Sargramostim

{{DrugProjectFormSinglePage |authorTag=Alberto Plate [1] |genericName=Sarramostin |aOrAn=a |drugClass=colony stimulating factor |indicationType=treatment |indication=granulocytopnia following induction chemotherapy in acute myelogenous leukemia, mobilization and following transplantation of autologous peripheral blood progentior cells, myeloid reconstitution after autologous bone marrow transplantation, myeloid reconstitution after allogeneic bone marrow transplantation and bone marrow transplantation failure or engraftment delay |adverseReactions=chest pain, peripheral edema, pruritus, rash, hypercholesterolemia, hypomagnesemia, weight loss, abdominal pain, diarrhea, dysphagia, GI hemorrhage, hematemesis, nausea, vomiting, acute myelogenous leukemia, increased bilirrubin, arthralgia, bone pain, myalgia, asthenia, intraocular hemorrhage, anxiety, elevated BUN, pharyngitis, fever, malaise and rigor |blackBoxWarningTitle=TITLE |blackBoxWarningBody=Condition Name: (Content) |offLabelAdultGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Sargramostim in adult patients. |offLabelAdultNoGuideSupport=There is limited information regarding Off-Label Non–Guideline-Supported Use of Sargramostim in adult patients. |offLabelPedGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Sargramostim in pediatric patients. |offLabelPedNoGuideSupport=There is limited information regarding Off-Label Non–Guideline-Supported Use of Sargramostim in pediatric patients. |contraindications=LEUKINE is contraindicated:

• in patients with excessive leukemic myeloid blasts in the bone marrow or peripheral blood (≥ 10%);
• in patients with known hypersensitivity to GM-CSF, yeast-derived products or any component of the product;
• for concomitant use with chemotherapy and radiotherapy.

Due to the potential sensitivity of rapidly dividing hematopoietic progenitor cells, LEUKINE should not be administered simultaneously with cytotoxic chemotherapy or radiotherapy or within 24 hours preceding or following chemotherapy or radiotherapy. In one controlled study, patients with small cell lung cancer received LEUKINE and concurrent thoracic radiotherapy and chemotherapy or the identical radiotherapy and chemotherapy without LEUKINE. The patients randomized to LEUKINE had significantly higher incidence of adverse events, including higher mortality and a higher incidence of grade 3 and 4 infections and grade 3 and 4 thrombocytopenia. |warnings=====Pediatric Use====

• Benzyl alcohol is a constituent of liquid LEUKINE and Bacteriostatic Water for Injection diluent. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants. Liquid solutions containing benzyl alcohol (including liquid LEUKINE) or lyophilized LEUKINE reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates.

Fluid Retention

• Edema, capillary leak syndrome, pleural effusion and/or pericardial effusion have been reported in patients after LEUKINE administration. In 156 patients enrolled in placebo-controlled studies using LEUKINE at a dose of 250 mcg/m2/day by 2-hour IV infusion, the reported incidences of fluid retention (LEUKINE vs. placebo) were as follows: peripheral edema, 11% vs. 7%; pleural effusion, 1% vs. 0%; and pericardial effusion, 4% vs. 1%. Capillary leak syndrome was not observed in this limited number of studies; based on other uncontrolled studies and reports from users of marketed LEUKINE, the incidence is estimated to be less than 1%. In patients with preexisting pleural and pericardial effusions, administration of LEUKINE may aggravate fluid retention; however, fluid retention associated with or worsened by LEUKINE has been reversible after interruption or dose reduction of LEUKINE with or without diuretic therapy. LEUKINE should be used with caution in patients with preexisting fluid retention, pulmonary infiltrates or congestive heart failure.

Respiratory Symptoms

• Sequestration of granulocytes in the pulmonary circulation has been documented following LEUKINE infusion and dyspnea has been reported occasionally in patients treated with LEUKINE. Special attention should be given to respiratory symptoms during or immediately following LEUKINE infusion, especially in patients with preexisting lung disease. In patients displaying dyspnea during LEUKINE administration, the rate of infusion should be reduced by half. If respiratory symptoms worsen despite infusion rate reduction, the infusion should be discontinued. Subsequent IV infusions may be administered following the standard dose schedule with careful monitoring. LEUKINE should be administered with caution in patients with hypoxia.

