Pegfilgrastim (udenyca, Neulasta) and biosimilar drugs are the pegylated forms of recombinant human granulocyte colony-stimulating factor analog of filgrastim that stimulates the production and differentiation of white blood cells.

Indications of Pegfilgrastim:

• Acute hematopoietic radiation injury syndrome (Neulasta only):

  • It is effective in increasing survival in patients acutely exposed to myelosuppressive doses of radiation.

• Prevention of chemotherapy-induced neutropenia (Neulasta and pegfilgrastim biosimilars):

  • It is helpful in decreasing the incidence of infection (as manifested by febrile neutropenia), in patients with non-myeloid malignancies receiving myelosuppressive cancer chemotherapy associated with a clinically significant incidence of febrile neutropenia.

Limitation of use:

• Pegfilgrastim products are not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplant.

Pegfilgrastim dose in adults:

Note:

Fulphila (pegfilgrastim-jmdb) and Udenyca (pegfilgrastim-cbqv) are approved as biosimilars to Neulasta (pegfilgrastim). In Canada, Lapelga is approved as a biosimilar to Neulasta (pegfilgrastim).

Pegfilgrastim Dose in the Prevention of chemotherapy-induced neutropenia (Neulasta and pegfilgrastim biosimilars):

• 6 mg S/C once per chemotherapy cycle, beginning at least 24 hours after completion of chemotherapy.

Note:

• Do not administer in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Pegfilgrastim dose in the treatment of acute Hematopoietic radiation injury syndrome (Neulasta only):

• 6 mg S/C once weekly for 2 doses.
• Baseline CBC should be checked before administration, but pegfilgrastim use should not be delayed if a CBC is not readily obtainable.
• Administer the first dose as soon as possible after suspected or confirmed radiation exposure greater than 2 gray (Gy).
• The second dose should be given 1 week after the first dose.

Pegfilgrastim Dose in Childrens

Pegfilgrastim Dose in the prevention of Chemotherapy-induced neutropenia:

• Administer once per chemotherapy cycle, beginning at least 24 hours after completion of chemotherapy.
• Do not administer in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

• Note:

  • The manufacturer does not recommend direct administration of doses <6 mg using the prefilled syringe as the graduation marks necessary for accurate measurement of doses other than 6 mg are not present on it.
  • Manufacturer weight-band dosing is comparable to 0.1 mg/kg/dose.

  • <10 kg:

    • 0.1 mg/kg (0.01 mL/kg) SubQ

  • 10 to 20 kg:

    • 1.5 mg (0.15 mL) SubQ

  • 21 to 30 kg:

    • 2.5 mg (0.25 mL) SubQ

  • 31 to <45 kg:

    • 4 mg (0.4 mL) SubQ

  • ≥45 kg:

    • SubQ: 6 mg (0.6 mL)

Pegfilgrastim dose in the treatment of acute hematopoietic radiation injury syndrome:

• Baseline CBC should be checked before administration, but pegfilgrastim use should not be delayed if a CBC is not readily obtainable.
• Administer 2 doses; the first dose as soon as possible after suspected or confirmed radiation exposure greater than 2 gray (Gy) and administer the second dose 1 week after the first dose.
• Note:
  • The manufacturer does not recommend direct administration of doses <6 mg using the prefilled syringe as the graduation marks necessary for accurate measurement of doses other than 6 mg are not present on it.
  • Manufacturer weight-band dosing is comparable to 0.1 mg/kg/dose.

  • <10 kg:

    • 0.1 mg/kg (0.01 mL/kg) SubQ

  • 10 to 20 kg:

    • 1.5 mg (0.15 mL) SubQ

  • 21 to 30 kg:

    • 2.5 mg (0.25 mL) SubQ

  • 31 to <45 kg:

    • 4 mg (0.4 mL) SubQ

  • ≥45 kg:

    • 6 mg (0.6 mL)SubQ

Pegfilgrastim Pregnancy Risk Category: C

• Some cases of adverse results in animal reproduction were found.

