palifermin


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palifermin

Kepivance

Pharmacologic class: Keratinocyte growth factor (KGF) (rDNA origin)

Therapeutic class: Biologic and immunologic agent

Pregnancy risk category C

Action

Produced by recombinant DNA technology in Escherichia coli; binds to KGF receptor on cell surface, resulting in epithelial cell proliferation, differentiation, and migration

Availability

Powder for injection (lyophilized): 6.25 mg in single-use vials

Indications and dosages

To decrease incidence and duration of severe oral mucositis in patients with hematologic malignancies who are receiving myelotoxic therapy requiring hematopoietic stem cell support

Adults: 60 mcg/kg/day I.V. bolus injection for 3 consecutive days before and 3 consecutive days after myelotoxic therapy, for a total of six doses. Give first three doses before myelotoxic therapy, with third dose given 24 to 48 hours before such therapy. Administer last three doses after myelotoxic therapy, with first of these given after (but on same day of) hematopoietic stem cell infusion and at least 4 days after most recent palifermin dose.

Contraindications

• Hypersensitivity to drug, its components, or E. coli-derived proteins

Precautions

Use cautiously in:
• patients with nonhematologic cancers
• use with melphalan 200 mg/m2 as a conditioning regimen (not recommended)
• elderly patients
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Reconstitute powder with 1.2 ml sterile water for injection to yield final concentration of 5 mg/ml.

Swirl vial gently during dissolution; don't shake or vigorously agitate.
• Don't filter reconstituted solution during preparation or administration.
• Use immediately (within 1 hour) after reconstituting; protect from light.
• When heparin is used to maintain I.V. line, use normal saline solution to rinse line before and after palifermin administration.
• Administer by I.V. bolus injection.
• Don't give within 24 hours before, during infusion of, or within 24 hours after myelotoxic chemotherapy.

Adverse reactions

CNS: dysesthesia

CV: hypertension

EENT: tongue discoloration or thickening

Musculoskeletal: pain, arthralgias

Skin: rash, pruritus, skin toxicities, erythema

Other: altered taste, edema, fever

Interactions

Drug-drug.Heparin: possible binding

Drug-diagnostic tests.Amylase, lipase: increased

Patient monitoring

• Monitor serum amylase and lipase levels frequently.

Patient teaching

• Instruct patient to report adverse reactions, including rash, itching, skin redness, swelling, discolored tongue, and altered taste.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

palifermin

(pa-liff-er-min) ,

Kepivance

(trade name)

Classification

Therapeutic: cytoprotective agents
Pharmacologic: keratinocyte growth factors
Pregnancy Category: C

Indications

To decrease incidence/duration of severe oral mucositis (at least WHO grade 3) associated with myelotoxic therapy in patients requiring stem cell support for hematologic malignancies.

Action

Enhances proliferation of epithelial cells.

Therapeutic effects

Decreased incidence/duration of mucositis.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Distributes into extravascular space.
Metabolism and Excretion: Unknown.
Half-life: 4.5 hr.

Time/action profile (levels)

ROUTEONSETPEAKDURATION
IVunknownend of doseunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity to palifermin or other E. coli-derived proteins.
Use Cautiously in: Obstetric: Use only if maternal benefit outweighs fetal risk; Lactation / Pediatric: Safety not established.

Adverse Reactions/Side Effects

Dermatologic

  • skin toxicity (most frequent)

Gastrointestinal

  • oral toxicity (most frequent)

Metabolic

  • ↑ amylase
  • ↑ lipase

Musculoskeletal

  • arthralgia (most frequent)

Neurologic

  • dysesthesia (most frequent)

Interactions

Drug-Drug interaction

Binds to and inactivates heparin (flush tubing between use).Administration within 24 hr after myelotoxic therapy (chemotherapy/radiation) ↑ severity and duration of mucositis.

Route/Dosage

Intravenous (Adults) 60 mcg/kg/day for 3 days before and 3 days after myelotoxic therapy.

Availability

Powder for injection: 6.25 mg/vial

Nursing implications

Nursing assessment

  • Assess level of oral mucositis prior to and periodically during therapy.
  • Lab Test Considerations: May cause ↑ serum lipase and amylase; usually reversible.
    • May cause proteinuria.

