Palifermin is a mucocutaneous epithelial human growth factor. It is indicated to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies who are receiving myelotoxic preparative regimens prior to an autologous hematopoietic stem cell transplant that are predicted to result in a high incidence of WHO Grade 3 or 4 mucositis. Palifermin is not recommended for use in patients with nonhematologic malignancies due to a potential for tumor proliferation or in patients receiving an allogeneic stem-cell transplantation or melphalan 200 mg/m2 as a conditioning regimen due to lack of efficacy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 2
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Palifermin is available as a single-dose, 5.16-mg lyophilized powder vial.
-Do not administer within 24 hours of myelotoxic chemotherapy.
Reconstitution:
-Slowly add 1.2 mL of Sterile Water for injection to the 5.16-mg lyophilized powder vial for a final vial concentration of 5 mg/mL.
-Swirl contents gently for about 3 minutes to completely dissolve the powder; do not shake or vigorously agitate the vial.
-Do not filter the reconstituted solution during preparation or administration.
-Storage after reconstitution: Use immediately if possible; may be stored in the refrigerator (2 to 8 degree C; 36 to 46 degrees F) in the carton for up to 24 hours. Do not freeze and protect from light.
Preparation:
-Withdraw the calculated dose from the reconstituted vial into a syringe; discard the unused portion of the vial.
Intravenous Injection:
-Allow palifermin to reach room temperature for up to 1 hour protected from light prior to the injection; discard if left at room temperature for more than 1 hour.
-Administer as an IV bolus injection.
-If heparin is used to maintain the IV line, rinse the line with saline prior to and after palifermin administration.
Vaginal edema and erythema were reported in postmarketing surveillance.
Edema was reported in 28% of patients with a hematologic malignancy who received mucositis prophylaxis with palifermin (n = 409) compared with 21% of patients who received placebo (n = 241) before and after a myelotoxic preparative regimen prior to hematopoietic stem cell support in a pooled analysis of 3 randomized trials and 1 pharmacokinetic study.
Rash (62% vs. 50%; grade 3, 3% vs. 2%), pruritus (35% vs. 24%), and erythema (32% vs. 22%) occurred more often in patients with a hematologic malignancy who received mucositis prophylaxis with palifermin (n = 409) compared with placebo (n = 241) before and after a myelotoxic preparative regimen prior to hematopoietic stem cell support in a pooled analysis of 3 randomized trials and 1 pharmacokinetic study. Cutaneous edema was also commonly reported with palifermin therapy. Following the first of 3 consecutive daily doses of palifermin, the median time to cutaneous toxicity onset was 6 days and the median duration was 5 days. Additionally, palmar-plantar erythrodysesthesia (hand and foot syndrome) was reported in postmarketing surveillance.
Dysesthesia, including hyperesthesia, hypoesthesia, and paresthesias, was reported in 12% of patients with a hematologic malignancy who received mucositis prophylaxis with palifermin (n = 409) compared with 7% of patients who received placebo (n = 241) before and after a myelotoxic preparative regimen prior to hematopoietic stem cell support in a pooled analysis of 3 randomized trials and 1 pharmacokinetic study. Dysesthesia was usually localized to the perioral region in patients who received palifermin.
Elevated amylase level/hyperamylasemia (62% vs. 54%; grade 3 or 4, 38% vs. 31%) and elevated lipase level (28% vs. 23%; grade 3 or 4, 11% vs. 5%) occurred more often in patients with a hematologic malignancy who received mucositis prophylaxis with palifermin (n = 409) compared with placebo (n = 241) before and after a myelotoxic preparative regimen prior to hematopoietic stem cell support in a pooled analysis of 3 randomized trials and 1 pharmacokinetic study. Peak amylase and lipase level elevations occurred during cytotoxic therapy and returned to baseline by the day of the hematopoietic stem cell infusion.
In clinical trials, 2% of 645 patients tested positive for antibodies to palifermin; none of these patients had evidence of neutralizing antibodies in a cell-based assay. The clinical significance of antibody formation to palifermin administration is unknown but may include lessened activity and/or cross-reactivity with other members of the fibroblast growth factor family of growth factors.
In a postmarketing safety study, the incidence of cataracts was evaluated in a subset of patients with multiple myeloma who received mucositis prophylaxis with palifermin before and after a high-dose melphalan preparative regimen prior to an autologous hematopoietic stem cell transplant. More patients who received palifermin compared with placebo (48% vs. 29%; difference of 17%; 95% CI, -11 to 46) developed cataracts or had cataract progression at month 12. Palifermin is not recommended for use with melphalan 200 mg/m2 as a conditioning regimen.
