Usage
Pegfilgrastim is prescribed to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. It is also indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation (hematopoietic subsyndrome of acute radiation syndrome). It belongs to the pharmacological classification of colony-stimulating factors (CSFs), specifically, it is a long-acting recombinant form of human granulocyte colony-stimulating factor (G-CSF). Pegfilgrastim stimulates the bone marrow to produce more neutrophils, a type of white blood cell crucial for fighting infections.
Alternate Names
Pegfilgrastim is also known as pegylated recombinant human G-CSF. Brand names include Neulasta, Neulasta Onpro, Fulphila, Fylnetra, Nyvepria, Stimufend, Udenyca, and Ziextenzo.
How It Works
Pharmacodynamics: Pegfilgrastim binds to specific cell surface receptors on hematopoietic progenitor cells in the bone marrow, stimulating their proliferation and differentiation into mature neutrophils. This leads to an increase in the number of circulating neutrophils, thus reducing the risk of infection.
Pharmacokinetics: Pegfilgrastim is administered subcutaneously. The pegylation (addition of polyethylene glycol) prolongs its half-life, allowing for once-per-chemotherapy-cycle dosing. It is primarily eliminated through neutrophil-mediated clearance, a self-regulating mechanism. As neutrophil counts rise, the clearance of pegfilgrastim increases, resulting in a rapid decline in serum concentrations. Metabolism and hepatic excretion are negligible. The pharmacokinetics in elderly patients is similar to that in adults. In pediatric patients, younger age groups may have higher exposure (AUC). Renal impairment does not significantly alter the pharmacokinetics of pegfilgrastim.
Mode of Action: Pegfilgrastim, like filgrastim, acts by binding to the G-CSF receptor, a transmembrane protein expressed on myeloid progenitor cells. Receptor binding triggers intracellular signaling pathways that promote neutrophil production.
Elimination Pathways: Primarily eliminated by neutrophil-mediated clearance, which increases with higher neutrophil counts. Metabolism and hepatic excretion are minimal.
Dosage
Standard Dosage
Adults: 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after cytotoxic chemotherapy administration.
Children: Dosing is weight-based:
- < 10 kg: 0.1 mg/kg subcutaneously once per chemotherapy cycle.
- 10-20 kg: 1.5 mg or 2 mg subcutaneously once per chemotherapy cycle.
- 21-30 kg: 2.5 mg subcutaneously once per chemotherapy cycle.
- 31-44 kg: 4 mg subcutaneously once per chemotherapy cycle.
- > 45 kg: 6 mg subcutaneously once per chemotherapy cycle.
Special Cases:
- Elderly Patients: No dose adjustment is generally necessary.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is expected.
- Patients with Comorbid Conditions: Monitor for adverse effects, particularly in patients with sickle cell disorders or pre-existing lung conditions.
Clinical Use Cases
Pegfilgrastim’s dosage remains consistent across various clinical settings involving myelosuppressive chemotherapy or radiation exposure. Specific scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations do not necessitate dosage adjustments beyond the standard recommendations.
Dosage Adjustments
No routine dose adjustments are recommended based on renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms.
Side Effects
Common Side Effects:
Bone pain (most common), pain in arms or legs, back pain.
Rare but Serious Side Effects:
Spleen rupture (characterized by left upper abdominal pain or left shoulder pain), acute respiratory distress syndrome (ARDS), serious allergic reactions (anaphylaxis), aortitis, alveolar hemorrhage, capillary leak syndrome, Sweet’s syndrome (acute febrile neutrophilic dermatosis).
Long-Term Effects:
Chronic complications from prolonged use are not well established.
Adverse Drug Reactions (ADR):
Spleen rupture, ARDS, serious allergic reactions, aortitis, alveolar hemorrhage, capillary leak syndrome, Sweet’s syndrome.
Contraindications
Hypersensitivity to pegfilgrastim or filgrastim. Caution in patients with sickle cell disorders, history of pulmonary issues, or pre-malignant myeloid conditions.
Drug Interactions
No specific drug interactions have been definitively identified. However, as it is primarily cleared by neutrophils, any drugs affecting neutrophil function could theoretically interact with pegfilgrastim. Administering pegfilgrastim 14 days before or 24 hours after cytotoxic chemotherapy is advised.
Pregnancy and Breastfeeding
Pregnancy Safety Category: Not assigned by the US FDA. Australian TGA category B3. Limited human data are available. Animal studies suggest potential for embryolethality and pregnancy loss at high doses. Not recommended during pregnancy or in women of childbearing potential not using contraception. Use only if the potential benefit outweighs the potential risk to the fetus.
It is unknown if pegfilgrastim is excreted in breast milk. Due to the potential for neonatal exposure, it is generally recommended to discontinue breastfeeding or the drug, considering the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Stimulates neutrophil production by binding to G-CSF receptors.
- Side Effects: Bone pain, injection site reactions; rarely, spleen rupture, ARDS, allergic reactions.
- Contraindications: Hypersensitivity to pegfilgrastim or filgrastim.
- Drug Interactions: None specifically identified.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 6 mg SC once per cycle for adults; weight-based dosing for children.
- Monitoring Parameters: Absolute neutrophil count (ANC), signs of infection, splenomegaly, respiratory function.
Popular Combinations
Used in conjunction with various chemotherapy regimens for non-myeloid malignancies.
Precautions
- General Precautions: Assess for hypersensitivity, sickle cell disease, and pre-existing pulmonary conditions.
- Specific Populations:
- Pregnant Women: Avoid unless clearly necessary.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: Monitor closely.
- Lifestyle Considerations: No specific restrictions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pegfilgrastim?
A: 6 mg subcutaneously once per chemotherapy cycle for adults. Pediatric dosing is weight-based, ranging from 0.1 mg/kg to 4 mg SC depending on the weight category.
Q2: How does Pegfilgrastim work?
A: It stimulates the bone marrow to produce neutrophils, thereby reducing the risk of febrile neutropenia in patients receiving chemotherapy.
Q3: What are the common side effects?
A: Bone pain is the most common side effect.
Q4: Are there any serious side effects?
A: Yes, though rare, serious side effects include spleen rupture, ARDS, and severe allergic reactions.
Q5: Can Pegfilgrastim be used during pregnancy?
A: It is generally not recommended during pregnancy unless the benefit clearly outweighs the risk.
Q6: Can it be used while breastfeeding?
A: It is not recommended during breastfeeding. Discontinue either breastfeeding or the drug.
Q7: How is Pegfilgrastim administered?
A: It is given as a subcutaneous injection.
Q8: How often is Pegfilgrastim administered?
A: Typically once per chemotherapy cycle, approximately 24 hours after chemotherapy administration.
Q9: What should be monitored in patients receiving Pegfilgrastim?
A: Monitor absolute neutrophil count (ANC), signs and symptoms of infection, and potential splenomegaly. Watch for respiratory symptoms, particularly in those at risk for ARDS.
