Leukine


Also found in: Dictionary, Wikipedia.

sargramostim (GM-CSF)

Leukine

Pharmacologic class: Granulocytemacrophage colony stimulating factor

Therapeutic class: Hematopoietic agent

Pregnancy risk category C

Action

Stimulates proliferation and differentiation of hematopoietic cells that activate mature granulocytes and macrophages of target cells

Availability

Liquid: 500 mcg/ml

Powder for injection: 250 mcg

Indications and dosages

Post peripheral blood progenitor cell (PBPC) transplantation

Adults: 250 mcg/m2/day I.V. over 24 hours or subcutaneously once daily, starting immediately after progenitor cell infusion

Mobilization of PBPCs into peripheral blood for collection by leukapheresis

Adults: 250 mcg/m2/day I.V. over 24 hours or subcutaneously once daily, continued throughout harvesting

Neutrophil recovery after chemotherapy in acute myelogenous leukemia Adults: 250 mcg/m2/day I.V. over 4 hours, starting 4 days after completion of chemotherapy induction

Bone-marrow transplantation failure or engraftment delay

Adults: 250 mcg/m2/day as 2-hour I.V. infusion for 14 days. If engraftment doesn't occur, may repeat after 7 days of drug hiatus.

Myeloid reconstitution after autologous or allogeneic bone-marrow transplantation

Adults: 250 mcg/m2/day as a 2-hour I.V. infusion, starting 2 to 4 hours after autologous bone marrow infusion and at least 24 hours after last chemotherapy or radiotherapy dose

Off-label uses

• Crohn's disease
• Melanoma
• Wound healing
• Mucositis
• Stomatitis
• Vaccine adjuvant

Contraindications

• Hypersensitivity to drug, its components, or yeast products
• Excessive leukemic myeloid blasts in bone marrow or peripheral blood (10% or more)
• Within 24 hours before or after chemotherapy or radiation therapy

Precautions

Use cautiously in:
• renal or hepatic insufficiency, fluid retention, pulmonary disorders, pulmonary infiltrates, heart failure, leukocytosis, transient supraventricular arrhythmias
• cancer patients undergoing sargramostim-mobilized PBPC collection
• patients receiving purged bone marrow or previously exposed to intensive chemotherapy or radiation therapy
• pregnant or breastfeeding patients
• children.

Administration

Don't give within 24 hours of chemotherapy or radiation therapy.
• Add 1 ml of sterile water to powder for injection by directing water stream against side of vial and swirling vial gently to disperse contents.
• Avoid shaking or agitating solution.
• For a final drug concentration below 10 mcg/ml, add human albumin 0.1% to saline solution; then dilute drug in normal saline solution.
• Infuse as soon as possible after reconstitution, but no more than 6 hours after mixing.
• Don't add other drugs to infusion; don't use in-line filter.

Adverse reactions

CNS: malaise, asthenia

CV: peripheral edema, tachycardia, hypotension, transient supraventricular tachycardia, pericardial effusion

GI: nausea, vomiting, diarrhea, anorexia, stomatitis, GI hemorrhage

GU: urinary tract disorder, abnormal renal function

Hematologic: blood dyscrasias, hemorrhage

Hepatic: hepatic damage

Musculoskeletal: joint pain, myalgia, bone pain

Respiratory: dyspnea, lung disorder

Skin: rash, alopecia

Other: fever, chills, sepsis, edema, first-dose reaction (respiratory distress, hypoxia, syncope, tachycardia, hypotension, flushing)

Interactions

Drug-drug.Corticosteroids, lithium: potentiation of myeloproliferative effects

Vincristine: severe peripheral neuropathy

Patient monitoring

• Monitor for dyspnea. Halve dosage and contact prescriber if dyspnea occurs.
• Assess CBC with white cell differential. Check for presence of blast cells, and watch for signs and symptoms of blood dyscrasias.
• Closely monitor vital signs and fluid intake and output. Stay alert for signs and symptoms of fluid overload.

Monitor liver function tests, and watch for evidence of hepatic damage and bleeding (especially GI hemorrhage).

Patient teaching

Tell patient sargramostim is a powerful drug that can cause significant adverse reactions. Teach him to recognize and report serious reactions at once.

Instruct patient to immediately report unusual bleeding or bruising or yellowing of skin or eyes.
• Tell patient drug may cause weakness and musculoskeletal pain.
• Inform patient that he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.

sargramostim

(sar-gram-oh-stim) ,

Leukine

(trade name),

rHu GM-CSF (recombinant human granulocyte/macrophage colony-stimulating factor)

(trade name)

Classification

Therapeutic: colony stimulating factors
Pharmacologic: biologic response modifiers
Pregnancy Category: C

Indications

Acceleration of bone marrow recovery after:
  • Autologous bone marrow transplantation in patients with non-Hodgkin’s lymphoma, acute lymphoblastic leukemia, or Hodgkin’s disease;
  • Allogenic bone marrow transplantation from HLA-matched donors.
Management of bone marrow transplant failure or engraftment delay.After induction chemotherapy for acute myelogenous leukemia (AML) in patients ≥55 yr.Mobilization and after transplant of autologous peripheral blood progenitor cells (PBPCs); increases harvest by leukapheresis.

