sargramostim (Rx)

>10%

Autologous BMT

• Abdominal pain (89%)
• Diarrhea (89%)
• Asthenia (66%)
• Malaise (57%)
• Rash (44%)
• Chest pain (11%)
• Peripheral edema (11%)

Acute myelogenous leukemia

• Fever (81%)
• Skin reaction (77%)
• Metabolic disease (58%)
• Nausea (58%)
• Vomiting (46%)
• Weight loss (37%)

Diarrhea (allogenic BMT 81%)

Nausea (allogenic BMT 70%)

Vomiting (allogenic BMT 70%)

Abdominal pain (allogenic BMT 38%)

Hyperbilirubinemia (allogenic BMT 30%)

Rigor (allogenic BMT 25%)

Cardiac dysrhythmia (BMT graft failure 25%)

Pericardial effusion (BMT graft failure 25%)

Pruritis (allogenic BMT 23%)

Increase serum BUN (allogenic BMT 23%)

Pharyngitis (allogenic BMT 23%)

Bone pain (allogenic BMT 21%)

Myalgia (BMT graft failure 18%)

Hypercholesterolemia (allogenic BMT 17%)

Hypomagnesemia (allogenic BMT 15%)

Chest pain (allogenic BMT 15%)

Hematemesis (allogenic BMT 13%)

GI hemorrhage (allogenic BMT 11%)

Intraocular hemorrhage (allogenic BMT 11%)

Dysphagia (allogenic BMT 11%)

Arthralgia (allogenic BMT 11%)

1-10%

Cardiac dysrhythmia (autologous BMT 4%)

Pericardial effusion (autologous BMT 4%)

<1%

Capillary leak syndrome

Frequency Not Defined

Anorexia

Fever

Malaise

Cerebral hemorrhage

Stomatitis

Elevated BUN and cholesterol

Renal failure

Sepsis

Contraindications

History of serious allergic reactions (eg, anaphylaxis to human GCSFs [such as sargramostim], yeast-derived products, or any component of the product)

>10% leukemic myeloid blasts in bone marrow or peripheral blood

Do not administer within 24 hr preceding or following chemotherapy or radiotherapy

Cautions

Caution in fluid retention, pulmonary infiltrates, CHF, lung disease, cardiac disease, hypoxia, hepatic/renal impairment; conditions may worsen

Solution should NOT be administered to neonates due to presence of benzyl alcohol in the formulation ant its association with "gasping syndrome"

Discontinue immediately if blast cells appear or disease progression occurs

Reformulated liquid devoid of sodium EDTA now available

Treatment may induce neutralizing anti-drug antibodies; incidence of anti-sargramostim neutralizing antibodies may be related to duration of exposure

A first dose effect characterized by respiratory distress, hypoxia, flushing, hypotension , syncope, and/or tachycardia, may occur with the first dose of the cycle and resolve with appropriate symptomatic treatment; symptoms do not usually occur with subsequent doses within that cycle

Edema, capillary leak syndrome, pleural and/or pericardial effusion; fluid retention shown to be reversible with dosage reduction or discontinuation with or without concomitant use of diuretics

If there is a rapid increase in blood counts (ANC ≥20,000/mm³, WBC >50,000/mm³, platelets >500,000/mm³), decrease dose by 50% or discontinue therapy; excessive blood counts should fall to normal within 3-7 days after discontinuation of therapy; monitor with differential twice weekly during treatment

Sequestration of granulocytes in pulmonary circulation and dyspnea reported; monitor respiratory symptoms during and following IV infusion; decrease infusion rate by 50% if dyspnea occurs; discontinue infusion if dyspnea persists despite reduction in rate of administration; subsequent doses may be administered at standard rate with careful monitoring

Supraventricular arrhythmia reported in uncontrolled studies during administration, particularly in patients with a previous history of cardiac arrhythmia

Serious hypersensitivity reactions, including anaphylactic reactions reported (see Contraindications)

May cause infusion-related reactions

Owing to the possibility of tumor growth potentiation, exercise caution when using this drug in any malignancy with myeloid characteristic

Avoid concomitant use of sargramostim and products that induce myeloproliferation (eg, lithium, corticosteroids)

Pregnancy

Limited available data on use in pregnant women are insufficient to inform the drug-associated risk of adverse developmental outcomes

