Sargramostim

Brand names Leukine; yeast derived (Saccharomyces cerevisiae) recombinant human granulocyte- macrophage colony-stimulating factor (rhGM-CSF)

Medication error Look-alike, sound-alike drug names potential USP reports that sargramostim has been confused with filgrastim and Sandostatin.(1)

Contraindications Contraindications: Patients with ≥10% leukemic myeloid blasts in bone marrow or and warnings peripheral blood; patients with known hypersensitivity to GM-CSF, products derived from yeast, or any product component; 24 hours before or after chemotherapy or radiotherapy treatment.(2) Warnings: Allergic reactions have been reported. Should this occur, discontinue the infusion and institute appropriate therapy.(2) Neonates should not receive liquid or lyophilized sargramostim reconstituted with BW due to the presence of benzyl alcohol.(2)

Infusion-related A first-dose response that includes respiratory distress, hypotension, tachycardia, and cautions flushing is common with infusion of the first dose of a cycle and usually resolves with treatment.(2) This does not recur with subsequent doses in the cycle.(2)

Dosage The products derived from Escherichia coli and Chinese hamster ovaries are not available in the United States. Some of the studies cited evaluated these products, which may have different potencies, specific activities, and adverse effects. Neutropenia Postchemotherapy neutropenia: 250 mcg/m2/day IV over 2 hours for up to 14 days(2-4) or 5 mcg/kg/day IV (bacteria [Escherichia coli] derived) over 4 hours for up to 21 days.(5) Alternatively, 5 mcg/kg/day sub-Q for up to 21 days following chemotherapy or irradiation.(6,7) (See the Comments section.) Bone marrow transplantation: 250 mcg/m2/day IV over 2 hours or sub-Q beginning 2–4 hours after transplant and not earlier than 24 hours after chemotherapy or after radiation until absolute neutrophil count (ANC) >1500 cells/mm3 for 3 consecu- tive or for 21 days.(2) Alternatively, 250 mcg/m2/day IV over 4 hours beginning after transplant for 21 days.(8) Premature and term neonates (reconstitute lyophilized product in SW to avoid benzyl alcohol) Neutropenia (≤31 weeks gestational age): 10 mcg/kg/day sub-Q × 5 days(9,10) Aplastic anemia: Nine children (0.7–19 years of age), received induction phase continuous infusion doses of either 8 mcg/kg/day increased after 14 days to 16 mcg/kg/day for up to 14 more days if the hematologic response was inadequate or doses of 16 mcg/kg/ day increased to 32 mcg/kg/day (Chinese hamster ovary cell derived).(11) After the induction phase, administration was changed to sub-Q dosing.(11) Eighteen children received a standard immunosuppressive regimen for 5 days and then GM-CSF at 250 mcg/m2/day sub-Q was started.(12) Mobilization of peripheral blood progenitor cells (PBPC): 250 mcg/m2/day IV over 24 hours or sub-Q once daily, continued through the period of PBPC cell collection(2)

Dosage adjustment None. Patients with existing renal or hepatic impairment should have renal function or in organ dysfunction liver function monitored at least every other week.(2)

Maximum dosage Not established. Some older reports have used 32 mcg/kg(12) or 1500 mcg/m2.(3) Adverse effects are more common at doses higher than 250 mg/m2/day.  776 Sargramostim

Additives The liquid product contains 1.1% benzyl alcohol, 40 mg/mL mannitol, 10 mg/mL sucrose, and 1.2 mg/mL tromethamine.(2) After reconstitution with BW or SW, each mL of the lyophilized product contains 40 mg mannitol, 10 mg sucrose, and 1.2 mg tromethamine.(2) BW contains benzyl alcohol. See Appendix C for information about potential benzyl alcohol toxicity in neonates.

Suitable diluents NS(2)

Maximum 250 (reconstituted lyophilized powder) or 500 mcg/mL (liquid)(2) concentration

Preparation and An in-line membrane filter should not be used when sargramostim is given IV.(2) delivery Stability: The lyophilized product reconstituted with SW must be used within 6 hours of reconstitution because it contains no preservatives.(2) If the final concentration will be <10 mcg/mL, albumin should be added to the NS diluent to achieve a final albumin concentration of 0.1% prior to the addition of sargramostim to prevent adsorption to the drug delivery system.(2) Add 1 mg albumin per mL of NS.(2) Compatibility: See Appendix D for PN compatibility information.

IV push Not indicated(2)

Intermittent infusion Usually infused over 2–4 hours(2-4)

Continuous infusion Not indicated

Other routes of The liquid product (500 mcg/mL) can be given sub-Q undiluted.(2) administration The lyophilized product is reconstituted to 250 mcg/mL and given sub-Q without further dilution.(2) Not for IM administration.

Comments The use of colony-stimulating factor decreased febrile neutropenia, length of hospitaliza- tion, and number of infectious episodes but did not shorten the duration of neutropenia nor lessen treatment delays in children with acute lymphocytic leukemia.(13) Monitoring: CBC with differential is recommended twice a week during therapy to evalu- ate for leukocytosis. If the ANC >20,000 cells/mm3, or the platelet count >500,000 cells/ mm3, the dose should be decreased by 50% or held.(2) Adverse effects: Children receiving multiple courses of sub-Q GM-CSF have experienced acute toxicities at various times during their dosing including fever, tachycardia, hypotension, and rash requiring discontinuation.(6) Sargramostim has the potential to activate the coagulation system in pediatric patients receiving bone marrow or stem cell transplant.(14) The severity of adverse reactions appears to be less with the yeast-derived product than those derived in Chinese hamster ovary cells or bacteria.(1) Pericardial and pleural effusions, myalgias, and volume overload are dose-limiting side effects in adults.(2) Although adverse effects have been reported in children, they are usually mild(4,5) and unrelated to dose.(3) However, cardiopulmonary symptoms occurred in a child receiving continuous infusion of 24 mcg/kg/day(10) and a deep vein thrombosis occurred in a child being treated for myelosuppressive chemotherapy, who inadvertently received 1500 mcg/m2/day for 7 days.(3)  777