Pegasta, the brand name for Pegfilgrastim, is a long-acting granulocyte colony-stimulating factor (G-CSF) analog. It is primarily used to prevent neutropenia, a condition characterized by a dangerously low count of neutrophils (a type of white blood cell), commonly induced by chemotherapy. Pegfilgrastim is a pegylated form of Filgrastim, designed to extend its half-life and improve patient compliance by reducing the frequency of administration.

Medical Uses

1. Prevention of Chemotherapy-Induced Neutropenia (CIN):

• Pegasta is administered as a supportive therapy to reduce the incidence, severity, and duration of neutropenia caused by myelosuppressive chemotherapy.
• By stimulating the production of neutrophils, it helps lower the risk of infection in cancer patients undergoing chemotherapy.

2. Mobilization of Hematopoietic Stem Cells:

• Pegfilgrastim is sometimes used in conjunction with other therapies to mobilize hematopoietic stem cells for autologous or allogeneic stem cell transplantation.

3. Febrile Neutropenia Prophylaxis:

• Reduces the risk of febrile neutropenia, a serious complication characterized by fever and infection in neutropenic patients.

Mechanism of Action

Pegfilgrastim works by mimicking the natural human granulocyte colony-stimulating factor (G-CSF). It stimulates the bone marrow to produce more neutrophils, a critical component of the immune system that helps fight infections.

1. G-CSF Receptor Binding:

• Pegfilgrastim binds to specific G-CSF receptors on hematopoietic precursor cells in the bone marrow.
• This binding stimulates the proliferation, differentiation, and activation of neutrophil precursors.

2. Extended Circulation:

• The pegylation process (attachment of polyethylene glycol) slows renal clearance, resulting in a longer half-life compared to Filgrastim.
• Pegfilgrastim is metabolized by neutrophils, which ensures its activity persists until neutrophil counts return to normal.

Pegasta(Pegfilgrastim) is a groundbreaking therapy in oncology supportive care, providing an effective solution to chemotherapy-induced neutropenia with its convenient single-dose regimen. Its pegylated formulation ensures prolonged activity, improved patient adherence, and comparable efficacy to daily Filgrastim injections. While generally well-tolerated, close monitoring is essential to manage rare but serious adverse effects such as splenic rupture and ARDS. Adfill represents a critical advancement in supportive oncology, significantly improving the quality of life and outcomes for cancer patients undergoing chemotherapy.

Advantages of Pegfilgrastim Over Filgrastim

Extended Half-Life:

• Pegfilgrastim requires a single dose per chemotherapy cycle, compared to daily Filgrastim injections.

Improved Patient Compliance:

• Reduced dosing frequency enhances convenience and adherence.

Similar Efficacy:

• Pegfilgrastim offers comparable or superior efficacy to Filgrastim in reducing chemotherapy-induced neutropenia.

Reduced Healthcare Burden:

• Fewer hospital visits due to its single-dose regimen.

Pharmacokinetics

Absorption and Distribution:

• Administered subcutaneously, Pegfilgrastim is slowly absorbed into systemic circulation.

Half-Life:

• Its half-life is approximately 15 to 80 hours, depending on neutrophil count.
• As neutrophil levels increase, Pegfilgrastim is cleared faster due to receptor-mediated degradation.

Metabolism:

• Pegfilgrastim is primarily metabolized by neutrophils.

Excretion:

• Degraded products are cleared via normal metabolic pathways.

Administration and Dosage

Formulation:

• Pegasta is available as a single-use prefilled syringe for subcutaneous injection.

Dosage:

• The recommended dose is 6 mg administered once per chemotherapy cycle.
• It is typically given 24-72 hours after the completion of chemotherapy to allow sufficient time for cytotoxic agents to clear from the body.

Special Populations:

• Pediatrics: Dosage is weight-based in pediatric patients.
• Elderly: No specific dose adjustment is required for elderly patients.

Contraindications

• Known hypersensitivity to Pegfilgrastim, Filgrastim, or any excipients in the formulation.
• Patients with a history of serious allergic reactions to G-CSF products.

Precautions

Splenic Rupture:

• Rare but serious cases of splenic rupture have been reported. Patients with left upper abdominal pain or shoulder tip pain should be evaluated immediately.

Acute Respiratory Distress Syndrome (ARDS):

• Pulmonary complications, including ARDS, have been observed in rare cases. Symptoms include cough, fever, and difficulty breathing.

Bone Pain:

• Commonly reported, but generally mild and manageable with analgesics.

Leukocytosis:

• Excessive elevation of white blood cell count (leukocytosis) may occur, though it is usually asymptomatic.

Capillary Leak Syndrome:

• Symptoms include hypotension, hypoalbuminemia, and edema. Immediate medical intervention is required.

Monitoring Requirements:

• Neutrophil counts should be regularly monitored to evaluate treatment response and detect potential leukocytosis.

Adverse Effects

Common Side Effects:

• Bone pain (most common).
• Injection site reactions (e.g., redness, swelling, or itching).
• Headache.
• Fatigue.
• Nausea.

Serious Adverse Effects:

Splenic Rupture:

• Symptoms include sudden left upper abdominal pain or referred pain to the shoulder.

ARDS:

• Dyspnea, hypoxia, and bilateral pulmonary infiltrates.

Anaphylaxis:

• Severe allergic reactions may require discontinuation and immediate treatment.

Capillary Leak Syndrome:

• Life-threatening condition requiring prompt medical attention.

Drug Interactions

Myelosuppressive Chemotherapy:

• Pegfilgrastim should not be administered within 14 days before or 24 hours after chemotherapy to avoid overlapping toxicities.

Radiation Therapy:

• May increase the risk of pulmonary toxicity.

Lithium:

• Co-administration may enhance neutrophil release, although clinical significance is uncertain.

Benefits Over Non-Pegylated G-CSF

Convenience:

• Single-dose administration improves patient convenience and compliance.

Prolonged Action:

• Sustains neutrophil levels for an extended period, reducing the need for frequent monitoring.

Fewer Side Effects:

• Reduced incidence of repeated injection-site reactions.