Pegex
Pegex Uses, Dosage, Side Effects, Food Interaction and all others data.
Pegex is a covalent conjugate of filgrastim and monomethoxypolyethylene glycol which binds to specific cell surface receptors of haematopoietic cells, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.
Pegex is a recombinant human granulocyte colony-stimulating factor (G-CSF) that promotes the production, proliferation, and maturation of neutrophils, which are white blood cells involved in both innate and adaptive immune responses. The safety and efficacy of pegfilgrastim in reducing the risk of febrile neutropenia and infections have been demonstrated in various tumor types and settings.
During chemotherapy-induced neutropenia, the clearance of pegfilgrastim is significantly reduced and the concentration of pegfilgrastim is sustained until the onset of neutrophil recovery. Serum concentrations of pegfilgrastim decline as the neutrophil count increases as neutrophil and neutrophil precursors are involved in cell-mediated clearance of the drug. Due the addition of polyethylene glycol group to its structure, Pegex is a long-acting form of filgrastim with an extended serum half-life and reduced renal clearance. Although it is more slowly absorbed than filgrastim, self-regulation of pegfilgrastim is more efficient and the drug effects are maintained during one chemotherapy cycle (2-3 weeks).
| Trade Name | Pegex |
| Availability | Prescription only |
| Generic | Pegfilgrastim |
| Pegfilgrastim Other Names | Granulocyte colony-stimulating factor pegfilgrastim, peg-filgrastim, Pegfilgrastim, pegfilgrastim-apgf, pegfilgrastim-bmez, pegfilgrastim-cbqv, pegfilgrastim-jmdb |
| Related Drugs | Neulasta, filgrastim, Zarxio, Neupogen, Udenyca, Granix, Leukine, sargramostim |
| Type | Injection |
| Formula | C845H1343N223O243S9 |
| Weight | 39000.0 Da (approximate, PEGylated) |
| Protein binding | The plasma protein binding of pegfilgrastim is unlikely. |
| Groups | Approved |
| Therapeutic Class | Hematopoietic drug |
| Manufacturer | Emcure Pharmaceuticals Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Patients With Cancer Receiving Myelosuppressive Chemotherapy: Pegex is used 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 used for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
Patients With Hematopoietic Subsyndrome Of Acute Radiation Syndrome: Pegex is used to increase survival in patients acutely exposed to myelosuppressive doses of radiation
Pegex is also used to associated treatment for these conditions: Chemotherapy Induced Neutropenia, Hematopoietic Subsyndrome of Acute Radiation Syndrome, Infection
How Pegex works
Neutrophils are short-lived immune cells that are highly susceptible to cell death following myelosuppressive chemotherapy. This marked reduction in neutrophil numbers during chemotherapy increases the risk of hospitalization, infection, and infection-related mortality. It also directly impacts the clinical outcome of patients if cases of febrile neutropenia requires dose reductions or schedule delay of chemotherapy, thus reducing the clinical efficacy of chemotherapy and patient benefit from receiving appropriate treatment.
G-CSF is an endogenous haematopoietic growth factor that stimulates granulopoietic cells of the neutrophil lineage. Pegex mimics its biological actions and binds to the same G-CSF receptor expressed on cells of myeloid lineage, such as granulocytic precursors and mature neutrophils. Upon binding of the ligand, G-CSF receptor undergoes a conformational change and activates several downstream signalling pathways including JAK/STAT, PI3K/AKT and MAPK/ERK. These pathways work to increase proliferation and differentiation of granulocyte progenitor cells, induce maturation of the progenitor cells, and enhance survival and function of mature neutrophils.
Dosage
Pegex dosage
Cancer patients receiving Myelosuppressive Chemotherapy: The recommended dosage of Pegex is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle in adults. For pediatric patients weight less than 10 kg is 0.1 mg (0.01 ml)/kg, 10-20 kg is 0.15 ml, 21-30 kg is 0.25 ml & 31-44 kg is 0.4 ml. Do not administer Pegex between 14 days before and 24 hours after administration of cytotoxic chemotherapy.
