Pegex

1.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy

Pegex 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.

Pegex 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

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

Pegex 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. Pegex 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. Pegex is used to reduce the risk of infection while you are being treated with cancer medicines.

Pegex 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, Pegex 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 Pegex 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 Pegex 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 Pegex 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 Pegex 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

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

Prior to use‚ remove the carton from the refrigerator and allow the Pegex 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 Pegex 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 Pegex 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 Pegex 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 Pegex

A healthcare provider must fill the On-body Injector with Pegex using the prefilled syringe and then apply the On-body Injector for Pegex 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 Pegex. Approximately 27 hours after the On-body Injector for Pegex is applied to the patient’s skin, Pegex will be delivered over approximately 45 minutes. A healthcare provider may initiate administration with the On-body Injector for Pegex on the same day as the administration of cytotoxic chemotherapy, as long as the On-body Injector for Pegex delivers Pegex no less than 24 hours after administration of cytotoxic chemotherapy.

The prefilled syringe co-packaged in Pegex OnproTM kit must only be used with the On-body Injector for Pegex. The prefilled syringe contains additional solution to compensate for liquid loss during delivery through the On-body Injector for Pegex. If the prefilled syringe co-packaged in Pegex 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 Pegex, the patient may receive less than the recommended dose.

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

The On-body Injector for Pegex 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 Pegex 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 Pegex for full administration information.

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

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 Pegex (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 Pegex will begin and how to monitor the On-body Injector for Pegex for completed delivery. Ensure patients understand how to identify signs of malfunction of On-body Injector for Pegex.

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

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

Before using Pegex, 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.

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

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

Pegex 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 Pegex 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 Pegex Onpro Injector is a special device placed on the skin that delivers your Pegex 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 Pegex 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 Pegex.

Store Pegex 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 Pegex syringe that has been left at room temperature for longer than 72 hours, or any Pegex syringe that has been left at room temperature for longer than 48 hours.

Keep Pegex 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 (Pegex only): To increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Prevention of chemotherapy-induced neutropenia (Pegex and Pegex 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: Pegex products are not indicated for mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplant.

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

See also:
What other drugs will affect Pegex?

Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, Pegex should be administered approximately 24 hrs after administration of cytotoxic chemotherapy. In clinical studies, Pegex has been safely administered 14 days before chemotherapy. Concomitant use of Pegex with any chemotherapeutic agent has not been evaluated in patients. In animal models, concomitant administration of Pegex 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 Pegex 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 Pegex with any other medicinal products.

Incompatibilities: Pegex is incompatible with sodium chloride solutions.

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

Clinical Trials: In randomised clinical studies in patients with malignancy receiving Pegex 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 Pegex following cytotoxic chemotherapy.

Laboratory Test: White blood cell counts (WBC) of ≥100 x 10⁹/L have been observed in <1% of patients receiving Pegex. 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 Pegex.

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 Pegex. 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. Pegex 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 Pegex.

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 Pegex (estimated reporting rate: 0.00038%).

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

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

Pegex 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 Pegex is approximately 39 kD.

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