Pegulicianine

There are no available data on pegulicianine use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal reproduction studies were not conducted with pegulicianine.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

There are no data on the presence of pegulicianine or its metabolites in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pegulicianine and any potential adverse effects on the breastfed infant from pegulicianine or from the underlying maternal condition.

No studies in animals have been conducted to evaluate the carcinogenic potential of pegulicianine.

The nonfluorescent major metabolite of pegulicianine was not mutagenic in nonclinical tests, i.e., in vitro reverse mutation test in bacteria (Ames test), in vitro chromosomal aberration test in human peripheral blood lymphocytes, and in vivo (mice) micronucleus test after intravenous doses up to 11.24 mg/kg (225 times the pegulicianine clinical dose of 1 mg/kg).

No reproductive and developmental toxicity studies in animals have been performed to evaluate the effects of pegulicianine on fertility.

Clinical trials experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of pegulicianine was evaluated in 726 patients who received a single dose of 1 mg/kg of pegulicianine. Among these 726 patients, 703 (97%) had breast cancer and 23 (3%) had other types of cancer. The mean age of the patients was 62 years (range: 36 years to 95 years), and 98% of them were female. Distribution by race was 82% White, 7% Black or African American, 6% Asian, and 5% other or unreported. Distribution by ethnicity was 3% Hispanic/Latino, 93% nonHispanic/Latino, and 4% unknown or unreported.

Adverse reactions occurring in ≥1% of patients receiving pegulicianine were hypersensitivity (1.4%, including anaphylaxis [4 out of 726]) and chromaturia (85%). Chromaturia resolved within 48 hours after administration in 93% of patients, with the longest time to resolution of 15 days.

Adverse reactions occurring in <1% of patients were skin discoloration after extravasation, nausea, dyspnea, pyrexia, and vomiting.