GRANIX SIDE EFFECTS

SIDE EFFECTS

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

• Fatal Splenic Rupture
• Acute Respiratory Distress Syndrome
• Serious Allergic Reactions
• Sickle Cell Disorders
• Glomerulonephritis
• Capillary Leak Syndrome
• Potential for Tumor Growth Stimulatory Effects on Malignant Cells
• Leukocytosis
• Simultaneous Use with Chemotherapy and Radiation Therapy Not Recommended
• Aortitis

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 to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Reactions In Adult Patients

GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian. In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of ≥10,000 x 10⁶/L after nadir was reached.

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-US-approved filgrastim product).

Leukocytosis

In clinical studies, leukocytosis (WBC counts > 100,000 x 10⁶/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies.

Additional Adverse Reactions

Other adverse reactions known to occur following administration of filgrastim products include myalgia, headache, vomiting, cutaneous vasculitis and thrombocytopenia.

Adverse Reactions In Pediatric Patients

GRANIX clinical trials safety data in pediatric patients are based upon the results of one single-arm clinical trial in 50 pediatric patients who received myelosuppressive chemotherapy for treatment of solid tumors without marrow involvement. In this study, GRANIX was administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy. The most common (>5%) adverse reactions included thrombocytopenia (34%), pyrexia (8%), pain in extremity (6%), headache (6%) and diarrhea (6%).

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to GRANIX with the incidence of antibodies to other products may be misleading.

Binding antibodies to GRANIX were detected using a validated bridging immunoassay. Anti-drug antibodies to tbo-filgrastim occurred in 1.4 % of 486 adult and pediatric patients. None of these patients had cross-reactive antibodies to the native G-CSF. All antibody responses were transient and of low titers.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of GRANIX. 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.

SRC: NLM .