Antineoplastic (Protein Synthesis Inhibitor)
PREGNANCY RECOMMENDATION: Contraindicated
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use omacetaxine in human pregnancy have been located. Reproduction studies conducted in one species suggest risk, but the absence of human pregnancy experience prevents a more complete assessment of embryo–fetal risk. Moreover, based on the mechanism of action, the drug may cause fetal harm.
FETAL RISK SUMMARY
Omacetaxine is a protein synthesis inhibitor that is given by SC injection. It is indicated for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. The drug is metabolized by plasma esterases to apparently inactive metabolites. Plasma protein binding is ≤50% and the mean half-life is about 6 hours (1).
Reproduction studies have been conducted in mice. In this species during organogenesis, doses that were about 50% of the recommended daily human dose based on BSA (RDHD) caused fetal toxicity, including embryo death, an increase in unossified bones/reduced bone ossification, and decreased fetal weights (1).
Carcinogenicity studies have not been conducted with omacetaxine. The drug was genotoxic in one assay but negative in two other assays. Studies in mice demonstrated adverse effects on male reproductive organs. SC doses that were about 2–3 times the clinical dose based on BSA caused bilateral degeneration of the seminiferous tubular epithelium in testes and hypospermia/aspermia in the epididymides.
It is not known if omacetaxine crosses the human placenta. The molecular weight (about 546), moderate plasma protein binding, and the mean half-life suggest that the drug will cross to the embryo–fetus.
BREASTFEEDING SUMMARY
No reports describing the use of omacetaxine during human lactation have been located.
The molecular weight (about 546), moderate plasma protein binding (≤50%), and the mean half-life (about 6 hours) suggest that the drug will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown, but the infant should be monitored for the most common (frequency ≥20%) adverse effects seen in adults. These effects include thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, pyrexia, infection, and lymphopenia (1).
Reference
1.Product information. Synribo. Teva Pharmaceuticals USA, 2012.