Drugs in Pregnancy and Lactation: Tenth Edition

AMIFOSTINE

Antineoplastic Cytoprotectant

PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk

BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible

PREGNANCY SUMMARY

No reports describing the use of amifostine in human pregnancy have been located. The animal reproduction data suggest risk, but the absence of human pregnancy experience prevents a more complete assessment. However, one of the indications for amifostine is the prevention of cisplatin-induced renal toxicity in women being treated for ovarian cancer. Thus, if a pregnant woman requires amifostine and gives informed consent, the maternal benefit from amifostine appears to outweigh the potential embryo–fetal risk. If inadvertent exposure occurs during pregnancy, the woman should be advised of the potential risk for adverse effects in the embryo and fetus.

FETAL RISK SUMMARY

Amifostine is an organic thiophosphate cytoprotective agent that is administered as an IV infusion. It is a prodrug that is dephosphorylated by a tissue enzyme to the active free thiol metabolite. Amifostine is indicated to reduce the cumulative renal toxicity associated with repeated doses of cisplatin in patients with ovarian cancer. It also is indicated to reduce the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid gland. Amifostine is rapidly metabolized to the active metabolite and subsequently to a less active metabolite. The plasma elimination half-life is very short, about 8 minutes.

Reproduction studies have been conducted in rabbits. Amifostine was embryotoxic in pregnant rabbits at a dose that was about 60% of the recommended human dose based on BSA (1).

Long-term studies have not been done to determine the carcinogenic or fertility impairment potential of amifostine, but the agent was not mutagenic in two tests. The active metabolite was mutagenic in some, but not other, tests and was not clastogenic (1).

It is not known if amifostine crosses the human placenta. The molecular weight of the prodrug (about 214) suggests that it will distribute to the embryo and/or fetus, but the very short plasma elimination half-life should limit the amount available for transfer.

BREASTFEEDING SUMMARY

No reports describing the use of amifostine during human lactation have been located. The molecular weight of the prodrug (about 214) suggests that it will be excreted into breast milk, but the very short plasma elimination half-life (about 8 minutes) should limit the amount. The effects of this potential exposure on a nursing infant are unknown. However, because the drug is given as a short IV infusion immediately before chemotherapy or radiation, and breastfeeding would be unlikely at this time, the risk of exposing an infant to amifostine when nursing is later resumed appears to be nil.

Reference

1.Product information. Ethyol. MedImmune Oncology, 2007.