Palifermin (Kepivance)
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Palifermin (Kepivance)

Kepivance®
(palifermin) For injection, for intravenous use

DRUG DESCRIPTION

Kepivance (palifermin) is a truncated human KGF produced by recombinant DNA technology in E coli. Kepivance is a water soluble, 140 amino acid protein with a molecular weight of 16.3 kilodaltons. It differs from endogenous human KGF in that the first 23 N terminal amino acids have been deleted to improve protein stability.

Kepivance is supplied as a sterile, white, preservative-free, lyophilized powder for intravenous injection after reconstitution with 1.2 mL of Sterile Water for Injection, USP. Reconstitution yields a clear, colorless solution of Kepivance (5 mg/mL) with a pH of6.5. Each single use vial of Kepi vance contains palifermin (6.25 mg),with L histidine (1.94 mg), mannitol (50 mg), polysorbate 20 (0.13 mg or 0.01% w/v), and sucrose (25 mg).

What are the possible side effects of palifermin (Kepivance)?

If you experience any of the following serious side effects from palifermin, seek emergency medical attention or contact your doctor immediately:

  • fever;
  • breathing problems;
  • skin and mucus membrane side effects such as rash, redness, swelling, itching, unusual sensations in the mouth, tongue color change, tongue thickening and changes in taste.

Other common side effects include:

  • swelling;
  • pain;
  • joint pain;
  • increases in blood pancreas enzymes;
  • increased blood pressure; or
  • protein in the...

Read All Potential Side Effects and See Pictures of Kepivance »

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Indications

Kepivance is a mucocutaneous epithelial human growth factor indicated to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support. Kepivance is indicated as supportive care for preparative regimens predicted to result in ≥ WHO Grade 3 mucositis in the majority of patients.

Limitations of Use

The safety and effcacy of Kepivance have not been established in patients with non-hematologic malignancies [see WARNINGS AND PRECAUTIONS]. I Kepivance is not recommended for use with melphalan 200 mg/m2 as a conditioning regimen [See Clinical Studies].

DOSAGE AND ADMINISTRATION

Recommended Dosage Regimen

The recommended dose of Kepi vance is 60 mcg/kg/day, administered as an intravenous bolus injection for 3 consecutive days before aiid 3 consecutive days after myelotoxic therapy, for a total of 6 doses. Administer the first 3 doses prior to myelotoxic therapy.

Administer the third dose 24 to 48 hours prior to beginning myelotoxic therapy [see DRUG INTERACTIONS].

Administer the last 3 doses after myelotoxic therapy is complete; Administer the first of these doses on the day of hematopoietic stem cell infusion after the infusion is completed, and more than 4 days after the most recent administration of Kepivance [see DRUG INTERACTIONS].

Preparation and Administration

Preparation

Prepare the solution for infusion, using aseptic technique, as follows:

  • Reconstitute Kepivance lyophilized powder with Sterile Water for Injection, USP (not supplied) by slowly injecting 1.2 mL of Sterile Water for Injection, USP to yield a final concentration of 5 mg/mL.
  • Swirl the contents gently during dissolution. Do not shake or vigorously agitate the viaL. Dissolution of Kepivance can take up to 3 minutes.
  • Visually inspect the solution for discoloration and particulate matter before administration. The reconstituted solution should be clear and colorless. Do not administer Kepivance if discoloration or particulates are observed. Do not fiter the reconstituted solution during preparation or administration. Do not freeze the reconstituted solution. Protect from light.
Administration
  • Administer Kepivance by intravenous bolus injection. If heparin is used to maintain an intravenous line, rinse the line with saline prior to and after Kepivance administration [see DRUG INTERACTIONS].
  • The reconstituted solution contains no preservatives and is intended for single use only. Discard any unused portion.
  • Following reconstitution, it is recommended that the product be used immediately. If not used immediately, the reconstituted solution of Kepivance may be stored refrigerated in its carton at 2° to 8°C (36° to 46°F) for up to 24 hours.
  • Prior to injection, allow Kepivance to reach room temperature for a maximum of i hour protected from light. Discard Kepivance left at room temperature for more than 1 hour.

