Pegfilgrastim - Uses, Dosage, Side Effects, and Drug Warnings

Overview:

Pegfilgrastim is a granulocyte colony-stimulating factor that promotes the growth and functioning of blood cells such as white blood cells, red blood cells, and platelets. Granulocyte colony-stimulating factor (G-CSF) is a protein that the body produces to stimulate the production of white blood cells. Pegfilgrastim is a long-acting, synthetic form of G-CSF that induces the production of white blood cells, particularly neutrophils. A neutrophil is one of the white blood cells which fights infection and is frequently reduced during cancer treatment. Neutropenia is defined as an absolute neutrophil count (ANC) of less than 500 cells/mm3 or an anticipated drop to less than 500 cells/mm3 within the next 48 hours. When this is in conjunction with a single oral temperature measurement of greater than 38.3 degrees Celsius (101 degrees Fahrenheit) or a temperature of greater than 38.0 degrees Celsius (100.4 degrees Fahrenheit) prolonged for over 60 minutes, it is termed febrile neutropenia. Pegfilgrastim is used to prevent or cure chemotherapy-induced neutropenia.

What Are the Risk Factors for Developing Febrile Neutropenia?

• Age over 65 years.

• The disease has progressed already.

• Earlier chemotherapy or radiation treatment.

• Pre-existing neutropenia or tumor-related bone marrow involvement.

• Infection.

• Open wounds or have undergone surgical intervention recently.

• Incomplete nutritional status.

• Renal function impairment.

• Insufficient liver function, as evidenced primarily by high bilirubin levels.

• Cardiovascular illness.

• Several comorbid conditions.

• Human immunodeficiency virus (HIV).

What Are the Indications of Pegfilgrastim?

• Patients with Cancer Undergoing Myelosuppressive Chemotherapy: Pegfilgrastim is indicated in patients with non-myeloid malignancies obtaining myelosuppressive anti-cancer drugs with a clinically significant occurrence of febrile neutropenia to reduce the risk of infection as demonstrated by febrile neutropenia.

• Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome: It is indicated to increase the survival rate in cancer patients.

What Are the Contraindications of Pegfilgrastim?

Hypersensitivity reactions to Pegfilgrastim are possible. As a result, it is not recommended for patients with an allergic reaction to Pegfilgrastim, Filgrastim, or the components used in the drug.

Dosage and Administration:

Dosage Strengths: 6 milligrams per 0.6 milliliters.

Dosage Form: Available in a prefilled syringe for both manual injection for subcutaneous injections and on-body injector (OBI-kit) to the patient's skin (abdomen or back of the arm).

On body injector (OBI) is not to be used in hematopoietic subsyndrome of acute radiation syndrome and pediatric patients.

Administration:

1. Patients with Cancer Receiving Myelosuppressive Chemotherapy: A single subcutaneous injection of six mg is given subcutaneously once per chemotherapy cycle. Pegfilgrastim should not be given 14 days before or 24 hours after cytotoxic chemotherapy.

2. Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome:

• Two doses of injection, each containing six mg, given subcutaneously one week apart. Give the first dose of injection after anticipating or confirming exposure to radiation levels greater than two gray (Gy), and the second dose should be taken after one week.

• A baseline complete blood count (CBC) should be taken at the beginning of the chemotherapy. If a CBC is unavailable, Pegfilgrastim should be administered immediately. Evaluate the patient's radiation exposure dose using public health information, biodosimetry, or clinical signs and symptoms like the onset of vomiting or lymphocyte depletion kinetics.

Dosage Administration in Pediatric Patients:

Pegfilgrastim Dosage for Pediatric Patients Weighing below 45 Kilograms

Warning and Precautions:

1. Splenic Rupture: Such as fatal cases, can take place after Pegfilgrastim administration. Patients who reported left upper abdominal or shoulder pain after taking Pegfilgrastim to check for an enlarged spleen or splenic rupture.

2. Acute Respiratory Distress Syndrome: Some patients who develop fever, lung infiltration, and respiratory distress should be evaluated for acute respiratory distress syndrome (ARDS), and discontinuation of the drug should be done.

3. Serious Allergic Reactions: Severe allergic reactions, such as anaphylaxis, can arise in patients receiving Pegfilgrastim. The major events occurred immediately after initial exposure. Anaphylaxis can reoccur within days of stopping anti-allergic treatment. In patients who have severe allergic reactions, Pegfilgrastim should be discontinued permanently. Never administer Pegfilgrastim if they are allergic to the components used in the drug.

4. Allergies to Acrylics: The acrylic adhesive is used in the Pegfilgrastim on-body injector (OBI). This product may cause a serious reaction in patients allergic to acrylic adhesives.

5. Use in Patients with Sickle Cell Disorders: Patients with sickle cell disorders who receive Pegfilgrastim may develop severe and sometimes fatal sickle cell crises. If a sickle cell crisis arises, discontinue the drug.

