Antineoplastic (Proteasome Inhibitor)
PREGNANCY RECOMMENDATION: Contraindicated
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of bortezomib in human pregnancy have been located. The drug caused developmental toxicity (growth restriction and death) at a dose one-half of the human clinical dose of 1.3 mg/m2 based on body surface area (HCD) in one of two species. Because the recommended dose is given over several weeks, use during pregnancy could result in multiple exposures of the embryo and/or fetus to a cytotoxic agent. The manufacturer recommends that women should be advised to use effective contraceptive measures to prevent pregnancy (1). Until human pregnancy data are available, the best course is to avoid the drug during pregnancy. However, if treatment is required during gestation, the decision to use bortezomib should be made on a case-by-case basis, but the woman should be advised of the potential risk to her embryo–fetus.
FETAL RISK SUMMARY
Bortezomib is a cytotoxic antineoplastic that is given as an IV bolus injection. It is the same class as carfilzomib. Bortezomib is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy. The mean elimination half-life after first dose has ranged 9–15 hours, but has not been fully characterized in multiple myeloma patients. Plasma protein binding is moderate (about 83%). Bortezomib undergoes some metabolism to inactive metabolites, but plasma levels of metabolites at 10 and 30 minutes after a dose were low compared with the parent compound (1).
Reproductive studies have been conducted in rats and rabbits. No teratogenicity was observed at the highest doses tested during organogenesis in rats and rabbits that were about 0.5 times the HCD. However, in rabbits given the highest dose during organogenesis, there was significant postimplantation loss and decreased number of live fetuses, as well as significant decreases in the weight of live fetuses (1).
Carcinogenic studies have not been conducted with bortezomib. The agent was not genotoxic in various tests, but did demonstrate clastogenic activity in one test. Although fertility studies have not been conducted, 6-month studies conducted for general toxicity in rats revealed degenerative changes in the ovaries and testes at doses that were approximately one-fourth and equivalent, respectively, to the HCD (1).
It is not known if bortezomib crosses the human placenta. The molecular weight (about 384), the long elimination half-life, the moderate plasma protein binding, and lack of rapid metabolism all suggest that the drug will cross to the embryo and/or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of bortezomib during human lactation have been located. It is not known if bortezomib is excreted into breast milk. The molecular weight (about 384), the long elimination half-life, the moderate plasma protein binding, and lack of rapid metabolism all suggest that the drug will be excreted in milk. Bortezomib is given as IV bolus injections over several weeks. The effects of this exposure on a nursing infant are unknown, as is the oral bioavailability. However, because the drug is cytotoxic, the best course is to not breastfeed during treatment.
Reference
1.Product information. Velcade. Millennium Pharmaceuticals, 2007.