sargramostim

REMS

Acceleration of bone marrow recovery after:
- Autologous peripheral blood progenitor cell (PBPC) or bone marrow transplantation in patients with non-Hodgkin’s lymphoma, acute lymphoblastic leukemia, or Hodgkin’s disease;
- Allogeneic bone marrow transplantation from HLA-matched donors.
Management of patients who have undergone allogeneic or autologous bone marrow transplantation in whom neutrophil recovery is delayed or has failed.
To shorten time to neutrophil recovery and to reduce the incidence of severe, life-threatening, or fatal infections after induction chemotherapy in patients with acute myeloid leukemia (AML).
Mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis in patients with cancer undergoing autologous hematopoietic stem cell transplantation.
To improve survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]).

Action ⬆ ⬇

Consists of a glycoprotein produced by recombinant DNA technique that is capable of binding to and stimulating the production, division, differentiation, and activation of granulocytes and macrophages.

Therapeutic effects:

Accelerated recovery of bone marrow after autologous or allogeneic bone marrow transplantation, resulting in decreased risk of infection and other complications.
Improvement in survival in patients with H-ARS.

Pharmacokinetics ⬆ ⬇

Absorption: After IV administration, absorption is essentially complete. Well absorbed after subcut administration.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: Unknown.

Time/Action Profile ⬆ ⬇

(noted as effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
Subcut, IV	rapid	unknown	3–7 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Presence of ≥10% leukemic myeloid blast cells in bone marrow or peripheral blood;
Hypersensitivity to granulocyte macrophage colony-stimulating factor (GM-CSF), yeast products, or additives (mannitol, tromethamine, or sucrose);
Lactation: Lactation;
Pedi: Products containing benzyl alcohol should not be used in newborns.

Use Cautiously in:

Pre-existing fluid retention, HF, or pulmonary infiltrates;
Pre-existing cardiac disease;
Myeloid malignancies;
Previous extensive radiation or chemotherapy (response may be limited);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Children <18 yr (for neutrophil recovery following induction chemotherapy in AML or autologous peripheral blood progenitor cell mobilization and collection) or < 2 yr (for autologous peripheral blood progenitor cells and bone marrow transplantation, allogeneic bone marrow transplantation, or treatment of delayed neutrophil recovery or graft failure) (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, capillary leak syndrome, pericardial effusion, transient supraventricular tachycardia

Derm: itching, rash

GI: diarrhea

MS: arthralgia, bone pain, myalgia

Neuro: headache, malaise, weakness

Resp: dyspnea, pleural effusion

Misc: chills, fever, infusion reactions

Interactions ⬆ ⬇

Drug-drug:

Lithium or corticosteroids may potentiate myeloproliferative effects of sargramostim (concurrent use should be undertaken cautiously).

Route/Dosage ⬆ ⬇

Autologous Peripheral Blood Progenitor Cell and Bone Marrow Transplantation

IV SC (Adults and Children ≥2 yr): Autologous peripheral blood progenitor cell transplantation—250 mcg/m²/day beginning immediately following infusion of progenitor cells and continue until absolute neutrophil count (ANC) >1500 cells/mm³ for 3 consecutive days.
IV (Adults and Children ≥2 yr): Autologous bone marrow transplantation—250 mcg/m²/day beginning 2–4 hrs after bone marrow infusion (once post-marrow infusion ANC <500 cells/mm³), and ≥24 hours after the last dose of chemotherapy or radiotherapy and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Allogeneic Bone Marrow Transplantation

IV (Adults and Children ≥2 yr): 250 mcg/m²/day beginning 2–4 hrs after bone marrow infusion (once post-marrow infusion ANC <500 cells/mm³), and ≥24 hours after the last dose of chemotherapy or radiotherapy and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Allogeneic or Autologous Bone Marrow Transplantation: Delayed or Failed Neutrophil Recovery

IV (Adults and Children ≥2 yr): 250 mcg/m²/day for 14 days; may be repeated after a 7-day rest between courses; if results are inadequate, a 3rd course at 500 mcg/m²/day for 14 days may be given after a 7-day rest.

Neutrophil Recovery Following Induction Chemotherapy for Acute Myeloid Leukemia

IV (Adults ≥55 yr): 250 mcg/m²/day started around Day 11 or 4 days after induction if Day 10 bone marrow is hypoplastic with <5% blast cells and continue until ANC >1500 cells/mm³ for 3 consecutive days (not to exceed 42 days).

