Is Mercaptopurine safe while breastfeeding?

Effects on the breastfed infant

In The Netherlands, 30 infants of mothers taking either azathioprine (n = 28) or mercaptopurine (n = 2) for inflammatory bowel disease during pregnancy and postpartum were followed at 1 to 6 years of age using a 43-item quality of life questionnaire. Of this cohort, 9 infants were breastfed for a mean of 7 months (range 3 to 13 months) No statistically significant differences were found between breastfed and formula-fed infants in any of the 12 domains of the survey.[19] In a multi-center study of women with inflammatory bowel disease in pregnancy (the PIANO registry), 102 women received a thiopurine (azathioprine or mercaptopurine) and another 67 received a thiopurine plus a biological agent (adalimumab, certolizumab, golimumab, infliximab, natalizumab, or ustekinumab) while breastfeeding their infants. Among those who received a thiopurine or combination therapy while breastfeeding, infant growth, development or infection rate was no different from 208 breastfed infants whose mothers received no treatment.[20] A national survey of gastroenterologists in Australia identified 21 infants who were breastfed by mothers taking a combination of allopurinol and a thiopurine (e.g. azathioprine, mercaptopurine) to treat inflammatory bowel disease. All had taken the combination during pregnancy also. Two postpartum infant deaths occurred, both at 3 months of age. One was a twin (premature birth-related) and the other from SIDS. The authors did not believe the deaths were medication related.[21] No information was provided on the extent of breastfeeding, drug dosages or the outcomes of the other infants.

Effects on milk supply

Relevant published information was not found as of the revision date.

Levels in milk

Mercaptopurine is the active metabolite of azathioprine. It is further metabolized to active metabolites including 6-methylmercaptopurine, thioguanine, 6-thioguanine nucleosides (6-TGNs) and 6-methylmercaptopurine nucleosides (6-MMPN). The enzyme thiopurine methyltransferase (TPMT) is responsible for metabolism of 6-TGNs. Deficiencies in this enzyme can lead to excessive toxicity. Maternal Levels. Mercaptopurine milk levels were measured in 2 patients receiving azathioprine following renal transplantation. In one, peak milk levels occurred 2 and 8 hours after a 75 mg oral dose and were 3.4 and 4.5 mcg/L, respectively. In the other, a peak milk level of 18 mcg/L occurred 2 hours after a 25 mg oral dose. Serum levels were not measured.[15] Four women receiving an immunomodulator to treat inflammatory bowel disease had metabolite levels measured in milk during the first 6 weeks postpartum. The abstract does not mention the specific drug and dose being taken, but the azathioprine metabolites 6-methylmercaptopurine (6-MMP) and 6-thioguanine nucleosides (6-TGNs) were measured. Although therapeutic levels were found in maternal serum, 6-MMP ( 650 mcg/L) and 6-TGNs were undetectable ( 123 mcg/L) in milk (time of collection not stated).[16] A woman was taking 50 mg daily of mercaptopurine for Crohn s disease during pregnancy and postpartum. A milk sample taken on the first day postpartum 4 hours after ingestion of the dose had no detectable levels ( 25 pmol/L) of mercaptopurine or its metabolites, 6-thioguanine and 6-methylmercaptopurine.[17] Infant Levels. Four infants were breastfed (3 exclusively, 1 rarely received formula) during maternal use of azathioprine orally in dosages of 1.2 to 2.1 mg/kg daily. All mothers and infants had the wild type TPMT *1/*1 genotype and all mothers had normal enzyme activity. At 3 to 3.5 months of age, all of the infants' had undetectable blood levels of 6-TGNs and 6-MMPN.[18]

Alternatives LactMed lists

• Azathioprine
• Budesonide
• Certolizumab Pegol
• Infliximab
• Mesalamine
• Prednisone