2015–2020 Biologics Monographs 2 – Proteins (BIO2) Expert Committee Wednesday – Thursday, September 27-28, 2017. USP – U.S., Rockville. Agenda _____ Goals and Anticipated Outcomes. To update EC’s 2015-2020 work plan 2. To update new proposals, revision proposals and EP activities 3.

Biosynthetic hematopoietic agent that principally affects the proliferation and differentiation of neutrophils within the bone marrow; a covalent conjugate of filgrastim (a human granulocyte colony-stimulating factor [G-CSF]) and monomethoxypolyethylene glycol (PEG). Uses for Pegfilgrastim Chemotherapy-induced Neutropenia Reduction of the risk of infectious complications (as manifested by febrile neutropenia) in patients with nonmyeloid malignancies receiving myelosuppressive antineoplastic therapy that is associated with a clinically important risk of severe neutropenia with fever. Efficacy comparable to that of filgrastim, but requires less frequent administration. Efficacy not established in patients receiving antineoplastic therapy associated with delayed myelosuppression (e.g., nitrosourea derivatives, mitomycin), in those receiving myelosuppressive doses of antimetabolites (e.g., cytarabine, fluorouracil), or in those receiving radiation therapy. (See Specific Drugs under Interactions.) Pegfilgrastim Dosage and Administration Administration Sub-Q Administration Administer by sub-Q injection. Do not shake the injection. Dosage Dosage modification based on body weight not required.

Adults Chemotherapy-induced Neutropenia Sub-Q 6 mg administered once per chemotherapy cycle. Do not administer during the 14 days before or 24 hours after administration of cytotoxic chemotherapy. (See Specific Drugs under Interactions.) Cautions for Pegfilgrastim Contraindications • Known hypersensitivity to pegfilgrastim, filgrastim, any ingredient in the formulation, or proteins derived from Escherichia coli. Empire earth 2 full version highly compressed psp download. Warnings/Precautions Warnings Splenic Rupture Splenic rupture (including fatalities) reported rarely following administration of filgrastim for peripheral blood progenitor cell (PBPC) mobilization in both healthy donors and patients with cancer.

Do not use pegfilgrastim for this purpose. Evaluate patients experiencing left upper abdominal or shoulder tip pain for the presence of splenomegaly or splenic rupture.

Respiratory Effects Adult respiratory distress syndrome (ARDS) reported in neutropenic patients with sepsis receiving filgrastim. Evaluate neutropenic patients receiving pegfilgrastim for the presence of ARDS if fever, lung infiltrates, or respiratory distress develops. If ARDS occurs, provide appropriate treatment for ARDS and discontinue or withhold pegfilgrastim until ARDS has resolved. Sickle Cell Disease Severe sickle cell crisis reported in patients with sickle cell disease (specifically, homozygous sickle cell anemia, sickle cell-hemoglobin C disease, and sickle cell-β+-thalassemia disease) receiving filgrastim for PBPC mobilization or following chemotherapy. Use pegfilgrastim with caution in patients with sickle cell disease and only after carefully considering potential risks and benefits. Patients with sickle cell disease should be well hydrated and monitored for sickle cell crisis during therapy. If severe sickle cell crisis occurs, initiate supportive care and consider interventions (e.g., therapeutic red blood cell exchange transfusion) to ameliorate the underlying event.

Sensitivity Reactions Possible sensitivity reactions (e.g., anaphylaxis, rash, urticaria). If serious sensitivity reactions occur, immediate medical intervention and drug discontinuance are required. General Precautions Chemotherapy and Radiation Therapy Safety and efficacy of concomitant radiation therapy not established. Administration during the 14 days before or 24 hours after administration of cytotoxic chemotherapy is not recommended.

(See Specific Drugs under Interactions.) Effect on Malignant Cells The possibility that pegfilgrastim could act as a growth factor for any tumor type has not been excluded; some tumor cells (including some lines of myeloid, T-lymphoid, lung, head and neck, and bladder tumor cells) shown to have receptors for G-CSF. Not studied in patients with myeloid malignancies or myelodysplastic syndrome (MDS). Immunogenicity Development of binding antibodies to filgrastim or pegfilgrastim reported in a small proportion of patients receiving these drugs; the nature and specificity of these antibodies have not been adequately studied. Possibility exists that an antibody directed against pegfilgrastim could cross-react with endogenous G-CSF, resulting in immune-mediated neutropenia. Laboratory Monitoring Perform CBC and platelet counts prior to administration of chemotherapy. Regular monitoring of hematocrit and platelet count also recommended. Specific Populations Pregnancy Category C.