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Pronunciation
(sar GRAM oh stim)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Acute myelogenous leukemia (AML) following induction chemotherapy in older adults (≥55 years of age) to shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death
Bone marrow transplant (allogeneic or autologous) failure or engraftment delay
Myeloid reconstitution after allogeneic bone marrow transplantation
Myeloid reconstitution after autologous bone marrow transplantation: Non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL), Hodgkin's lymphoma
Peripheral stem cell transplantation: Mobilization and myeloid reconstitution following autologous peripheral stem cell transplantation
Pregnancy Risk Factor
C
Pregnancy Considerations
Clinical effects to the fetus: Animal reproduction studies have not been conducted. It is not known whether sargramostim can cause fetal harm when administered to a pregnant woman or can affect reproductive capability. Sargramostim should be given to a pregnant woman only if clearly needed.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to sargramostim, yeast-derived products, or any component of the formulation; concurrent (24 hours preceding/following) myelosuppressive chemotherapy or radiation therapy; patients with excessive (≥10%) leukemic myeloid blasts in bone marrow or peripheral blood
Warnings/Precautions
Concerns related to adverse effects:
• Allergic reactions: Anaphylaxis or other serious allergic reactions have been reported; discontinue immediately if occur.
Disease-related concerns:
• Cardiac disease: Use with caution in patients with pre-existing cardiac problems or HF. Transient supraventricular arrhythmias have been reported in patients with history of arrhythmias.
• Fluid retention: Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported. Use with caution in patients with pre-existing fluid retention; may worsen.
• Hepatic impairment: Use with caution in patients with hepatic impairment; monitor hepatic function in patients with history of hepatic dysfunction. Bilirubin and transaminase elevations have been observed with use.
• Renal impairment: Use with caution in patients with renal impairment; monitor renal function in patients with history of renal dysfunction. Serum creatinine elevations have been observed with use.
• Respiratory problems: Dyspnea may occur; monitor respiratory symptoms during and following infusion. Decrease infusion rate by 50% if dyspnea occurs; discontinue with persistent dyspnea. Use with caution in patients with hypoxia, pulmonary infiltrates, or pre-existing lung disease.
Concurrent drug therapy issues:
• Cytotoxic chemotherapy/radiotherapy: Simultaneous administration, or administration 24 hours preceding/following cytotoxic chemotherapy or radiotherapy is not recommended.
Other warnings/precautions:
• Benzyl alcohol: Solution contains benzyl alcohol which has been associated with "gasping syndrome" in neonates.
• Blood counts: If there is a rapid increase in blood counts (ANC >20,000/mm3, WBC >50,000/mm3, or platelets >500,000/mm3), decrease dose by 50% or discontinue drug (counts will fall to normal within 3-7 days after discontinuing drug).
• First dose effect: There is a “first-dose effect” (refer to Adverse Reactions for details) which is seen (rarely) with the first dose of a cycle and does not usually occur with subsequent doses within that cycle.
• Tumor growth factor: May potentially act as a growth factor for any tumor type, particularly myeloid malignancies; caution should be exercised when using in any malignancy with myeloid characteristics. Tumors of nonhematopoietic origin may have surface receptors for sargramostim. Discontinue use if disease progression occurs during treatment.
Adverse Reactions
>10%:
Cardiovascular: Hypertension (34%), pericardial effusion (4% to 25%), edema (13% to 25%), chest pain (15%), peripheral edema (11%), tachycardia (11%)
Central nervous system: Fever (81%), malaise (57%), headache (26%), chills (25%), anxiety (11%), insomnia (11%)
Dermatologic: Rash (44%), pruritus (23%)
Endocrine & metabolic: Hyperglycemia (25%), hypercholesterolemia (17%), hypomagnesemia (15%)
Gastrointestinal: Diarrhea (≤89%), nausea (58% to 70%), vomiting (46% to 70%), abdominal pain (38%), weight loss (37%), anorexia (13%), hematemesis (13%), dysphagia (11%), gastrointestinal hemorrhage (11%)
Genitourinary: Urinary tract disorder (14%)
Hepatic: Hyperbilirubinemia (30%)
Neuromuscular & skeletal: Weakness (66%), bone pain (21%), arthralgia (11% to 21%) myalgia (18%)
Ocular: Eye hemorrhage (11%)
Renal: BUN increased (23%), serum creatinine increased (15%)
Respiratory: Pharyngitis (23%), epistaxis (17%), dyspnea (15%)
Miscellaneous: Antibody formation (2%)
1% to 10%: Respiratory: Pleural effusion (1%)
<1%, postmarketing, and/or case reports: Allergic reaction, anaphylaxis, arrhythmia, capillary leak syndrome, constipation, dizziness, eosinophilia; first-dose effect (syndrome with respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia occurring with the first dose of a treatment cycle); injection site reaction, lethargy, leukocytosis, liver function abnormalities (transient), pain, pericarditis, prothrombin time prolonged, rigors, sore throat, supraventricular arrhythmia (transient), thrombocytosis, thrombophlebitis, thrombosis
Metabolism/Transport Effects
None known.