Treatment-emergent infection was reported significantly more often with palifermin compared with placebo (50% or 47% vs. 25%) in patients who received a high-dose melphalan preparative regimen in a 3-arm, randomized, double-blind trial (n = 281). Palifermin is not recommended for use with melphalan 200 mg/m2 as a conditioning regimen.
Fever was reported in 39% of patients with a hematologic malignancy who received mucositis prophylaxis with palifermin (n = 409) compared with 34% of patients who received placebo (n = 241) before and after a myelotoxic preparative regimen prior to hematopoietic stem cell support in a pooled analysis of 3 randomized trials and 1 pharmacokinetic study.
Pain (16% vs. 11%) and arthralgia (10% vs. 5%) were reported more often in patients with a hematologic malignancy who received mucositis prophylaxis with palifermin (n = 409) compared with placebo (n = 241) before and after a myelotoxic preparative regimen prior to hematopoietic stem cell support in a pooled analysis of 3 randomized trials and 1 pharmacokinetic study.
Dysgeusia/altered taste (12% vs. 7%) and mouth/tongue discoloration or thickness (17% vs. 8%) occurred more often in patients with a hematologic malignancy who received mucositis prophylaxis with palifermin (n = 409) compared with placebo (n = 241) before and after a myelotoxic preparative regimen prior to hematopoietic stem cell support in a pooled analysis of 3 randomized trials and 1 pharmacokinetic study.
Palifermin enhances the growth of human epithelial tumor cell lines in vitro and increases the rate of tumor cell line growth in human carcinoma xenograft models. Due to the risk stimulating keratinocyte growth factor receptor-expressing, non-hematopoietic tumors, palifermin is not indicated for use in patients with a non-hematologic malignancy.
Palifermin may cause fetal harm if used during pregnancy, based on data from animal studies. However, there are no data in humans to assess the drug-associated risk in pregnant patients Increased post-implantation loss and decreased fetal body weights occurred in the off-spring of female rabbits following palifermin doses that resulted about 5 times the exposure (AUC) observed in humans at the recommended dose. Additionally, increased skeletal variations were reported in the off-spring of female rats who received palifermin doses that resulted about 35 times the exposure observed in humans at the recommended dose.
There is a risk of male and female infertility with palifermin therapy, based on data from animal studies. Decreased epididymal sperm counts in male rats and increased implantation loss and decreased fertility index in female rats were observed when palifermin was administered IV daily at doses that were 5-fold higher than the recommended human dose.
It is not known if palifermin is secreted in human milk or if it has effects on the breast-fed child or on milk production. Due to the risk of serious adverse reactions in a nursing child, discontinue breast-feeding during palifermin therapy and for at least 2 weeks after the last dose.
For mucositis prophylaxis:
Palifermin was not effective in decreasing the incidence of severe mucositis in patients with hematologic malignancies receiving myelotoxic therapy in the setting of allogeneic hematopoietic stem cell support.
-as supportive care to decrease the incidence and duration of severe mucositis in patients with hematologic malignancies who are receiving a myelotoxic preparative regimen followed by an autologous hematopoietic stem cell transplantation that is predicted to result in a high incidence of WHO Grade 3 or higher mucositis:
Due to lack of efficacy, palifermin is not recommended for use with melphalan 200 mg/m2 as a conditioning regimen.
Intravenous dosage:
Adults: 60 micrograms/kg IV once daily for 3 consecutive days before and 3 consecutive days after myelotoxic therapy for a total of 6 doses. Do not administer within 24 hours before, during, or within 24 hours after myelotoxic chemotherapy; concomitant use of palifermin and chemotherapy led to increased severity and duration of oral mucositis in a clinical trial. Administer doses 1, 2, and 3 prior to myelotoxic therapy; give dose 3 at 24 to 48 hours before myelotoxic therapy is started. Administer doses 4, 5, and 6 after myelotoxic therapy is complete. Give dose 4 on the same day as the hematopoietic stem cell infusion but after the infusion is complete and at least 7 days after dose 3 was given. The incidence of World Health Organization (WHO) grade 3 or 4 mucositis was significantly less with palifermin therapy compared with placebo (63% vs. 98%; p less than 0.001) in patients with hematologic cancers who received myelosuppressive conditioning therapy prior to an autologous hematopoietic stem-cell transplantation (HSCT) in a randomized, double-blind, phase 3 trial (n = 212). The median duration of WHO grade 3 or 4 mucositis was 6 (range, 1 to 22) days in the palifermin arm and 9 (range, 1 to 27) days in the placebo arm (p less than 0.001). Additionally, patients who received palifermin required significantly less parenteral or transdermal opioid analgesics for mucositis (morphine equivalents, 212 mg vs. 535 mg; p less than 0.001) for a significantly shorter amount of time (7 vs. 11 days; p less than 0.001) compared with patients who received placebo in this study. Conditioning chemotherapy was administered starting 1 day after total-body irradiation and consisted of etoposide 60 mg/kg IV given 4 days prior to HSCT and cyclophosphamide 100 mg/kg IV given 2 days prior to HSCT.
