Sargramostim
Sargramostim (Leukine)
Sargramostim
(sar- GRAM-oh-stim)
Pregnancy Category: C GM-CSF Leukine (Rx)

Classification: Colony-stimulating factor

Action/Kinetics: A granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in a yeast expression system. GM-CSF stimulates the proliferation and differentiation of hematopoietic progenitor cells. It stimulates partially committed progenitor cells to divide and differentiate in the granulocyte-macrophage pathways. Division, maturation, and activation are induced through GM-CSF binding to specific receptors located on the surface of target cells. Also activates mature granulocytes and macrophages. Increases the cytotoxicity of monocytes toward certain neoplastic cell lines as well as activates polymorphonuclear neutrophils, thus inhibiting the growth of tumor cells. Sargramostim differs from the naturally occurring GM-CSF by one amino acid and by a different carbohydrate moiety. Peak levels: 2-3 hr, depending on the dose. t 1/2, initial: 12-17 min; t 1/2, terminal: 1.6-2.6 hr, depending on the dose. Neutralizing antibodies have been detected in a small number of clients.

Uses: Increased myeloid recovery in clients with non-Hodgkin's lymphoma, ALL, and Hodgkin's disease undergoing autologous bone marrow transplantation. Bone marrow transplantation failure or engraftment delay. To shorten recovery time to neutrophil recovery and to decrease the incidence of severe and life-threatening infections in older adult clients with AML. To mobilize hematopoietic progenitor cells into peripheral blood collection by leukapheresis. For acceleration of myeloid recovery in allogenic bone marrow transplantation from human lymphocyte antigen-matched related donors. Investigational: To increase WBC counts in clients with myelodysplastic syndrome and in AIDS clients taking AZT; to correct neutropenia in clients with aplastic anemia; to decrease the nadir of leukopenia secondary to myelosuppressive chemotherapy and to decrease myelosuppression in preleukemic clients; and to decrease organ system damage following transplantation, especially in the liver and kidney.

Contraindications: More than 10% leukemic myeloid blasts in the bone marrow or peripheral blood. Known hypersensitivity to GM-CSF, yeast-derived products, or any component of the product. Simultaneous use with cytotoxic chemotherapy or radiotherapy or use within 24 hr preceding or following chemotherapy or radiotherapy.

Special Concerns: Use with caution in clients with preexisting cardiac disease and hypoxia and during lactation. Safety and effectiveness have not been determined in children although it appears the drug is no more toxic in children than in adults. May aggravate fluid retention in clients with preexisting peripheral edema, or pleural or pericardial effusion. Insufficient data on effectiveness of sargramostim in increasing myeloid recovery after peripheral blood stem cell transplantation. It is possible that sargramostim can act as a growth factor for any tumor type, especially myeloid malignancies; thus, use with caution in any malignancy with myeloid characteristics.

Side Effects: First-dose effects (rare): Respiratory distress, hypoxia, flushing, hypotension, syncope, tachycardia. CV: Hypertension, hemorrhage edema, hypotension, peripheral edema, cardiac event, tachycardia, pericardial effusion, pleural effusion, capillary leak syndrome. GI: N&V;, diarrhea, abdominal pain, GI disorder, stomatitis, dyspepsia, anorexia, hematemesis, dysphagia, GI hemorrhage constipation, abdominal distension, liver damage. CNS: Neuroclinical, neuromotor, neuropsychiatric, and neurosensory side effects. Paresthesia, headache, CNS disorder, insomnia, anxiety. Respiratory: Pulmonary event, pharyngitis, lung disorder, epistaxis, dyspnea, rhinitis. Hematologic: Blood dyscrasias, thrombocytopenia, leukopenia, petechia, agranulocytosis, coagulation disorders. Musculoskeletal: Bone pain, arthralgia, asthenia. Dermatologic: Rash, alopecia, pruritus. GU: Urinary tract disorder, hematuria, abnormal kidney function. Miscellaneous: Fever, infection, malaise, weight loss, chills, pain, chest pain, allergy, sepsis eye hemorrhage, back pain, weight gain, sweating.

Laboratory Test Alterations: Glucose, BUN, cholesterol, bilirubin, serum creatinine, ALT, alkaline phosphatase. Albumin, calcium.

Overdose Management: Symptoms: Dyspnea, malaise, nausea, fever, rash, sinus tachycardia, chills, headache. Treatment: Discontinue therapy. Monitor for increases in WBCs and for respiratory symptoms.

Drug Interactions: Drugs such as corticosteroids and lithium may the myeloproliferative effects of sargramostim. The effect of sargramostim may be limited in those who have received alkylating agents, anthracycline antibiotics, or antimetabolites.

How Supplied: Injection: 500 mcg/mL; Powder for injection: 250 mcg, 500 mcg

Dosage
?IV Infusion, SC Myeloid reconstitution after autologous or allogenic bone marrow transplantation.
250 mcg/m ²/day for 21 days as a 2-hr infusion beginning 2-4 hr after the autologous bone marrow infusion and greater than 24 hr after the last dose of chemotherapy and 12 hr after the last dose of radiotherapy. Do not give drug until the postmarrow infusion absolute neutrophil count is less than 500 cells/mm ³.
Bone marrow transplantation failure or engraftment delay.
250 mcg/m ²/day for 14 days as a 2-hr IV infusion. If engraftment has not occurred, therapy may be repeated after 7 days off therapy. A third course of 250 mcg/m ²/day may be undertaken after another 7 days off therapy. However, if no response occurs after three courses, it is unlikely the drug will be beneficial.
Neutrophil recovery following chemotherapy in acute myelogenous leukemia.
250 mcg/m ²/day given over a 4-hr period staring at about day 11 or 4 days following completion of induction chemotherapy. Use if the day 10 bone marrow is hypoplastic with less than 5% blasts. If a second cycle of therapy is needed, give about 4 days after the completion of chemotherapy if the bone marrow is hypoplastic with less than 5% blasts. Continue therapy until an absolute neutrophil count greater than 1,500/mm ³ is noted for 3 consecutive days or a maximum of 42 days. If a severe adverse reaction occurs, decrease the dose by 50% or discontinue temporarily until the drug reaction is reduced.
Mobilization of peripheral blood progenitor cells (PBPCs).
250 mcg/m ²/day IV over 24 hr or SC once daily. Use this dose throughout the PBPC collection period. If the WBC count is greater than 50,000 cells/mm ³, reduce the dose by 50%. If sufficient numbers of progenitor cells are not collected, use other mobilization therapy.
Postperipheral blood progenitor cell transplantation.
250 mcg/m ²/day IV over 24 hr or SC once daily beginning immediately after infusion of progenitor cells and continuing until an absolute neutrophil count greater than 1,500 is reached for 3 consecutive days.