Kepivance

What is Kepivance used for?

Kepivance is a prescription medicine that is used to lower how often mouth sores form and shorten how long they last.

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 of 6.5. Each single-dose vial of Kepivance 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).

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, mammary 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, Kepivance 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 (> 15-fold higher than average therapeutic concentrations in humans). In nude mouse xenograft models, three consecutive daily treatments of Kepivance 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 of 7 KGF receptor-expressing human tumor cell lines.

Before taking Kepivance, tell your doctor:

• If you are allergic to Kepivance; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you are being treated with melphalan.
• If you are breast-feeding. Do not breast-feed while you take Kepivance and for 2 weeks after your last dose.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Kepivance with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Kepivance?

• Tell all of your health care providers that you take Kepivance. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may add to the chance of getting some types of cancer. Talk with the doctor.
• This medicine may affect fertility. This may lead to not being able to get pregnant or father a child. If this happens, it is not known if fertility will go back to normal.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking Kepivance, call your doctor right away.

How is Kepivance best taken?

Use Kepivance as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

What are the side effects of Kepivance that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Numbness or tingling in the mouth.
• Color change or thick tongue.
• Change in taste.
• Fever.
• Swelling.

What are some other side effects of Kepivance?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Joint pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Kepivance?

• If you need to store Kepivance at home, talk with your doctor, nurse, or pharmacist about how to store it.

Label

Principal Display Panel – 6.25 mg/1.2 mL Carton Label

6 x 6.25 mg/vial Single Use Vials

• sobi
• Kepivance®
  (palifermin)
• For Injection
• 6.25 mg/vial
• Dosage – See Package Insert
• No U.S. Standard of Potency
• US Patent Numbers:
• 6,420,531 B1; 5,824,643; and 5,677,278