Sargramostim (Leukine) Injection is a recombinant granulocyte-macrophage colony-stimulating factor that is used to stimulate hematopoiesis. It is used as an immunostimulatory that is used in the recovery of leukocytes following chemotherapy.

Sargramostim (Leukine) Injection Uses:

• Acute myeloid leukemia (following induction chemotherapy):

  • To decrease time to neutrophil recovery and to minimize the incidence of severe, life-threatening, or fatal infections after induction chemotherapy in adults 55 years of age and older with acute myeloid leukemia (AML).

• Allogeneic bone marrow transplantation (myeloid reconstitution):

  • Acceleration of myeloid reconstitution in pediatric patients aged 2 years and older and adults undergoing allogeneic bone marrow transplantation from HLA-matched donors.

• Allogeneic or autologous bone marrow transplantation (treatment of delayed neutrophil recovery or graft failure):

  • Treatment of delayed or failed neutrophil recovery in pediatric patients aged 2 years or older and adults post allogeneic or autologous bone marrow transplantation.

• Autologous peripheral blood progenitor cell mobilization and collection:

  • Mobilization of hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis in adults with cancer undergoing autologous hematopoietic stem cell transplantation.

• Autologous peripheral blood progenitor cell and bone marrow transplantation:

  • To accelerate myeloid reconstitution following autologous peripheral blood progenitor cell transplantation or bone marrow transplantation in pediatric patients aged 2 years or older and adults with acute lymphoblastic leukemia (ALL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL).

• Hematopoietic radiation injury syndrome (acute):

  • Treatment to increase survival due to acute exposure to myelosuppressive radiation doses (hematopoietic syndrome of acute radiation syndrome [H-ARS]) in infants, children, adolescents, and adults.

• Off Label Use of Sargramostim in Adults:

  • Primary prophylaxis of neutropenia in patients receiving chemotherapy (outside transplant and AML) or who are at high risk for neutropenic fever

Sargramostim (Leukine) Dose in Adults

Sargramostim (Leukine) Injection Dose in the treatment of Acute myeloid leukemia (following induction chemotherapy):

• Adults ≥55 years:

  • IV: 250 mcg/m²/day (infused over 4 hours) starting approximately on day 11 or 4 days after completion of induction chemotherapy (if day 10 bone marrow is hypoplastic with <5% blasts), continue until ANC >1,500/mm³ for 3 consecutive days or a maximum of 42 days.
  • If ANC >20,000/mm³, withhold treatment or cut the dose by half.
  • Do not administer within 24 hours before or after chemotherapy or radiation therapy.
  • If the second cycle of chemotherapy is needed, administer ~4 days after the completion of chemotherapy if the bone marrow is hypoplastic with <5% blasts
  • Stop sargramostim immediately if leukemic regrowth occurs. If grade 3 or 4 adverse reactions occur, decrease dose by half or temporarily hold therapy until the reaction resolves.

Sargramostim (Leukine) Injection Dose in the treatment of Allogeneic bone marrow transplantation (myeloid reconstitution):

• IV: 250 mcg/m²/day (infused over 2 hours), begin 2 to 4 hours after the marrow infusion and at least 24 hours after chemotherapy or radiotherapy, do not start until the post marrow infusion ANC is <500/mm³, and continue until ANC >1,500/mm³ for 3 consecutive days.
• If WBC >50,000/mm³ or ANC >20,000/mm³, withhold treatment or cut the dose by half.
• If grade 3 or 4 adverse reactions occur, decrease dose by half or temporarily stop the dose until the reaction resolves.
• If blast cells appear or disease progresses, stop treatment.

Sargramostim (Leukine) Injection Dose in the treatment of Allogeneic or autologous bone marrow transplantation (treatment of delayed neutrophil recovery or graft failure):

• IV: 250 mcg/m²/day (infused over 2 hours) for 14 days; If engraftment has not occurred after 7 days off sargramostim, may repeat.
• If neutrophil recovery still has not occurred after 7 days off sargramostim, the third course of 500 mcg/m²/day for 14 days may be tried.
• If there is still no improvement, it is unlikely that a further increase in dose will be beneficial.
• If grade 3 or 4 adverse reactions occur, reduce the dose by half or temporarily withhold the dose until the reaction resolves.
• If blast cells appear or disease progresses, stop treatment immediately.
• If WBC >50,000/mm³ or ANC >20,000/mm³, withhold treatment or cut dose by half.