6. Glomerulonephritis: It has been reported in patients taking Pegfilgrastim. The diagnosis is based on azotemia (elevated levels of urine and nitrogen in the blood), hematuria (blood in the urine) both clinically and microscopically, proteinuria (presence of protein in the urine), and a renal biopsy. In most cases, glomerulonephritis gets addressed after Pegfilgrastim is reduced or discontinued. If causality is suspected, consider reducing the dose or discontinuing the drug.

7. Leukocytosis: White blood cell (WBC) counts of 100 x 109/L or higher have been noticed in patients taking Pegfilgrastim. CBC Monitoring is advised all through Pegfilgrastim therapy.

8. Capillary Leak Syndrome: Pegfilgrastim can cause leakage of fluid from blood vessels into the tissues. This is known as capillary leak syndrome (CLS). CLS symptoms can develop quickly and can become life-threatening. If the patient experiences any of the following symptoms, seek immediate medical attention.

• Edema and urinating less than usual.
• Breathing difficulty, swelling abdomen and feeling full.
• Dizziness and lethargy.

9. Potential for Tumor Growth Stimulatory Effects on Malignant Cells: On tumor cell lines, the granulocyte colony-stimulating factor (G-CSF) receptor, which Pegfilgrastim activates has been discovered.

10. Potential Device Failures: Due to the device not functioning as designed, patients receiving Pegfilgrastim through the on-body injector (OBI) have reported missing or partial doses. If a dose is missed or delivered partially, patients may be more likely to experience neutropenia, febrile neutropenia, and infection than if the dose was correctly administered. Advise patients using the OBI to immediately notify the doctor to assess the need for dose replacement if they assume the device did not function as planned.

11. Aortitis: This can happen as soon as the first week of therapy. Generalized signs and symptoms include fever, abdominal pain, malaise, back pain, and elevated inflammatory markers (c-reactive protein and white blood cell count). Aortitis should be considered in patients who experience these symptoms with no known cause. If aortitis is anticipated, immediately discontinue Pegfilgrastim.

12. Nuclear Imaging: Increased activity of bone marrow hematopoietic cells in response to treatment with growth factor has been linked to transient positive bone imaging changes. This should be taken into account while analyzing the results of bone imaging.

For Patients:

What Is Pegfilgrastim?

Pegfilgrastim is a synthetic form of granulocyte colony-stimulating factor (G-CSF). G-CSF is a substance that promotes the growth of neutrophils, a type of white blood cell that helps the body to fight infection and is produced by the body. The use of Pegfilgrastim in acute radiation syndrome is evaluated only in animal studies because it is not feasible to evaluate in human studies.

Before One Take Pegfilgrastim, Inform the Healthcare Provider if the Patient Is Suffering from Conditions Like

• Sickle cell anemia.

• Kidney disorders.

• Allergic to latex (the prefilled syringe's needle cap is made of dry natural rubber derived from latex).

• Pregnant or planning to have a baby (it is unknown whether Pegfilgrastim will harm the unborn child).

• Lactation (it is unknown whether Pegfilgrastim will pass through the breast milk).

• Inform the doctor about the list of medications taken currently.

How to Use Pegfilgrastim?

It is a clear, colorless solution with a prefilled single-dose syringe containing six milligrams of Pegfilgrastim for subcutaneous injection and a 27-gauge, 1/2-inch needle.

The Pegfilgrastim prefilled syringe lacks graduation marks and is only intended to administer the entire contents of the syringe (six milligrams per 0.6 milliliters). The use of the prefilled syringe for subcutaneous administration of pediatric patients weighing less than 45 kilograms who need doses less than the full contents of the syringe is not advised.

What Are the Side Effects of Pegfilgrastim?

Common Side Effects:

The most common side effect associated with Pegfilgrastim is bone pain and pain in the arms and legs. Although, the pain is manageable with nonsteroidal anti-inflammatory drugs (NSAIDs). However, NSAIDs may not be viable for managing pain in some patients, like the elderly or those with kidney disease. Antihistamines have recently been investigated as a potentially acceptable alternative to help alleviate the bone pain associated with Pegfilgrastim administration.

Additional Side Effects:

• Fever, shortness of breath, difficulty breathing, fast breathing; hives; rash; itching; difficulty swallowing or breathing; increased heart rate; or sweating.

• Swelling of the face, abdomen, ankles, throat, around the mouth, and eyes. Discoloration of the urine and reduced urination.

• Pain in the left upper abdomen and left side of the shoulder, back pain, not feeling well, dizziness, and tiredness.

• Unusual bleeding or bruising, fever, or exhaustion.

What if the Regular Dose Got Missed?

If the patient misses a dose of Pegfilgrastim, inform the doctor about it and plan for the next dose.

How Is Pegfilgrastim Stored?

Refrigerate between 36 and 46 degrees Fahrenheit (two degrees and eight degrees Celcius) in the carton to avoid direct light. Do not shake the solution in the syringe. Syringes stored at room temperature for more than 48 hours should be discarded. Avoid freezing; if it froze, thaw the syringe in the refrigerator before using it. If the syringe has been frozen more than once, discard it.

What if an Overdose of Pegfilgrastim Occurs?