HOW SUPPLIED

Dosage Forms and Strengths

6.25 mg lyophilized powder in single-use vials.

Kepivance is supplied as a lyophilized powder in single use vials containing 6.25 mg of palifermin. Kepivance vials are supplied in:

  • a dispensing pack containing 3 vials (NDC 66658- 112-03)
  • a dispensing pack containing 6 vials (NDC 66658-112-06)
  • a distribution case containing 4 dispensing packs (NDC 66658-112-24) (4 x 6 vial dispensing packs (24 x 6.25 mg/vial)).

Store Kepivance vials in the dispensing pack in its carton refrigerated at 2° to 8°C (36° to 46°F) until time of use. Protect from light.

Manufactured by: Swedish Orphan Biovitrum AB (publ) SE- 112 76 Stockholm, Sweden.

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The most common adverse reactions attributed to Kepivance were skin toxicities (rash, eryhema, edema, pruritus), oral toxicities (dysesthesia, tongue discoloration, tongue thickening, alteration of taste), pain, arthralgias, and dysesthesia. The median time to onset of cutaneous toxicity was 6 days following the first of 3 consecutive daily doses of Kepivance, with a median duration of 5 days. In patients receiving Kepivance, dysesthesia (including hyperesthesia, hypoesthesia, and paresthesia) was usually localized to the perioral region, whereas in patients receiving placebo dysesthesias were more likely to occur in extremities.

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data described in Table 1 and the discussion below reflect exposure to Kepivance in 409 patients with hematologic malignancies who were enrolled in 3 randomized, placebo-controlled clinical trials and a phannacokinetic study. Patients received Kepivance either before, or before and after, regimens of myelotoxic chemotherapy, with or without total body irradiation (TBI), followed by hematopoietic stem cell support. Kepivance was administered in daily doses ranging from 5 to 80 mcg/g/day. The total dose of Kepi vance ranged from 15 to 480 mcg/g with a median of360 mcg/g. The population had a median age of 48 years (range: 41 to 60 years), 62% were male and 83% were White with 7.4 % Black and 6.2 % Hispanic. Non Hodgkin's lymphoma (NHL) was the most common malignancy followed by Hodgkin's disease, multiple myeloma, and leukemia.

The most common serious adverse reaction attibuted to Kepivance was skin rash, reported in less than 1 % (3/409) of patients treated. Grade 3 skin rashes occurred in 3% of patients (9/409) receiving Kepivance and 2% (5/241) receiving placebo.

Table 1. Incidence of Adverse Reactions Occurring with a Between-Group Difference of ≥ 5%

BODY SYSTEM
Adverse Event
Kepivance
(n = 409)
%
Placebo
(0 = 241)
%
BODY AS A WHOLE
  Edema 28 21
  Pain 16 11
  Fever 39 34
GASTROINTESTINAL
  Mouthlongue Thickness or Discoloration 17 8
MUSCCULOSKELETAL
  Arhralgia 10 5
SKIN AND APPENDAGES
  Rash 62 50
  Pruritus 35 24
  Eryhema 32 22
SPECIAL SENSES
  Taste Altered 16 8
CENTRAL NERVOUS SYSTEM/PERIPHERAL NERVOUS SYSTEM
  Dysesthesia - Hyperesthesia/hypoesthesia/ paresthesia 12 7
METABOLIC
Elevated serum lipase    
  All grades 28 23
  Grade 3 and 4 11 5
Elevated serum amylase    
  All grades 62 54
  Grade 3 and 4 38 31

Cataracts: In a postmárketing safety study, the incidence of cataracts was numerically higher among patients receiving Kepivaoce than in the control population. (See Clinical Studies).