Pegfilgrastim use during breastfeeding:

• It is unknown if breast milk secretes pegfilgrastim.
• The manufacturer states that the decision to breastfeed during therapy is based on the risks and benefits to the infant as well as the benefits to the mother.

Pegfilgrastim Dose adjustment in renal disease:

There are no dosage adjustments provided in the manufacturer’s labeling; however, in a pharmacokinetic study, renal dysfunction had no effect on pegfilgrastim pharmacokinetics.

Pegfilgrastim Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

See Warnings and Precautions also.

Adverse reaction incidences based on studies including concomitant docetaxel therapy.

Common Side Effects of Pegfilgrastim:

• Neuromuscular & skeletal:
  • Ostealgia

Rare Side Effects of Pegfilgrastim:

• Neuromuscular & skeletal:
  • Limb pain

Contraindications to Pegfilgrastim and Biosimilars:

• Hypersensitivity (severe allergic reaction) to pegfilgrastim or filgrastim or any other component of the formulation
• Hypersensitivity to E. coli-derived protein.

Warnings and precautions

• Aortitis

  • Pegfilgrastim can cause aortitis in early therapy. This is usually the first week of treatment.
  • Aortitis is characterized by generalized fever, abdominal pain and malaise, as well as increased inflammatory markers (e.g, creactive protein, WBC count).
  • Patients who experience aortitis may be at risk.
  • Pegfilgrastim should not be used if there is suspicion of aortitis.

• Capillary leak syndrome

  • Capillary leak syndrome can be caused by granulocyte colony-stimulating factor. It may present with hypotension, hypoalbuminemia and edema.
  • Capillary leak syndrome episodes can vary in severity and frequency.
  • Capillary leak syndrome may require intensive care and close monitoring.
  • If treatment is not received promptly, it can be fatal.

• Hypersensitivity

  • Anaphylaxis or fatal allergic reactions can occur during treatment. These symptoms may recur in a few days.
  • It should be discontinued permanently in the event of severe reactions.
  • Patients who have had a history of severe allergic reactions to filgrastim or pegfilgrastim products are not advised to use it. It can cause skin rash, urticaria and generalized erythema as well as flushing.

• Nephrotoxicity:

  • Glomerulonephritis can be diagnosed as the presence of azotemia and microscopic or macroscopic hemoturia. Proteinuria and renal biopsy may also occur. The treatment can be stopped or dose reduced.
  • It is important to monitor the renal function regularly.

• Hematologic effects

  • Pegfilgrastim has been shown to cause leukocytosis (WBC >=100,000./mm3). Therefore, strict monitoring of blood counts during therapy is required.

• Syndrome of respiratory distress

  • It can also lead to acute respiratory distress syndrome (ARDS).
  • Patients may present with pulmonary symptoms like fever, pulmonary infiltrates or respiratory distress for ARDS.
  • If ARDS is suspected, Pegfilgrastim products must be immediately withdrawn.

• Splenic rupture

  • Pegfilgrastim can cause severe bleeding, which could be fatal. Patients complaining of pain in the left upper abdomen or shoulder should be evaluated.

• Sickle cell disease:

  • Patients with sickle cells may develop life-threatening sickle disease if they are treated with pegfilgrastim products.

Pegfilgrastim (including biosimilars of pegfligrastim): Drug Interaction

Monitoring parameters:

• Complete blood count (with differential) and platelet count should be checked before chemotherapy and as clinically necessary for observing chemotherapy-induced neutropenia.
• CBC should be checked at baseline (do not delay administration if CBC not readily available);
• Estimate absorbed radiation dose in case of hematopoietic radiation injury syndrome.
• Monitor fever
• Signs/symptoms of allergic reactions, aortitis, glomerulonephritis (azotemia, hematuria, proteinuria).
• Capillary leak syndrome symptoms including hypotension, hypoalbuminemia, edema, and hemoconcentration.
• Observing for left upper abdominal pain, shoulder tip pain, or splenomegaly
• Monitoring for pulmonary infiltrates, and respiratory distress.
• Monitor for sickle cell crisis in patients with sickle cell anemia.

