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  • Fondaparinux

    Could I ask your advice please? I am a pharmacist. We have a patient who we are treating with fondaparinux in pregnancy and who would very much like to breastfeed. She cannot have low molecular weight heparins but danaparoid is also a possibility although it is more difficult to give. I have looked through your previous postings and see you have said fondaparinux would be safe previously but I also saw a posting on danaparoid which said you would not give in the first few days postnatally as it might appear in colostrum. Why is this and which of the two drugs would you prefer to give in a breastfeeding mother?
    Thanks very much for your help

  • #2

    First let me describe something about molecular weight and transfer into human milk. The first 4-6 days postpartum, the milk compartment is quite open and porous and most any drug can readily enter colostrum at this point. That said, the volume of colostrum is so low (30-60 cc per day) that ultimately the absolute mg dose transferred to the infant is infinitesimally low. So we don't really worry too much about drugs during the colostral phase (first 4-6 days). After about 6 days, the milk volume increases rapidly to about 400-600 cc per day. This is when we carefully consider the dose of the drug transferred via milk. Also, after 6 days, the milk compartment tightens up significantly and becomes very similar to the blood-brain barrier, where drugs must be small in molecular weight ( < 700 daltons), and quite lipophilic, and non-polar, to enter the milk compartment. It really is very similar to the blood-brain barrier.

    Hence with fondaparinux, heparin, low molecular weight heparins, etc, the high molecular weights of these products virtually eliminate their entry into human milk, after 4 days. We have good data on the LMW heparins, and heparin that confirms this.

    While we do not have data on fondaparinux, I am quite certain that it would not enter milk much after 4 days, and due to its structure, it would not be orally bioavailable in the infant, as it would be totally unstable in the infants gut. For the first four days postpartum, I would assume that it would enter colostrum at about the same level as is in the plasma, but the limited volume of colostrum and its poor oral bioavailability would probably preclude absorption of very much if any at all.

    As Danaparoid, I think it has been withdrawn in the USA, but may still be available elsewhere. It is a derivative of heparin, and similarly would not likely be orally bioavailable or likely penetrate mature milk.

    Personally, I'd prefer fondaparinux.

    Tom Hale PH.D.


    • #3
      My daughter was diagnosed with Factor V Leiden, back in 2011 to complicate matters she has Heparin-induced thrombocytopenia and May-Thurner syndrome (MTS). Last year she found out that she was pregnant and the search was on to find a safe blood thinner that would allow for her to breast feed. Prior to her pregnancy she was prescribed Ellquis, thru out her pregnancy she was given Fondapariux Injections
      The Lactation Consultant at the Labor & Delivery unit verified that this combination would be safe for her to use during breast-feeding. Her baby is now 1 week old and they successful bridged her over from the fondaparinux injections back to ellquis all while the baby breast fed, there have been no issues to date. The baby was delivered at Tampa General Hospital’s Women’s Center. in Tampa, Florida


      • #4

        Fondaparinux sodium (Arixtra) is rated an L3-no data-probably compatible. "As a pentasaccharide, it would neither be likely to enter the milk compartment due to its large molecular weight, or be orally bioavailable in an infant if any drug managed to reach the milk compartment. No data are available on the transmission of fondaparinux sodium to a nursing infant, but based on the kinetic profile it is highly unlikely that it would be passed to the infant." (Medications and Mothers' Milk database, Dr Thomas Hale PhD). Monitor your infant for rare-bruising on the skin, blood in urine, vomit or stool.

        Apixaban (Eliquis) is rated an L4-no data-possibly hazardous. "At this time there are no data regarding the transfer of apixaban into human milk. The manufacturer reports that apixaban is excreted into rodent milk (about 12% of the maternal dose). Based on this medications small volume of distribution and high pKa it will likely enter human milk. At this time we recommend the use of alternatives with more data in lactation (e.g. LMWH, warfarin) when suitable to treat the maternal condition." (Medications and Mothers' Milk database, Dr Thomas Hale PhD).

        Sandra Lovato R.N.
        InfantRisk Center


        • #5
          Thank you for you for your response, the baby is now 5 weeks old and no bruising has been noted. At this time the mother is taking 2.5 mg of Elliquist twice daily without incidence. I will forward this data to her hematologist for review. As started earlier the mother is HIT Positive so we are left with little alternatives


          • #6
            Even I'd prefer fondaparinux.