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Leukine

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Leukine

Side Effects
Interactions

SIDE EFFECTS

Autologous and Allogeneic Bone Marrow Transplantation

LEUKINE (sargramostim) is generally well tolerated. In three placebo-controlled studies enrolling a total of 156 patients after autologous BMT or peripheral blood progenitor cell transplantation, events reported in at least 10% of patients who received IV LEUKINE (sargramostim) or placebo were as reported in Table 6.

Table 6: Percent of AuBMT Patients Reporting Events

Events by Body System LEUKINE
(n=79)
Placebo
(n=77)
Events by Body System LEUKINE
(n=79)
Placebo
(n=77)
Body, General Metabolic, Nutritional Disorder
Fever 95 96 Edema 34 35
Mucous membrane dis order 75 78 Peripheral edema 11 7
Asthenia 66 51 Respiratory System
Malaise 57 51 Dyspnea 28 31
Sepsis 11 14 Lung disorder 20 23
Digestive System Hemic and Lymphatic System
Nausea 90 96 Blood dyscrasia 25 27
Diarrhea 89 82 Cardiovascular System
Vomiting 85 90 Hemorrhage 23 30
Anorexia 54 58 Urogenital System
GI disorder 37 47 Urinary tract disorder 14 13
GI hemorrhage 27 33 Kidney function abnormal 8 10
Stomatitis 24 29 Nervous System
Liver damage 13 14 CNS disorder 11 16
Skin and Appendages      
Alopecia 73 74      
Rash 44 38      

No significant differences were observed between LEUKINE (sargramostim) and placebo-treated patients in the type or frequency of laboratory abnormalities, including renal and hepatic parameters. In some patients with preexisting renal or hepatic dysfunction enrolled in uncontrolled clinical trials, administration of LEUKINE (sargramostim) has induced elevation of serum creatinine or bilirubin and hepatic enzymes (see WARNINGS). In addition, there was no significant difference in relapse rate and 24 month survival between the LEUKINE (sargramostim) and placebo-treated patients.

In the placebo-controlled trial of 109 patients after allogeneic BMT, events reported in at least 10% of patients who received IV LEUKINE (sargramostim) or placebo were as reported in Table 7.

Table 7: Percent of Allogeneic BMT Patients Reporting Events

Events by Body System LEUKINE
( n =53)
Placebo
(n=56)
Events by Body System LEUKINE
(n=53)
Placebo
(n=56)
Body, General Metabolic /Nutritional Disorders
Fever 77 80 Bilirubinemia 30 27
Abdominal pain 38 23 Hyperglycemia 25 23
Headache 36 36 Peripheral edema 15 21
Chills 25 20 Increased creatinine 15 14
Pain 17 36 Hypomagnesemia 15 9
Asthenia 17 20 Increased SGPT 13 16
Chest pain 15 9 Edema 13 11
Back pain 9 18 Increased alk . phosphatase 8 14
Digestive System Respiratory System
Diarrhea 81 66 Pharyngitis 23 13
Nausea 70 66 Epsitaxis 17 16
Vomiting 70 57 Dyspnea 15 14
Stomatitis 62 63 Rhinitis 11 14
Anorexia 51 57 Hemic and Lymphatic System
Dyspepsia 17 20 Thrombocytopenia 19 34
Hematemesis 13 7 Leukopenia 17 29
Dysphagia 11 7 Petechia 6 11
GI hemorrhage 11 5 Agranulo cytosis 6 11
Constipation 8 11 Urogenital System
Skin and Appendages Hematuria 9 21
Rash 70 73 Nervous System
Alopecia 45 45 Paresthesia 11 13
Pruritis 23 13 Insomnia 11 9
Musculo -skeletal System Anxiety 11 2
Bone pain 21 5 Laboratory Abnormalities*
Arthralgia 11 4 High glucose 41 49
Special Senses Low albumin 27 36
Eye hemorrhage 11 0 High BUN 23 17
Cardio vascular System Low calcium 2 7
Hypertension 34 32 High cholesterol 17 8
Tachycardia 11 9      
*Grade 3 and 4 laboratory abnormalities only. Denominators may vary due to missing laboratory measurements.

There were no significant differences in the incidence or severity of GVHD, relapse rates and survival between the LEUKINE (sargramostim) and placebo-treated patients.

Adverse events observed for the patients treated with LEUKINE (sargramostim) in the historically-controlled BMT failure study were similar to those reported in the placebo-controlled studies. In addition, headache (26%), pericardial effusion (25%), arthralgia (21%) and myalgia (18%) were also reported in patients treated with LEUKINE (sargramostim) in the graft failure study.

