Endocrine/Metabolic (Somatostatin Analog)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of pasireotide in human pregnancy have been located. The animal data suggest risk, but the absence of human pregnancy experience prevents a full assessment of the embryo–fetal risk. If a woman becomes pregnant while receiving the drug, she should be informed of the potential risk, including abortion, to her embryo and/or fetus.
FETAL RISK SUMMARY
Pasireotide is a cyclohexapeptide somatostatin analog that is given as an SC injection. It is in the same subclass as octreotide. Pasireotide is indicated for the treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative. The drug is not metabolized. Plasma protein binding is moderate (88%) and the calculated effective half-life is about 12 hours (1).
Reproduction studies have been conducted in rats and rabbits. In rats throughout organogenesis, doses resulting in exposures that were 4 times or higher than the maximum therapeutic dose based on AUC (MHD) caused maternal toxicity. Exposures less than the human clinical exposure based on BSA caused a significant increase in implantation loss and decreased viable fetuses, corpora lutea, and implantation sites. In addition, restricted growth was noted in rat pups exposed during prenatal and postnatal studies but was reversible after weaning. In rabbits through organogenesis, an exposure that was 7 times the MHD caused maternal toxicity. At exposures less than the MHD, an increased incidence of skeletal malformations was observed in offspring (1).
Long-term studies for carcinogenesis were negative in rats and mice. Pasireotide was not mutagenic or genotoxic in several assays. As noted above, fertility studies in rats caused harm. In addition, abnormal cycles or acyclicity were observed (1).
It is not known if pasireotide crosses the human placenta. The molecular weight (about 1313) suggests that passage would be limited, but the moderate plasma protein binding and long effective half-life could increase the possibility for crossing to the embryo–fetus.
BREASTFEEDING SUMMARY
No reports describing the use of pasireotide during human breastfeeding have been located. The molecular weight (about 1313) suggests that excretion into breast milk will be limited, but the moderate plasma protein binding (88%) and long effective half-life (12 hours) could increase the possibility for excretion. The effect of this exposure on a nursing infant is unknown. The most common (≥20%) adverse reactions in adults were diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, and diabetes mellitus (1). Because of these potential risks, the best course is to not breastfeed.
Reference
1.Product information. Signifor. Novartis Pharmaceuticals, 2012.