 and 30mg rivaroxaban have reported very small amounts in breast milk, with the relative infant doses being between 1.3 and 5%.

Infant side-effects are unlikely

From the reports available, most infants were not breastfed. However, in one case report the mother was taking 15mg daily and partially breastfed her infant until 18 months. No adverse effects were reported and all normal developmental progress was made.

Other DOACs

Apixaban and edoxaban are not recommended during breastfeeding. If these are the most suitable choice for the mother’s clinical condition, their use in breastfeeding should be discussed with a specialist, such as UKDILAS.

Apixaban

Limited evidence from 4 women taking apixaban 5mg twice daily indicates that levels in breast milk are quite high, with relative infant doses between 12.8 and 21%. None of the infants were breastfed, so it is unknown how much the infant will absorb, and whether this will be clinically significant. Until further published evidence is available, apixaban is not recommended during breastfeeding.

Edoxaban

Only small amounts of edoxaban are expected to pass into breastmilk based on its pharmacokinetic properties. However, since there is no published evidence available, edoxaban is not recommended during breastfeeding.

Monitoring the infant

The infant should be monitored for any side-effects as a precautionary measure. This way will quickly pick up any potential issues. Usually some further investigation is required before attributing any side-effects to the medicine.

Bruising and bleeding

Monitor the infant for any signs of bruising and bleeding, for example blood in vomit, urine, or stools.

Feeding well

Ensure the infant continues to feed well and gains weight.

What we have considered

In order to make these recommendations, we have considered the following:

  • the published information that is available;
  • the properties of the medicines, including pharmacokinetics;
  • how likely it is that the oral anticoagulant may pass into breast milk;
  • once in the breast milk, how likely it is that the infant may absorb a clinically significant amount;
  • how likely the infant might get side-effects from this exposure, and how this can be managed.