Does Leukine (sargramostim) cause side effects?

Leukine (sargramostim) is a colony-stimulating factor used to increase the number of white blood cells in patients with low white blood cell counts (neutropenia).

  • It is a man-made form of the naturally-occurring protein, granulocyte, macrophage-colony stimulating factor (GM-CSF).
  • GM-CSF is produced in the body by the immune system and stimulates the formation of white blood cells, including the granulocyte and the macrophage.
  • Granulocytes and macrophages take part in the inflammatory reaction.
  • They are responsible for detecting and destroying harmful bacteria and some fungi. 

Common side effects of Leukine include:

Serious side effects of Leukine include:

Drug interactions of Leukine include drugs that may potentiate Leukine's myeloproliferative effects, such as lithium and corticosteroids.

Tell your doctor if you are pregnant or plan to become pregnant before using Leukine; it may harm a fetus. There are no studies to determine if Leukine passes into breast milk. Consult your doctor before breastfeeding.

What are the important side effects of Leukine (sargramostim)?

The most common side effects while taking sargramostim are:

Leukine (sargramostim) side effects list for healthcare professionals

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

  • Hypersensitivity Reactions
  • Infusion Related Reactions
  • Risk of Severe Myelosuppression when Leukine Administered within 24 Hours of Chemotherapy or Radiotherapy
  • Effusions and Capillary Leak Syndrome
  • Supraventricular Arrhythmias
  • Leukocytosis
  • Potential Effect on Malignant Cells
  • Immunogenicity
  • Risk of Serious Adverse Reactions in Infants Due to Benzyl Alcohol Preservative

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Autologous Peripheral Blood Progenitor Cell (PBPC) And Bone Marrow Transplantation

Studies 301, 302 and 303 enrolled a total of 156 patients after autologous or allogeneic marrow or PBPC transplantation. In these placebo-controlled studies, pediatric and adult patients received once-daily intravenous infusions of Leukine 250 mcg/m² or placebo for 21 days.

In Studies 301, 302, and 303, there was no difference in relapse rate between the Leukine and placebo-treated patients. Adverse reactions reported in at least 10% of patients who received intravenous Leukine or at a rate that was at least 5% higher than the placebo arm are shown in Table 1.

Table 1: Adverse Reactions after Autologous Marrow or PBPC Transplantation in at Least 10% of Patients Receiving Intravenous Leukine or at Least 5% Higher than the Placebo Arm

Adverse Reactions by Body SystemLeukine
(n=79) %
Placebo
(n=77) %
Adverse Reactions by Body SystemLeukine
(n=79) %
Placebo
(n=77) %
Body, GeneralMetabolic, Nutritional Disorder
Fever9596Edema3435
Mucous membrane disorder7578Peripheral edema117
Asthenia6651Respiratory System
Malaise5751Dyspnea2831
Sepsis1114Lung disorder2023
Digestive SystemBlood and Lymphatic System
Nausea9096Blood dyscrasia2527
Diarrhea8982Cardiovascular Vascular System
Vomiting8590Hemorrhage2330
Anorexia5458Urogenital System
GI disorder3747Urinary tract disorder1413
GI hemorrhage2733Nervous System
Stomatitis2429CNS disorder1116
Liver damage1314
Skin and Appendages
Alopecia7374
Rash4438

Additional Clinically Significant Adverse Reactions Occurring In Less Than 10% Incidence

Investigations

Elevated creatinine, elevated bilirubin, elevate transaminases

Allogeneic Bone Marrow Transplantation

In the placebo-controlled trial of 109 patients after allogeneic BMT (Study 9002), acute graft-vshost disease occurred in 55% on the Leukine arm and in 59% on the placebo arm. Adverse reactions reported in at least 10% of patients who received IV Leukine or at a rate at least 5% higher than the placebo arm are shown in Table 2.

