Valrubicin

Pregnancy Category C.

Valrubicin can cause fetal harm if a pregnant woman is exposed to the drug systemically. Such exposure could occur after perforation of the urinary bladder during valrubicin therapy. Daily intravenous doses of 12 mg/kg (about one sixth of the recommended human intravesical dose on a mg/m² basis) given to rats during fetal development caused fetal malformations. A dose of 24 mg/kg (about one third the recommended human intravesical dose on a mg/m² basis) caused numerous, severe alterations in the skull and skeleton of the developing fetuses. This dose also caused an increase in fetal resorptions and a decrease in viable fetuses. Thus, valrubicin is embryo-toxic and teratogenic. There are no preclinical studies of the effects of intra-vesical valrubicin on fetal development and no adequate and well controlled studies of valrubicin in pregnant women. If valrubicin is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women who might become pregnant should be advised to avoid doing so during therapy with valrubicin.

It is not known whether valrubicin is excreted in human milk. Nevertheless, the drug is highly lipophilic and any exposure of infants to valrubicin could pose serious health risks. Women should discontinue nursing before the initiation of valrubicin therapy.

The carcinogenic potential of valrubicin has not been evaluated, but the drug does cause damage to DNA in vitro. Valrubicin was mutagenic in in vitro assays in Salmonella typhimurium and Escherichia coli. Valrubicin was clastogenic in the chromosomal aberration assay in CHO cells. Studies of the effects of valrubicin on male or female fertility have not been done.