No

Colony Stimulating Factor

Myeloid reconstitution after autologous bone marrow transplantation:

Non-Hodgkin's lymphoma (NHL)

Acute lymphoblastic leukemia (ALL)

Hodgkin's lymphoma

Metastatic breast cancer

Myeloid reconstitution after allogeneic bone marrow transplantation

Peripheral stem cell transplantation

Metastatic breast cancer

Non-Hodgkin's lymphoma

Hodgkin's lymphoma

Multiple myeloma

Acute myelogenous leukemia (AML) following induction chemotherapy in older adults 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

Safety and efficacy of GM-CSF given simultaneously with cytotoxic chemotherapy have not been established. Concurrent treatment may increase myelosuppression.

C

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.

GM-CSF is contraindicated in the following instances:

Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any known component of the product

Simultaneous administration with cytotoxic chemotherapy or radiotherapy or administration 24 hours preceding or following chemotherapy is recommended. Use with caution in patients with pre-existing cardiac problems, hypoxia, fluid retention, pulmonary infiltrates or congestive heart failure, renal or hepatic impairment.

Growth factor potential: Use with caution with myeloid malignancies. Precaution should be exercised in the usage of GM-CSF in any malignancy with myeloid characteristics. GM-CSF can potentially act as a growth factor for any tumor type, particularly myeloid malignancies. Tumors of nonhematopoietic origin may have surface receptors for GM-CSF.

There is a "first-dose effect" (refer to Adverse Reactions for details) which is rarely seen with the first dose and does not usually occur with subsequent doses.

>10%:

"First-dose" effects: Fever, hypotension, tachycardia, rigors, flushing, nausea, vomiting, dyspnea

Central nervous system: Neutropenic fever

Dermatologic: Alopecia

Endocrine & metabolic: Polydipsia

Gastrointestinal: Nausea, vomiting, diarrhea, stomatitis, GI hemorrhage, mucositis

Neuromuscular & skeletal: Bone pain, myalgia

1% to 10%:

Cardiovascular: Chest pain, peripheral edema, capillary leak syndrome

Central nervous system: Headache

Dermatologic: Rash

Endocrine & metabolic: Fluid retention

Gastrointestinal: Anorexia, sore throat, stomatitis, constipation

Hematologic: Leukocytosis

Local: Pain at injection site

Neuromuscular & skeletal: Weakness

Respiratory: Dyspnea, cough

<1%: Hypotension, flushing, pericardial effusion, transient supraventricular arrhythmias, pericarditis, malaise, thrombophlebitis, anaphylactic reaction

The maximum amount that can be safely administered in single or multiple doses has not been determined

Treatment: Discontinue therapy and carefully monitor the patient for WBC increase and respiratory symptoms

Increased toxicity: Lithium, corticosteroids may potentiate myeloproliferative effects

The manufacturer currently recommends that solutions which are reconstituted with sterile water should be used within 6 hours (due to a lack of a preservative) and that solution reconstituted with bacteriostatic water should be used within 20 days. The manufacturer recommends that further diluted solutions be discarded if not used within 6 hours

Sargramostim should be stored at 2°C to 8°C (36°F to 46°F)

Vials should not be frozen or shaken

Sargramostim is stable after dilution in 1 mL of bacteriostatic or nonbacteriostatic sterile water for injection for 30 days at 2°C to 8°C or 25°C

Sargramostim may also be further diluted in 0.9% sodium chloride to a concentration of greater than or equal to 10 mcg/mL for I.V. infusion administration; this diluted solution is stable for 48 hours at room temperature and refrigeration

If the final concentration of sargramostim is <10 mcg/mL, human albumin should be added to the saline prior to the addition of sargramostim to prevent absorption of the components to the delivery system

It is recommended that 1 mg of human albumin/1 mL of 0.9% sodium chloride (eg, 1 mL of 5% human albumin/50 mL of 0.9% sodium chloride) be added

Standard diluent: Dose greater than or equal to 250 mcg/25 mL NS

Incompatible with dextrose-containing solutions

Stimulates proliferation, differentiation and functional activity of neutrophils, eosinophils, monocytes, and macrophages, as indicated:

G-CSF (Filgrastim): Yes

GM-CSF (Sargramostim): Yes

Eosinophil proliferation/differentiation:

G-CSF (Filgrastim): No

GM-CSF (Sargramostim): Yes

Macrophage proliferation/differentiation:

G-CSF (Filgrastim): No

GM-CSF (Sargramostim): Yes

Neutrophil migration:

G-CSF (Filgrastim): Enhanced

GM-CSF (Sargramostim): Inhibited

Onset of action: Increase in WBC in 7-14 days

Duration: WBC will return to baseline within 1 week after discontinuing drug

Half-life: 2 hours

Time to peak serum concentration: S.C.: Within 1-2 hours

Children and Adults: I.V. infusion over greater than or equal to 2 hours or S.C.