Sargramostim (Leukine) Injection Dose in the treatment of Autologous peripheral blood progenitor cell mobilization and collection:

• IV, SubQ: 250 mcg/m²/day IV (infused over 24 hours) or SubQ once daily;
• continue the same dose throughout the peripheral blood progenitor cell collection period.
• If WBC >50,000/mm³, reduce the dose by half.

Note:

• The optimal schedule for peripheral blood progenitor cell collection has not been established (usually begun 5 days after sargramostim and continued daily until protocol specified targets are achieved).
• If adequate numbers of progenitor cells are not collected, consider other mobilization therapy.

Sargramostim (Leukine) Injection Dose in the treatment of Autologous peripheral blood progenitor cell transplantation (myeloid reconstitution):

• IV, SubQ: 250 mcg/m²/day IV (infused over 24 hours) or SubQ once daily beginning immediately following infusion of progenitor cells; continue until ANC is >1,500/mm³ for 3 consecutive days.
• Do not administer within 24 hours before or after chemotherapy or radiation therapy.

Sargramostim (Leukine) Injection Dose in the treatment of Autologous bone marrow transplantation (myeloid reconstitution):

• IV: 250 mcg/m²/day (infused over 2 hours), begin 2 to 4 hours after the marrow infusion and at least 24 hours after chemotherapy or radiotherapy, do not start until the post marrow infusion ANC is <500/mm³, and continue until ANC >1,500/mm³ for 3 consecutive days.
• Do not administer within 24 hours before or after chemotherapy or radiation therapy.

Sargramostim (Leukine) Injection Dose in the treatment of Hematopoietic radiation injury syndrome (acute):

• SubQ: Adults >40 kg: 7 mcg/kg once daily;
• begin as soon as possible after suspected or confirmed exposure to radiation doses >2 (gray) Gy;
• do not delay sargramostim if CBC is not readily available;
• continue sargramostim until ANC remains >1,000/mm³ for 3 consecutive CBCs (obtain CBCs approximately every 3 days) or ANC more than 10,000/mm³ after radiation-induced nadir.

• Off-label dosing:

  • SubQ: 250 mcg/m /day;
  • continue until ANC >1,000/mm³.
  • ASCO guidelines recommend start within 24 hours of exposure of a dose ≥2 gray (Gy) and/or significant fall in absolute lymphocyte count, or for anticipated neutropenia <500/mm³ for ≥7 days.

Sargramostim (Leukine) Injection Dose in the treatment of Primary prophylaxis of neutropenia in patients receiving chemotherapy (outside transplant and AML) or who are at high risk for neutropenic fever (off-label):

• SubQ: 250 mcg/m²/day beginning at least 24 hours after chemotherapy administration; continue until ANC >1,500/mm³ for 3 consecutive days.
• May approximate dose to the nearest vial size.

Sargramostim (Leukine) Dose in Childrens

Sargramostim (Leukine) Injection Dose in the treatment of Neutrophil recovery (myeloid reconstitution):

Dose in the treatment of Allogeneic bone marrow transplantation:

• Infants ≥5 months and Children <2 years: Limited data available:

  • IV: 250 mcg/m²/day infused over 4 hours once daily;
  • begin on day 0 of the BMT and administer the first dose after marrow infusion completed and continue for 21 days;
  • stop if ANC >20,000/mm³

• Children ≥2 years and Adolescents:

  • IV: 250 mcg/m²/day infused over 2 hours;
  • begin 2 to 4 hours after the marrow infusion and at least 24 hours post-chemotherapy or radiotherapy;
  • do not start until the post marrow infusion ANC is <500/mm³ and continue until ANC >1,500/mm³ for 3 consecutive days
  • If WBC >50,000/mm³ or ANC >20,000/mm³, withhold treatment or decrease the dose by half.
  • If grade 3 or 4 adverse reactions occur, reduce dose by half or temporarily stop the dose until the reaction resolves.
  • If blast cells appear or disease progresses, stop treatment.

Sargramostim (Leukine) Injection Dose in the treatment of Autologous bone marrow transplantation:

• Children ≥2 years and Adolescents:

  • IV: 250 mcg/m²/day infused over 2 hours;
  • begin 2 to 4 hours after the marrow infusion and at least 24 hours after chemotherapy or radiotherapy;
  • do not start until the post marrow infusion ANC is <500/mm³ and continue until ANC >1,500/mm³ for 3 continuous days.
  • Do not administer within 24 hours before or after chemotherapy or radiation therapy.

