Kepivance Side Effects

Generic Name: palifermin

Please note - some side effects for Kepivance may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Kepivance - for the Consumer

Kepivance

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Kepivance:

Change in taste; joint pain; skin reactions (rash, irritation, redness, swelling, itching); tingling, numbness, prickling, or burning sensation around the mouth or on the skin; tongue thickening or discoloration.

Seek medical attention right away if any of these SEVERE side effects occur when using Kepivance:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Kepivance Side Effects - for the Professional

Kepivance

The most common adverse reactions attributed to Kepivance were skin toxicities (rash, erythema, 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 pharmacokinetic 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/kg/day. The total dose of Kepivance ranged from 15 to 480 mcg/kg with a median of 360 mcg/kg. 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 attributed 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 (n = 241) %
BODY AS A WHOLE
Edema	28	21
Pain	16	11
Fever	39	34
GASTROINTESTINAL
Mouth/Tongue Thickness or Discoloration	17	8
MUSCULOSKELETAL
Arthralgia	10	5
SKIN AND APPENDAGES
Rash	62	50
Pruritus	35	24
Erythema	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 postmarketing safety study, the incidence of cataracts was numerically higher among patients receiving Kepivance than in the control population..

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 of hematopoietic stem cell infusion. Amylase was mainly salivary in origin.

Immunogenicity

As with all therapeutic proteins, there is a potential 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, serum samples from patients treated with Kepivance were tested for antibodies to Kepivance using an electrochemiluminescence-based binding assay. Twelve of 645 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 erythema;
• Palmar-plantar Erythrodysaesthesia Syndrome (also known as “hand-foot syndrome”)

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Side Effects by Body System - for Healthcare Professionals

Dermatologic

Dermatologic side effects for palifermin in relation to placebo therapy have included rash (62% vs. 50%), pruritus (35% vs. 24%), and erythema (32% vs. 22%).

Skin rash was the most common serious side effect reported.

Clinical studies (n=409) reported the occurrence of grade 3 skin rash in 14 patients (9 palifermin, 5 placebo) resulting in the discontinuation of treatment in 7 patients (5 palifermin, 2 placebo).

Following the first 3 consecutive days of administration, the median time to cutaneous side effects is 6 days with a median duration of 5 days.

Other

Following the first 3 consecutive days of administration, the median time to cutaneous side effects, including edema, is 6 days with a median duration of 5 days.

Other side effects for palifermin in relation to placebo therapy have included edema (28% vs. 21%), pain (16% vs. 11%), fever (39% vs. 34%) and perianal pain (12% vs. 5%). Other side effects of palifermin following a single 90 mcg/kg IV dose include fatigue (26%) and headache (23%).

Gastrointestinal

Gastrointestinal side effects for palifermin in relation to placebo therapy have included mouth/tongue thickness and/or discoloration (17% vs. 8%) and altered taste (16% vs. 8%). Oral/perioral dysesthesia and white film coating of the mouth or tongue has also been reported.

Musculoskeletal

Musculoskeletal side effects for palifermin in relation to placebo therapy have included arthralgia (10% vs 5%).

Nervous system

Dysthesias in palifermin treated patients have generally been reported as localized to the perioral region. In contrast, patients receiving placebo have generally reported dysthesias in extremities.

Nervous system side effects for palifermin in relation to placebo therapy have included dysthesias (12% vs. 7%). Types of dysthesias reported have included hyperesthesia, hypoesthesia, and paresthesia.

Oncologic

There are no available data on the effects of palifermin on stimulation of KGF receptor- expressing, non- hematopoietic tumors in patients.

At concentrations greater than 15 times the average therapeutic human concentration palifermin has been reported to enhance the growth of human epithelial tumor cell lines in vitro.

In nude mouse xenograft models, doses 25 and 67 times higher than the recommended human dose administered daily for 3 consecutive weeks and repeated weekly for 4 to 6 weeks may have resulted in a dose-dependent increase in the growth rate of 1 of 7 KGF receptor- expressing human tumor cell lines.

Oncologic side effects have included enhancement in the growth of human epithelial tumor cell lines in vitro and an increase in the rate of tumor cell line growth in a human carcinoma xenograft model.

Metabolic

Metabolic side effects for palifermin in relation to placebo therapy have included elevated serum lipase grade 3 (28% vs. 23%), elevated serum lipase grade 4 (11% vs. 5%), elevated serum amylase grade 3 (62% vs. 54%), and elevated serum amylase grade 4 (38% vs. 31%).

In clinical studies, the elevated serum lipase and amylase levels were reversible with peak increases recorded during the period of cytotoxic therapy. Levels returned to baseline by the day of PBPC infusion. There are no reports of required treatment intervention.

The increased amount of amylase is reported to be predominantly salivary in origin.

Cardiovascular

Hypertension was reported with doses of 60 mcg/kg and 80 mcg/kg in patients undergoing hematopoietic transplantation. This effect appeared to be transient. There are no reports of treatment discontinuation due to hypertension.

Cardiovascular side effects have included hypertension.

Genitourinary

There have been reports of 2+ or greater proteinuria in patients treated with palifermin; however, a causal relationship between palifermin and proteinuria has not been established.

Genitourinary side effects have included proteinuria.

General

In general, doses of 80 mcg/kg administered intravenously 3 doses prior to and 3 doses after myeloablative chemotherapy/TBI produced the same type of side effects seen with 60 mcg/kg doses; however, a higher level of severity was reported with the higher dose.

Respiratory

Respiratory side effects for palifermin in relation to placebo therapy have included cough (34% vs. 28%) and rhinitis (17% vs. 9%).

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