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Anticoagulants, thrombocyte aggregation inhibitors and fibrinolytics
Treatment with anticoagulants (heparin and derivatives), as well as with thrombin- and factor Xa-inhibitors, is acceptable during breastfeeding. Except for low dose acetylsalicylic acid, all other thrombocyte aggregation inhibitors should be used during lactation only if other alternatives are lacking. There are no human studies on the usage of fibrinolytics and antihemorrhagics during lactation.
4.7.1
Heparin and danaparoid
Heparin does not pass into the mother’s milk nor is it absorbed in relevant quantities in the gastrointestinal tract. This is also expected for the low molecular-weight preparations, certoparin , dalteparin , enoxaparin , nadroparin , reviparin and tinzaparin . In a study of 15 women who received 2,500 IU dalteparin daily after caesarean section, the anti-Xa activity in the plasma of the mother and in the milk were measured as indicators for heparin effects. While a maximum of 0.308 IE/mL was measured in the plasma, the peak value in the milk was 0.037 IE/mL. The M/P ratio showed values between 0.025 and 0.224. The authors calculated, on the basis of the highest activity values in the milk, a 5.4% share of the maternal weight-related dose within 24 hours, assuming a daily intake of 250 mL milk for a newborn on the 5th day of life. If one also considers that heparin is practically not absorbed orally, no risk should be expected through the mother’s milk ( ). Studies on the use of the heparin antidote protamin during breastfeeding are not available. Due to its molecular structure and the half-life of 24 minutes for the protamin-heparin complex, appreciable oral availability through the mother’s milk seems unlikely.
Danaparoid apparently does not pass into the mother’s milk in clinically relevant amounts. In milk samples of five patients, the anti-Xa activity was only 0–0.07 IE/mL although values in the maternal plasma between 0.15 IE/mL and 0.45 IE/mL were reached ( ). Other case reports also describe only a minimal passage into the colostrum ( ). Even when transfer into the mother’s milk cannot be completely ruled out, danaparoid is broken down by the baby’s digestive enzymes.
Recommendation
During treatment with unfractionated heparin, low-molecular heparins or danaparoid, breastfeeding may continue without limitation. When indicated, protamin can be used during breastfeeding. Limiting breastfeeding does not seem to be justifiable.
4.7.2
Thrombin- and factor Xa-inhibitors
A mother treated with lepirudin for heparin-induced thrombocytopenia received 3 months subcutaneously 2 × 50 mg daily during breastfeeding. Three hours after the lepirudin injection, a therapeutic concentration of 0.73 mg/L of hirudin was found in the maternal plasma. At the same time, there was no hirudin detectable (<0.1 mg/L) in the milk. The breastfed baby showed no symptoms whatsoever ( ). There are no clinical data available for desirudin . However, owing to a similar molecular structure (polypeptide with a high molecular weight) problems with the breastfed baby would hardly be expected. There are, as yet, no data on tolerance for the hirudin analog, bivalirudin , during breastfeeding. Due to its high molecular weight and the short half-life, an appreciable intake via the mother’s milk seems unlikely. There is also, as yet, no experience with the use of argatroban during breastfeeding. The manufacturer refers to the transfer of the substance into the milk of rodents. It is not known whether argatroban is bioavailable orally. However, due to the molecular structure, this seems unlikely. As yet, no data have been provided on the oral thrombin inhibitor dabigatran . The oral bioavailability has been given as 6.5%.
Undesirable effects for the breastfed child after using the factor Xa-inhibitor fondaparinux have not been described up to now and seem unlikely due to the molecular structure ( pentasaccharide ). Rivaroxaban and apixaban are insufficiently researched. Data from animal experiments indicate passage of the substance into the mother’s milk. Due to the high oral bioavailability (rivaroxaban 80–100%, apixaban ca. 50%) intolerance in the infant cannot be ruled out.
Recommendation
With lepirudin, desirudin, bivalirudin and fondaparinux, any limitation on breastfeeding does not seem justifiable. Argatroban and the orally bioavailable medications, dabigatran, rivaroxaban and apixaban should only be used when there is a lack of alternatives. Decisions on limiting breastfeeding should be made in individual cases.
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