Is Azathioprine safe while breastfeeding?

Effects on the breastfed infant

Three infants were breastfed during long-term maternal azathioprine 75 to 100 mg daily and methylprednisolone use following renal transplantation. All three infants had no abnormal blood counts, no increased frequency of infections and above average growth rates.[ 10 , 18 ] The IgA levels in one mother s breastmilk were measured and found to be normal.[ 10 ] One infant was breastfed for 6 days after birth by a mother who was taking 75 mg of azathioprine daily in addition to cyclosporine. Nursing was interrupted for 4 days, then partial breastfeeding was reestablished. The infant showed no signs of renal or neurologic toxicity or hirsutism during long-term follow up.[ 19 ] Twelve infants were breastfed for up to 12 months during maternal use of azathioprine 50 to 100 mg daily (6 with concomitant cyclosporine) following kidney or kidney-pancreas transplantation. Kidney function was normal in all infants when measured after breastfeeding had ceased. The growth and psychomotor development of all infants was normal.[ 20 ] One infant was exclusively breastfed for 10.5 months during maternal use of azathioprine 100 mg daily, cyclosporine and prednisone. Partial breastfeeding continued for 2 years. The infant thrived with normal growth at 12 months. The mother also breastfed a second child while on the same drug regimen.[ 21 ] 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. At 3 to 3.5 months of age, all infants were healthy and were within the 50th to 95th percentiles on growth charts.[ 17 ] The authors reported 2 additional infants who received azathioprine via breastmilk with no adverse reactions detected.[ 22 ] In another case series, 4 infants were breastfed (partially in 1 case, not stated in the others) during maternal use of azathioprine. Two mothers took 100 mg daily, 1 took 75 mg daily and 1 took 50 mg daily and partially breastfed her preterm infant. All were t

Effects on milk supply

Cases of hyperprolactinemia and galactorrhea with normal prolactin have been reported rarely in patients taking azathioprine.[ 40 , 41 ]

Levels in milk

Azathioprine is rapidly metabolized to the active metabolite mercaptopurine which is further metabolized to active metabolites including 6-methylmercaptopurine, thioguanine, 6-thioguanine nucleosides (6-TGNs), 6-methylmercaptopurine, and 6-methylmercaptopurine nucleosides (6-MMPNs). 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 mother who was 2 days postpartum, peak colostrum 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 mother who was 7 days postpartum, a peak mercaptopurine milk level of 18 mcg/L occurred 2 hours after a 25 mg oral dose.[ 10 ] The milk levels of these 2 mothers correspond to 0.05% and 0.6% of the maternal weight-adjusted dosages, respectively. Infant serum levels were not measured. 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-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).[ 11 ] A case series described 2 mothers who took 100 mg azathioprine daily while breastfeeding. Each mother collected milk samples over a 24-hour period, 5 and 6 samples, respectively. Mercaptopurine was undetectable ( 5 mcg/L) in all samples. The authors estimated that the maximum dose of mercaptopurine that a completely breastfed infant would receive would be 0.09% of the maternal weight-adjusted dosage or 0.07% of the dose given to infants following cardiac transplantation.[ 12 ] Ten women who were taking aza

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