Laboratory Test Findings: Reversible elevations in serum lipase and amylase, which did not require treatment, were reported in 28% and 62% of patients receiving Kepivance and 23% and 54%of patients receiving placebo. In general, peak increases were observed during the period of cytotoxic therapy and returned to baseline by the day ofhernatopoietic stem cell infusion. Amylase was mainly salivary in origin.

Immunogenicity

As with all therapeutic proteins, there is a poteiltial for immunogenicity. The clinical significance of antibodies to Kepivance is unknown but may include decreased activity and/or cross reactivity with other members of the FGF family of growth factors.

In clinical trials, semm samples from patients treated with Kepivance were tested for antibodies to Kepivance using an electrochemiluminescence-based binding assay. Twelve of645 patients (2%) tested positive;none had evidence of neutralizing activity in a cell-based assay.

The incidence of antibody positivity is highly dependent on the specific assay and its sensitivity. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to Kepivance with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Kepivance in the stem cell transplant setting. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Vaginal edema and eryhema;
  • Palmar-plantar Eryhrodysaesthesia Syndròme (also known as "hand-foot syndrome")

Read the Kepivance (palifermin) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

In vitro and in vivo data showed that palifermin interacts with unfractionated as well as low molecular weight heparins. Heparin co-administration resulted in a 5fold increase in palifermin systemic exposure. Avoid co-administration ofpalifermin with heparin. If heparin is used to maintain an intravenous line, rinse the line with saline prior to and after Kepivance administration [see CLINICAL PHARMACOLOGY]

Do not administer Kepivance within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy [see DOSAGE AND ADMINISTRATION and Clinical Studies] In a clinical trial, administration of Kepivance within 24 hours of chemotherapy resulted in increased severity and duration of oral mucositis.

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Potential for Stimulation of Tumor Growth

The safety and effcacy of Kepivance have not been established in patients with non-hematologic malignancies. The effects of Kepivance on stimulation ofKGF receptor-expressing, non-hematopoietic tumors in patients are not known. Kepivance has been shown to enhance the growth of human epithelial tumor cell lines in vitro and to increase the rate of tumor cell line growth in a human carcinoma xenograft model [see CLINICAL PHARMACOLOGY]

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertiity

Carcinogenicity: No treatment-related increase in the incidence of neoplastic lesions occuned in transgenic rasH2 mice treated with 9 weekly intravenous doses of pal if ermin, at 167-fold higher than the recommended human dose (on a mcg/kg basis).

Mutagenicity: No clastogenic or mutagenic effects ofpalifermin were observed in mammalian chromosomal aberration or Ames genotoxicity assays.

Impairment of Fertilty: Reproductive performance, fertility, and sperm assessment parameters were not affected when palifermin was administered intravenously to male and female rats prior to and during mating at doses up to 100 mcg/g/day. Decreased epididymal sperm counts, and increased post-implantation losses were observed at doses ≥ 300 mcg/kg/day (5-fold higherthan the recommended human dose, on a mcg/g basis). Increased pre-implantation loss and a decreased fertility index were observed at a palifermin dose of 1000 mcg/g/day.

Use In Specific Populations

No gender-related differences were observed in the pharmacokinetìcs of Kepi vance at doses ≤ 60 mcg/kg.

Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies of Kepivance in pregnant woman. Palifermin is embryotoxic in rabbits and rats. In reproductive toxicology studies, increased post-implantation loss and decrease in fetal body weight were observed in both rabbit (2.5 times the maximum recommended human dose [MRHD], adjusted for body weight) and rat (8 times the MRHD, on a mcg/kg basis) [see Nonclinical Toxicology] Kepivance should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether Kepivance is secreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Kepivance, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of Kepivance have not been established in children.

Geriatric Use

Clinical studies of Kepi vance did not include suffcient numbers of subjects aged 65 years and older to determine whether they responded differently from younger subjects. [see CLINICAL PHARMACOLOGY]

Patients with Renal Impairment

No dose adjustment is recommended for patients with renal impairment [see CLINICAL PHARMACOLOGY]

Patients with Hepatic Impairment

The phanacokinetic profie in patients with hepatic insufficiency has not been assessed.

