Included as part of the PRECAUTIONS section.

Potential for Stimulation of Tumor Growth

The safety and effcacy of Kepivance have not been established in patients with non-hematologic malignancies. The effects of Kepivance on stimulation ofKGF 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]

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertiity

Carcinogenicity: No treatment-related increase in the incidence of neoplastic lesions occuned in transgenic rasH2 mice treated with 9 weekly intravenous doses of pal if ermin, at 167-fold higher than the recommended human dose (on a mcg/kg basis).

Mutagenicity: No clastogenic or mutagenic effects ofpalifermin were observed in mammalian chromosomal aberration or Ames genotoxicity assays.

Impairment of Fertilty: Reproductive performance, fertility, and sperm assessment parameters were not affected when palifermin was administered intravenously to male and female rats prior to and during mating at doses up to 100 mcg/g/day. Decreased epididymal sperm counts, and increased post-implantation losses were observed at doses ≥ 300 mcg/kg/day (5-fold higherthan the recommended human dose, on a mcg/g basis). Increased pre-implantation loss and a decreased fertility index were observed at a palifermin dose of 1000 mcg/g/day.

Use In Specific Populations

No gender-related differences were observed in the pharmacokinetìcs of Kepi vance at doses ≤ 60 mcg/kg.

Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies of Kepivance in pregnant woman. Palifermin is embryotoxic in rabbits and rats. In reproductive toxicology studies, increased post-implantation loss and decrease in fetal body weight were observed in both rabbit (2.5 times the maximum recommended human dose [MRHD], adjusted for body weight) and rat (8 times the MRHD, on a mcg/kg basis) [see Nonclinical Toxicology] Kepivance should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether Kepivance is secreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Kepivance, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of Kepivance have not been established in children.

Geriatric Use

Clinical studies of Kepi vance did not include suffcient numbers of subjects aged 65 years and older to determine whether they responded differently from younger subjects. [see CLINICAL PHARMACOLOGY]

Patients with Renal Impairment

No dose adjustment is recommended for patients with renal impairment [see CLINICAL PHARMACOLOGY]

Patients with Hepatic Impairment

The phanacokinetic profie in patients with hepatic insufficiency has not been assessed.

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.