Overdosage can cause leukocytosis and bone pain. Symptoms of edema (swelling due to fluid accumulation), dyspnea (shortness of breath), and pleural effusion (fluid accumulation in the lungs) have been reported in a single patient who received Pegfilgrastim on eight consecutive days by mistake. In case if overdose occurs, the patient should be closely monitored for the signs and symptoms of adverse effects and treated accordingly.

For Doctors:

Pegfilgrastim:

Pegfilgrastim is a covalent conjugate of human G-CSF (filgrastim) and monomethoxypolyethylene glycol. Filgrastim is a 175 amino acid protein soluble in water with a molecular weight of about 19 kilodaltons (kD). Filgrastim is produced by bacterial fermentation of an E. Coli strain that has been genetically engineered with a plasmid containing the human G-CSF gene. To make Pegfilgrastim, a 20 kD monomethoxypolyethylene glycol molecule is covalently bound to filgrastim's N-terminal methionyl residue. Pegfilgrastim has a molecular weight of about 39 kD on average.

What Is the Mechanism of Action of Pegfilgrastim?

Pegfilgrastim is a granulocyte colony-stimulating factor with a long half-life. Pegfilgrastim is covalently bound to a polyethylene glycol molecule, resulting in a longer action duration. It prevents febrile neutropenia by increasing neutrophil levels in the body by stimulating neutrophil proliferation, differentiation, and maturation. It also helps mature neutrophils live longer.

Pharmacodynamics:

The pharmacokinetics of Pegfilgrastim was found to be highly variable. Pegfilgrastim has a half-life of 15 to 80 hours after subcutaneous injection.

Pharmacokinetics:

Pegfilgrastim's pharmacokinetics were nonlinear, and clearance decreased with increasing doses.

Neutrophil binding to the receptors is essential to Pegfilgrastim clearance, and serum clearance is directly related to the neutrophil count. In addition to neutrophil counts, the patient's weight is important. After receiving a normalized dose for body weight, patients with higher body weights had higher systemic exposure to Pegfilgrastim.

What Is the Nonclinical Toxicology of Pegfilgrastim?

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Pegfilgrastim has not been studied for carcinogenicity or mutagenesis.

At combined weekly doses approximately 6 to 9 times higher than the recommended human dose, Pegfilgrastim did not affect reproductive performance or fertility in male or female rats (based on the body's surface area).

Use in Specific Populations

Pregnancy: Available data on Pegfilgrastim use in pregnant women is inadequate to assess if there was a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. These studies found no link between Pegfilgrastim use during pregnancy and adverse maternal or fetal outcomes.

Lactation: There is no information currently available on the presence of Pegfilgrastim in human milk, its impact on breastfeeding children, or its effects on milk production. These products are poorly secreted into breast milk and are not absorbed orally by neonates. The developmental and health benefits should be considered together with the mother's clinical needs for Pegfilgrastim and any adverse effects on the child from Pegfilgrastim.

Pediatric Use: The use of Pegfilgrastim in pediatric patients for chemotherapy-induced neutropenia depends on sufficient and well-controlled adult studies, with additional pharmacokinetic and safety data in pediatric sarcoma patients. The use of Pegfilgrastim to improve survival in pediatric patients acutely exposed to myelosuppressive radiation doses is based on animal efficacy studies.

Geriatric Use: Out of the 932 cancer patients who received Pegfilgrastim for clinical trials, 139 (15 percent) were 65 years and older, and 18 (2 percent) were 75. There were no overall differences in safety or efficiency between patients aged 65 and older and younger.

Clinical Studies:

Patients with Cancer Receiving Myelosuppressive Chemotherapy:

• Pegfilgrastim was investigated in three randomized, double-blind, placebo-controlled trials. Pegfilgrastim was tested in three randomized, double-blind, placebo-controlled trials. The first and second studies were active-controlled trials that used Doxorubicin 60 mg/m2, and Docetaxel 75 mg/m2 delivered every 21 days for up to four cycles to treat metastatic breast cancer. The first study examined the effectiveness of a set dosage of Pegfilgrastim.

• The second study used a weight-adjusted dosage. Similar chemotherapy regimens have been reported to result in a 100 percent occurrence of severe neutropenia with a mean duration of five to seven days and a 30 percent to 40 percent incidence of febrile neutropenia in the absence of growth factor support. Based on the correlation observed in Pegfilgrastim studies between the duration of severe neutropenia and the incidence of febrile neutropenia, the duration of severe neutropenia was selected as the main endpoint in both studies, and Pegfilgrastim efficacy was demonstrated by establishing comparability to Pegfilgrastim-treated patients in the mean days of severe neutropenia.

• On day Two of Study 1, 157 participants were randomly assigned to be given a single subcutaneous injection of Pegfilgrastim six milligrams.

• In Study 2, 310 patients were randomly assigned to either a single subcutaneous injection of Pegfilgrastim (100 micrograms per kilogram) on day Two of each chemotherapy cycle or daily subcutaneous filgrastim (5 micrograms per kilogram) commencing on day Two of each chemotherapy cycle.

• Both investigations demonstrated that the mean days of severe neutropenia of Pegfilgrastim-treated patients did not surpass those of Pegfilgrastim-treated patients by more than one day in cycle 1 of the study.