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(See WARNINGS, Splenic Rupture, Acute Respiratory Distress Syndrome (ARDS), Allergic Reactions, and Sickle Cell Disorders.)

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Neulasta® (pegfilgrastim) cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to Neulasta® (pegfilgrastim) use and for approximating rates.

The data described below reflect exposure to Neulasta® (pegfilgrastim) in 932 patients. Neulasta® (pegfilgrastim) was studied in placebo- and active-controlled trials (n = 467, and n = 465, respectively). The population encompassed an age range of 21 to 88 years. Ninety-two percent of patients were female. The ethnicity of the patients was as follows: 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with solid tumors (breast [n = 823], lung and thoracic tumors [n = 53]) or lymphoma (n = 56) received Neulasta® (pegfilgrastim) after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.

In the placebo-controlled trial, bone pain occurred at a higher incidence in Neulasta® (pegfilgrastim) - treated patients as compared to placebo-treated patients. The incidence of other

commonly reported adverse events were similar in the Neulasta® (pegfilgrastim) - and placebo-treated patients, and were consistent with the underlying cancer diagnosis and its treatment with chemotherapy. The data in Table 2 reflect those adverse events occurring in at least 10% of patients treated with Neulasta® (pegfilgrastim) in the placebo-controlled study.

Table 2. Adverse Events Occurring in ≥ 10%^a of Patients in the Placebo-Controlled Study

In the active controlled studies, common adverse events occurred at similar rates and severities in both treatment arms (Neulasta® (pegfilgrastim) , n = 465; Filgrastim, n = 331). These adverse experiences occurred at rates between 72% and 15% and included: nausea, fatigue, alopecia, diarrhea, vomiting, constipation, fever, anorexia, skeletal pain, headache, taste perversion, dyspepsia, myalgia, insomnia, abdominal pain, arthralgia, generalized weakness, peripheral edema, dizziness, granulocytopenia, stomatitis, mucositis, and neutropenic fever.

Bone Pain

The analysis of bone pain described below is based on a composite analysis using multiple, related, adverse event terms.

In the placebo-controlled study, the incidence of bone pain was 57% in Neulasta® (pegfilgrastim) -treated patients compared to 50% in placebo-treated patients. Bone pain was generally reported to be of mild-to-moderate severity.

Among patients experiencing bone pain, approximately 37% of Neulasta® (pegfilgrastim) - and 31% of placebo-treated patients utilized non-narcotic analgesics and 10% of Neulasta® (pegfilgrastim) - and 9% of placebo-treated patients utilized narcotic analgesics.

In the active-controlled studies, the use of non-narcotic and narcotic analgesics in association with bone pain was similar between Neulasta® (pegfilgrastim) - and Filgrastim-treated patients. No patient withdrew from study due to bone pain.

Laboratory Abnormalities

In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with non-myeloid malignancies receiving Neulasta® (pegfilgrastim) . Leukocytosis was not associated with any adverse effects.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.

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 sample handling, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Neulasta® (pegfilgrastim) with the incidence of antibodies to other products may be misleading.

Cytopenias resulting from a neutralizing antibody response to exogenous growth factors have been reported on rare occasions in patients treated with other recombinant growth factors. There is a theoretical possibility that an antibody directed against pegfilgrastim may cross-react with endogenous G-CSF, resulting in immune-mediated neutropenia. This has not been observed in clinical studies of Neulasta® (pegfilgrastim) .

Postmarketing Experience

The following adverse reactions have been identified during postapproval of Neulasta® (pegfilgrastim) . 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.

• splenic rupture (see WARNINGS: Splenic Rupture)
• acute respiratory distress syndrome (ARDS) (see WARNINGS: Acute Respiratory Distress Syndrome)
• allergic reactions (see WARNINGS: Allergic Reactions)
• sickle cell crisis (see WARNINGS: Sickle Cell Disorders)
• injection site reactions (pain, induration, and local erythema)
• generalized erythema and flushing
• Sweet's syndrome (acute febrile neutrophilic dermatosis)

No formal drug interaction studies between Neulasta® (pegfilgrastim) and other drugs have been performed. Drugs such as lithium may potentiate the release of neutrophils; patients receiving lithium and Neulasta® (pegfilgrastim) should have more frequent monitoring of neutrophil counts.

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.

Last reviewed on RxList: 6/27/2008
This monograph has been modified to include the generic and brand name in many instances.