Is Azatioprin Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use Azatioprin? Is Azatioprin safe for nursing mother and child? Does Azatioprin extracts into breast milk? Does Azatioprin has any long term or short term side effects on infants? Can Azatioprin influence milk supply or can Azatioprin decrease milk supply in lactating mothers?

Even though it is metabolized to mercaptopurine, just tiny amounts of this drug have been found in breast milk (4 - 18 micrograms/liter). Among several breastfed infants of mothers who were treated with Azatioprin failed to be detected in the blood nor side effects were found. Long-term infectious diseases were not more common among exposed infants. Exposition would be minimized if nursing is resumed 3 hours after last dose.

Most experts consider breastfeeding during Azatioprin to be acceptable.[1][2][3][4][5][6][7][8] Studies in women with inflammatory bowel disease, systemic lupus erythematosus or transplantation taking doses of Azatioprin up to 200 mg daily for immunosuppression have found either low or unmeasurable levels of the active metabolites in milk and infant serum. Some evidence indicates a lack of adverse effects on the health and development of infants exposed to Azatioprin during breastfeeding up to 3.5 years of age, but long-term follow-up for effects such as carcinogenesis have not been performed. Mothers with decreased activity of the enzyme that detoxifies Azatioprin metabolites may transmit higher levels of drug to their infants in breastmilk. Cases of mild, asymptomatic neutropenia have been reported, so it might be desirable to monitor exclusively breastfed infants with a complete blood count with differential, and liver function tests if Azatioprin is used during lactation, although some authors feel that monitoring is unnecessary.[9] Avoiding breastfeeding for 4 hours after a dose should markedly decrease the dose received by the infant in breastmilk.[10]

Three infants were breastfed during long-term maternal Azatioprin 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.[11][19] The IgA levels in one mother's breastmilk were measured and found to be normal.[11] One infant was breastfed for 6 days after birth by a mother who was taking Azatioprin 75 mg 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.[20] Twelve infants were breastfed for up to 12 months during maternal use of Azatioprin 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.[21] One infant was exclusively breastfed for 10.5 months during maternal use of Azatioprin 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.[22] Four infants were breastfed (3 exclusively, 1 rarely received formula) during maternal use of Azatioprin 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.[16] The authors reported 2 additional infants who received Azatioprin via breastmilk with no adverse reactions detected.[23] In another case series, 4 infants were breastfed (partially in 1 case, not stated in the others) during maternal use of Azatioprin. 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 taking several other medications concurrently. One infant was followed up at 1 month, 2 at 2 months and 1 at 1 year of age. No adverse events were reported in any of the infants and all were growing and developing normally.[13] Six infants whose mothers were breastfeeding and taking Azatioprin were monitored monthly for the duration of their breastfeeding with blood counts and for evidence of infection. One infant developed a low blood count and breastfeeding was discontinued; the other 5 infants continued to breastfeed apparently without harm. The dosages of Azatioprin, concurrent medications and the extent of breastfeeding were not reported in the brief published abstract.[24] Ten infants, 3 preterm, were breastfed during maternal intake of Azatioprin in single oral doses of 75 to 150 mg daily. No signs of immunosuppression were seen in the infants during the first 28 days postpartum. In 7 of the infants, white cell and neutrophil counts were performed between days 1 and 28 postpartum. One infant had a borderline low neutrophil count but a normal white cell count.[14] A survey of women with autoimmune hepatitis found that 8 infants of 4 women had been breastfed (extent not stated) during maternal Azatioprin use in unspecified dosages. No adverse effects were reported by the mothers.[25] An infant was breastfed (extent not stated) from birth to the age of 3 months during maternal therapy with Azatioprin 100 mg (1.4 mg/kg) daily. During the 6 months of follow-up, the infant thrived and had no infections.[18] A nonrandomized, prospective study in Austria followed the infants of 23 women with inflammatory bowel disease who were treated in one clinic. Mothers who received Azatioprin (median dose 150 mg daily; range 100 to 250 mg daily) for treatment breastfed for a median of 6 months (range 1 to 18 months) and those who did not take Azatioprin breastfed for a median of 8 months (range 3.5 to 23 months). Follow-up occurred at a median of 3.3 years in the Azatioprin-exposed infants (n = 15) and 4.7 years in the unexposed infants (n = 15). No differences were found in mental or physical development between the two groups of infants. More infants who were unexposed to Azatioprin had more than 2 colds annually and more conjunctivitis episodes than in the unexposed group. No difference was seen in the numbers of other infections between the groups.[26] In The Netherlands, 30 infants of mothers taking either Azatioprin (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.[27] In France, 30 infants of 29 mothers who took Azatioprin 50 to 175 mg daily during pregnancy and nursed for at least 1 month