Action and Spectrum

Actions and Spectrum: 

• The mechanism of action of palifermin involves its interaction with the epithelial cells in the body. It specifically binds to and activates the keratinocyte growth factor receptor (KGFR) on the surface of epithelial cells in various tissues, including the skin, gastrointestinal tract, and oral mucosa. Activation of KGFR leads to the stimulation of cell proliferation, differentiation, and migration. 
• By stimulating the proliferation and differentiation of epithelial cells, palifermin helps protect and regenerate tissues susceptible to damage caused by high-dose chemotherapy and radiation therapy. These tissues include the lining of the mouth, throat, and intestines. palifermin promotes the growth and repair of the epithelial cells, thus reducing the severity and duration of mucositis, a common and painful side effect of cancer treatment characterized by inflammation and ulceration of the mucous membranes. 
• The spectrum of activity of palifermin is primarily limited to the epithelial cells in the oral mucosa, gastrointestinal tract, and skin. It does not directly affect cancer cells or other non-epithelial cell types. palifermin’s action is particular to promoting the growth and regeneration of epithelial cells, making it helpful in preventing and managing mucositis. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Rash (62%) 

Pruritus (35%) 

Edema (28%) 

Mouth/tongue thickness/discoloration (17%) 

Pain (16%) 

Dysesthesia (12%) 

Fever (39%) 

Erythema (32%) 

Elevated serum lipase (28%) 

proteinuria (17%) 

Taste altered (16%) 

Elevated serum amylase (62%) 

1-10% 

Hypertension (7%) 

Antibody formation (2%) 

Arthralgia (10%) 

<1% 

Vaginal erythema 

Cataracts 

Rhinitis 

Cough 

Vaginal edema 

Perianal pain 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: palifermin should not be used in individuals with known hypersensitivity or allergic reactions to palifermin or its components. Signs of hypersensitivity may include rash, itching, swelling, dizziness, or difficulty breathing. If any of these symptoms occur, medical attention should be sought immediately. 
• Tumor growth: palifermin is not indicated for use in individuals with head and neck region tumors, such as squamous cell carcinoma. This is because palifermin may stimulate the growth of existing tumor cells. The safety and efficacy of palifermin have not been established in these patient populations. 
• Pediatric use: The use of palifermin in pediatric patients has not been extensively studied, and its safety and efficacy have yet to be established in this population. Therefore, palifermin is not recommended for use in children and adolescents. 
• Pregnancy and breastfeeding: The effects of palifermin on pregnancy and breastfeeding are not well-known. Pregnant or breastfeeding individuals should consult their healthcare provider before using palifermin to assess the potential risks and benefits. 

Caution: 

• Potential tumor stimulation: palifermin has the potential to stimulate the growth of existing tumor cells. Therefore, its use should be carefully considered in patients with a history of tumors, including solid tumors and hematologic malignancies. The potential benefits of palifermin should be weighed against the risks in these patients. 
• Monitoring of tumor status: Patients receiving palifermin should be closely monitored for any signs of tumor growth or disease progression. Regular clinical evaluations, imaging studies, and laboratory tests may be necessary to assess the response to treatment and the status of any underlying tumors. 
• Interactions with chemotherapy and radiation therapy: palifermin is primarily used with high-dose chemotherapy and radiation therapy. However, the timing of palifermin administration of these treatments is crucial. palifermin should not be administered within 24 hours before, during, or 24 hours after chemotherapy or radiation therapy. This is because palifermin can enhance the toxic effects of these treatments on tumor cells, potentially reducing their effectiveness. 
• Fluid retention: palifermin may cause fluid retention, leading to swelling and edema. Patients with pre-existing conditions such as congestive heart failure or renal impairment may be at a higher risk. Close monitoring of fluid balance and appropriate management of fluid retention should be implemented in these patients. 
• Use in elderly patients: Elderly patients may be more susceptible to the fluid-retaining effects of palifermin. Additionally, caution should be exercised when using palifermin in elderly patients with comorbidities, as they may be more vulnerable to adverse effects. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

<b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

palifermin, also known as keratinocyte growth factor-1 (KGF-1), is a recombinant human protein structurally and functionally like endogenous human KGF. Here are some critical aspects of the pharmacology of palifermin: 

palifermin binds specifically to the keratinocyte growth factor receptor (KGFR), which is predominantly expressed on the surface of epithelial cells. This binding activates signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway, leading to cellular proliferation, differentiation, and migration. palifermin stimulates the growth and repair of epithelial cells, particularly in the oral mucosa, gastrointestinal tract, and skin.  

