Pegfilgrastim

1.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy

Pegfilgrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Pegfilgrastim is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

1.2 Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome

​Pegfilgrastim is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Pegfilgrastim injection is used to treat neutropenia (low white blood cells) that is caused by cancer medicines. It is a synthetic (man-made) form of a substance that is naturally produced in your body called a colony stimulating factor. Pegfilgrastim helps the bone marrow to make new white blood cells.

When certain cancer medicines are used to fight cancer cells, they also affect the white blood cells that fight infections. Pegfilgrastim is used to reduce the risk of infection while you are being treated with cancer medicines.

Pegfilgrastim is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Pegfilgrastim is used in certain patients with the following medical conditions:

• Harvesting of peripheral blood stem cells, prior to autologous stem-cell transplantation.

2.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy

​The recommended dosage of Pegfilgrastim is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1. Do not administer Pegfilgrastim between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

2.2 Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome

​The recommended dose of Pegfilgrastim is two doses, 6 mg each, administered subcutaneously one week apart. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1. Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Administer the second dose one week after the first dose.

​Obtain a baseline complete blood count (CBC). Do not delay administration of Pegfilgrastim if a CBC is not readily available. Estimate a patient’s absorbed radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.

2.3 Administration

Pegfilgrastim is administered subcutaneously via a single-dose prefilled syringe for manual use or for use with the On-body Injector for Pegfilgrastim which is co-packaged with a single-dose prefilled syringe. Use of the On-body Injector for Pegfilgrastim is not recommended for patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome. Use of the On-body Injector for Pegfilgrastim has not been studied in pediatric patients.

Prior to use‚ remove the carton from the refrigerator and allow the Pegfilgrastim prefilled syringe to reach room temperature for a minimum of 30 minutes. Discard any prefilled syringe left at room temperature for greater than 48 hours.

Visually inspect parenteral drug products (prefilled syringe) for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Pegfilgrastim if discoloration or particulates are observed.

The needle cap on the prefilled syringes contains dry natural rubber (derived from latex); persons with latex allergies should not administer these products.

​Pediatric Patients weighing less than 45 kg

​The Pegfilgrastim prefilled syringe is not designed to allow for direct administration of doses less than 0.6 mL (6 mg). The syringe does not bear graduation marks, which are necessary to accurately measure doses of Pegfilgrastim less than 0.6 mL (6 mg) for direct administration to patients. Thus, the direct administration to patients requiring dosing of less than 0.6 mL (6 mg) is not recommended due to the potential for dosing errors. Refer to Table 1.

2.4 Special Healthcare Provider Instructions for the On-body Injector for Pegfilgrastim

A healthcare provider must fill the On-body Injector with Pegfilgrastim using the prefilled syringe and then apply the On-body Injector for Pegfilgrastim to the patient’s skin (abdomen or back of arm). The back of the arm may only be used if there is a caregiver available to monitor the status of the On-body Injector for Pegfilgrastim. Approximately 27 hours after the On-body Injector for Pegfilgrastim is applied to the patient’s skin, Pegfilgrastim will be delivered over approximately 45 minutes. A healthcare provider may initiate administration with the On-body Injector for Pegfilgrastim on the same day as the administration of cytotoxic chemotherapy, as long as the On-body Injector for Pegfilgrastim delivers Pegfilgrastim no less than 24 hours after administration of cytotoxic chemotherapy.

The prefilled syringe co-packaged in Pegfilgrastim OnproTM kit must only be used with the On-body Injector for Pegfilgrastim. The prefilled syringe contains additional solution to compensate for liquid loss during delivery through the On-body Injector for Pegfilgrastim. If the prefilled syringe co-packaged in Pegfilgrastim Onpro kit is used for manual subcutaneous injection, the patient will receive an overdose. If the single-dose prefilled syringe for manual use is used with the On-body Injector for Pegfilgrastim, the patient may receive less than the recommended dose.

Do not use the On-body Injector for Pegfilgrastim to deliver any other drug product except the Pegfilgrastim prefilled syringe co-packaged with the On-body Injector for Pegfilgrastim.

The On-body Injector for Pegfilgrastim should be applied to intact, non-irritated skin on the arm or abdomen.