Action

Consists of a glycoprotein produced by recombinant DNA technique that is capable of binding to and stimulating the production, division, differentiation, and activation of granulocytes and macrophages.

Therapeutic effects

Accelerated recovery of bone marrow after autologous bone marrow transplantation, resulting in decreased risk of infection and other complications.

Pharmacokinetics

Absorption: After IV administration, absorption is essentially complete. Well absorbed after subcut administration.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: Unknown.

Time/action profile (noted as effects on blood counts)

ROUTEONSETPEAKDURATION
Subcut, IVrapidunknown3–7 days

Contraindications/Precautions

Contraindicated in: Presence of ≥10% leukemic myeloid blast cells in bone marrow or peripheral blood;Hypersensitivity to granulocyte macrophage colony-stimulating factor (GM-CSF), yeast products, or additives (mannitol, tromethamine, or sucrose); Pediatric: Products containing benzyl alcohol should not be used in newborns.
Use Cautiously in: Pre-existing fluid retention, HF, or pulmonary infiltrates;Pre-existing cardiac disease;Myeloid malignancies;Previous extensive radiation or chemotherapy (response may be limited); Obstetric: Use only if clearly needed; Lactation / Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)
  • malaise
  • weakness

Respiratory

  • dyspnea

Cardiovascular

  • pericardial effusion
  • peripheral edema
  • transient supraventricular tachycardia

Gastrointestinal

  • diarrhea

Dermatologic

  • itching (most frequent)
  • rash (most frequent)

Musculoskeletal

  • arthralgia (most frequent)
  • bone pain (most frequent)
  • myalgia (most frequent)

Miscellaneous

  • chills
  • fever
  • first-dose reaction

Interactions

Drug-Drug interaction

Lithium or corticosteroids may potentiate myeloproliferative effects of sargramostim (concurrent use should be undertaken cautiously).

Route/Dosage

After Bone Marrow Transplantation
Intravenous (Adults) 250 mcg/m2/day for 21 days.
Failure/Delay of Engraftment after Bone Marrow Transplantation
Intravenous (Adults) 250 mcg/m2/day for 14 days; may be repeated after a 7-day rest between courses; if results are inadequate, a 3rd course at 500 mcg/m2/day for 14 days may be given after a 7-day rest.
After Chemotherapy for AML
Intravenous (Adults) 250 mcg/m2/day started around day 11 or 4 days after induction if day 10 bone marrow is hypoplastic with <5% blast cells and continued until absolute neutrophil count (ANC) >1500 cells/mm3 for 3 consecutive days (not to exceed 42 days); if adverse reactions occur, decrease dose by 50% or temporarily discontinue.
Mobilization of PBPCs
Intravenous Subcutaneous (Adults) 250 mcg/m2/day continued throughout collection of PBPCs.
After PBPC Transplantation
Intravenous Subcutaneous (Adults) 250 mcg/m2/day continued until ANC >1500 cells/mm3 for 3 consecutive days.

Availability

Powder for injection: 250 mcg/vial
Solution for injection: 500 mcg/vial

Nursing implications

Nursing assessment

  • Monitor heart rate, BP, and respiratory status during and immediately after infusion. If dyspnea develops, slow infusion rate by half. Reassess; medication may need to be discontinued. Assess for peripheral edema daily throughout therapy. Capillary leak syndrome (swelling of feet or lower legs, sudden weight gain, dyspnea) and pleural or pericardial effusion may occur, usually at doses >32 mcg/kg/day.
  • Monitor for first-dose reaction (flushing, hypotension, syncope, weakness). Does not recur with first dose of each course but may occur with first dose of more than 1 course.
  • Assess for fever daily during therapy. Usually mild and dose-related and resolves with discontinuation or administration of antipyretics.
  • Assess for arthralgias and myalgias, usually in lower extremities, which tend to occur when granulocyte counts are returning to normal. May also cause mild to moderate bone pain, possibly from bone marrow expansion. Usually occurs over 1–3 days before myeloid recovery and occurs in the sternum, spine, pelvis, and long bones. Treat with analgesics.
  • Lab Test Considerations: Obtain a CBC with differential and platelet count before chemotherapy and twice weekly during therapy to avoid leukocytosis. Monitor ANC; may increase rapidly. If ANC >20,000/mm3 or 10,000/mm3 after the nadir has occurred or if platelet count >500,000/mm3, interrupt administration and reduce dose by half or discontinue. Excessive blood levels usually return to baseline 3–7 days after discontinuation of therapy. If blast cells appear, sargramostim should be discontinued.
    • Monitor renal and hepatic function before and biweekly throughout therapy in patients with renal or hepatic dysfunction. May cause ↑ BUN, creatinine, and hepatic enzymes.
    • May cause ↓ serum albumin concentrations.

