May 6, 2016
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Kepivance

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Kepivance




Side Effects
Interactions

SIDE EFFECTS

The most common adverse reactions attributed to Kepivance were skin toxicities (rash, erythema, edema, pruritus), oral toxicities (dysesthesia, tongue discoloration, tongue thickening, alteration o f 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 o f a drug cannot be directly compared to rates in the clinical trials o f 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 o f 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 o f 360 mcg/kg. The population had a median age o f 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) o f patients treated. Grade 3 skin rashes occurred in 3% of patients (9/409) receiving Kepivance and 2% (5/241) receiving placebo.

Table 1: Incidence o f Adverse Reactions Occurring with a Between-Group Difference o f ≥ 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 o f cataracts was numerically higher among patients receiving Kepivance 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% o f 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 o f antibodies to Kepivance is unknown but may include decreased activity and/or cross reactivity with other members o f the FGF family o f 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 o f 645 patients (2%) tested positive; none had evidence o f neutralizing activity in a cell-based assay.

The incidence o f antibody positivity is highly dependent on the specific assay and its sensitivity. Additionally, the observed incidence o f antibody positivity in an assay may be influenced by several factors including sample handling, timing o f sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence o f 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 o f Kepivance in the stem cell transplant setting. Because these reactions are reported voluntarily from a population o f 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”)

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 with no noticeable effect on the pharmacodynamics of either drug. 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 o f chemotherapy resulted in increased severity and duration o f oral mucositis.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 4/19/2016

Side Effects
Interactions

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