Drug Interactions
Bleomycin: Sargramostim may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Risk C: Monitor therapy
Storage
Store at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake.
Solution for injection: May be stored for up to 20 days at 2°C to 8°C (36°F to 46°F) once the vial has been entered. Discard remaining solution after 20 days.
Powder for injection: Preparations made with SWFI should be administered as soon as possible, and discarded within 6 hours of reconstitution. Preparations made with bacteriostatic water may be stored for up to 20 days at 2°C to 8°C (36°F to 46°F).
I.V. infusion administration: Preparations diluted with NS are stable for 48 hours at room temperature and refrigeration.
Reconstitution
Powder for injection: May be reconstituted with preservative free SWFI or bacteriostatic water for injection (with benzyl alcohol 0.9%). Gently swirl to reconstitute; do not shake.
Sargramostim may also be further diluted in 25-50 mL NS to a concentration ≥10 mcg/mL for I.V. infusion administration.
If the final concentration of sargramostim is <10 mcg/mL, 1 mg of human albumin/1 mL of NS (eg, 1 mL of 5% human albumin/50 mL of NS) should be added.
Compatibility
Stable in NS, sterile water for injection, bacteriostatic water; incompatible with dextrose-containing solutions.
Y-site administration: Compatible: Amikacin, aminophylline, aztreonam, bleomycin, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefepime, cefotaxime, cefotetan, cefuroxime, cimetidine, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, dexamethasone sodium phosphate, diphenhydramine, dopamine, doxorubicin, doxycycline, droperidol, etoposide, famotidine, fentanyl, floxuridine, fluconazole, fluorouracil, furosemide, gentamicin, granisetron, heparin, ifosfamide, immune globulin, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, metoclopramide, metronidazole, minocycline, mitoxantrone, pentostatin, piperacillin/tazobactam, potassium chloride, prochlorperazine edisylate, promethazine, ranitidine, teniposide, ticarcillin/clavulanate, trimethoprim/sulfamethoxazole, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, ampicillin, ampicillin/sulbactam, chlorpromazine, haloperidol, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, imipenem/cilastatin, lorazepam, methylprednisolone sodium succinate, mitomycin, morphine, nalbuphine, ondansetron, piperacillin, sodium bicarbonate, tobramycin. Variable (consult detailed reference): Amphotericin B, amsacrine, ceftazidime, ceftriaxone, ganciclovir, idarubicin, vancomycin.
Compatibility in syringe: Incompatible: Ceftriaxone.
Mechanism of Action
Stimulates proliferation, differentiation and functional activity of neutrophils, eosinophils, monocytes, and macrophages, as indicated.
Pharmacodynamics/Kinetics
Onset of action: Increase in WBC: 7-14 days
Duration: WBCs return to baseline within 1 week of discontinuing drug
Half-life elimination: I.V.: 60 minutes; SubQ: 2.7 hours
Time to peak, serum: SubQ: 1-3 hours
Dosage
Children (unlabeled use) and Adults: I.V. infusion over ≥2 hours or SubQ: Rounding the dose to the nearest vial size enhances patient convenience and reduces costs without clinical detriment
Myeloid reconstitution after allogeneic or autologous bone marrow transplant: I.V.: 250 mcg/m2/day (over 2 hours), begin 2-4 hours after the marrow infusion and ≥24 hours after chemotherapy or radiotherapy, when the post marrow infusion ANC is <500 cells/mm3, and continue until ANC >1500 cells/mm3 for 3 consecutive days
If a severe adverse reaction occurs, reduce dose by 50% or temporarily discontinue the dose until the reaction abates
If blast cells appear or progression of the underlying disease occurs, discontinue treatment
If ANC >20,000 cells/mm3, interrupt treatment or reduce the dose by 50%
Neutrophil recovery following chemotherapy in AML: I.V.: 250 mcg/m2/day (over 4 hours) starting approximately on day 11 or 4 days following the completion of induction chemotherapy, if day 10 bone marrow is hypoplastic with <5% blasts
If a second cycle of chemotherapy is necessary, administer ~4 days after the completion of chemotherapy if the bone marrow is hypoplastic with <5% blasts
Continue sargramostim until ANC is >1500 cells/mm3 for 3 consecutive days or a maximum of 42 days
Discontinue sargramostim immediately if leukemic regrowth occurs
If a severe adverse reaction occurs, reduce the dose by 50% or temporarily discontinue the dose until the reaction abates
If ANC >20,000 cells/mm3, interrupt treatment or reduce the dose by 50%
Mobilization of peripheral blood progenitor cells: I.V., SubQ: 250 mcg/m2/day I.V. over 24 hours or SubQ once daily
Continue the same dose through the period of PBPC collection
The optimal schedule for PBPC collection has not been established (usually begun by day 5 and performed daily until protocol specified targets are achieved)
If WBC >50,000 cells/mm3, reduce the dose by 50%
If adequate numbers of progenitor cells are not collected, consider other mobilization therapy
Postperipheral blood progenitor cell transplantation: I.V., SubQ: 250 mcg/m2/day I.V. over 24 hours or SubQ once daily beginning immediately following infusion of progenitor cells and continuing until ANC is >1500 cells/mm3 for 3 consecutive days is attained
BMT failure or engraftment delay: I.V.: 250 mcg/m2/day over 2 hours for 14 days
May be repeated after 7 days off therapy if engraftment has not occurred
If engraftment still has not occurred, a third course of 500 mcg/m2/day for 14 days may be tried after another 7 days off therapy; if there is still no improvement, it is unlikely that further dose escalation will be beneficial
If a severe adverse reaction occurs, reduce the dose by 50% or temporarily discontinue the dose until the reaction abates
If blast cells appear or disease progression occurs, discontinue treatment
If ANC >20,000 cells/mm3, interrupt treatment or reduce the dose by 50%
Dosage: Combination Regimens
Leukemia, acute myeloid: MEC-G (AML Induction)
Lymphoma, non-Hodgkin's (Burkitt): CODOX-M/IVAC
Administration: I.V.