Potential Nursing Diagnoses

Risk for infection (Indications)

Implementation

  • Administer 2–4 hr after bone marrow transplant and no earlier than 24 hr after cytotoxic chemotherapy or 12 hr after last dose of radiotherapy.
    • Refrigerate but do not freeze powder, reconstituted solution, or diluted solution. Reconstitute with 1 mL of sterile water without preservatives injected toward side of vial. Swirl gently to avoid foaming. Do not shake. Solution should be clear and colorless. Discard if left at room temperature for >6 hr. Vial is for 1-time use only.
  • Subcutaneous: Administer reconstituted solution without further dilution.
  • Intravenous Administration
  • pH: 7.1–7.7.
  • Intermittent Infusion: Diluent: Dilute in 0.9% NaCl.Concentration: If final concentration is <10 mcg/mL, add 1 mg human albumin per 1 mL of 0.9% NaCl before addition of sargramostim to prevent absorption of the components of the drug delivery system. Do not administer with an in-line filter.
  • Rate: Usually infused over 2–4 hr. Has been administered over 30–60 min, over 5–12 hr, and as a continuous infusion over 24 hr.
    • After bone marrow transplantation or failure of engraftment: Administer over 2 hr.
    • Chemotherapy for AML: Administer over 4 hr.
    • Mobilization of PBPCs or PBPC transplant: Administer as a continuous infusion over 24 hr.
  • Y-Site Compatibility: amikacin, aminocaproic acid, aminophylline, aztreonam, bleomycin, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefepime, cefotaxime, cefotetan, ceftriaxone, cefuroxime, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, dexamethasone sodium phosphate, diphenhydramine, dopamine, doxorubicin hydrochloride, doxycycline, droperidol, etoposide, famotidine, fentanyl, floxuridine, fluconazole, fluorouracil, furosemide, gentamicin, granisetron, heparin, idarubicin, ifosfamide, immune globulin, levofloxacin, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, metoclopramide, metronidazole, mitoxantrone, pentostatin, piperacillin/tazobactam, potassium chloride, prochlorperazine, promethazine, ranitidine, rituximab, sodium acetate, teniposide, ticarcillin/clavulanate, trastuzumab, trimethoprim/sulfamethoxazole, vinblastine, vincristine, zidovudine
  • Y-Site Incompatibility: acyclovir, ampicillin, ampicillin/sulbactam, cefoperazone, chlorpromazine, ganciclovir, haloperidol, hydrocortisone, hydromorphone, hydroxyzine, imipenem/cilastatin, lorazepam, methylprednisolone sodium succinate, mitomycin, morphine, nalbuphine, nesiritide, ondansetron, sodium bicarbonate, tobramycin
  • Additive Incompatibility: Do not admix with other medications.

Patient/Family Teaching

  • Explain purpose of sargramostim to patient.
  • Instruct patient to notify health care professional if dyspnea or palpitations occur.

Evaluation/Desired Outcomes

  • Acceleration of bone marrow recovery and decreased incidence of infection in patients after autologous and allogenic bone marrow transplantation, bone marrow transplant failure or engraftment delay, chemotherapy for AML, and PBPC transplantation.

Leukine®

Sargramostim Oncology A formulation of GM-CSF used for cell recovery in Pts with ↓ cell counts due to chemotherapy with Immunex. See GM-CSF.
References in periodicals archive ?
Professor John Hamilton who led the research at the University of Melbourne in Australia, said that not only can blocking GM-CSF, which is also known as Leukine, suppress the actual disease, it can also reduce pain in sufferers.
He is credited as being a pioneer in the field of cytokines and cytokine receptors, directing the development of multiple marketed products including Leukine, (GM-CSF), Prokine (IL-2) and Enbrel (soluble TNF receptor-Fc fusion protein) as well as the regulatory approval of Bexxar (radiolabeled anti-CD20) and the novel vaccine adjuvant, MPL.
A laboratory-made version of GM-CSF called Leukine has been used for years to boost the immune systems of certain cancer patients.
Exciting A laboratory-made version cal led Leukine has been used for years to boost the immune systems of certain cancer patients.
Lead researcher Professor Huntington Potter said: "Our study, along with the drug's track record for safety, suggests Leukine should be tested in humans as a potential treatment for Alzheimer's disease.
Specifically, when given with Bayer AG's Leukine following Genentech Inc.
The company will continue operations in Washington State for the manufacture of Leukine, the company's white blood cell growth factor.
The Federal Trade Commission proposed an order that would allay antitrust concerns by making Immunex sell its cancer-fighting drug Leukine to Schering AG.
In the new agreement, AHP has agreed to return to Immunex the ex-North american rights to Leukine (sargramostim), Mobist (FLT-3 ligand) and Interleukin-15 (IL-15).
Indeed, Immunex received FDA approval to market Leukine in early March 1991, well over two years after the units offering.
29 Summary sales data 29 Company specific sales data 32 Neupogen/Neulasta 32 Neutrogin/Granocyte 33 Leukine 33 Current Biosimilar Activity 34 USA 34 European Union 34 Current biosimilar activity in the rest of the world 35 Human Insulin 37 What is it?
Neupogen, Neulasta, or Leukine may be administered to patients between chemotherapy cycles to help quickly restore lowered white blood cell counts to normal levels (a condition known as neutropenia).