In uncontrolled Phase I/II studies with LEUKINE (sargramostim) in 215 patients, the most frequent adverse events were fever, asthenia, headache, bone pain, chills and myalgia. These systemic events were generally mild or moderate and were usually prevented or reversed by the administration of analgesics and antipyretics such as acetaminophen. In these uncontrolled trials, other infrequent events reported were dyspnea, peripheral edema, and rash.

Reports of events occurring with marketed LEUKINE (sargramostim) include arrhythmia, fainting, eosinophilia, dizziness, hypotension, injection site reactions, pain (including abdominal, back, chest, and joint pain), tachycardia, thrombosis, and transient liver function abnormalities.

In patients with preexisting edema, capillary leak syndrome, pleural and/or pericardial effusion, administration of LEUKINE may aggravate fluid retention (see WARNINGS). Body weight and hydration status should be carefully monitored during LEUKINE (sargramostim) administration.

Adverse events observed in pediatric patients in controlled studies were comparable to those observed in adult patients.

Acute Myelogenous Leukemia

Adverse events reported in at least 10% of patients who received LEUKINE (sargramostim) or placebo were as reported in Table 8.

Table 8: Percent of AML Patients Reporting Events

Events by Body System LEUKINE
( n =52)
Placebo
(n=47)
Events by Body System LEUKINE
(n=52)
Placebo
(n =47)
Body, General Metabolic/Nutritional Disorder
Fever (no infection) 81 74 Metabolic 58 49
Infection 65 68 Edema 25 23
Weight loss 37 28 Respiratory System
Weight gain 8 21 Pulmonary 48 64
Chills 19 26 Hemic and LymphaticSystem
Allergy 12 15 Coagulation 19 21
Sweats 6 13 Cardiovascular System
Digestive System Hemorrhage 29 43
Nausea 58 55 Hypertension 25 32
Liver 77 83 Cardiac 23 32
Diarrhea 52 53 Hypotension 13 26
Vomiting 46 34 Urogenital System
Stomatitis 42 43 GU 50 57
Anorexia 13 11 Nervous System
Abdominal distention 4 13 Neuro-clinical 42 53
Skin and Appendages Neuro-motor 25 26
Skin 77 45 Neuro-psych 15 26
Alopecia 37 51 Neuro-sensory 6 11

Nearly all patients reported leukopenia, thrombocytopenia and anemia. The frequency and type of adverse events observed following induction were similar between LEUKINE (sargramostim) and placebo groups. The only significant difference in the rates of these adverse events was an increase in skin associated events in the LEUKINE (sargramostim) group (p=0.002). No significant differences were observed in laboratory results, renal or hepatic toxicity. No significant differences were observed between the LEUKINE (sargramostim) and placebo-treated patients for adverse events following consolidation. There was no significant difference in response rate or relapse rate.

In a historically-controlled study of 86 patients with acute myelogenous leukemia (AML), the LEUKINE (sargramostim) 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 (sargramostim) treated patients had progressive increase in circulating monocytes and promonocytes and blasts in the marrow which reversed when LEUKINE (sargramostim) 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).15

Antibody Formation

Serum samples collected before and after LEUKINE (sargramostim) treatment from 214 patients with a variety of underlying diseases have been examined for immunogenicity based on the presence of antibodies. Neutralizing antibodies were detected in five of 214 patients (2.3%) after receiving LEUKINE (sargramostim) by continuous IV infusion (three patients) or subcutaneous injection (SC)(two patients) for 28 to 84 days in multiple courses. All five patients had impaired hematopoiesis before the administration of LEUKINE (sargramostim) and consequently the effect of the development of anti-GM-CSF antibodies on normal hematopoiesis could not be assessed. Antibody studies of 75 patients with Crohn's disease receiving LEUKINE (sargramostim) by subcutaneous injection with normal hematopoiesis and no other immunosuppressive drugs showed one patient (1.3%) with detectable neutralizing antibodies. The clinical relevance of the presence of these antibodies are unknown. Drug-induced neutropenia, neutralization of endogenous GM-CSF activity and diminution of the therapeutic effect of LEUKINE (sargramostim) secondary to formation of neutralizing antibody remain a theoretical possibility. Serious allergic and anaphylactoid reactions have been reported with LEUKINE (sargramostim) but the rate of occurrence of antibodies in such patients has not been assessed.

Read the Leukine (sargramostim) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Interactions between LEUKINE (sargramostim) and other drugs have not been fully evaluated. Drugs which may potentiate the myelo proliferative effects of LEUKINE (sargramostim) , such as lithium and corticosteroids, should be used with caution.

REFERENCES

15. Buchner T, Hiddemann W, Koenigsmann M, et al. Recombinant human granulocyte-macrophage colony stimulating factor after chemotherapy in patients with acute myeloid leukemia at higher age or after relapse. Blood 1991; 78(5):1190-1197.

Read the Leukine Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 8/12/2008
This monograph has been modified to include the generic and brand name in many instances.

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