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

No data are available regarding overdosage with Kepivance.

CONTRAINDICATIONS

None

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

KGF is an endogenous protein in the fibroblast growth factor (FGF) family that binds to the KGF receptor. Binding of KGF to its receptor has been reported to result in proliferation, differentiation, and migration of epithelial cells. The KGF receptor, one of four receptors in the FGF family, has been reported to be present on epithelial cells in many tissues examined including the tongue, buccal mucosa, esophagus, stomach, intestine, salivary gland, lung, liver, pancreas, kidney, bladder, mammar gland, skin (hair follicles and sebaceous gland), and the lens of the eye. The KGF receptor has been reported to not be present on cells of the hematopoietic lineage. Endogenous KGF is produced by mesenchymal cells and is upregulated in response to epithelial tissue injury.

In mice and rats, Kepi vance enhanced proliferation of epithelial cells (as measured by Ki67 immunohistochemical staining and BrDU uptake) and demonstrated an increase in tissue thickness of the tongue, buccal mucosa, and gastrointestinal tract. Kepivance has been studied in murine models of chemotherapy and radiation- induced gastrointestinal injury. In such models, administration of Kepivance prior to and/or after the cytotoxic insult improved survival and reduced weight loss compared to control animals.

Kepivance has been shown to enhance the growth of human epithelial tumor cell lines in vitro at concentrations ≥ 10 mcg/mL (> l5-fold higher than average therapeutic concentrations in humans). In nude mouse xenograft models; three consecutive daily treatments of Kepi vance at doses of 1,500 and 4,000 mcg/kg (25- and 67-fold higher than the recommended human dose, respectively) repeated weekly for 4 to 6 weeks were associated with a dose-dependent increase in the growth rate of 1 of7 KGF receptor-expressing human tumor cell lines.

Pharmacodynamics

Epithelial cell proliferation was assessed by Ki67 immunohistochemical staining in healthy subjects. A 3-fold or greater increase in Ki67 staining was observed in buccal biopsies from 3 of 6 healthy subjects given Kepivance at 40 mcg/g/day intravenously for 3 days, when measured 24 hours after the third dose. Dose-dependent epithelial cell proliferation was observed in healthy subjects given single intravenous doses of 120 to 250 mcg/g 48 hours post-dosing.

Pharmacokinetics

The pharmacokinetics of Kepivance Were studied in healthy subjects and patients with hematologic malignancies. After single intravenous doses of20 to 250 mcg/kg in healthy subjects and 60 mcglg in cancer patients, Kepivance concentrations declined over 95% in the first 30 minutes post-dose. A slight increase or plateau in concentration occuned at approximately 1 to 4 hours, followed by a terminal decline phase. Kepivance exhibited linear pharmacokinetics with extravascular distribution. In cancer patients compared with healthy subjects, after a 60 mcg/kg single dose of Kepivance the average total body clearance (CL) was 2- to 4-fold higher, and volume of distribution at steady state (Vss) was 2-fold higher. The elimination half-life was similar between healthy subjects and cancer patients (average 4.5 hours with a range of3.3 to 5.7 hours). No accumulation of Kepivance occurred after 3 consecutive daily doses of 20 and 40 mcg/kg in healthy subjects or 60 mcg/kg in cancer patients.

The potential pharmacokinetic interaction between palifermin and heparin was evaluated in a single-dose study in 27 healthy subjects receiving palifermin (60 mcg/kg) co-administered with and without therapeutic levels of unfractionated heparin. This co-administration resulted in a 5-fold increase in palifermin AUC and 80% decrease in the mean CL. There was no significant effect ofpalifermin on heparin activity with respect to activated parial thromboplastin time (aPTT). The clinical relevance of this observed increase in palifermin systemic exposure is unclear [see DRUG INTERACTIONS].

