Sargramostim

Pronunciation: sar-GRUH-moe-STIM
Class: Colony stimulating factor

Trade Names

Leukine
- Powder for injection, lyophilized 250 mcg

Pharmacology

Supports survival, proliferation, and differentiation of hematopoietic progenitor cells; induces partially committed progenitor cells to divide and differentiate in granulocyte-macrophage pathways; activates mature granulocytes and macrophages; promotes proliferation of megakaryocytic and erythroid progenitors.

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Pharmacokinetics

Absorption

C max is 5 to 5.4 ng/mL, AUC is 640 to 680 ng/mL•min, and T max is 1 to 3 h postinjection.

Elimination

Mean Cl rate is 420 to 430 mL/min/m 2 and t ½ is 60 minutes.

Indications and Usage

Myeloid reconstitution after autologous bone marrow transplantation and after bone marrow transplantation failure or graft failure; promotion of early engraftment or engraftment delay; treatment of neutropenia associated bone marrow transplant; induction chemotherapy in acute myelogenous leukemia (AML); mobilization and following transplantation of autologous PBPC; and myeloid reconstitution after allogeneic BMT.

Unlabeled Uses

Increase WBC counts in patients with myelodysplastic syndromes and in AIDS patients receiving zidovudine; decrease nadir of leukopenia secondary to myelosuppressive chemotherapy; decrease myelosuppression in preleukemic patients; correct neutropenia in aplastic anemia patients; decrease transplantation-associated organ system damage.

Contraindications

Excessive leukemic myeloid blasts in bone marrow or peripheral blood; hypersensitivity to granulocyte-macrophage colony-stimulating factor, yeast-derived products, or any component of product; simultaneous administration with cytotoxic chemotherapy or radiotherapy, or administration 24 h preceding or following chemotherapy or radiotherapy.

Dosage and Administration

Bone Marrow Transplant Failure or Engraftment Delay
Adults

IV 250 mcg/m 2 /day for 14 days.

Myeloid Reconstitution After Bone Marrow Transplantation
Adults

IV 250 mcg/m 2 /day for 21 days (first dose given 2 to 4 h after transplant).

Neutrophil Recovery Following Chemotherapy in AML
Adults

IV 250 mcg/m 2 /day over a 4-h period starting around day 11 or 4 days following the completion of induction chemotherapy, if the day 10 bone marrow is hypoplastic with less than 5% blasts.

Mobilization of PBPC
Adults

IV 250 mcg/m 2 /day over 24 h or subcutaneously once daily. Continue at the same dose through the period of PBPC collection.

Postperipheral Blood Progenitor Cell Transplantation
Adults

IV 250 mcg/m 2 /day over 24 h or subcutaneously once daily beginning immediately following infusion of progenitor cells and continuing until an ANC of more than 1,500 for 3 consecutive days is attained.

General Advice

  • Reconstitute with 1 mL sterile water for injection (without preservative); do not re-enter vial. Discard any unused portion.
  • During reconstitution, direct sterile water at side of vial and gently swirl contents to prevent foaming during dissolution. Avoid excessive or vigorous agitation; do not shake.
  • Dilute in sodium chloride 0.9% injection to prepare IV infusion. If final concentration is less than 10 mcg/mL, add human albumin to make final concentration of 0.1% to saline before adding sargramostim to prevent absorption to drug delivery system. For final concentration of albumin 0.1%, add 1 mg human albumin/1 mL saline 0.9% injection. Give within 6 h after reconstitution. Discard any unused portion after 6 h.

Storage/Stability

Refrigerate sterile powder, reconstituted solution, and diluted solution for injection. Do not freeze or shake.

Drug Interactions

Antineoplastics

Do not use concomitantly.

Corticosteroids or lithium

May potentiate myeloproliferative effects of sargramostim.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Tachycardia.

CNS

Anxiety.

Dermatologic

Pruritus.

EENT

Eye hemorrhage.

GI

Abdominal pain; hematemesis; dysphagia.

Hematologic

Bilirubinemia.

Metabolic

Metabolic disorder; weight gain.

Respiratory

Pharyngitis.

Miscellaneous

Bone pain; arthralgia; malaise; chest pain.

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established. However, available data indicate that sargramostim does not exhibit any greater toxicity in children than in adults.

Hypersensitivity

Reactions are infrequent and have ranged from serious allergic or anaphylactic reactions to transient rashes and local injection site reactions.

Renal Function

Monitor patients closely and use with caution.

Hepatic Function

Monitor patients closely and use with caution.

Benzyl alcohol

Benzyl alcohol as a preservative has been associated with fatal “gasping syndrome” in premature infants.

Concomitant chemotherapy and radiotherapy

Since rapidly dividing cells are particularly sensitive to cytotoxic chemotherapy and radiotherapy, sargramostim should not be given within 24 h of chemotherapy or within 12 h of radiotherapy.

Growth factor potential

Administer with caution in patients with myeloid malignancies.

Cardiac patients

Monitor patients closely and use with caution.

Respiratory symptoms

It may be necessary to decrease rate of infusion by 50% if dyspnea occurs during administration.

Overdosage

Symptoms

Dyspnea, malaise, nausea, fever, rash, sinus tachycardia, headache and chills, increases in WBC no more than 200,000 cells/mm 3 .

Patient Information

  • Reassure patient that hypotension with flushing and syncope has rarely occurred with first dose.
  • Stress importance of follow-up for laboratory tests.
  • Instruct patient to inform health care provider if any of the following symptoms occur: dyspnea, malaise, nausea, fever, rash, rapid heart rate, headache, chills.

Copyright © 2009 Wolters Kluwer Health.

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