Palifermin – Uses, Dosage, Side Effects, Interaction

Palifermin is a modified truncated form of human keratinocyte growth factor produced by recombinant DNA technology. Palifermin is used to treat oral sores and ulcers to prevent and treat oral mucositis that arise as a result of chemo- and radiotherapy. Palifermin is a recombinant human keratinocyte growth factor (KGF). It is 140 residues long and is produced using E. coli. Palifermin was granted FDA approval on 15 December 2004.^[rx]

Mechanism of action

Palifermin has been shown to protect oral and intestinal epithelia from the effects of radiation and chemotherapy, though the exact mechanism is not well understood.^[rx] As a recombinant keratinocyte growth factor (KGF), palifermin may promote cell proliferation, reducing the severity of oral mucositis in patients in the relevant treatment groups.^[rx] Agonism of fibroblast growth factor 2 may be predominantly responsible for this effect.^[rx] The endogenous form if palifermin is expressed in the kidney of rats.^[rx]

Keratinocyte growth factor (KGF) resides in the family of fibroblast growth factor (FGF). The drug’s target is the KGF receptor. Through the binding of this drug to the aforementioned receptor, Palifermin stimulates epithelial cell proliferation, differentiation, and upregulation of cytoprotective mechanisms to reduce the symptoms of oral mucositis

Used in the prevention or treatment of oral mucositis (mouth ulcers arising from chemotherapy), Kepivance binds to the human keratinocyte growth factor (KGF) receptor on buccal cell surfaces. Kepivance acts as both a cell growth and survival factor by stimulating epithelial cell proliferation, differentiation, and migration around the tongue and mouth. The KGF receptor is found on many tissues, particularly around the tongue, esophagus, salivary gland and other gastrointestinal tract organs.

Indications

• When patients with blood cancers (leukemia and lymphoma) receive high-dose chemotherapy and radiation therapy to undergo bone marrow transplantation, they usually get severe oral mucositis.^[rx] Palifermin reduces the incidence and duration of severe oral mucositis^[rx][rx] by protecting those cells and stimulating the growth of new epithelial cells to build up the mucosal barrier.
• Palifermin is also being studied in the preve

Use in Cancer

Palifermin is approved to prevent and treat:

• Oral mucositis that is severe. It may be used in adults and children whose blood cancer is being treated with high-dose chemotherapy and radiation therapy, followed by stem cell rescue.

Palifermin is also being studied in the prevention and treatment of common side effects in other types of cancer.

Contraindications

• Kepivance is contraindicated in patients with known hypersensitivity to E coli-derived
  proteins, palifermin, or any other component of the product.
• a patient who is producing milk and breastfeeding

Dosage

Strengths: 6.25 mg

Mucositis

• 60 mcg/kg IV (as a bolus) once a day, administered for 3 consecutive days before and 3 consecutive days after myelotoxic therapy
• Prior to myelotoxic therapy: The third dose should be administered 24 to 48 hours prior to beginning the myelotoxic agent.
• Following myelotoxic therapy: The first dose should be administered on the day of hematopoietic stem cell infusion after the infusion is complete, AND at least 7 days after the most recent dose of this drug.
• Decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy in the setting of autologous hematopoietic stem cell support
• Supportive care for preparative regiments predicted to result in greater than or equal to WHO Grade 3 mucositis in the majority of patients

Administration advice:

• This drug should be given as a IV bolus injection; the solution should not be filtered.
• If heparin is used, IV lines should be rinsed with saline prior to and after administration.
• Prior to administration, this drug should be allowed to reach room temperature for up to 1 hour (protected from light); however, this drug will need to be discarded in excursions exceeding 1 hour.
• Unopened vials: Store refrigerated (2 to 8C), and protect from light. Do not freeze.
• Reconstituted solution: The solution may be stored refrigerated (2 to 8C) and protected from light in its carton for up to 24 hours; the solution should be discarded after 24 hours if it is not used.
• Reconstituted solutions left at room temperature for longer than 1 hour should be discarded.
• Compatible: Sterile water for injection
• Other medications should not be added to solutions containing this drug.

General:

• Safety and efficacy have not been established in patients with non-hematologic malignancies.
• This drug was not effective in decreasing severe mucositis in patients with hematologic malignancies who were receiving myelotoxic therapy with allogenic hematopoietic stem cell support.
• Once reconstituted, it is recommended that this drug is used immediately.
• Limitation of use: Treatment is not recommended for use with melphalan 200 mg/m2 as a conditioning regimen.

Side Effects

The Most Common

• thick tongue
• Fever
• The skin rash in severe condition
• change in color of the tongue
• change in the ability to taste food
• increased or decreased feelings when touched, especially in and around the mouth
• burning or tingling, especially in and around the mouth
• joint pain
• fever
• rash
• hives
• red or itching skin
• difficulty breathing or swallowing
• swelling of the hands, feet, ankles, or lower legs

More common

• Bad, unusual, or unpleasant (after) taste
• blurred vision
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• change in taste
• difficulty with moving
• discoloration of the tongue
• dizziness
• flushing or redness of the skin
• headache
• increased sensitivity to pain
• increased sensitivity to touch
• itching skin
• muscle pain or stiffness
• nervousness
• pain
• pain in the joints
• pounding in the ears
• rash (mild)
• slow or fast heartbeat
• swelling
• thickening of the tongue
• tingling in the hands and feet
• unusually warm skin

Rare

• • redness or swelling of the vagina
• redness, swelling, or pain of the skin
• scaling of the skin on the hands and feet
• ulceration of the skin
• Pain (including joint pain)
• Increase in blood pancreas enzymes
• Increased blood pressure
• Proteinuria
• Difficulty breathing
• Changes in cutaneous or mucous membrane appearance/feel (redness/rash, swelling, itching, change in color or thickness of tongue, changes in taste

Drug Interactions

Pregnancy and Lactation

FDA Pregnancy Category C

Pregnancy

Kepivance™ has been shown to be embryotoxic in rabbits and rats when given in doses that are 2.5 and 8 times the human dose, respectively. Increased post-implantation loss and decreased fetal body weights were observed when
Kepivance™ was administered to pregnant rabbits from days 6 to 18 of gestation at IV doses ≥ 150 mcg/kg/day (2.5-fold higher than the recommended human dose). However, treatment with these doses was also associated with maternal toxicity (clinical signs and
reductions in body weight gain/food consumption). No evidence of developmental toxicity was observed in rabbits at doses up to 60 mcg/kg/day. Increased post-implantation loss, decreased fetal body weight, and/or increased skeletal variations were observed when Kepivance™ was administered to pregnant rats from days 6 to 17 or 19 of gestation at IV doses ≥ 500 mcg/kg/day (> 8-fold higher than the
recommended human dose). Treatment with these doses was also frequently associated with maternal toxicity (clinical signs and body weight effects). No evidence of developmental toxicity was observed in rats at doses up to 300 mcg/kg/day.
There are no adequate and well-controlled studies on pregnant women. Kepivance™ should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Lactation

It is not known whether Kepivance™ is excreted in human milk. Because many drugs are excreted in human milk‚ caution should be exercised when Kepivance™ is administered to a nursing woman. The safety and effectiveness of Kepivance™ in pediatric patients have not been
established.