Results from a pharmacokinetics study in 24 subjects with varing degrees of renal impairment demonstrated that renal impairment has little or no influence on Kepivance phanacokinetics [see Use in Spectfc Populations].

In a single-dose study, subjects received a l80-mcg/kg or 90-mcg/g dose of palifermin administered by intravenous bolus injection. Subjects over the age of 65 (n=8) had an approximately 30% lower rate ofCL on average than those 65 and younger (n=19). No dosè adjustment is recommended for the geriatric population [see Use in Spectfc Populations].

Reproductive and Developmental Toxicology

In animal reproductive toxicity studies, paliferminis embryotoxic at doses that are 2.5 times (rabbits) and 5 to > 8 times (rats) the MRHD, based on body weight (mcg/kg). Pregnant rabbits received intravenous palifermin during organogenesis at doses equivalent to 1.0 and 2.5 times the MRHD, based on body weight (mcg/kg). Increased post-implantation loss and decreased fetal body weights occuned along with maternal toxicity (clinical signs and reductions in body weight gain/food consumption) at doses 2.5 times the MRHD.

In pregnant rats, animals received intravenous palifermin during organogenesis at doses of 5 to > 8 times the MRHD based on body weight (mcg/kg). Increased post-implantation loss, decreased fetal body weight, and/or increased skeletal variations occurred in the presence of maternal toxicity at doses > 8 times the MRHD.

Clinical Studies

Autologous transplantation preparative regimens that include total body irradiation

The safety and effcacy of Kepivance in decreasing the incidence and duration of severe oral mucositis in patients with hematologic malignancies (NHL, Hodgkin's disease, acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, or multiple myeloma) receiving myelotoxic therapy requiring hematopoietic stem cell support were established in a randomized placebo-controlled clinical trial of212 patients (Study 1) and a randomized, schedule-ranging, placebo-controlled clinical trial of 169 patients (Study 2).

In Study 1, patients received high-dose cytotoxic therapy consisting of fractionated total-body inadiation (TBI) (12 Gy total dose), high-dose etoposide (60 mg/g), and high-dose cyclophosphamide (100 mg/g) followed by hematopoietic stem cell support. Patients were randomized to receive either Kepivance (n = 106) or placebo (n = 106). Kepivance 60 mcg/g was administered as a daily intravenous injection for 3 consecutive days prior to initiation of cytotoxic therapy and for 3 consecutive days following infusion of hematopoietic stem cells. The major effcacy outcome was the number of days during which patients experienced severe oral mucositis (Grade 3/4 on the WHO (World Health Organization) scale)1. Other analyses included the incidence, duration, and severity of oral mucositis and the use of opioid analgesia. There was no evidence of a delay in time to hematopoietic recovery in patients who received Kepivance as compared to patients who received placebo. The results of Study 1 are presented in Table 2 and Figure 1.

Table 2: Study 1 Effcacy Outcomes

Effcacy Variable Kepivance
(60 mcg/kg/day)
(n = 106)
Placebo
(n = 106)
Median (25th, 75th percentile) Days of WHO Grade 3/4 Oral Mucositis* 3 (0,6) 9 (6, 13)
Incidence of WHO Grade 3/4 Oral Mucositis 63% (67/06) 98% (104/106)
Median (25th, 75th percentile) Days of WHO Grade 3/4 Oral Mucositis in Affected Patients 6 (3, 8)
(n = 67)
9 (6, 13)
(n = 104)
Incidence of WHO Grade 4 Oral Mucositis 20% 62%
Median (25th, 75th percentile) Cumulative Opiod Dose (morphine mg equivalents) 212 (3, 558) 535 (269, 1429)
* P < 0.001 compared to placebo, using Generalized Cochran-Mantel-Haenszel (CMH) test stratified for study center.

