Antineoplastic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of panitumumab in human pregnancy have been located. The animal reproduction data suggest risk, but the absence of human pregnancy experience prevents a more complete assessment of embryo and fetal risk. Until such data are available, the best course is to avoid the use of this antineoplastic in pregnancy. Women of reproductive age should use effective contraception. However, colorectal cancer can be fatal, so if a woman requires therapy with panitumumab and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the potential risk for severe adverse effects in the embryo and fetus.
FETAL RISK SUMMARY
Panitumumab is a recombinant, human immunoglobulin G2 (IgG2) kappa monoclonal antibody. Panitumumab specifically binds to the human epidermal growth factor receptor (EGFR). It is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
Panitumumab may cause severe, infusion-related toxicity, including hypotension and other adverse effects. The use of premedication before infusion was not standardized in clinical trials, so the efficacy of premedication to prevent infusion reactions is unknown (1). However, since premedication is recommended with other monoclonal antibodies, it is reasonable to use acetaminophen and an antihistamine (e.g., diphenhydramine) before each infusion of panitumumab. Moreover, hypotension in a pregnant woman could have deleterious effects on placental perfusion resulting in embryo and fetal harm.
Reproduction studies have been conducted in cynomolgus monkeys. When panitumumab was given to monkeys during organogenesis (gestational days 20–50) in weekly doses that were 1.25–5 times the recommended human dose based on body weight (RHD), significant increases in embryolethal or abortifacient effects were observed. No structural anomalies in the offspring were observed (1).
The carcinogenic or mutagenic effects of panitumumab have not been studied. Panitumumab may adversely affect fertility. In female cynomolgus monkeys given weekly doses that were 1.25–5 times the RHD, prolonged menstrual cycles and/or amenorrhea were observed. The menstrual cycle irregularities were accompanied by both a decrease and delay in peak progesterone and 17β-estradiol levels. Normal menstrual cycles returned in most monkeys when panitumumab was stopped. A no-effect dose for menstrual cycle irregularities was not determined. No adverse effects were observed microscopically in reproductive organs of male cynomolgus monkeys given doses up to about 5 times the RHD for 26 weeks. However, the effects of this exposure on male fertility were not studied (1).
It is not known if panitumumab crosses the human placenta. The high molecular weight (about 147,000) suggests that it will not cross. As IgG does cross and, therefore, panitumumab may also cross. However, panitumumab was not detected in the serum of neonates from panitumumab-treated cynomolgus monkeys, but anti-panitumumab antibody titers were present in 14 of 27 offspring (1).
BREASTFEEDING SUMMARY
No reports describing the use of panitumumab during lactation have been located. The very high molecular weight (about 147,000) suggests that it will not be excreted into breast milk. However, human IgG is excreted into milk and, therefore, panitumumab may also be excreted (1). The effects of this potential exposure on a nursing infant are unknown, but immunosuppression and other severe adverse effects are potential complications.
Reference
1.Product information. Vectibix. Amgen, 2006.