Kepivance

Generic Name: Palifermin
Class: Cell Stimulants and Proliferants
Chemical Name: 24-163 fibroblast growth factor 7 (human)
Molecular Formula: C729H1156N204O207S10
CAS Number: 162394-19-6

Introduction

Biosynthetic (recombinant DNA-derived) analog of human keratinocyte growth factor; mucosal protectant.1 2 3 4 5

Uses for Kepivance

Chemotherapy-induced Oral Mucositis

Reduction in the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic chemotherapy followed by hematopoietic stem cell transplantation.1 2 5 6

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Also has reduced soreness of the mouth and throat, opiate analgesic requirements, and need for parenteral nutrition in patients with severe oral mucositis.1 2 5 6

Kepivance Dosage and Administration

Administration

IV Administration

Administer by direct IV injection.1

Do not administer during or within 24 hours before or after infusion of myelotoxic chemotherapy.1 (See Potentiation of Oral Mucositis under Cautions.)

Reconstitution

Reconstitute with sterile water for injection according to manufacturer’s directions to prepare a solution containing 5 mg/mL.1 Swirl vial gently during dissolution; do not shake or vigorously agitate.1 Dissolution should take <3 minutes.1 Do not filter reconstituted solutions during preparation or administration.1

Dosage

Adults

Chemotherapy-induced Oral Mucositis
IV

Initially, 60 mcg/kg daily, administered by direct IV injection on 3 consecutive days before and 3 consecutive days after myelotoxic chemotherapy (total of 6 doses).1

Administer the first 3 doses (doses 1–3) on the 3 consecutive days prior to myelotoxic chemotherapy, with the third dose administered 24–48 hours before such chemotherapy.1 Administer the last 3 doses (doses 4–6) on the 3 consecutive days after myelotoxic chemotherapy, with the first of the 3 doses (i.e., dose 4) administered after, but on the same day as, hematopoietic stem cell infusion and at least 4 days after the previous dose (dose 3) of the drug.1

Special Populations

No special population recommendations at this time.1

Cautions for Kepivance

Contraindications

  • Known hypersensitivity to Escherichia coli-derived proteins, palifermin, or any ingredient in the formulation.1

Warnings/Precautions

Major Toxicities

Potentiation of Oral Mucositis

Increased severity and duration of oral mucositis observed in patients receiving palifermin within 24 hours of chemotherapy administration, presumably because of increased sensitivity of rapidly dividing epithelial cells to chemotherapy after palifermin treatment.1 Do not administer during or within 24 hours before or after infusion of myelotoxic chemotherapy.1

General Precautions

Stimulation of Tumor Growth

Safety and efficacy not established in patients with nonhematological malignancies.1 Potential for stimulation of growth of nonhematologic tumors that express the keratinocyte growth factor receptor not established.1 Has been reported to stimulate growth of human epithelial tumor cell lines in vitro at concentrations >15-fold higher than average therapeutic concentrations in humans.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether distributed into milk.1 Use with caution.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

Experience in patients ≥65 years of age insufficient to determine whether they respond differently than younger adults.1

Common Adverse Effects

Arthralgia,1 dysesthesia (hyperesthesia, hypoesthesia, paresthesia),1 edema,1 3 5 elevated serum amylase1 5 or lipase concentrations,1 5 erythema,1 3 5 fever,1 3 mouth or tongue thickness or discoloration,1 pain,1 pruritus,1 3 rash,1 3 5 taste alteration.1 3

Interactions for Kepivance

No formal drug interaction studies performed.1

Severity of oral mucositis associated with myelotoxic chemotherapy may be enhanced if palifermin is administered within 24 hours of myelotoxic chemotherapy.1 (See Potentiation of Oral Mucositis under Cautions.)

Kepivance Pharmacokinetics

Absorption

Onset

Dose-dependent epithelial cell proliferation observed 48 hours after single IV doses of 120–250 mcg/kg in healthy individuals.1

Elimination

Half-life

Mean 4.5 hours (range 3.3–5.7 hours).1

Special Populations

Following a single dose of 60 mcg/kg, total body clearance averaged twofold to fourfold higher and volume of distribution at steady state averaged twofold higher in cancer patients compared with healthy individuals.1

Stability

Storage

Parenteral

Powder for Injection

Lyophilized powder and reconstituted solutions: 2–8°C; protect from light.1

Reconstituted solutions (5 mg/mL in sterile water for injection): Should be used immediately, but may be stored for ≤24 hours at 2–8°C.1

Prior to injection, allow solution to reach room temperature for ≤1 hour but protect from light.1 Discard solutions left at room temperature for >1 hour.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Binds to heparin in vitro; if administered via an IV line maintained with heparin, flush line with 0.9% sodium chloride solution prior to and following palifermin administration.1

Actions

  • Stimulates the proliferation, migration, and differentiation of epithelial cells.1 4

  • Shown to enhance the growth of human epithelial tumor cell lines in vitro and in animal studies.1 (See Stimulation of Tumor Growth under Cautions.)

Advice to Patients

  • Importance of advising patients about potential adverse mucocutaneous effects (e.g., rash, erythema, edema, pruritus, perioral dysesthesia, tongue discoloration, tongue thickening, taste alteration) and of informing clinicians if these or other adverse effects occur during therapy.1

  • Importance of advising patients about in vitro and in vivo evidence of tumor growth stimulation by palifermin in nonhematopoietic tissues.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Palifermin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

6.25 mg

Kepivance

Amgen

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Amgen. Kepivance (palifermin) prescribing information. Thousand Oaks, CA; 2004 Dec 15.

2. Spielberger R, Stiff P, Bensinger W et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004; 351:2590-8. [IDIS 525466] [PubMed 15602019]

3. Meropol NJ, Somer RA, Gtheil J et al. Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant. J Clin Oncol. 2003; 21:1452-8. [IDIS 497767] [PubMed 12697866]

4. Stiff P. Mucositis associated with stem cell transplanation: current status and innovative approaches to management. Bone Marrow Transplant. 2001; 27 (suppl 2):S3-11. [IDIS 465249] [PubMed 11436115]

5. Anon. Palifermin: AMJ 9701, KGF-Amgen, recombinant human keratinocyte growth factor, rHu-KGF. Drug R D. 2004; 5:351-4.

6. Garfunkel AA. Oral mucositis—the search for a solution. N Engl J Med. 2004; 351:2649-51. Editorial. [IDIS 525469] [PubMed 15602026]

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