Table 2: Adverse Reactions after Allogeneic Marrow Transplantation in at Least 10% of Patients Receiving Intravenous Leukine or at Least 5% Higher than the Placebo Arm

Adverse Reactions by Body SystemLeukine
(n=53) %
Placebo
(n=56) %
Adverse Reactions by Body SystemLeukine
(n=53) %
Placebo
(n=56) %
Body, GeneralEye hemorrhage110
Fever7780Cardiovascular System
Abdominal pain3823Hypertension3432
Headache3636Tachycardia119
Chills2520Metabolic / Nutritional Disorders
Pain1736Bilirubinemia3027
Asthenia1720Hyperglycemia2523
Chest pain159Peripheral edema1521
Digestive SystemIncreased creatinine1514
Diarrhea8166Hypomagnesemia159
Nausea7066Increased SGPT1316
Vomiting7057Edema1311
Stomatitis6263Respiratory System
Anorexia5157Pharyngitis2313
Dyspepsia1720Epistaxis1716
Hematemesis137Dyspnea1514
Dysphagia117Rhinitis1114
GI hemorrhage115Blood and Lymphatic System
Skin and AppendagesThrombocytopenia1934
Rash7073Leukopenia1729
Alopecia4545Nervous System
Pruritus2313Paresthesia1113
Musculoskeletal SystemInsomnia119
Bone pain215Anxiety112
Arthralgia114Laboratory Abnormalities*
Special SensesHigh glucose4941
Low albumin3627
High BUN1723
* Grade 3 and 4 laboratory abnormalities only. Denominators may vary due to missing laboratory measures.

Acute Myeloid Leukemia Following Induction Chemotherapy

Nearly all patients in both arms developed leukopenia, thrombocytopenia, and anemia. Adverse reactions reported in at least 10% of patients who received Leukine or at least 5% higher than the placebo arm are reported in Table 3.

Table 3: Adverse Reactions after Treatment of AML in at Least 10% of Patients Receiving Intravenous Leukine or at Least 5% Higher than the Placebo Arm

Adverse Reactions by Body SystemLeukine
(n=52) %
Placebo
(n=47) %
Adverse Reactions by Body SystemLeukine
(n=52) %
Placebo
(n=47) %
Body, GeneralMetabolic / Nutritional Disorder
Fever (no infection)8174Metabolic Laboratory Abnormalities5849
Infection6568Edema2523
Weight loss3728Respiratory System
Chills1926Pulmonary toxicity4864
Allergy1215Blood and Lymphatic System
Digestive SystemCoagulation1921
Nausea5855Cardiovascular System
Liver toxicity7783Hemorrhage2943
Diarrhea5253Hypertension2532
Vomiting4634Cardiac2332
Stomatitis4243Hypotension1326
Anorexia1311Urogenital System
Skin and AppendagesGU abnormalities5057
Skin Reactions7745Nervous System
Alopecia3751Neuro-clinical4253
Neuro-motor2526
Neuro-psych1526

There was no significant difference between the arms in the proportion of patients achieving complete remission (CR; 69% in the Leukine group and 55% in the placebo group).

There was also no significant difference in relapse rates; 12 of 36 patients who received Leukine and five of 26 patients who received placebo relapsed within 180 days of documented CR (p=0.26). The study was not sized to assess the impact of Leukine treatment on response.

Graft Failure
  • In a historically controlled study of 86 patients with AML, the Leukine treated group exhibited an increased incidence of weight gain (p=0.007), low serum proteins, and prolonged prothrombin time (p=0.02) when compared to the control group.
  • Two Leukine treated patients had progressive increase in circulating monocytes and promonocytes and blasts in the marrow, which reversed when Leukine was discontinued.
  • The historical control group exhibited an increased incidence of cardiac events (p=0.018), liver function abnormalities (p=0.008), and neurocortical hemorrhagic events (p=0.025).
  • Headache (26%), pericardial effusion (25%), arthralgia (21%), and myalgia (18%) were also reported in patients treated with Leukine in the graft failure study.

