Palifermin (1 brand name, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- KEPIVANCE
Contraindications
None
Drug Interactions
In vitroand in vivodata showed that palifermin interacts with unfractionated as well as low molecular weight heparins with no noticeable effect on the pharmacodynamics of either drug. If heparin is used to maintain an intravenous line, rinse the line with saline prior to and after Kepivance administration [see Clinical Pharmacology ( 12.3)] . Do not administer Kepivance within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy [see Dosage and Administration ( 2.1) and Clinical Studies ( 14)]. In a clinical trial, administration of Kepivance within 24 hours of chemotherapy resulted in increased severity and duration of oral mucositis.
Mechanism of Action
KGF is an endogenous protein in the fibroblast growth factor (FGF) family that binds to the KGF receptor. Binding of KGF to its receptor has been reported to result in proliferation, differentiation, and migration of epithelial cells. The KGF receptor, one of four receptors in the FGF family, has been reported to be present on epithelial cells in many tissues examined including the tongue, buccal mucosa, esophagus, stomach, intestine, salivary gland, lung, liver, pancreas, kidney, bladder, mammary gland, skin (hair follicles and sebaceous gland), and the lens of the eye. The KGF receptor has been reported to not be present on cells of the hematopoietic lineage. Endogenous KGF is produced by mesenchymal cells and is upregulated in response to epithelial tissue injury. In mice and rats, Kepivance enhanced proliferation of epithelial cells (as measured by Ki67 immunohistochemical staining and BrDU uptake) and demonstrated an increase in tissue thickness of the tongue, buccal mucosa, and gastrointestinal tract. Kepivance has been studied in murine models of chemotherapy and radiation-induced gastrointestinal injury. In such models, administration of Kepivance prior to and/or after the cytotoxic insult improved survival and reduced weight loss compared to control animals. Kepivance has been shown to enhance the growth of human epithelial tumor cell lines in vitroat concentrations ≥ 10 mcg/mL (> 15-fold higher than average therapeutic concentrations in humans). In nude mouse xenograft models, three consecutive daily treatments of Kepivance at doses of 1,500 and 4,000 mcg/kg (25- and 67-fold higher than the recommended human dose, respectively) repeated weekly for 4 to 6 weeks were associated with a dose-dependent increase in the growth rate of 1 of 7 KGF receptor-expressing human tumor cell lines.