Autologous Peripheral Blood Progenitor Cell Mobilization and Collection

IV SC (Adults ): 250 mcg/m²/day continued throughout collection of PBPCs.

Acute Exposure to Myelosuppressive Doses of Radiation (H-ARS)

SC (Adults and Children >40 kg): 7 mcg/kg once daily continued until ANC >1000 cells/mm³ for 3 consecutive CBC's or is >10,000 cells/mm³ after a radiation-induced nadir.
SC (Children 15–40 kg): 10 mcg/kg once daily continued until ANC >1000 cells/mm³ for 3 consecutive CBC's or is >10,000 cells/mm³ after a radiation-induced nadir.
SC (Children <15 kg): 12 mcg/kg once daily continued until ANC >1000 cells/mm³ for 3 consecutive CBC's or is >10,000 cells/mm³ after a radiation-induced nadir.

Availability ⬆ ⬇

Lyophilized powder for injection: 250 mcg/vial
Solution for injection: 500 mcg/mL

Assessment ⬆ ⬇

Monitor heart rate, BP, and respiratory status during and immediately after infusion. If dyspnea develops, slow infusion rate by half. Reassess; medication may need to be discontinued. Assess for peripheral edema daily throughout therapy. Capillary leak syndrome (swelling of feet or lower legs, sudden weight gain, dyspnea) and pleural or pericardial effusion may occur, usually at doses >32 mcg/kg/day.
Monitor for first-dose reaction (flushing, hypotension, syncope, weakness). Does not recur with first dose of each course but may occur with first dose of more than 1 course.
Assess for fever daily during therapy. Usually mild and dose-related and resolves with discontinuation or administration of antipyretics.
Assess for arthralgias and myalgias, usually in lower extremities, which tend to occur when granulocyte counts are returning to normal. May also cause mild to moderate bone pain, possibly from bone marrow expansion. Usually occurs over 1–3 days before myeloid recovery and occurs in the sternum, spine, pelvis, and long bones. Treat with analgesics.

Lab Test Considerations:

Obtain a CBC with differential and platelet count before chemotherapy and twice weekly during therapy to avoid leukocytosis. Monitor ANC; may increase rapidly. If ANC >20,000/mm³ or 10,000/mm³ after the nadir has occurred or if platelet count >500,000/mm³, interrupt administration and reduce dose by half or discontinue. Excessive blood levels usually return to baseline 3–7 days after discontinuation of therapy. If blast cells appear, sargramostim should be discontinued.
- For H-ARS, obtain baseline CBC with differential and then serial CBCs every third day until ANC remains >1,000/mm³ for 3 consecutive CBCs. Do not delay administration if CBC is not readily available. Continue administration of sargramostim until ANC remains >1,000/mm³ for 3 consecutive CBCs or exceeds 10,000/mm³ after a radiation-induced nadir.
- Monitor renal and hepatic function before and biweekly throughout therapy in patients with renal or hepatic dysfunction. May cause ↑ BUN, serum creatinine, and hepatic enzymes.
- May cause ↓ serum albumin concentrations.

Implementation ⬆ ⬇

Administer 2–4 hr after bone marrow transplant and no earlier than 24 hr after cytotoxic chemotherapy or 12 hr after last dose of radiotherapy.
- For H-ARS, estimate a patient’s absorbed radiation dose (level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings (time to onset of vomiting or lymphocyte depletion kinetics). Administer sargramostim as soon as possible after suspected or confirmed exposure to radiation doses >2 gray (Gy).
- Refrigerate but do not freeze powder, reconstituted solution, or diluted solution. Reconstitute with 1 mL of sterile water without preservatives injected toward side of vial. Swirl gently to avoid foaming. Do not shake. Solution is clear and colorless; do not administer solutions that are cloudy, discolored or contain particulate matter. Discard if left at room temperature for >6 hr. Vial is for one-time use only.
SC: Administer reconstituted solution without further dilution.