Pharmacodynamics: 

The pharmacodynamics of palifermin primarily involve its effects on epithelial cell growth and tissue regeneration. Here are the critical pharmacodynamic aspects of palifermin: 

• Epithelial cell proliferation: palifermin binds to the keratinocyte growth factor receptor (KGFR) on the surface of epithelial cells, particularly in the oral mucosa, gastrointestinal tract, and skin. This binding stimulates signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway, leading to increased cellular proliferation. The enhanced proliferation of epithelial cells promotes tissue growth and regeneration. 
• Epithelial cell differentiation: Besides promoting cell proliferation, palifermin also induces the differentiation of epithelial cells. It triggers the expression of genes associated with epithelial differentiation, leading to the maturation of epithelial cells and the restoration of tissue integrity. This process is critical in the context of oral mucositis, where the epithelial lining of the mouth is damaged during cancer treatment. 
• Tissue protection and repair: By stimulating epithelial cell proliferation and differentiation, palifermin provides tissue protection and facilitates the repair of damaged mucosa. This is crucial in preventing and treating oral mucositis, a common side effect of chemotherapy and radiation therapy. palifermin’s effects help reduce the severity and duration of mucositis, improving patient comfort and allowing for a more consistent cancer treatment schedule. 
• Modulation of the inflammatory response: palifermin has been shown to have anti-inflammatory effects. It can modulate the production of pro-inflammatory cytokines and chemokines, potentially reducing the inflammatory response associated with tissue damage caused by cancer treatment. By dampening inflammation, palifermin may contribute to the mitigation of mucositis-related symptoms. 

Pharmacokinetics: 

Absorption 

palifermin is administered intravenously, meaning it is directly infused into the bloodstream. As a result, absorption is not a relevant factor for palifermin. 

Distribution 

Following intravenous administration, palifermin is rapidly distributed within the body. It interacts with the keratinocyte growth factor receptor (KGFR) on the surface of epithelial cells in various tissues, such as the oral mucosa, gastrointestinal tract, and skin. This distribution allows palifermin to exert its pharmacodynamic effects on these target tissues. 

Metabolism 

palifermin is a recombinant human protein, and as such, it undergoes metabolism like endogenous proteins. It is primarily metabolized by proteolytic enzymes in the tissues. The exact details of its metabolism, including specific enzymes involved, are not extensively described in the available literature. 

Elimination and Excretion 

The elimination of palifermin from the body occurs primarily through renal excretion. Approximately 70-80% of the administered dose is excreted unchanged in the urine within 24 hours. The exact elimination half-life of palifermin is relatively short, estimated to be around 3-5 hours. 

Adminstartion

Administration: 

• Dosage: The recommended dosage of palifermin may vary depending on the specific treatment protocol and the patient’s characteristics. It is typically expressed in terms of milligrams (mg) or micrograms (mcg) per kilogram (kg) of body weight.  
• Route of Administration: palifermin is administered exclusively through intravenous infusion. It is diluted in sterile saline or dextrose solution and infused into a vein over a specified period.  
• Timing: palifermin is usually administered before and following chemotherapy or radiation therapy. The exact timing of administration may vary depending on the specific treatment regimen. It is generally given at least 24 hours before chemotherapy or radiation therapy and continued for several days afterward.  
• Duration of Administration: palifermin administration depends on the specific treatment protocol and individual patient factors. Typically, the infusion is completed over about 15-30 minutes.  
• Monitoring: Patients receiving palifermin should be closely monitored during and after administration for any signs of adverse reactions or side effects. Regular clinical evaluations, including assessments of oral mucositis or other relevant conditions, may be conducted to monitor treatment response. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: palifermin 

Why do we use palifermin? 

palifermin, known by its brand name Kepivance, is primarily used in oncology to prevent and treat oral mucositis, a common side effect of high-dose chemotherapy and radiation therapy. Here are the primary uses of palifermin: 

• Prevention of Oral Mucositis: palifermin is used to prevent the development of oral mucositis in patients undergoing high-dose chemotherapy with a high risk of mucositis. It is administered before and after chemotherapy to help protect and regenerate the oral mucosa, reducing the severity and duration of mucositis. This can improve patient comfort, maintain nutrition, and provide a more consistent cancer treatment schedule. 
• Treatment of Oral Mucositis: palifermin can also be used to treat established mucositis in patients who develop oral mucositis despite preventive measures. By stimulating the growth and repair of the oral mucosa, palifermin helps alleviate mucositis’s symptoms, such as pain, inflammation, and ulceration.