Cardiovascular Symptoms

• Occasional transient supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a previous history of cardiac arrhythmia. However, these [[arrhythmias] have been reversible after discontinuation of LEUKINE. LEUKINE should be used with caution in patients with preexisting cardiac disease.

Renal and Hepatic Dysfunction

• In some patients with preexisting renal dysfunction or hepatic dysfunction enrolled in uncontrolled clinical trials, administration of LEUKINE has induced elevation of serum creatinine or bilirubin and hepatic enzymes. Dose reduction or interruption of LEUKINE administration has resulted in a decrease to pretreatment values. However, in controlled clinical trials the incidences of renal dysfunction and hepatic dysfunction were comparable between LEUKINE (250 mcg/m2/day by 2-hour IV infusion) and placebo-treated patients. Monitoring of renal function and hepatic function in patients displaying renal or hepatic dysfunction prior to initiation of treatment is recommended at least every other week during LEUKINE administration.

|clinicalTrials=====Autologous and Allogeneic Bone Marrow Transplantation====

• LEUKINE is generally well tolerated. In three placebo-controlled studies enrolling a total of 156 patients after autologous BMT or peripheral blood progenitor cell transplantation, events reported in at least 10% of patients who received IV LEUKINE or placebo were as reported in TABLE 6.

• No significant differences were observed between LEUKINE and placebo-treated patients in the type or frequency of laboratory abnormalities, including renal and hepatic parameters. In some patients with preexisting renal or hepatic dysfunction enrolled in uncontrolled clinical trials, administration of LEUKINE has induced elevation of serum creatinine or bilirubin and hepatic enzymes (see WARNINGS). In addition, there was no significant difference in relapse rate and 24 month survival between the LEUKINE and placebo-treated patients.
• In the placebo-controlled trial of 109 patients after allogeneic BMT, events reported in at least 10% of patients who received IV LEUKINE or placebo were as reported in TABLE 7.

• There were no significant differences in the incidence or severity of GVHD, relapse rates and survival between the LEUKINE and placebo-treated patients. Adverse events observed for the patients treated with LEUKINE in the historically-controlled BMT failure study were similar to those reported in the placebo-controlled studies. In addition, headache (26%), pericardial effusion (25%), arthralgia (21%) and myalgia (18%) were also reported in patients treated with LEUKINE in the graft failure study.
• In uncontrolled Phase I/II studies with LEUKINE in 215 patients, the most frequent adverse events were fever, asthenia, headache, bone pain, chills and myalgia. These systemic events were generally mild or moderate and were usually prevented or reversed by the administration of analgesics and antipyretics such as acetaminophen. In these uncontrolled trials, other infrequent events reported were dyspnea, peripheral edema, and rash.
• Reports of events occurring with marketed LEUKINE include arrhythmia, fainting, eosinophilia, dizziness, hypotension, injection site reactions, pain (including abdominal, back, chest, and joint pain), tachycardia, thrombosis, and transient liver function abnormalities.
• In patients with preexisting edema, capillary leak syndrome, pleural effusion and/or pericardial effusion, administration of LEUKINE may aggravate fluid retention. Body weight and hydration status should be carefully monitored during LEUKINE administration.
• Adverse events observed in pediatric patients in controlled studies were comparable to those observed in adult patients.

Acute Myelogenous Leukemia

|alcohol=Alcohol-Sargramostim interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. }}

Sargramostim

Clinical data
ATC code	L03AA09 (WHO)
Identifiers
IUPAC name Human granulocyte macrophage colony stimulating factor
CAS Number	83869-56-1
DrugBank	BTD00035
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C639H1006N168O196S8
Molar mass	14434.5 g/mol

Sargramostim is a recombinant granulocyte macrophage colony-stimulating factor which functions as a immunostimulator.

It is produced in yeast.