Based on animal studies, sargramostim may cause embryofetal harm; administration to pregnant rabbits during organogenesis resulted in adverse developmental outcomes including increased spontaneous abortion at systemic exposures ≥1.3 times the human exposure expected at the recommended human dose

Advise pregnant women of the potential risk to a fetus

Lactation

No information regarding the presence of drug in human milk, the effects on the breastfed child, or the effects on milk production

Administration of sargramostim to rabbits during lactation resulted in reduction in postnatal offspring survival; advise a lactating woman not to breastfeed during treatment and for at least 2 weeks after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant granulocyte macrophage colony stimulating factor; acts on hematopoietic cells to stimulate proliferation & differentiation particularly into neutrophils, monocytes/macrophages & myeloid-derived dendritic cells & some end cell function activity

Absorption

Peak plasma concentration: 16.7 ng/mL (IV); 3.03 ng/mL (SC)

AUC: 32.9 ng·hr /mL (IV); 21.3 ng·hr/mL (SC)

Bioavailability: 75% (SC)

Distribution

Vd: 96.8 L (IV)

Excretion

Half-life elimination: 3.84 h (IV); 1.4 h (SC)

Clearance: 17.2 L/h (IV); 23 L/h

IV Incompatibilities

Y-site: acyclovir, amphotericin B(?), ampicillin, ampicillin/sulbactam, amsacrine(?), cefoperazone, ceftazidime(?), chlorpromazine, ganciclovir, haloperidol, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, imipenem/cilastatin, lorazepam, methylprednisolone sodium succinate, mitomycin, morphine, nalbuphine, ondansetron, piperacillin, sodium bicarbonate, tobramycin, vancomycin in albumin-containing solns

IV Compatibilities

Y-site (partial list): bleomycin, carboplatin, carmustine, cisplatin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, diphenhydramine, dopamine, doxorubicin, doxycycline, fentanyl, fluorouracil, furosemide, heparin, idarubicin, ifosfamide, MgSO4, mechlorethamine, meperidine, methotrexate, metronidazole, teniposide, vancomycin in albumin-free solns, vinblastine

Preparation

Lyophilized powder

• Reconstitute with 1 mL of diluent; do not mix contents of vials reconstituted with different diluents together
• Reconstitute with either sterile water for injection (without preservative) or bacteriostatic water for injection
• Use reconstituted sargramostim vials within 6 hr following dilution for IV infusion; do not re-enter or reuse the vial
• Discard any unused portions

Solution

• For SC injection: Administer without further dilution

• For IV infusion

  • Dilute in 0.9% NaCl Final concentration of diluted sargramostim <10 mcg/mL, add albumin (Human) at a final concentration of 0.1% to 0.9% NaCl prior to addition of sargramostim to prevent adsorption to the components of the drug delivery system
  • To obtain a final concentration of 0.1% albumin (Human), add 1 mg Albumin (Human) per 1 mL 0.9% NaCl (eg, use 1 mL 5% albumin [Human] in 50 mL 0.9% NaCl)

SC Administration

Do not administer simultaneously with or within 24 hr preceding cytotoxic chemotherapy or radiotherapy or within 24 hr following chemotherapy

Sargramostim injection is formulated as a sterile solution preserved with 1.1% benzyl alcohol; injection should appear clear, colorless single-dose solution

Use only sargramostim for injection (lyophilized powder) reconstituted with sterile water for injection without preservatives when administering to neonates or infants to avoid benzyl alcohol exposure

IV Administration

Do NOT use an inline membrane filter for IV infusion In absence of compatibility and stability information, do not add other medication to infusion solutions containing sargramostim

Use only 0.9% NaCl to prepare IV infusion solutions

Visually inspect for particulate matter and discoloration prior to administration; if particulate matter is present or the solution is discolored, vial should not be used

Usual infusion over 2-4 hr, although longer, shorter or continuous infusions have been done

Storage

Unused vials

• Refrigerate at 2-8°C (36-46°F) in the original carton to protect from light; do not freeze or shake; do not use beyond the expiration date printed on the vial

Diluted solutions or reconstituted vials

• Refrigerate at 2-8°C (36-46°F) for up to 20 days once the vial has been entered; discard any remaining solution after 20 days; do not freeze