Children and Adolescents: Not recommended by guidelines. The FDA-approved dosage is 60 micrograms/kg IV once daily for 3 consecutive days before and 3 consecutive days after myelotoxic therapy for a total of 6 doses. Do not administer within 24 hours before, during, or within 24 hours after myelotoxic chemotherapy; concomitant use of palifermin and chemotherapy led to increased severity and duration of oral mucositis in a clinical trial. Administer doses 1, 2, and 3 prior to myelotoxic therapy; give dose 3 at 24 to 48 hours before myelotoxic therapy is started. Administer doses 4, 5, and 6 after myelotoxic therapy is complete. Give dose 4 on the same day as the hematopoietic stem cell infusion but after the infusion is complete and at least 7 days after dose 3 was given. There was a significant reduction in severe mucositis in pediatric patients who received palifermin prophylaxis compared with no prophylaxis (risk ratio = 0.81; 95% CI, 0.69 to 0.95; p = 0.008) in an analysis of 9 clinical trials (n = 1,434); however, routine use of palifermin in this population is not recommended due to the risk of adverse effects and long-term negative effects on cancer outcomes.
Maximum Dosage Limits:
-Adults
60 micrograms/kg IV daily for 6 doses.
-Geriatric
60 micrograms/kg IV daily for 6 doses.
-Adolescents
60 micrograms/kg IV daily for 6 doses.
-Children
60 micrograms/kg IV daily for 6 doses.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Dalteparin: (Moderate) The co-administration of palifermin and unfractionated heparin may result in a 4 to 5-fold increase in palifermin exposure; however, this interaction does not appear to affect the pharmacodynamics of either drug. If heparin is used to maintain an IV line, rinse the line with saline prior to and after palifermin administration. The palifermin AUC value was increased by 5-fold and the mean clearance was decreased by 80% after a single 60 mcg/kg dose of palifermin was administered with therapeutic levels of unfractionated heparin compared with no heparin in 27 healthy subjects. The activated partial thromboplastin time (aPTT) was not affected by this interaction. The palifermin AUC value was increased by 425% and the palifermin clearance, volume of distribution, and half-life was decreased by 76.5%, 73.1%, and 38.8%, respectively, following the administration of palifermin 40 mcg/kg/day for 3 days in combination with therapeutic levels of unfractionated heparin compared with no heparin in 31 healthy subjects. Palifermin administration results in a dose-dependent epithelial cell proliferation that may be assessed by Ki67 immunohistochemical staining. In this study, the pharmacokinetics of palifermin did not affect Ki67 expression in buccal biopsies. The co-administration of palifermin and low-molecular weight heparins (LMWHs), such as enoxaparin and dalteparin, is expected to have a similar interaction.
Enoxaparin: (Moderate) The co-administration of palifermin and unfractionated heparin may result in a 4 to 5-fold increase in palifermin exposure; however, this interaction does not appear to affect the pharmacodynamics of either drug. If heparin is used to maintain an IV line, rinse the line with saline prior to and after palifermin administration. The palifermin AUC value was increased by 5-fold and the mean clearance was decreased by 80% after a single 60 mcg/kg dose of palifermin was administered with therapeutic levels of unfractionated heparin compared with no heparin in 27 healthy subjects. The activated partial thromboplastin time (aPTT) was not affected by this interaction. The palifermin AUC value was increased by 425% and the palifermin clearance, volume of distribution, and half-life was decreased by 76.5%, 73.1%, and 38.8%, respectively, following the administration of palifermin 40 mcg/kg/day for 3 days in combination with therapeutic levels of unfractionated heparin compared with no heparin in 31 healthy subjects. Palifermin administration results in a dose-dependent epithelial cell proliferation that may be assessed by Ki67 immunohistochemical staining. In this study, the pharmacokinetics of palifermin did not affect Ki67 expression in buccal biopsies. The co-administration of palifermin and low-molecular weight heparins (LMWHs), such as enoxaparin and dalteparin, is expected to have a similar interaction.
