Safety of ifosfamide during pregnancy: A comprehensive analysis

Objective

Little is known regarding the safety of ifosfamide in pregnant women and some case reports were associated with oligohydramnios. In the study, we performed a comprehensive analysis of the available data regarding the safety of ifosfamide in pregnant women.

Material and methods

First, we performed a case-by-case review of the cases related to ifosfamide use during pregnancy that were spontaneously reported in the French Pharmacovigilance Database. Second, we reviewed cases from the literature. Finally, we performed a disproportionality analysis on VigiBase, the WHO global safety database (VigiBase), to assess the association between ifosfamide and selected adverse events in pregnant women.

Results

A total of 27 cases of ifosfamide use during pregnancy were identified. No congenital malformation was reported. Main adverse events were intrauterine growth restriction (n = 15, 56 %) and oligohydramnios or anhydramnios (n = 15, 56 %). Pregnancy resulted in intrauterine fetal death in 5 (19 %) cases, all being treated with ifosfamide before the 21th week of gestation. All livebirths (n = 22) were preterm, associated with neonatal acute renal failure in 5 (23 %) cases. In addition, 3 (14 %) neonatal deaths were reported within the first week of life in neonates having anuria. In VigiBase, which has over 263,145 spontaneous safety reports related to pregnancy, we found a significant increased reporting of oligohydramnios, intrauterine growth restriction and neonatal acute renal failure with ifosfamide compared to other antineoplastic agents.

Conclusion

Altogether, this comprehensive analysis supports that ifosfamide may induce fetal nephrotoxicity in pregnant women. It can result in intrauterine growth restriction, oligohydramnios and neonatal acute renal failure, as well as fetal death especially for early exposure during the first half of pregnancy.