We recently discussed this issue in conference and I thought it might be worth sharing a few interesting points:
Azathioprine is normally converted to the active metabolite 6-mercaptopurine. However, in pregnancy the placenta can metabolize azathioprine to thiouric acid, an inactive metabolite. In addition the fetal liver does not have inosinatopyrophosphorylase which therefore largely protects the fetus from exposure to active compounds.
Azathioprine has been classed as FDA category D – positive evidence of risk.
Despite conflicting data, general expert opinion suggests that azathioprine may be considered for use during pregnancy in certain situations (where the potential benefits outweigh potential risks).
In terms of breast feeding, in a small study, active metabolites have been detected in small quantities in breast milk. Overall the significance of this remains to be fully determined. Manufacturers have taken the official stance to warn against breast feeding while taking the drug.
As with all considerations of alterations in immunosuppressive dosing, careful consideration of risks and benefits should be explored in detail with the treating physician before any change is undertaken.
Nice post Finnian. For what its worth, here in gastroenterology we strongly recommend that patients (with IBD) who are on 6-MP or azathioprine continue therapy throughout pregnancy as flares during pregnancy carry greater risk to the fetus than risks of the drug itself. The CESAME study (Coelho et al, Gut 2011; 60(2): 198-203) followed 215 pregnancies and found increased incidence of low birth weight but no increase in congenital anomalies, and a non-significant increase in prematurity. Reassuring. Regarding breast feeding, we generally regard it as safe, and thus encourage breast feeding after full consultation with the patient. Thanks again for a wonderful post!
Excellent short & practical post