Figure 1: Study 1 - Incidence of Oral Mucositis by Maximum Grade WHO Oral Mucositis Scale

Incidence of Oral Mucositis by Maximum Grade WHO Oral Mucositis Scale - Illustration

Study 2 was a randomized, multi-center, placebo-controlled trial comparing varying schedules of Kepivance. All patients received high-dose cytotoxic therapy consisting of fractionated TBI (I2cGy total dose), high-dose etoposide (60 mglkg), and high-dose cyclophosphaiide (75-100 mg/g) followed by hematopoietic stem cell support. The results for Study i were supported by results observed in the subset of patients in Study 2 who received the same dose and schedule of Kepi vance administered in Study 1. One ann of Study 2 that included patients who received Kepivance for 3 consecutive days prior to initiation of cytotoxic therapy, a dose given on the last day ofTBI prior to etoposide, and for 3 consecutive days following infusion of hematopoietic stem cells was prematurely closed by the Safety Committee for lack of effcacy and a trend towards increased severity and duration of oral mucositis as compared to placebo-treated patients, The Safety Committee attributed the safety finding to Kepivance having been administered within 24 hours of chemotherapy, which resulted in an increased sensitivity of the rapidly dividing epithelial cells in the immediate post-chemotherapy period [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS]

Lack of Effcacy: Autologous transplantation preparative regimen using high dose melphalan

In a post approval study, Study 3, designed to determine the effcacy of Kepivance with a high dose melphalan preparative regimen, patients with multiple myeloma were evaluated in a multicenter, randomized, double-blind, placebo-controlled triaL. The conditioning regimen was melphalan (200 mg/m2) on day -2 followed by autologous hematopoietic stem cell support. A total of281 patients were randomized to 3 ans: Kepivance before melphalan on days -6, -5, -4 and afer melphalan on days 0, I, and 2 (pre-post) (n=115); Kepivance before melphalan on days -6, -5, -4 (pre) (n=109); or placebo (n=57).

The main outcome of the study was maximum severity of WHO oral mucositis. The median age of enrolled patients was 57 years (range 32-69), and 55% were male. The results are presented in Figure 2. The prespecified primary analysis was a comparison between the Kepivance pre-post and pre arms to placebo. The incidence of WHO Grade 3 and 4 in the Kepivance pre-post arm was 38%, compared to 37% in the placebo arm. There were no significant differences between either of the Kepivance regimens and the placebo arm in the incidence of severe oral mucositis.

Figure 2: Incidence of Oral Mucositis by Maximum Grade WHO Oral Mucositis Scale in High Dose Melphalan Study

Incidence of Oral Mucositis - Illustration

A subset of subjects enrolled in the multiple myeloma study were included in an evaluation for the risk of cataract development in patients receiving Kepivance treatment. Ophthalmologic examinations were performed on 101 patients enrolled in a double-blind, randomized, placebo-controlled study of two different schedules of Kepivance (pre and post chemotherapy and pre chemotherapy only) for reduction in severity of oral mucositis in subjects with multple myeloma receiving high dose melphalan followed by autologous peripheral blood stem cell transplantation. For the primary cataract endpoint of incidence of cataact development or cataract progression at Month 12, there was a greater proportion of subjects that experienced cataract development in the Kepivance group: 48% (25/52) compared with the placebo group; 29% (4/14) (diffèrence of 17 (95% CI: -11, 46)) [see ADVERSE REACTIONS - Clinical Trial Experience]

REFERENCE

1. WHO Oral Mucositis Scale: Grade 1 = soreness/eryhema; Grade 2 = eryhema, ulcers, can eat solids; Grade 3 = ulcers, requires liquid diet only; Grade 4 = alimentation not possible

Last reviewed on RxList: 12/7/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Advise patients to report the following to health care providers:

Inform patients

  • That the safety and efficacy of Kepivance have not been established in patients with non-hematologic malignancies [see INDICATIONS and WARNINGS AND PRECAUTIONS]
  • Of the evidence of tumor growth and stimulation in cell culture and in animal models of non-hematopoietic human tumors (see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

