324 Preconceptional counseling is advised and termination of immunosuppressive therapy should be attempted where possible. Azathioprine has a category D pregnancy rating by the FDA. It has been associated with congenital malformations in pregnant mice,293 and low levels of the 6-thioguanine nucleotides are detectable in the newborns of mothers treated for Crohn’s disease (Table 8).295 Teratogenicity associated with azathioprine therapy therefore is a theoretical consideration,293 but increased birth defects have not been reported in mothers receiving this treatment,323-325,330-333 nor have there been apparent adverse consequences of breast

feeding by treated mothers.333 Nevertheless, these human experiences have

been anecdotal, and there has not been a comprehensive human selleck chemicals llc study establishing the safety of azathioprine in pregnant women. These findings, however, do justify caution when using azathioprine during pregnancy.323-325 Autoimmune hepatitis can improve during pregnancy, and this improvement may allow reductions in immunosuppressive therapy during pregnancy.334,335 Intuitively, little or no treatment during pregnancy is a desirable protective measure for the mother and fetus. Exacerbations Everolimus chemical structure of disease commonly follow delivery as blood estrogen levels fall.334 The frequency of exacerbation after delivery has been variously reported between 12%-86%.324,332,335 Its occurrence must be anticipated, and conventional medchemexpress therapy must be resumed pre-emptively 2 weeks before anticipated delivery and maintained throughout the postpartum period. Contraception should be advised in women with advanced liver disease and features of portal hypertension because they are at risk for variceal hemorrhage during pregnancy.330 Patients with near-zero erythrocyte concentrations of thiopurine methyltransferase activity are at risk for myelosuppression during azathioprine treatment.291,292 Only 0.3%-0.5% of the population has a severe enzyme deficiency,336-340 and not all patients with a deficiency of

this degree experience bone marrow failure.341 Individuals with abnormally decreased but not extreme reductions in thiopurine methyltransferase activity (heterozygous state) tolerate azathioprine satisfactorily at the low dose of 50 mg320 and the level of enzyme activity may actually increase with continued administration of the drug.320,342,343 The rarity of severe azathioprine-induced myelosuppression, the low dose of azathioprine used in conventional treatment (50 mg-150 mg daily), and the inability to reliably predict risk by phenotypic and genotypic assessments have not supported routine screening for thiopurine methyltransferase activity in AIH. Pretreatment cytopenia, cytopenia developing during therapy, or the administration of higher than conventional doses of azathioprine (>150 mg daily) justifies determination of enzyme activity.