Kepivance

Kepivance treatment should be supervised by a physician experienced in the use of anti-cancer therapy. Posology Adults The recommended dosage of Kepivance is 60 micrograms/kg/day, administered as an intravenous bolus injection for three consecutive days before and three consecutive days after myeloablative radiochemotherapy for a total of six doses.

The duration between last dose of Kepivance before myeloablative radiochemotherapy and the first dose of Kepivance after myeloablative radiochemotherapy should be at least seven days.

Pre- myeloablative radiochemotherapy:

The first three doses should be administered prior to myeloablative therapy, with the third dose 24 to 48 hours before myeloablative radiochemotherapy. Medicinal product no longer authorised 3 Paediatric population The safety and efficacy of Kepivance in children aged 0 to 18 years have not been established.

2 but no recommendation on a posology can be made. 2). 2). Caution should be used when dosing patients with hepatic impairment. Older people Safety and efficacy has not been evaluated in older people. 2 but no recommendation on dose adjustment can be made.

Method of administration Intravenous use. Kepivance should not be administered subcutaneously due to poor local tolerability. Reconstituted Kepivance should not be left at room temperature for more than one hour, and should be protected from light.

6. 6.

Safety data are based on patients with haematological malignancies enrolled in randomised, placebo- controlled clinical studies, including one pharmacokinetic study, and post marketing experience. g. oedema, including peripheral oedema, and hypertrophia of oral structures.

These reactions were primarily mild to moderate in severity and were reversible. Median time to onset was approximately 6 days following the first of 3 consecutive daily doses of Kepivance, with a median duration of approximately 5 days.

Pain and arthralgia are other common adverse reactions, consistent with Kepivance treated patients having received less opioid analgesia than placebo-treated patients (see Table 2). Hypersensitivity, including Anaphylactic reactions, has also been associated with palifermin.

Table 1. Adverse reactions from clinical trials and spontaneous reporting The frequency listed below is defined using the following convention: very common (> 1/10), common (≥ 1/100 to < 1/10), not known (frequency cannot be estimated from available data).

g. redness, bumps), Tongue oedema Skin and subcutaneous tissue disorders Very common: Common: Not known: Rash, pruritus and erythema Skin hyperpigmentation Palmar-plantar erythrodysaesthesia syndrome (dysaesthesia, erythema, oedema on the palms and soles) Musculoskeletal and connective tissue disorders Reproductive system and breast disorders Very common: Not known Arthralgia Vaginal oedema and vulvovaginal erythema General disorders and administration site conditions Very common: Common: Oedema, oedema peripheral, pain and pyrexia Lip swelling, eyelid oedemaMedicinal product no longer authorised 6 Investigations Not known: Very common: Face oedema, oedema mouth Blood amylase increased and Lipase Increased1 1 Kepivance may cause increased lipase and amylase levels in some patients with or without symptoms of abdominal pain or backache.

Use with chemotherapy Kepivance should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of cytotoxic chemotherapy. In a clinical trial, administration of Kepivance within 24 hours of chemotherapy resulted in an increased severity and duration of oral mucositis.

2). Visual acuity KGF receptors are known to be expressed on the lens of the eye. 1). Long term effects are not yet known. Medicinal product no longer authorised 4 Non-haematological malignancies Kepivance is a growth factor that stimulates the proliferation of KGF receptor expressing epithelial cells.

The safety and efficacy of Kepivance has not been established in patients with KGF receptor expressing non-haematological malignancies. Palifermin should therefore not be given to patients with known or suspected non-haematological malignancies.

Lack of efficacy and risk of infection with high dose melphalan conditioning regimen In a postmarketing clinical trial investigating multiple myeloma patients receiving melphalan 200 mg/m2 as conditioning regimen, palifermin administration with four days between the last pre dose and the first post dose did not show a therapeutic benefit in the frequency or duration of severe oral mucositis compared to placebo.

6%). Compared with the placebo group, the pre/post-chemotherapy group had a higher incidence of herpes virus infection (9% vs 0%), oral fungal infection (7% vs 2%) and sepsis/septic shock (12% vs 2%). 1). Palifermin should not be used in association with myeloablative chemotherapy-only conditioning.

1, or to Escherichia coli-derived proteins.