No information provided.

The safety and efficacy of Kepivance® have not been established in patients with non-hematologic malignancies. The effects of Kepivance® on stimulation of KGF receptor-expressing, non-hematopoietic tumors in patients are not known. Kepivance® has been shown to enhance the growth of human epithelial tumor cell lines in vitro and to increase the rate of tumor cell line growth in a human carcinoma xenograft model (see CLINICAL PHARMACOLOGY, Mechanism of Action).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity

The carcinogenic potential of Kepivance® has not been evaluated in long-term animal studies.

Mutagenicity

No clastogenic or mutagenic effects of Kepivance® were observed in the Ames or mammalian chromosomal aberration assays; however, such studies are generally not informative for biological products.

Impairment of Fertility

When Kepivance® was administered intravenously daily to male and female rats prior to and during mating, reproductive performance, fertility, and sperm assessment parameters were not affected at doses up to 100 mcg/kg/day. Systemic toxicity (clinical signs of toxicity and/or body weight effects), decreased epididymal sperm counts, and increased post-implantation loss were observed at doses ≥ 300 mcg/kg/day (5-fold higher than the recommended human dose). Increased pre-implantation loss and a decreased fertility index were observed at a Kepivance® dose of 1,000 mcg/kg/day.

Pregnancy Category C

Kepivance® has been shown to be embryotoxic in rabbits and rats when given in doses that are 2.5 and 8 times the human dose, respectively.

Increased post-implantation loss and decreased fetal body weights were observed when Kepivance® was administered to pregnant rabbits from days 6 to 18 of gestation at IV doses ≥ 150 mcg/kg/day (2.5-fold higher than the recommended human dose). However, treatment with these doses was also associated with maternal toxicity (clinical signs and reductions in body weight gain/food consumption). No evidence of developmental toxicity was observed in rabbits at doses up to 60 mcg/kg/day.

Increased post-implantation loss, decreased fetal body weight and/or increased skeletal variations were observed when Kepivance® was administered to pregnant rats from days 6 to 17 or 19 of gestation at IV doses ≥ 500 mcg/kg/day (> 8-fold higher than the recommended human dose). Treatment with these doses was also frequently associated with maternal toxicity (clinical signs and body weight effects). No evidence of developmental toxicity was observed in rats at doses up to 300 mcg/kg/day.

There are no adequate and well-controlled studies in pregnant women. Kepivance® should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Lactating Women

It is not known whether Kepivance® is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Kepivance® is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Kepivance® in pediatric patients have not been established.

Geriatric Use

Clinical studies of Kepivance® did not include sufficient numbers of subjects age 65 years and over to determine whether they respond differently from younger subjects. Among 409 patients with hematologic malignancies who received Kepivance® in clinical studies, 9 (2%) were ≥ age 65.

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