Bexarotene
Risk Factor: XM
Class: ANTINEOPLASTICS
Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers
Fetal Risk Summary
Bexarotene is a member of a subclass of retinoids that selectively binds and activates retinoid X receptor subtypes (RXRa, RXRb, and RXRg). These subtypes then interact with various receptor partners to function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene is indicated for the treatment of refractory cutaneous manifestations of cutaneous T-cell lymphoma. Four active metabolites have been identified (1).
In reproduction studies with pregnant rats during organogenesis, an oral dose (4 mg/kg/day) approximately one-third of the area under the plasma concentration curve in humans at the recommended dose (RHD) caused incomplete ossification (1). When a 16 mg/kg/day dose (about 1.33 times the RHD) was given, cleft palate, depressed eye bulge/microphthalmia, and small ears were observed. Doses greater than 10 mg/kg/day caused embryo and fetal death. The no effect dose was one-sixth the RHD (1). Studies on fertility and carcinogenicity have not been conducted, but tests for mutagenicity or clastogenicity were negative (1).
It is not known if bexarotene crosses the human placenta. The molecular weight (about 348) is low enough, however, that transfer to the fetus should be expected.
Bexarotene is contraindicated in pregnancy. No reports describing its use during human pregnancy have been located. Pregnancy should be excluded and the use of effective contraception (two reliable forms used simultaneously) confirmed before bexarotene therapy is started in women of childbearing age. If these criteria are met, therapy should be initiated on the second or third day of a normal menstrual cycle. The contraceptive methods should be used for 1 month before therapy, during therapy, and for 1 month after stopping therapy. The manufacturer also recommends that monthly pregnancy tests be repeated monthly during treatment (1). In addition, male patients with sexual partners who are pregnant, possibly pregnant, or who could become pregnant, should use condoms during sexual intercourse during therapy and for 1 month after therapy has been stopped (1).
Breast Feeding Summary
No reports describing the use of bexarotene in human lactation have been located. The molecular weight (about 348) is low enough that excretion into breast milk should be expected. Because of the unknown amounts present in milk and the potential for serious adverse effects in a nursing infant, women receiving bexarotene should probably not breast feed.
References
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Product information. Targretin. Ligand Pharmaceuticals, 2001.