A missed dose could occur due to an On-body Injector for Pegfilgrastim failure or leakage. If the patient misses a dose, a new dose should be administered by single-dose prefilled syringe for manual use, as soon as possible after detection.

Refer to the Healthcare Provider Instructions for Use for the On-body Injector for Pegfilgrastim for full administration information.

2.5 Advice to Give to Patients Regarding Administration via the On-body Injector for Pegfilgrastim

Advise patients to avoid activities such as traveling, driving, or operating heavy machinery during hours 26-29 following application of the On-body Injector for Pegfilgrastim (this includes the 45-minute delivery period plus an hour post-delivery). Patients should have a caregiver nearby for the first use.

Refer the patient to the dose delivery information written on the Patient Instructions for Use. Provide training to patients to ensure they understand when the dose delivery of Pegfilgrastim will begin and how to monitor the On-body Injector for Pegfilgrastim for completed delivery. Ensure patients understand how to identify signs of malfunction of On-body Injector for Pegfilgrastim.

See also:
What is the most important information I should know about Pegfilgrastim?

You should not use this medication if you are allergic to Pegfilgrastim or filgrastim (Neupogen).

Before using Pegfilgrastim, tell your doctor if you have sickle cell disorder, chronic myeloid leukemia, myelodysplasia (also called "preleukemia"), or if you are allergic to latex.

Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

Pegfilgrastim is usually given once per chemotherapy cycle. This medication should not be given within 14 days before or 24 hours after you receive chemotherapy.

Pegfilgrastim is injected under the skin, usually once per chemotherapy cycle. A healthcare provider may teach you how to properly use the medication by yourself.

Pegfilgrastim should not be given within 14 days before or 24 hours after you receive chemotherapy.

Read and carefully follow any Instructions for Use provided with your medicine. Do not use Pegfilgrastim if you don't understand all instructions for proper use. Ask your doctor or pharmacist if you have questions.

Prepare your injection only when you are ready to give it. Do not use if the medicine looks cloudy, has changed colors, or has particles in it. Call your pharmacist for new medicine.

Do not shake the prefilled syringe or you may ruin the medicine.

The Pegfilgrastim Onpro Injector is a special device placed on the skin that delivers your Pegfilgrastim dose at a specific time. You will need to wear the device for 27 hours before the dose begins. The timed dose will then be released from the device slowly over a 45-minute period.

While wearing Pegfilgrastim Onpro, you or a caregiver will need to check the device to make sure it is working properly.

Each prefilled syringe or Onpro Injector is for one use only. Throw it away after one use, even if there is still medicine left inside.

You may need frequent medical tests to help your doctor determine how long to treat you with Pegfilgrastim.

Store Pegfilgrastim in its original package in the refrigerator, protected from light. Do not freeze.

Take a prefilled syringe out of the refrigerator and let it reach room temperature for 30 minutes before injecting your dose.

Throw away any unused Pegfilgrastim syringe that has been left at room temperature for longer than 72 hours, or any Pegfilgrastim syringe that has been left at room temperature for longer than 48 hours.

Keep Pegfilgrastim Onpro refrigerated until you are ready to wear it. Do not use an Onpro device that has been left out of a refrigerator for longer than 12 hours.

Use a needle and syringe only once and then place them in a puncture-proof "sharps" container. Follow state or local laws about how to dispose of this container. Keep it out of the reach of children and pets.

Use: Labeled Indications

Hematopoietic radiation injury syndrome, acute (Pegfilgrastim only): To increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Prevention of chemotherapy-induced neutropenia (Pegfilgrastim and Pegfilgrastim biosimilars): To decrease the incidence of infection (as manifested by febrile neutropenia), in patients with nonmyeloid malignancies receiving myelosuppressive cancer chemotherapy associated with a clinically significant incidence of febrile neutropenia.

Limitation of use: Pegfilgrastim products are not indicated for mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplant.

Note: Pegfilgrastim (Pegfilgrastim-jmdb), Udenyca (Pegfilgrastim-cbqv), and Pegfilgrastim (Pegfilgrastim-bmez) are approved as biosimilars to Pegfilgrastim (Pegfilgrastim). In Canada, Lapelga is approved as a biosimilar to Pegfilgrastim (Pegfilgrastim).