Sargramostim (Leukine) Injection Dose in the treatment of Delayed neutrophil recovery or graft failure (allogeneic or autologous bone marrow transplantation):

• Children ≥2 years and Adolescents:

  • IV: 250 mcg/m²/day infused over 2 hours for 2 weeks;
  • may repeat a 14-day course if engraftment has not occurred after 7 days off sargramostim.
  • If no neutrophil recovery even after 1 week off sargramostim, the third course of 500 mcg/m²/day for 2 weeks may be attempted.
  • If there is still no improvement, it is unlikely that further dose escalation will be beneficial.
  • If WBC >50,000/mm³ or ANC >20,000/mm³, withhold treatment or reduce the dose by 50%.
  • If grade 3 or 4 adverse reactions occur, decrease dose by 50% or temporarily stop the dose until the reaction resolves.
  • If blast cells appear or disease progresses, stop treatment immediately.

Sargramostim (Leukine) Injection Dose in the treatment of acute hematopoietic radiation injury syndrome:

• Weight-directed dosing:

  • Infants, Children, and Adolescents:

    • Start as soon as possible after suspected or confirmed exposure to radiation doses >2 gray (Gy);
    • do not delay sargramostim if CBC is not readily available;
    • continue sargramostim until ANC remains >1,000/mm³ for 3 consecutive CBCs (obtain CBCs approximately every 3 days) or ANC exceeds 10,000/mm³ post radiation-induced nadir.
    • <15 kg:
      • SubQ: 12 mcg/kg once daily
    • 15 to 40 kg:
      • SubQ: 10 mcg/kg once daily
    • >40 kg:
      • SubQ: 7 mcg/kg once daily

• BSA-directed dosing: Limited data available:

  • Children and Adolescents:

    • SubQ: 250 mcg/m²/day;
    • continue until ANC >1,000/mm³.
    • Note: ASCO guidelines recommend starting within 24 hours of exposure of a dose ≥2 Gy and/or significant reduction in absolute lymphocyte count, or for anticipated neutropenia <500/mm³ for ≥7 days.

Sargramostim (Leukine) Injection Dose in the treatment of high-risk Neuroblastoma: Limited data available:

• Infants, Children, and Adolescents:

  • SubQ or IV: 250 mcg/m² once daily for 14 days during cycles 1, 3, and 5, starting 3 days before administration of dinutuximab (each cycle is 28 days) as part of a multi-drug regimen that includes dinutuximab, isotretinoin, and aldesleukin.

Sargramostim (Leukine) Injection Pregnancy Risk Category: C

• In animal reproduction studies, side effects were observed.
• Limited data are available on the use of this product in pregnant women.
• Some dosage forms might contain benzyl Alcohol (absorbed in pregnant women because of association with the gasping syndrome for premature infants).
• If you need to inject this medication, it is recommended that you use lyophilized powder with preservative-free sterilized water.

Use of Sargramostim during lactation

• It is unknown if breast milk contains sargramostim.
• Breastfeeding is not recommended for infants undergoing treatment. It should be stopped for at least two weeks after the last dose of sargramostim.

Dose in Kidney Disease:

No dosage adjustments provided by the manufacturer.

Dose in Liver disease:

No dosage adjustments provided by the manufacturer.

Side Effects of Sargramostim (Leukine) Injection:

• Cardiovascular:

  • Hypertension
  • Edema
  • Pericardial Effusion
  • Chest Pain
  • Peripheral Edema
  • Tachycardia

• Central Nervous System:

  • Malaise
  • Headache
  • Chills
  • Anxiety
  • Insomnia

• Dermatologic:

  • Skin Changes
  • Skin Rash
  • Pruritus

• Endocrine & Metabolic:

  • Elevated Serum Glucose
  • Weight Loss
  • Decreased Serum Albumin
  • Hyperglycemia
  • Hypomagnesemia

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal Pain
  • Anorexia
  • Hematemesis
  • Dysphagia
  • Gastrointestinal Hemorrhage

• Genitourinary:

  • Urinary Tract Infection

• Hepatic:

  • Hyperbilirubinemia

• Neuromuscular & Skeletal:

  • Asthenia
  • Ostealgia
  • Arthralgia
  • Myalgia

• Ophthalmic:

  • Retinal Hemorrhage

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Pharyngitis
  • Epistaxis
  • Dyspnea

• Miscellaneous:

  • Fever
  • Laboratory Test Abnormality

Less Common Side Effects of Sargramostim (Leukine) Injection:

• Immunologic:

  • Antibody development

• Respiratory:

  • Pleural effusion

Contraindications to Sargramostim (Leukine) Injection:

Hypersensitivity (history of a serious allergic reaction, including anaphylaxis) to human granulocyte-macrophage colony-stimulating factors such as sargramostim, yeast-derived products, or any component of the formulation.