IV Administration:

Intermittent Infusion: Diluent: Dilute in 0.9% NaCl.Concentration: If final concentration is 10 mcg/mL, add 1 mg human albumin per 1 mL of 0.9% NaCl before addition of sargramostim to prevent absorption of the components of the drug delivery system. Do not administer with an in-line filter.
Rate: Usually infused over 2–4 hr. Has been administered over 30–60 min, over 5–12 hr, and as a continuous infusion over 24 hr.
- After bone marrow transplantation or failure of engraftment: Administer over 2 hr.
- Chemotherapy for AML: Administer over 4 hr.
- Mobilization of PBPCs or PBPC transplant: Administer as a continuous infusion over 24 hr.
Y-Site Compatibility:
- amikacin
- aminocaproic acid
- aminophylline
- aztreonam
- bleomycin
- butorphanol
- calcium gluconate
- carboplatin
- carmustine
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- ceftriaxone
- cefuroxime
- cisplatin
- clindamycin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- dexamethasone sodium phosphate
- diphenhydramine
- dopamine
- doxorubicin hydrochloride
- doxycycline
- droperidol
- etoposide
- famotidine
- fentanyl
- floxuridine
- fluconazole
- fluorouracil
- furosemide
- gentamicin
- granisetron
- heparin
- idarubicin
- ifosfamide
- immune globulin
- levofloxacin
- magnesium sulfate
- mannitol
- meperidine
- mesna
- methotrexate
- metoclopramide
- metronidazole
- mitoxantrone
- pentostatin
- piperacillin/tazobactam
- potassium chloride
- prochlorperazine
- promethazine
- rituximab
- sodium acetate
- teniposide
- trastuzumab
- trimethoprim/sulfamethoxazole
- vinblastine
- vincristine
- zidovudine
Y-Site Incompatibility:
- acyclovir
- ampicillin
- ampicillin/sulbactam
- chlorpromazine
- ganciclovir
- haloperidol
- hydrocortisone
- hydromorphone
- hydroxyzine
- imipenem/cilastatin
- lorazepam
- methylprednisolone sodium succinate
- mitomycin
- morphine
- nalbuphine
- ondansetron
- sodium bicarbonate
- tobramycin
Additive Incompatibility: Do not admix with other medications.

Patient/Family Teaching ⬆ ⬇

Explain purpose of sargramostim to patient.
Instruct patient administering subcut sargramostim at home in correct technique for administration, care and disposal of equipment.
Advise patient to notify health care professional if signs and symptoms of allergic reactions (skin rash over entire body, hives, trouble breathing, wheezing, swelling around mouth or eyes, a fast heartbeat, sweating, dizziness or feeling faint), infusion-related reaction (trouble breathing, skin flushing, a fast pulse, dizziness or feeling faint) during or soon after infusion, capillary leak syndrome (swelling or puffiness of feet or ankles, and urinating less than usual, swelling of your abdomen and feeling of fullness, sudden weight gain, swollen legs or feet, trouble breathing, dizziness or feeling faint, general feeling of tiredness) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications during therapy.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during and for at least 2 wk after last dose of sargramostim.

Evaluation/Desired Outcomes ⬆ ⬇

Acceleration of bone marrow recovery and decreased incidence of infection in patients after autologous and allogeneic bone marrow transplantation, bone marrow transplant failure or engraftment delay, chemotherapy for AML, and PBPC transplantation.
Improvement in survival in patients with H-ARS.

US Brand Names ⬆ ⬇

Pot. Nursing Diagnoses ⬆ ⬇

Risk for infection(Indications)

Code ⬆

NDC Code

0024- sanofi-aventis U.S. LLC
- 0024-5843- Leukine
  - 0024-5843-05- 5 VIAL in 1 CARTON (0024-5843-05) > 1 mL in 1 VIAL (0024-5843-01)

0024- sanofi-aventis U.S. LLC
- 0024-5844- Leukine
  - 0024-5844-01- 1 VIAL, MULTI-DOSE in 1 CARTON (0024-5844-01) > 1 mL in 1 VIAL, MULTI-DOSE

0024- sanofi-aventis U.S. LLC
- 0024-5844- Leukine
  - 0024-5844-05- 5 VIAL in 1 CARTON (0024-5844-05) > 1 mL in 1 VIAL

71837- Partner Therapeutics, Inc
- 71837-5843- Leukine
  - 71837-5843-5- 5 VIAL, SINGLE-DOSE in 1 CARTON (71837-5843-5) > 1 mL in 1 VIAL, SINGLE-DOSE (71837-5843-1)

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