See also:
What other drugs will affect Pegfilgrastim?

Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, Pegfilgrastim should be administered approximately 24 hrs after administration of cytotoxic chemotherapy. In clinical studies, Pegfilgrastim has been safely administered 14 days before chemotherapy. Concomitant use of Pegfilgrastim with any chemotherapeutic agent has not been evaluated in patients. In animal models, concomitant administration of Pegfilgrastim and 5-fluorouracil (5-FU) or other antimetabolites has been shown to potentiate myelosuppression.

Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes. This should be considered when interrupting bone-imaging results.

Possible interactions with other haematopoietic growth factors and cytokines have not been specifically investigated in clinical studies.

The potential for interaction with lithium, which also promotes the release of neutrophils, has not been specifically investigated. There is no evidence that such an interaction would be harmful.

The safety and efficacy of Pegfilgrastim have not been evaluated in patients receiving chemotherapy associated with delayed myelosuppression eg, nitrosoureas.

Specific interaction or metabolism studies have not been performed, however, clinical studies have not indicated an interaction of Pegfilgrastim with any other medicinal products.

Incompatibilities: Pegfilgrastim is incompatible with sodium chloride solutions.

See also:
What are the possible side effects of Pegfilgrastim?

Clinical Trials: In randomised clinical studies in patients with malignancy receiving Pegfilgrastim after cytotoxic chemotherapy, most adverse events were caused by the underlying malignancy or cytotoxic chemotherapy.

The most frequently reported and very common study drug-related adverse effect was bone pain. Bone pain was generally of mild-to-moderate severity, transient and could be controlled in most patients with standard analgesics.

Gastrointestinal Disorders: Nausea was observed in healthy volunteers more frequently than in patients receiving chemotherapy.

Very common (≥10%) and common (≥1%, <10%) adverse effects in clinical studies are seen in the table as follows.

Laboratory Abnormalities: Reversible, mild to moderate elevations in uric acid, with no associated clinical effects, were common; reversible, mild to moderate elevations in alkaline phosphatase and lactate dehydrogenase, with no associated clinical effects, were very common in patients receiving Pegfilgrastim following cytotoxic chemotherapy.

Laboratory Test: White blood cell counts (WBC) of ≥100 x 10⁹/L have been observed in <1% of patients receiving Pegfilgrastim. No adverse events directly attributable to this degree of leucocytosis have been reported. Such elevation in WBC is transient, typically seen 24-48 hrs after administration and is consistent with the pharmacodynamic effects of Pegfilgrastim.

Post-Marketing: Immune System Disorders: Allergic-type reaction, including anaphylaxis, skin rash, urticaria, angioedema, dyspnoea, hypotension, erythema and flushing, occurring on initial or subsequent treatment have rarely been reported in patients receiving Pegfilgrastim. In some cases, symptoms have recurred with rechallenge, suggesting a causal relationship. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. Pegfilgrastim should be permanently discontinued in patients who experience a serious allergic reaction.

Gastrointestinal Disorders: Very rare cases of splenic rupture have been reported during treatment with Pegfilgrastim.

Skin and Subcutaneous Tissue Disorders: Rare cases of Sweet's syndrome (acute febrile dermatosis) have been reported.

Reactions of cutaneous vasculitis have been reported in patients with cancer receiving Pegfilgrastim (estimated reporting rate: 0.00038%).

Each 0.5 mL pre-filled syringe or 1 mL vial contains Pegfilgrastim 6 mg.

Pegfilgrastim also contains the following excipients: Sodium acetate trihydrate, polysorbate 80, benzyl alcohol and water for injection.

Pegfilgrastim is a covalent conjugate of recombinant human granulocyte colony-stimulating factor (G-CSF) (filgrastim) and monomethoxypolyethylene glycol. Filgrastim is a water-soluble 175 amino acid protein with a molecular weight of approximately 19 kiloDaltons (kD). Filgrastim is obtained from the bacterial fermentation of a strain of Escherichia coli transformed with a genetically engineered plasmid containing the human G-CSF gene. The average molecular weight of Pegfilgrastim is approximately 39 kD.

Pegfilgrastim is supplied as an injectable solution in pre-filled syringes and vials. The injectable solution is sterile, clear and colorless.