Warnings and precautions

• Cardiovascular effects

  • Patients with previous cardiac arrhythmia have had supraventricular arrhythmia observed during sargramostim administration.
  • After discontinuing sargramostim, these arrhythmias were reversible.
  • Patients with a history of cardiac disease should be cautious.

• Effusions/capillary leak syndrome

  • There have been reports of edema, capillary leak syndrome, and pleural effusion.
  • Fluid retention may occur in patients who have preexisting pleural or pericardial effusions. However, fluid retention can be reversed by reducing or stopping Sargramostim.
  • Patients with fluid retention, pulmonary infection, or congestive cardiac failure should be cautious.
  • During sargramostim treatment, be sure to monitor your body weight and hydration.

• Hypersensitivity

  • Severe allergic and anaphylactic reactions were observed. If you experience an allergic reaction, stop immediately and seek treatment.
  • For severe allergic reactions, discontinue use permanently

• Immunogenicity:

  • Sargramostim treatment may result in neutralizing anti-drug antibody.
  • The duration of sargramostim treatment may influence the formation of antibodies. Therefore, it is important to use sargramostim only for the minimum amount of time.

• Infusion reactions

  • Infusion-related reactions may occur after IV administration of Sargramostim; symptoms include respiratory distress and hypoxia, flushing, hypotension and/or syncope.
  • Infusion reactions usually resolve after symptomatic treatment. They do not typically occur with subsequent doses in the same treatment cycle.
  • Watch out for signs and symptoms, especially if you have a preexisting condition.
  • Reduce the infusion rate to 50% if dyspnea occurs or you experience other acute symptoms.
  • Stop sargramostim injection if symptoms persist or worsen despite rate reduction.
  • You can continue IV infusions after an infusion reaction with careful observation.

• Leukocytosis

  • With sargramostim, white blood cell counts exceeding 50,000/mm were reported.
  • Complete blood counts (CBC) should be performed with differential at least twice a week.
  • The patient's clinical situation will determine whether treatment should be reduced or interrupted.
  • Within 3-7 days, blood counts that are high after stopping treatment will return to baseline or normal levels.
  • Dose reduction or discontinuation may be necessary if there is a rapid rise in blood count (ANC >20,000/mm3 and platelets >500,000/mm3).

Sargramostim: Drug Interaction

Monitoring parameters:

• CBC with differential (twice weekly during treatment); when monitoring for hematopoietic radiation injury syndrome, obtain CBCs every 3 days.
• vital signs.
• hydration status.
• weight.
• monitor for signs/symptoms of hypersensitivity or infusion-related reactions.

How to administer Sargramostim (Leukine) Injection?

It is administered as a subcutaneous injection or intravenous infusion. Administer at around the same time every day.

IV:

• Infuse over 2 hours, 4 hours, or 24 hours (indication-specific).
• An in-line membrane filter should NOT be used for intravenous administration.

SubQ:

• Administer subcutaneously into the thigh, abdomen (avoid waistline and within 2 inches of the navel), or the outer upper arm; change injection sites (injection sites should be at least 1 inch apart from prior injection sites).
• Do not inject into tender, bruised, red, or hard areas; avoid areas with scars or stretch marks. No further dilution needed.

Mechanism of action of Sargramostim (Leukine) Injection:

Sargramostim, a colony-stimulating factor, stimulates the proliferation, differentiation and functional activity neutrophils and monocytes.

The onset of action:

• Increase in WBC in 7 to 14 days

Duration:

• WBCs return to baseline within 1 to 2 weeks of discontinuing the drug

Bioavailability:

• SubQ: 75% (compared to IV)

Half-life elimination:

• Children 6 months to 15 years:
  • IV: Median: 1.6 hours; range: 0.9 to 2.5 hours;
  • SubQ: Median: 2.3 hours (0.3 to 3.8 hours) (Stute 1995)
• Adults: IV: 3.84 hours; SubQ: 1.4 hours

Time to peak, serum:

• IV: During or immediately after infusion;
• SubQ: 2.5 to 4 hours

International Brand Names of Sargramostim:

• Leukine
• Interberin

Sargramostim Brand Names in Pakistan:

No Brands Available in Pakistan.