Immunogenicity

  • As with all therapeutic proteins, there is the potential for immunogenicity with Leukine.
  • The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
  • Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, duration of treatment, concomitant medications, and underlying disease.
  • For these reasons, comparison of the incidence of antibodies to sargramostim in the studies described below with the incidence of antibodies in other studies or other products may be misleading.
  • In 214 patients with a variety of underlying diseases, neutralizing anti-sargramostim antibodies were detected in 5 patients (2.3%) after receiving Leukine by continuous IV infusion (3 patients) or SC injection (2 patients) for 28 to 84 days in multiple courses (as assessed by GMCSF dependent human cell-line proliferation assay).
  • All 5 patients had impaired hematopoiesis before the administration of Leukine, and consequently the effect of the development of antisargramostim antibodies on normal hematopoiesis could not be assessed.
  • Antibody studies of 75 patients with Crohn's disease (a disease for which Leukine is not indicated), with normal hematopoiesis and no other immunosuppressive drugs, receiving Leukine daily for 8 weeks by SC injection, showed 1 patient (1.3%) with detectable neutralizing anti-sargramostim antibodies (as assessed by GM-CSF dependent human cell-line proliferation assay).
  • In an experimental use trial where Leukine was given for an extended period, 53 patients with melanoma in complete remission (a disease for which Leukine is not indicated) received adjuvant therapy with Leukine 125 mcg/m² once daily (maximum dose 250 mcg) from day 1 to 14 every 28 days for 1 year.
  • Serum samples from patients assessed at day 0, 2 weeks, 1 month, and 5 and/or 12 months were tested retrospectively for the presence of anti-sargramostim antibodies.
  • Of 43 evaluable patients (having at least 3 timepoint samples post treatment), 42 (97.7%) developed anti-sargramostim binding antibody as assessed by ELISA and confirmed using an immunoprecipitation assay. Of these 42 patients, 41 had sufficient sample and were further tested:
    • 34 patients (82.9%) developed anti-sargramostim neutralizing antibodies (as determined by a cell based luciferase reporter gene neutralizing antibody assay);
    • 17 (50%) of these patients did not have a sustained pharmacodynamic effect of Leukine by day 155 as assessed by WBC counts.
    • This study provided limited assessment of the impact of antibody formation on the safety and efficacy of Leukine.
  • Serious allergic and anaphylactoid reactions have been reported with Leukine, but the rate of occurrence of antibodies in such patients has not been assessed.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Leukine in clinical trials and/or postmarketing surveillance. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Infusion related reactions including dyspnea, hypoxia, flushing, hypotension, syncope and/or tachycardia
  • Serious allergic reactions/hypersensitivity, including anaphylaxis, skin rash, urticaria, generalized erythema, and flushing
  • Effusions and capillary leak syndrome
  • Supraventricular arrhythmias
  • Leukocytosis including eosinophilia
  • Thromboembolic events
  • Pain, including chest, abdominal, back, and joint pain
  • Injection site reactions

What drugs interact with Leukine (sargramostim)?

Concomitant Use With Products That Induce Myeloproliferation

  • Avoid the concomitant use of Leukine and products that induce myeloproliferation (such as lithium and corticosteroids).
  • Such products may increase the myeloproliferative effects of Leukine.
  • Monitor patients receiving both Leukine and products that induce myeloproliferation frequently for clinical and laboratory signs of excess myeloproliferative effects.

Summary

Leukine (sargramostim) is a medication prescribed to increase the number of white blood cells in patients with low white blood cell counts (neutropenia). Common side effects of Leukine include stomach pain, mild to moderate fever, weakness, chills, headache, nausea, vomiting, diarrhea, rash, muscle and bone pain, shortness of breath, weight loss, leg and arm swelling, and injection site reactions. Leukine may harm a fetus. There are no studies to determine if Leukine passes into breast milk. Consult your doctor before breastfeeding.

Treatment & Diagnosis

Medications & Supplements

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 6/4/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
CONTINUE SCROLLING FOR RELATED SLIDESHOW