On-body injector:

• Monitor for evidence of device malfunction.

How to administer Pegfilgrastim?

SubQ:

• It should be given subcutaneously.
• A fixed-dose of 6 mg is not recommended in infants, children, or adolescents <45 kg.
• Pegfilgrastim can be given via prefilled syringes for manual subcutaneous administration or as a kit for use with the On-body injector (Neulasta).
• The manufacturer does not recommend direct administration of doses <6 mg using the prefilled syringe as the graduation marks necessary for accurate measurement of doses other than 6 mg are not present on it. use caution to avoid dosing errors.

Manual subcutaneous administration:

• It should be injected subcutaneously on the outer upper arms, abdomen (except within 2 inches of the navel), front middle thigh, or upper outer buttocks.
• Before injection, the prefilled syringe should be allowed for at least half-hour to reach room temperature.
• In order to prevent accidental needle sticks, needle guard should be activated.

The on-body injector (Neulasta):

• The On-body injector (OBI) should be filled by a health care provider before applying to the patient’s skin.
• It should be injected into the non-irritated skin on the back of the arm or abdomen (only use the back of the arm if the caregiver is available to monitor OBI injection status).
• The OBI system will deliver pegfilgrastim over 45 minutes approximately 27 hours after application.
• The OBI delivery system can be given on the same day of chemotherapy for at least 24 hours after chemotherapy administration.
• Before dosage, the OBI should be kept dry for 3 hours.
• Any additional materials can dislodge the cannula and result in a missed or incomplete dose, therefore they should not be used to hold the OBI.
• A health-care provider should be notified immediately by the patient regarding any OBI malfunctions or undesirable effects.
• Any OBI leakage can lead to a missed dose,manual subcutaneous injection should be given as soon as possible in case of any missed dose.
• OBI should not be exposed to oxygen-rich environments (eg, hyperbaric chambers), MRI, x-ray (including airport x-ray), CT-scan, ultrasound, or radiation treatment (may damage injector system).
• OBI should be kept at least 4 inches away from electrical equipment, including cell phones, cordless phones, microwaves, and other common appliances (injector may not work properly).
• Patients with acute hematopoietic radiation injury syndrome are not recommended to use OBI.
• The OBI has not been studied in pediatric patients. Refer to prescribing information for further details.

Ayy loss during delivery can be replaced by overfill in the prefilled syringe provided in the OBI kit. It is not recommended for manual subcutaneous injection as it will result in higher than the recommended dose. A lower than recommended dose can result due to the use of prefilled syringe intended for manual injection to fill the OBI. The OBI is only for use with pegfilgrastim, delivery of other medications is not recommended.

Mechanism of action of Pegfilgrastim:

• Pegfilgrastim stimulates the maturation, activation and production of neutrophils, resulting in increased neutrophil migration.
• Pegfilgrastim has a longer duration of action than filgrastim, and a lower renal clearance.

Half-life elimination: SubQ:

Pediatrics (100 mcg/kg dose):

• 0 to 5 years: 30.1 ± 38.2 hours.
• 6 to 11 years: 20.2 ± 11.3 hours;.
• 12 years and older: 21.2 ± 16 hours.

Adults:

• 15 to 80 hours.
• Pharmacokinetics (in adults) were comparable between manual subcutaneous injection and the On-body injector system.

Excretion:

• Primarily through binding to neutrophils

International Brand Names of Pegfilgrastim:

• Fulphila
• Neulasta
• Neulasta Onpro
• Udenyca
• Lapelga
• Neulasta
• G-Lasta
• Imupeg
• Neulasta
• Neulastim
• Neulastym
• Neupopeg
• PEG Neutropine
• Peg-Grafeel
• Pegasta
• Pegfilgrast
• Peglasta
• Pegneufil
• Pegstim
• Ristempa

Pegfilgrastim Brand Names in Pakistan:

No Brands Available in Pakistan.