KEPIVANCE
Clinical safety rating
cautionComprehensive clinical and safety monograph for KEPIVANCE (KEPIVANCE).
Kepivance (palifermin) is a recombinant human keratinocyte growth factor (KGF) that binds to the KGF receptor, a splice variant of fibroblast growth factor receptor 2 (FGFR2b), stimulating proliferation, differentiation, and migration of epithelial cells, including those in the gastrointestinal tract.
| Metabolism | Metabolized via proteolytic degradation; no specific CYP450 involvement. |
| Excretion | Primarily renal; approximately 90% of the dose is excreted unchanged in urine within 24 hours via glomerular filtration and tubular secretion. Minimal biliary/fecal elimination (<5%). |
| Half-life | Terminal elimination half-life is approximately 4.5 hours in healthy adults. In patients with renal impairment (CrCl <30 mL/min), half-life is prolonged up to 2-fold, requiring dose adjustment. The half-life supports once-daily dosing for 3 consecutive days before chemotherapy. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution at steady state (Vd_ss) is approximately 0.2 L/kg, indicating limited extravascular distribution, consistent with a large protein-bound molecule. Does not distribute extensively into tissues. |
| Bioavailability | Subcutaneous administration: Absolute bioavailability is approximately 90% compared to intravenous administration. Not available orally; only given subcutaneously. |
| Onset of Action | Subcutaneous administration: Onset of clinical effect (reduction in oral mucositis severity) is typically observed after completion of the dosing regimen (3 days prior to chemotherapy) and manifests during the subsequent chemotherapy cycle. No immediate clinical effect. |
| Duration of Action | Duration of clinical effect (reduction in incidence and duration of severe oral mucositis) spans the period of chemotherapy-induced mucosal damage and recovery, typically lasting 2–3 weeks per cycle. The drug is given prophylactically before chemotherapy, not for active treatment. |
| Molecular Weight | 14000 |
60 mcg/kg/day intravenously for 3 consecutive days before and 3 consecutive days after myelotoxic therapy.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment is recommended for renal impairment, but monitor serum creatinine. |
| Liver impairment | No specific dose adjustment for Child-Pugh class A or B; use caution in severe impairment. |
| Pediatric use | Safety and efficacy not established; no recommended pediatric dose. |
| Geriatric use | No specific dose adjustment, but consider age-related renal and hepatic function decline. |
| 1st trimester | Limited data; manufacturer advises avoidance unless benefit outweighs risk. Animal studies show increased fetal mortality and developmental delays. |
| 2nd trimester | Limited data; consider risk-benefit. No adequate human studies. |
| 3rd trimester | Limited data; consider risk-benefit. Potential for adverse effects on fetal growth and development. |
Clinical note
Comprehensive clinical and safety monograph for KEPIVANCE (KEPIVANCE).
| Placental transfer | Human data not available. In animal studies, palifermin crossed the placenta and was associated with fetal abnormalities. Expected to cross due to molecular size. |
| Breastfeeding | Not known whether Kepivance is excreted in human milk. Because many drugs are excreted and due to potential for serious adverse reactions in nursing infants, advise against breastfeeding during treatment and for at least 2 weeks after last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | KEPIVANCE (palifermin) is a recombinant human keratinocyte growth factor. No adequate and well-controlled studies in pregnant women. In animal reproduction studies, palifermin was not teratogenic in rats or rabbits at doses up to 100 mg/kg/day (IV), which produced exposures approximately 40 and 80 times the human exposure at the recommended clinical dose of 60 mcg/kg/day, based on AUC. However, there are no human data. Risk in first trimester: unknown; second and third trimesters: unknown. |
| Fetal Monitoring | No specific maternal or fetal monitoring requirements beyond routine pregnancy management. Monitor for adverse effects such as skin rash, pruritus, erythema, edema, and mucositis, which are common in non-pregnant patients. No fetal monitoring indicated. |
| Fertility Effects | Palifermin did not impair fertility in male and female rats administered up to 100 mg/kg/day IV (approximately 40 times the human exposure). No human data on fertility effects. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to palifermin or any excipientsHistory of any malignancyNon-hematologic tumors (e.g., lung, head and neck)
| Precautions | Potential for stimulation of epithelial tumor growth (use caution in patients with non-hematologic malignancies)., Risk of allergic reactions including anaphylaxis., May cause oral mucosal thickening and dental abnormalities., Avoid use within 24 hours before or after myelotoxic chemotherapy. |
| Food/Dietary | No specific food interactions have been reported for KEPIVANCE. Maintain adequate nutrition and hydration as recommended by your healthcare provider. |
| Clinical Pearls | KEPIVANCE (palifermin) is a recombinant human keratinocyte growth factor used to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies undergoing myelotoxic therapy requiring hematopoietic stem cell support. Administer as a 3-day course of 60 mcg/kg/day IV bolus for 3 consecutive days before and 3 consecutive days after myelotoxic therapy. Must be given at least 24 hours before and after chemotherapy; do not administer within 24 hours of chemotherapy due to risk of enhanced cytotoxicity. Monitor for skin reactions, oral/perioral edema, and taste alteration. Contraindicated in patients with known hypersensitivity to E. coli-derived proteins. |
| Patient Advice | KEPIVANCE reduces the severity and duration of mouth sores caused by high-dose chemotherapy. · It is given as a short intravenous infusion once daily for 3 days before and 3 days after your chemotherapy. · You may experience swelling of the mouth, tongue, or lips; skin rash; or changes in taste. Report these to your healthcare team. · Do not receive KEPIVANCE within 24 hours before or after chemotherapy. · Inform your doctor if you have any allergies, especially to E. coli-derived products. |
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