Heparin: (Moderate) The co-administration of palifermin and unfractionated heparin may result in a 4 to 5-fold increase in palifermin exposure; however, this interaction does not appear to affect the pharmacodynamics of either drug. If heparin is used to maintain an IV line, rinse the line with saline prior to and after palifermin administration. The palifermin AUC value was increased by 5-fold and the mean clearance was decreased by 80% after a single 60 mcg/kg dose of palifermin was administered with therapeutic levels of unfractionated heparin compared with no heparin in 27 healthy subjects. The activated partial thromboplastin time (aPTT) was not affected by this interaction. The palifermin AUC value was increased by 425% and the palifermin clearance, volume of distribution, and half-life was decreased by 76.5%, 73.1%, and 38.8%, respectively, following the administration of palifermin 40 mcg/kg/day for 3 days in combination with therapeutic levels of unfractionated heparin compared with no heparin in 31 healthy subjects. Palifermin administration results in a dose-dependent epithelial cell proliferation that may be assessed by Ki67 immunohistochemical staining. In this study, the pharmacokinetics of palifermin did not affect Ki67 expression in buccal biopsies. The co-administration of palifermin and low-molecular weight heparins (LMWHs), such as enoxaparin and dalteparin, is expected to have a similar interaction.
Low Molecular Weight Heparins: (Moderate) The co-administration of palifermin and unfractionated heparin may result in a 4 to 5-fold increase in palifermin exposure; however, this interaction does not appear to affect the pharmacodynamics of either drug. If heparin is used to maintain an IV line, rinse the line with saline prior to and after palifermin administration. The palifermin AUC value was increased by 5-fold and the mean clearance was decreased by 80% after a single 60 mcg/kg dose of palifermin was administered with therapeutic levels of unfractionated heparin compared with no heparin in 27 healthy subjects. The activated partial thromboplastin time (aPTT) was not affected by this interaction. The palifermin AUC value was increased by 425% and the palifermin clearance, volume of distribution, and half-life was decreased by 76.5%, 73.1%, and 38.8%, respectively, following the administration of palifermin 40 mcg/kg/day for 3 days in combination with therapeutic levels of unfractionated heparin compared with no heparin in 31 healthy subjects. Palifermin administration results in a dose-dependent epithelial cell proliferation that may be assessed by Ki67 immunohistochemical staining. In this study, the pharmacokinetics of palifermin did not affect Ki67 expression in buccal biopsies. The co-administration of palifermin and low-molecular weight heparins (LMWHs), such as enoxaparin and dalteparin, is expected to have a similar interaction.
Palifermin is a recombinant human keratinocyte growth factor (KGF). KGF is an endogenous protein in the fibroblast growth factor family; it binds to the KGF receptor resulting in proliferation, differentiation, and migration of epithelial cells. The KGF receptor is present on epithelial cells in many tissues 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.
Palifermin is administered intravenously (IV). It exhibits linear pharmacokinetics with extravascular distribution. Following a single dose of palifermin 60 micrograms/kg IV in cancer patients, the mean clearance was 1,730 mL/hr/kg and the average elimination half-life was 4.5 (range, 3.3 to 5.7) hours. The average total body clearance and steady state volume of distribution were 2- to 4-fold higher and 2-fold higher, respectively, in cancer patients compared with healthy subjects.
-Route-Specific Pharmacokinetics
Intravenous Route
After an IV dose, palifermin concentrations decline greater than 95% in the first 30 minutes post-dose and have a slight increase or plateau at approximately 1 to 4 hours followed by a terminal elimination phase. Following a single dose of palifermin 60 micrograms/kg IV in cancer patients, the mean AUC(0-inf) value was 38.2 nanogram x hour/mL. Palifermin exposure does not increase linearly with increasing doses. No accumulation occurred after 3 consecutive daily doses.
-Special Populations
Renal Impairment
In a pharmacokinetic study (n = 24), varying degrees of renal impairment did not affect the pharmacokinetic parameters of palifermin.
Pediatrics
Age (range, 1 to 16 years) did not affect the pharmacokinetic parameters of palifermin over a dose range of 40 to 80 micrograms (mcg)/kg in a phase 1 trial (n = 27). After an IV dose, palifermin concentrations decline in the first 30 minutes post-dose and increase at approximately 2 to 4 hours in some subjects followed by a second, slow decline phase. Following a single dose of palifermin 60 mcg/kg IV in pediatric cancer patients, the mean half-life range was 2.6 to 5.6 hours, the mean clearance was 2,481 (range, 1,700 to 3,460) mL/hour/kg, and the mean AUC(0-inf) value was 46.1 (range, 22.8 to 81.6) nanograms x hour/mL. No accumulation occurred after 3 consecutive daily doses.
Geriatric
Following a single 180-microgram (mcg)/kg or 90-mcg/kg IV dose, the average palifermin clearance value was approximately 30% lower in subjects older than 65 years (n = 8) compared with subjects aged 65 and younger (n = 19).