Potential Nursing Diagnoses

Acute pain (Indications)
Impairedoral mucous membrane (Indications)

Implementation

  • Do not administer palifermin within 24 hr before, during infusion, or 24 hr after infusion of myelotoxic chemotherapy.
    • Administer doses for 3 consecutive days before (third dose 24–48 hr prior to chemotherapy) and 3 consecutive days after myelotoxic chemotherapy (fourth dose on same day as hematopoietic stem cells infusion after infusion is completed and at least 4 days after most recent palifermin administration) for a total of 6 doses.
  • Intravenous Administration
  • pH: No Data.
  • Diluent: Reconstitute palifermin powder by slowly injecting 1.2 mL of sterile water for injection aseptically.Concentration: 5 mg/mL. Swirl gently; do not shake or vigorously agitate. Solution should be clear and colorless; do not administer solution that is discolored or contains particulate matter. Dissolution usually takes less than 3 minutes. Administer immediately after reconstitution or refrigerate and administer within 24 hr. Do not freeze. Allow to reach room temperature for up to 1 hr. Protect from light. Discard palifermin after expiration date or if left at room temperature for more than 1 hr.
  • Rate: Administer via bolus injection. Do not use a filter.
  • Y-Site Incompatibility: heparin. If heparin solution is used to maintain IV line, flush with 0.9% NaCl prior to and after use of palifermin.

Patient/Family Teaching

  • Explain the purpose of palifermin to patient.
  • Inform patient of evidence of tumor growth and stimulation in cell culture and animal models.
  • Advise patient to notify health care professional if rash, erythema, edema, pruritus, oral/perioral dysesthesia (tongue discoloration, tongue thickening, alteration of taste) occur.

Evaluation/Desired Outcomes

  • Decrease in incidence and duration of oral mucositis in patients receiving myelotoxic therapy requiring hematopoietic stem cell support.
References in periodicals archive ?
There is some example of novel intervention that possibly will improve outcomes for specific populations but consequence in raised costs including $1,000 per contrast-enhanced magnetic resonance imaging screening, which is 10 times the cost of screening mammography in breast cancer [25]; $48,000 per patient per year for the use of intensity-modulated radiation therapy to treat prostate cancer; $1,800 per positronemission tomography scan for cancer staging [23,4]; $1,800 per month for gefitinib (Iressa) for the treatment of lung cancer; $50,000 per patient per year for trastuzumab (Herceptin) in the treatment of HER2-positive breast cancer [16,8] and more than $8,000 for a 6-day course of palifermin (Kepivance) in the treatment of oral mucositis.
Palifermin stimulates proliferation and modifies differentiation in epithelial cells, including those of the oral mucosa [Sonis, 2007].
The ONS Putting Evidence Into Practice materials recommend the following prevention strategies: (a) a regular oral care protocol that includes patient education; (b) palifermin, a keratinocyte growth factor, in patients receiving high-dose chemotherapy, radiation, and allogeneic or autologous stem cell transplantion (it is not indicated for Abby's regimen); or (c) cryotherapy (ice chips) for patients receiving melphalan or bolus 5-FU because of their short half-lives (this has not been studied for Abby's regimen).
The intent of our study was to determine whether the use of Palifermin (a recombinant human keratinocyte growth factor) would allow us to increase the dose of Melphalan beyond the current standard," Dr.
The Food and Drug Administration has approved the recombinant human keratinocyte growth factor palifermin as the only drug indicated to reduce the incidence and duration of severe oral mucositis in patients with hematologic cancers who require hematopoietic stem cell transplantation after chemoradiotherapy.
Palifermin, also in its third phase, helps treat sores that form in the mouths of patients who are undergoing chemotherapy.
Cinacalcet and palifermin are investigational products in clinical development.
He has also worked at Amgen, Nycomed R&D and Sterling Winthrop in a variety of preclinical and clinical development roles, with contributions to a number of marketed products, including interferon alfacon1, palifermin, anakinra and romiplostim.
bolus 5-fluorouracil, melphalan) * Palifermin for autologous hematopoietic stem cell transplantation for hematologic malignancies Effectiveness Not Established * Allopurinol * Aloe vera * Amifostine * Anti-inflammatory rinses * Antimicrobial agents * Benzydamine hydrochloride * Flurbiprofen tooth patch * Granulocyte-colony-stimulating factor (subcutaneous) * Granulocyte macrophage-colonystimulating factor (subcutaneous) * Immunoglobin * L-alanyl-l-glutamine * Low-level laser therapy * Multiagent ("magic") rinses * Pilocarpine * Povidone-iodine * Tetracaine * Zinc supplements Effectiveness Unlikely * Iseganan Not Recommended for Practice * Chlorhexidine * Granulocyte macrophage-colony-stimulating factor mouthwash * Sucralfate Note.
Known as Palifermin, the drug is still in clinical trials, although it could be approved as early as next year.
Amgen, Thousand Oaks, CA, announced it has submitted a Biologics License Application (BLA) with the US Food and Drug Administration (FDA) for palifermin, a first-in-class investigational compound in development for oral mucositis (mouth sores).