Advise patients to report the following to health care providers:

Inform patients

  • That the safety and efficacy of Kepivance have not been established in patients with non-hematologic malignancies [see INDICATIONS and WARNINGS AND PRECAUTIONS]
  • Of the evidence of tumor growth and stimulation in cell culture and in animal models of non-hematopoietic human tumors (see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

Kepivance®
(palifermin) For injection, for intravenous use

DRUG DESCRIPTION

Kepivance (palifermin) is a truncated human KGF produced by recombinant DNA technology in E coli. Kepivance is a water soluble, 140 amino acid protein with a molecular weight of 16.3 kilodaltons. It differs from endogenous human KGF in that the first 23 N terminal amino acids have been deleted to improve protein stability.

Kepivance is supplied as a sterile, white, preservative-free, lyophilized powder for intravenous injection after reconstitution with 1.2 mL of Sterile Water for Injection, USP. Reconstitution yields a clear, colorless solution of Kepivance (5 mg/mL) with a pH of6.5. Each single use vial of Kepi vance contains palifermin (6.25 mg),with L histidine (1.94 mg), mannitol (50 mg), polysorbate 20 (0.13 mg or 0.01% w/v), and sucrose (25 mg).

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

Kepivance®
(palifermin) For injection, for intravenous use

DRUG DESCRIPTION

Kepivance (palifermin) is a truncated human KGF produced by recombinant DNA technology in E coli. Kepivance is a water soluble, 140 amino acid protein with a molecular weight of 16.3 kilodaltons. It differs from endogenous human KGF in that the first 23 N terminal amino acids have been deleted to improve protein stability.

Kepivance is supplied as a sterile, white, preservative-free, lyophilized powder for intravenous injection after reconstitution with 1.2 mL of Sterile Water for Injection, USP. Reconstitution yields a clear, colorless solution of Kepivance (5 mg/mL) with a pH of6.5. Each single use vial of Kepi vance contains palifermin (6.25 mg),with L histidine (1.94 mg), mannitol (50 mg), polysorbate 20 (0.13 mg or 0.01% w/v), and sucrose (25 mg).

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

Kepivance®
(palifermin) For injection, for intravenous use

DRUG DESCRIPTION

Kepivance (palifermin) is a truncated human KGF produced by recombinant DNA technology in E coli. Kepivance is a water soluble, 140 amino acid protein with a molecular weight of 16.3 kilodaltons. It differs from endogenous human KGF in that the first 23 N terminal amino acids have been deleted to improve protein stability.

Kepivance is supplied as a sterile, white, preservative-free, lyophilized powder for intravenous injection after reconstitution with 1.2 mL of Sterile Water for Injection, USP. Reconstitution yields a clear, colorless solution of Kepivance (5 mg/mL) with a pH of6.5. Each single use vial of Kepi vance contains palifermin (6.25 mg),with L histidine (1.94 mg), mannitol (50 mg), polysorbate 20 (0.13 mg or 0.01% w/v), and sucrose (25 mg).

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

Kepivance Patient Information Including Side Effects

Brand Names: Kepivance

Generic Name: palifermin (Pronunciation: PAL ee FER min)

What is palifermin (Kepivance)?

Palifermin is a human keratinocyte growth factor (KGF) produced by recombinant DNA technology.

Palifermin is used to reduce the chance of developing sores and ulcers in the mouth and to shorten the time with sores or ulcers in patients with blood cancers who receive high doses of chemotherapy and radiation therapy before bone marrow transplants.

Palifermin may also be used for purposes other than those listed in this medication guide.

What are the possible side effects of palifermin (Kepivance)?

If you experience any of the following serious side effects from palifermin, seek emergency medical attention or contact your doctor immediately:

  • fever;
  • breathing problems;
  • skin and mucus membrane side effects such as rash, redness, swelling, itching, unusual sensations in the mouth, tongue color change, tongue thickening and changes in taste.

