Treanda Use In Pregnancy & Lactation

Pregnancy: Risk Summary: In animal reproduction studies, intraperitoneal administration of bendamustine to pregnant mice and rats during organogenesis at doses 0.6 to 1.8 times the maximum recommended human dose (MRHD) resulted in embryo-fetal and/or infant mortality, structural abnormalities, and alterations to growth (see Data). There are no available data on bendamustine hydrochloride use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data: Animal data: Bendamustine hydrochloride was intraperitoneally administered once to mice from 210 mg/m² (approximately 1.8 times the MRHD) during organogenesis and caused an increase in resorptions, skeletal and visceral malformations (exencephaly, cleft palates, accessory rib, and spinal deformities) and decreased fetal body weights. This dose did not appear to be maternally toxic and lower doses were not evaluated. Repeat intraperitoneal administration of bendamustine hydrochloride to mice on gestation days 7-11 resulted in an increase in resorptions from 75 mg/m² (approximately 0.6 times the MRHD) and an increase in abnormalities from 112.5 mg/m² (approximately 0.9 times the MRHD) similar to those seen after a single intraperitoneal administration.
Bendamustine hydrochloride was intraperitoneally administered once to rats from 120 mg/m² (approximately the MRHD) on gestation days 4, 7, 9, 11, or 13 and caused embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses. A significant increase in external [effect on tail, head, and herniation of external organs (exomphalos)] and internal (hydronephrosis and hydrocephalus) malformations were seen in dosed rats.
Lactation: Risk Summary: There are no data on the presence of bendamustine hydrochloride or its metabolites in either human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with TREANDA, and for at least 1 week after the last dose.
Females and Males of Reproductive Potential: TREANDA can cause fetal harm when administered to a pregnant woman (see Pregnancy as previously mentioned).
Pregnancy Testing: Pregnancy testing is recommended for females of reproductive potential prior to initiation of treatment with TREANDA.
Contraception: Females: TREANDA can cause embryo-fetal harm when administered to pregnant women (see Pregnancy as previously mentioned). Advise female patients of reproductive potential to use effective contraception during treatment with TREANDA and for at least 6 months after the final dose.
Males: Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with TREANDA and for at least 3 months after the final dose (see Pharmacology: Nonclinical Toxicology under Actions).
Infertility: Males: Based on findings from clinical studies, TREANDA may impair male fertility. Impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in male patients treated with alkylating agents, especially in combination with other drugs. In some instances spermatogenesis may return in patients in remission, but this may occur only several years after intensive chemotherapy has been discontinued. Patients should be warned of the potential risk to their reproductive capacities.
Based on findings from animal studies, TREANDA may impair male fertility due to an increase in morphologically abnormal spermatozoa. The long-term effects of TREANDA on male fertility, including the reversibility of adverse effects, have not been studied (see Pharmacology: Nonclinical Toxicology under Actions).