Leukine

What is Leukine?

Leukine is a man-made form of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a substance produced by the body. It stimulates the growth of certain white blood cells that are important in the body’s fight against infection.

Acute Radiation Syndrome: The effectiveness of Leukine for this use was only studied in animals because it could not be studied in people.

Description

Sargramostim is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in a yeast (S. cerevisiae) expression system. Sargramostim is a glycoprotein of 127 amino acids characterized by three primary molecular species having molecular masses of 19,500, 16,800 and 15,500 Daltons.

The amino acid sequence of sargramostim differs from the natural human GM-CSF by a substitution of leucine at position 23, and the carbohydrate moiety may be different from the native protein. Sargramostim differs from human GM-CSF by one amino acid at position 23, where leucine is substituted for arginine.

LEUKINE (sargramostim) for injection is supplied as a sterile, preservative-free, white lyophilized powder in a single-dose vial for subcutaneous or intravenous use. Each single-dose vial delivers 250 mcg sargramostim. Inactive ingredients are mannitol (40 mg), sucrose (10 mg), and tromethamine (1.2 mg). Reconstitution with 1 mL of the appropriate diluent (sterile water for injection or bacteriostatic water for injection) yields a solution containing 250 mcg/mL sargramostim at a pH range of 7.1 – 7.7 with a deliverable volume of 1 mL (250 mcg).

Mechanism of Action

Sargramostim (GM-CSF) belongs to a group of growth factors termed colony-stimulating factors which support survival, clonal expansion, and differentiation of hematopoietic progenitor cells. GM-CSF induces partially committed progenitor cells to divide and differentiate in the granulocyte-macrophage pathways which include neutrophils, monocytes/macrophages and myeloid-derived dendritic cells.

GM-CSF is also capable of activating mature granulocytes and macrophages. GM-CSF is a multilineage factor and, in addition to dose-dependent effects on the myelomonocytic lineage, can promote the proliferation of megakaryocytic and erythroid progenitors. However, other factors are required to induce complete maturation in these two lineages. The various cellular responses (i.e., division, maturation, activation) are induced through GM-CSF binding to specific receptors expressed on the cell surface of target cells.

The biological activity of GM-CSF is species-specific. Consequently, in vitro studies have been performed on human cells to characterize the pharmacological activity of GM-CSF. In vitro exposure of human bone marrow cells to GM-CSF at concentrations ranging from 1-100 ng/mL results in the proliferation of hematopoietic progenitors and in the formation of pure granulocyte, pure macrophage, and mixed granulocyte macrophage colonies. Chemotactic, anti-fungal, and anti-parasitic activities of granulocytes and monocytes are increased by exposure to GM-CSF in vitro. GM-CSF increases the cytotoxicity of monocytes toward certain neoplastic cell lines and activates polymorphonuclear neutrophils to inhibit the growth of tumor cells.

Who should not use Leukine?

Do not take Leukine if you have had a serious allergic reaction to human GM-CSF, such as sargramostim, products that are made from yeast, or any of the ingredients in Leukine. See the end of this leaflet for a complete list of ingredients in Leukine.

What should I tell my healthcare provider before using Leukine?

Before receiving Leukine, tell your healthcare provider about all your medical conditions, including if you:

• have heart or lung disease
• are allergic to benzyl alcohol
• are pregnant or plan to become pregnant. It is not known if Leukine will harm your unborn baby. See “What are the possible side effects of Leukine?” Talk to your healthcare provider about the type of Leukine that is right for you.
• are breastfeeding or plan to breastfeed. It is not known if Leukine passes into your breast milk. Do not breast feed during treatment and for at least 2 weeks after your last dose of Leukine.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I use Leukine?

• Leukine comes in two ways: as a solution or as a powder to be mixed for injection.
• Leukine is given as an injection under your skin (subcutaneous injection) by a healthcare provider.
• If your healthcare provider decides that the subcutaneous injections can be given at home by you or your caregiver, see the detailed Instructions for use that comes with your Leukine for information on how to draw up and inject a dose of Leukine.
• If your healthcare provider gives you Leukine for injection (powder) to be mixed, carefully follow your healthcare provider’s instructions on how to store, mix, draw up and inject the medicine.
• You and your caregiver should be shown how to prepare and inject Leukine before you use it, by your healthcare provider.
• Your healthcare provider will tell you how much Leukine to inject and when to inject it. Do not change your dose or stop Leukine unless your healthcare provider tells you to.
• If you are also receiving chemotherapy or radiation therapy, your dose of Leukine should be injected at least 24 hours before or 24 hours after your dose of chemotherapy and at least 24 hours before your dose of radiation therapy. Your healthcare provider will do blood tests to monitor your white blood cell count and, if necessary, adjust your Leukine dose.
• If you are receiving Leukine because you have been suddenly (acutely) exposed to an amount of radiation that can affect your bone marrow (Acute Radiation Syndrome), you will need to have blood tests about every 3 days during treatment with Leukine to check your white blood cell count until it returns to normal.
• If your child needs to receive Leukine for Acute Radiation Syndrome, follow your healthcare provider’s instructions. Leukine injection contains the preservative benzyl alcohol.
• If you miss a dose of Leukine, talk to your healthcare provider about when you should give your next dose.