Existing clinical data suggest that starting GM-CSF between 24 and 72 hours subsequent to chemotherapy may provide optimal neutrophil recover; continue therapy until the occurrence of an absolute neutrophil count of 10,000/mL after the neutrophil nadir

The available data suggest that rounding the dose to the nearest vial size may enhance patient convenience and reduce costs without clinical detriment

Myeloid reconstitution after peripheral stem cell, allogeneic or autologous bone marrow transplant: I.V.: 250 mcg/m²/day for 21 days to begin 2-4 hours after the marrow infusion on day 0 of autologous bone marrow transplant or greater than or equal to 24 hours after chemotherapy or 12 hours after last dose of radiotherapy

If a severe adverse reaction occurs, reduce or temporarily discontinue the dose until the reaction abates

If blast cells appear or progression of the underlying disease occurs, disrupt treatment

Interrupt or reduce the dose by half if ANC is >20,000 cells/mm³

Patients should not receive sargramostim until the postmarrow infusion ANC is <500 cells/mm³

Neutrophil recovery following chemotherapy in AML: I.V.: 250 mg/m²/day over a 4-hour period starting ~day 11 or 4 days following the completion of induction chemotherapy, if day 10 bone marrow is hypoblastic with <5% blasts

If a second cycle of chemotherapy is necessary, administer ~4 days after the completion of chemotherapy if the bone marrow is hypoblastic with <5% blasts

Continue sargramostim until ANC is >1500 cells/mm³ for 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

Mobilization of peripheral blood progenitor cells: I.V.: 250 mcg/m²/day over 24 hours or S.C. 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.: 250 mcg/m²/day over 24 hours or S.C. once daily beginning immediately following infusion of progenitor cells and continuing until ANC is >1500 for 3 consecutive days is attained

BMT failure or engraftment delay: I.V.: 250 mcg/m²/day for 14 days as a 2-hour infusion

The dose can 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 or temporarily discontinue the dose until the reaction abates

If blast cells appear or disease progression occurs, discontinue treatment

Vital signs, weight, CBC with differential, platelets, renal/liver function tests, especially with previous dysfunction, WBC with differential, pulmonary function

Excessive leukocytosis: ANC >20,000/mm³ or WBC >50,000 cells/mm³

May cause drowsiness

None reported

No information available to require special precautions

No effects or complications reported

You may experience bone pain (request analgesic), nausea and vomiting (small frequent meals may help), hair loss (reversible). Report fever, chills, unhealed sores, severe bone pain, difficulty breathing, swelling or pain at infusion site. Avoid crowds or exposure to infected persons; you will be susceptible to infection. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Can premedicate with analgesics and antipyretics; control bone pain with non-narcotic analgesics; do not shake solution; when administering GM-CSF subcutaneously, rotate injection sites

Injection: 250 mcg, 500 mcg

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"American Society of Clinical Oncology. Recommendations for the Use of Hematopoietic Colony-Stimulating Factors: Evidence-Based, Clinical Practice Guidelines," J Clin Oncol, 1994, 12(11):2471-508.

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Grant SM and Heel RC, "Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (rGM-CSF). A Review of Its Pharmacological Properties and Prospective Role in the Management of Myelosuppression," Drugs, 1992, 43(4):516-60.

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.

Lifton R and Bennett JM, "Clinical Use of Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor in Neutropenia Associated With Malignancy," Hematol Oncol Clin North Am, 1996, 10(4):825-39.

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.

Tarr PE, "Granulocyte-Macrophage Colony-Stimulating Factor and the Immune System," Med Oncol, 1996, 13(3):133-40.

Trissel LA, Bready BB, Kwan JW, et al, "Visual Compatibility of Sargramostim With Selected Antineoplastic Agents, Anti-infectives, or Other Drugs During Simulated Y-Site Injection," Am J Hosp Pharm, 1992, 49(2):402-6.