Can premedicate with analgesics and antipyretics (eg, acetaminophen) to control adverse events (eg, fever, chills, myalgia, etc); control bone pain with non-narcotic analgesics I.V. infusion should be over 2-24 hours; incompatible with dextrose-containing solutions. An in-line membrane filter should NOT be used for intravenous administration.
Administration: Other
Administer by SubQ (undiluted). Do not shake solution. When administering GM-CSF subcutaneously, rotate injection sites.
Administration: I.V. Detail
pH: 7.1-7.7
Monitoring Parameters
Vital signs, hydration status, weight, CBC with differential twice weekly during therapy, renal/liver function tests at least biweekly during therapy (in patients displaying renal or hepatic dysfunction prior to initiation of treatment), pulmonary function
Reference Range
Excessive leukocytosis: ANC >20,000/mm3 or WBC >50,000 cells/mm3
Test Interactions
May interfere with bone imaging studies; increased hematopoietic activity of the bone marrow may appear as transient positive bone imaging changes
Patient Education
This medication can only be administered by infusion or injection. Report immediately any redness, swelling, pain, or burning at infusion/injection site; difficulty breathing; or chest pain. You will require frequent blood tests during treatment. You may experience bone, joint, or muscle pain; nausea, vomiting, or loss of appetite; hair loss (reversible); diarrhea; headache; dizziness; or insomnia. At any time during treatment, report chest pain or palpitations, signs or symptoms of edema (eg, swollen extremities, difficulty breathing, rapid weight gain), onset of severe headache, acute back or chest pain, muscular tremors, or seizure activity.
Additional Information
Reimbursement Hotline (Leukine®): 1-800-321-4669
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Dysphagia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness
Mental Health: Effects on Psychiatric Treatment
May be used to treat clozapine-induced agranulocytosis; lithium may potentiate the release of neutrophils; use with caution
Nursing: Physical Assessment/Monitoring
Use with caution in presence of pre-existing cardiac problems or hepatic, renal, or pulmonary impairment. Patient must be monitored closely during and following infusion for respiratory symptoms and "first-dose effect" (hypotension, tachycardia, flushing, and syncope with the first dose of a cycle). Premedication may be used to control adverse events. Monitor for respiratory symptoms, fluid balance (I and O), rash, hypotension, tachycardia, GI disturbance (diarrhea, stomatitis, mucositis), myalgia, and bone pain.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Leukine®: 250 mcg [contains sucrose 10 mg/mL]
Injection, solution:
Leukine®: 500 mcg/mL (1 mL) [contains benzyl alcohol, sucrose 10 mg/mL]
References
Lieschke GJ and Burgess AW, “Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor,” (1) N Engl J Med, 1992, 327(1):28-35.
Lieschke GJ and Burgess AW, “Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor,” (2) N Engl J Med, 1992, 327(2):99-106.
Mayer D and Bednarczyk EM, “Interaction of Colony-Stimulating Factors and Fluorodeoxyglucose F18 Positron Emission Tomography,” Ann Pharmacother, 2002, 36(11):1796-9.
Smith TJ, Khatcheressian J, Lyman GH, et al, “2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline,” J Clin Oncol, 2006, 24(19):3187-205.
Stute N, Furman WL, Schell M, et al, “Pharmacokinetics of Recombinant Human Granulocyte - Macrophage Colony - Stimulating Factor in Children After Intravenous and Subcutaneous Administration,” J Pharm Sci, 1995, 84(7):824-8.
Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, “Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection,” August 16, 2010. Available at http://www.aidsinfo.nih.gov
International Brand Names
Lexi-Comp.com
Last full review/revision October 2011
Content last modified October 2011
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