What are the possible side effects of Leukine?

Leukine may cause serious side effects, including:

• Serious allergic reactions. Leukine can cause serious allergic reactions that can be severe. Get medical help right away if you get any of the following signs or symptoms of a serious allergic reaction with Leukine, including: skin rash over your entire body, hives, trouble breathing, wheezing, swelling around your mouth or eyes, a fast heartbeat, sweating, and dizziness or feeling faint.
• Infusion related reactions. When Leukine is given as an infusion, it can cause reactions during or soon after an infusion. Tell your healthcare provider or nurse right away if you develop trouble breathing, skin flushing, a fast pulse, dizziness or you feel faint during or soon after your infusion.
• Too much body fluid (fluid retention) and Capillary Leak Syndrome. Leukine can cause you to have too much fluid in your body, and fluid may leak from blood vessels into your body’s tissues. This can happen anywhere in your body, including around your heart and lungs. This condition is called “Capillary Leak Syndrome” (CLS). CLS can quickly cause you to have symptoms that may become life-threatening. Get emergency medical help right away if you develop any of the following symptoms:
  • swelling or puffiness of your feet or ankles, and are urinating less than usual
  • swelling of your stomach area (abdomen) and feeling of fullness
  • sudden weight gain
  • swollen legs or feet
  • trouble breathing
  • dizziness or feeling faint
  • a general feeling of tiredness
• Abnormal heart rhythm. An abnormal heart rhythm may happen during treatment with Leukine, especially in people with a history of an abnormal heart rhythm.
• Increased white blood cell count. Leukine can cause your white blood cell count to increase too high (leukocytosis). Your healthcare provider will check your blood during treatment with Leukine.
• Risks of using Leukine in newborns, babies born with a low birth weight, and in pregnant women. Some forms of Leukine may contain the preservative benzyl alcohol. Medicines that contain benzyl alcohol, including Leukine, can cause serious side effects that can lead to death in newborns and babies born with a low birth weight. Avoid using Leukine containing benzyl alcohol in newborns, babies born with a low birth weight, and in pregnant women. If Leukine needs to be given to your newborn or baby with a low birth weight, or in pregnant women, talk to your healthcare provider about this risk and which form of Leukine to use.

The most common side effects of Leukine in people who receive an autologous bone marrow transplant include: fever, nausea, diarrhea, vomiting, mouth sores, weakness and lack of energy, generally do not feel well, decreased appetite, rash, stomach and intestine problems, fluid buildup.

The most common side effects of Leukine in people who receive an allogeneic bone marrow transplant include: diarrhea, fever, nausea, rash, vomiting, mouth sores, decreased appetite, hair loss, stomach-area (abdomen) pain, headache and high blood pressure.

The most common side effects of Leukine Leukine in people with AML include: fever, liver problems, skin reactions, infections, abnormal amount of salts and other minerals in the blood, nausea, diarrhea, urinary tract problems, lung problems, vomiting, nervous system problems, mouth sores, hair loss and weight loss.

These are not all the possible side effects of Leukine.
Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Leukine

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Leukine for a condition for which it was not prescribed. Do not give Leukine to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Leukine that is written for health professionals.

How should I store Leukine?

• Store Leukine in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze Leukine.
• Do not shake.
• Store Leukine vials in the original carton to protect from light.
• Do not use Leukine beyond the expiration date printed on the vial label.
• Used vials with remaining Leukine should be stored in the refrigerator and used within 20 days (be sure to mark down the date you first used the vial).
• Throw away (dispose of) any remaining Leukine after 20 days.

Keep Leukine out of the reach of children.

What are the ingredients in Leukine?

Active ingredient: sargramostim

Inactive ingredients:

Leukine injection: benzyl alcohol
Leukine for injection: mannitol, sucrose, tromethamine

Label

PRINCIPAL DISPLAY PANEL – NDC: 71837-5843-1 – 250 MCG LYOPHILIZED POWDER FOR INJECTION VIAL LABEL

PRINCIPAL DISPLAY PANEL – NDC: 71837-5843-5 – 250 MCG LYOPHILIZED POWDER FOR INJECTION 5-COUNT CARTON LABEL