Other common side effects include:

  • swelling;
  • pain;
  • joint pain;
  • increases in blood pancreas enzymes;
  • increased blood pressure; or
  • protein in the urine.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to FDA at 1-800-FDA-1088.

Read the Kepivance (palifermin) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about palifermin (Kepivance)?

Palifermin is given as an I .V. (in the vein) infusion for three days before you get chemotherapy and then three days after. Palifermin should not be given to you within 24 hours of your chemotherapy treatment.

If you experience any of the following serious side effects from palifermin, seek emergency medical attention or contact your doctor immediately:

  • fever;
  • breathing problems;
  • skin and mucus membrane side effects such as rash, redness, swelling, itching, unusual sensations in the mouth, tongue color change, tongue thickening and changes in taste.
Side Effects Centers

Kepivance Patient Information including How Should I Take

What should I discuss with my healthcare provider before receiving palifermin (Kepivance)?

Palifermin is given as an I .V. (in the vein) infusion for three days before you get chemotherapy and then three days after. Palifermin should not be given to you within 24 hours of your chemotherapy treatment.

Before you start receiving palifermin, tell your health care professional if you are allergic to other products made from E. coli proteins.

Palifermin can cause possible tumor growth if it is used for nonblood related cancers. Talk to your doctor if you have any questions.

If you experience any of the following serious side effects from palifermin, seek emergency medical attention or contact your doctor immediately:

  • fever;
  • breathing problems;
  • skin and mucus membrane side effects such as rash, redness, swelling, itching, unusual sensations in the mouth, tongue color change, tongue thickening and changes in taste.

Other common side effects include:

  • swelling;
  • pain;
  • joint pain;
  • increases in blood pancreas enzymes;
  • increased blood pressure; or
  • protein in the urine.

Palifermin has not yet been shown to be safe and effective in patients being treated for forms of cancer other than leukemia or lymphoma.

Palifermin is in the FDA pregnancy category C. This means that it is not known whether palifermin will be harmful to an unborn baby. Do not use palifermin without first talking to your doctor if you are pregnant or could become pregnant during treatment. Discuss with your doctor the appropriate use of birth control during treatment with palifermin if necessary.

It is not known whether palifermin passes into breast milk. Do not take palifermin without first talking to your doctor if you are breast feeding a baby.

How should I use palifermin (Kepivance)?

Palifermin is administered as an intravenous (into the vein) infusion. Most often, palifermin is administered in a hospital or clinic setting. If you are administering palifermin at home, your healthcare provider will give you detailed instructions regarding preparation, administration, and storage of the medication.

Your doctor will determine the correct amount and frequency of treatment with palifermin Talk to your doctor if you have any questions or concerns regarding the treatment schedule.

Palifermin vials should be stored in the refrigerator. Palifermin vials should be protected from light. Store palifermin in the original carton until it is used. Do not freeze palifermin products.

Side Effects Centers

Kepivance Patient Information including If I Miss a Dose

What happens if I miss a dose (Kepivance)?

Contact your doctor if you miss a dose of palifermin.

What happens if I overdose (Kepivance)?

If an overdose of palifermin is suspected, seek emergency medical attention or contact your healthcare provider immediately.

Symptoms of a palifermin overdose are not well known but may include headache.

What should I avoid while using palifermin (Kepivance)?

Palifermin is given as an I .V. (in the vein) infusion for three days before you get chemotherapy and then three days after. Palifermin should not be given to you within 24 hours of your chemotherapy treatment.

What other drugs will affect palifermin (Kepivance)?

Palifermin can interact with heparin. If heparin is used to maintain your IV, your IV must be flushed with saline before and after palifermin.

Other medications may interact with palifermin. Talk to your doctor and pharmacist before taking any other prescription or over-the-counter medicines, including vitamins, minerals, and herbal products, during treatment with palifermin.

Where can I get more information?

Your healthcare provider may have additional information about palifermin that you may read.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 2.03. Revision date: 12/15/2010.

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