Pegfilgrastim

Summary

Pegfilgrastim (Neulasta) is a long-acting PEGylated G-CSF used to reduce the incidence of infection, as manifested by febrile neutropenia, in patients receiving myelosuppressive chemotherapy. It is also indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation. Its extended half-life allows single-dose administration per chemotherapy cycle.

Mechanism of Action

Pegfilgrastim is a covalent conjugate of recombinant human G-CSF (filgrastim) with a 20 kDa polyethylene glycol molecule. It binds to the G-CSF receptor on hematopoietic progenitor cells, stimulating proliferation, differentiation, and activation of neutrophil precursors, thereby increasing circulating neutrophil counts. PEGylation reduces renal clearance, extending half-life to allow once-per-chemotherapy-cycle dosing.

Routes of Administration

Goals & Uses

• Reduction of chemotherapy dose delaysOncologic Supportive CareHigh
• Prevention of febrile neutropeniaInfection PreventionHigh
• Peripheral blood stem cell mobilizationHematology / TransplantationModerate
• Radiation injury mitigation (hematopoietic subsyndrome of acute radiation syndrome)Radiation Emergency MedicineModerate

Contraindications

• Hypersensitivity to filgrastim, pegfilgrastim, or PEGAllergy/ImmunologicHigh
• Administration within 14 days before and 24 hours after cytotoxic chemotherapyTiming/Drug InteractionHigh

Adverse Effects

• Sickle cell crisisHematologicRare
• Acute respiratory distress syndrome (ARDS)PulmonaryRare
• Injection site reactionsLocalCommon
• Splenic ruptureGastrointestinal/HematologicRare
• AortitisCardiovascularRare
• Bone pain / musculoskeletal painMusculoskeletalCommon

Drug Interactions

• Cytotoxic chemotherapy agentsHigh
• LithiumLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Patients with latex allergyAllergyRelative
• Pediatric patients < 45 kg receiving fixed 6 mg dosePediatricRelative
• Patients with sickle cell diseaseHematologic DisorderRelative

Regulatory Status

• European UnionApprovedApproved: Reduction in duration of neutropenia and incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancyApproved by EMA 2002. Multiple biosimilars approved including Ziextenzo, Pelgraz, Grasustek.
• United StatesApprovedApproved: To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs, To increase survival in patients acutely exposed to myelosuppressive doses of radiation (hematopoietic subsyndrome of acute radiation syndrome)Approved by FDA January 2002. Multiple biosimilars approved. Brand name Neulasta by Amgen.
• United KingdomApprovedApproved: Reduction in duration of neutropenia and incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancyApproved via MHRA; biosimilars available post-Brexit.

FDA approved in January 2002 (Neulasta, Amgen). Multiple biosimilars approved in the US and EU. On-body injector (Onpro kit) approved for subcutaneous self-administration. Biosimilars include Ziextenzo, Fylnetra, Stimufend, Udenyca, Nyvepria, and others.

Evidence & Sources

No sources recorded yet.