No reports describing the use of crizanlizumab-tmca in pregnancy have been located. The animal data suggest moderate risk, but the absence of human pregnancy experience prevents a complete assessment of the embryo-fetal risk.
No reports describing the use of crizanlizumab-tmca during human lactation have been located. The molecular weight (about 146,000) suggests that clinically significant amounts will not be excreted into milk. However, some high molecular weight compounds, such as human IgG, are excreted into milk during the first few days after birth. The long elimination half-life (about 25 days) of obinutuzumab will allow the drug to be in the maternal circulation for long periods and excretion into milk might occur. Even if excreted, the drug will probably be digested in the infant's gastrointestinal tract. The most common adverse reactions observed in adults are nausea, arthralgia, back pain, and pyrexia (1). If a woman is receiving this drug while breastfeeding, her nursing infant should be monitored for these effects.
Crizanlizumab (Adakveo)
Pregnancy Recommendation:No Human Data—Animal Data Suggest Moderate Risk
Breastfeeding Recommendation:No Human Data—Probably Compatible
Crizanlizumab-tmca is an IV selectin blocker indicated to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. The elimination half-life is 10.6 and 7.6 days in healthy volunteers and patients with sickle cell disease, respectively (1).
Animal Data: Animal reproduction studies have been conducted with crizanlizumab-tmca in monkeys. A non-dose-related increase in fetal loss (abortions and still births) was observed with doses that were 2.8 and 16 times the human clinical exposure based on the AUC in patients with sickle cell disease at 5 mg/kg/dose once every 4 weeks (CE) administered every 2 weeks from organogenesis through delivery. This was higher in the third trimester. No abnormalities in growth and development through 6 months postpartum were observed. However, on postnatal day 28, crizanlizumab-tmca levels were detected in the infant monkeys (1).
No studies evaluating carcinogenicity or mutagenicity have been conducted. No impairment of fertility was observed in male or female monkeys (1).
Placental Transfer: It is not known if crizanlizumab-tmca crosses the placenta. The molecular weight (about 146,000) suggests that passage of the drug across the placenta will be limited, at least in the first half of pregnancy. However, the long elimination half-life may result in fetal exposure late in pregnancy because many high molecular weight drugs, such as human IgG, cross at that time.