Hematopoietic Subsyndrome of Acute Radiation Syndrome: The recommended dose of Pegex is two doses of 6 mg each, administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy) & the second dose one week after the first dose. For dosing in pediatric patients weighing less than 45 kg, refer to Myelosuppressive Chemotherapy dosing system.
Side Effects
Bone or musculoskeletal pain, hypersensitivity reactions (e.g. urticaria, skin rash, angioedema, erythema, flushing, dyspnoea, hypotension, cutaneous vasculitis, SC tissue disorders), splenomegaly, glomerulonephritis, leukocytosis, pulmonary AR (e.g. interstitial pneumonia; pulmonary oedema, infiltrates and fibrosis).
Toxicity
The maximum safe dose of pegfilgrastim has not been established; however, the highest dose used in clinical trials was 300 mcg/kg. Overdosage of pegfilgrastim may result in leukocytosis and bone pain. Events of edema, dyspnea, and pleural effusion have been reported in a single patient who self-administered pegfilgrastim on 8 consecutive days in error. In the event of overdose, the patient should be monitored for signs and symptoms of toxicity and responded with appropriate general supportive care.
Precaution
Mifepristone & Misoprostol combination should not give to anyone else. Administration must be under the supervision of a qualified physician. The combination of Mifepristone & Misoprostol has been prescribed for the patients specific condition, it may not be the correct treatment for another patients, and may be dangerous to the other women if she is or were to become pregnant. Any intrauterine device (IUD) should be removed before treatment with Mifepristone begins. Menstrual Regulation (MR) by surgery is recommended in cases when combination of Mifepristone & Misoprostol fails to cause Menstrual Regulation. Patients who have an ongoing pregnancy at last visit have a risk of fetal malformation resulting from the treatment. Surgical termination/MVA (Manual vaccum Aspiration) is recommended to manage Menstrual Regulation (MR)/termination of pregnancy failures.
Interaction
No formal drug interaction studies between Pegex and other drugs have been performed.
Food Interaction
No interactions found.Pegex Drug Interaction
Moderate: bevacizumabUnknown: lorazepam, celecoxib, sulfamethoxazole / trimethoprim, ubiquinone, docusate, pancrelipase, dexamethasone, meperidine, aprepitant, fentanyl, loperamide, metoprolol, metoprolol, polyethylene glycol 3350, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, ondansetron
Pegex Disease Interaction
Volume of Distribution
Pegex appears to have a volume of distribution of approximately 170L.[A33290]
Elimination Route
Pegex has a lower absolute bioavailability than filgrastim following subcutaneous administration. The absorption of pegfilgrastim is largely dependent on the lymphatic system due to the attached PEG group contributing to the large size of the drug. It is slowly absorbed following subcutaneous administration with a time to peak concentration (Tmax) of about 1-2 days.
Half Life
The serum half-life of Pegex is highly variable depending on the absolute neutrophil count, with the range of 15 to 80 hours following subcutaneous administration. The median serum half-life of 42 hours.
Clearance
Pegex has a self-regulating clearance that involves neutrophil-induced clearance. The clearance is dependent on the number of neutrophils and body weight of the patient: the clearance increases with increasing number of granulocytes and lower body weights. Pegex is not eliminated from the circulation until neutrophils start to recover following chemotherapy-induced neutropenia and its clearance is increased as neutrophil counts also increase. The apparent serum clearance is 14 mL/h/kg.
Elimination Route
The polyethylene glycol moiety limits the renal clearance by glomerular filtration of pegfilgrastim, making neutrophil-mediated clearance as the predominant route of elimination. This elimination pathway is initiated by the binding of pegfilgrastim to the G-CSF receptor on the neutrophil cell surface, leading to the internalization of the pegfilgrastim-receptor complex via endocytosis and subsequent degradation inside the cell. While hepatic clearance has not been well characterized for pegfilgrastim, its non-PEGylated precursor filgrastim is known to be unaffected by changes in hepatic clearance.
Pregnancy & Breastfeeding use
Pregnancy: Pregnancy category C. There are no adequate and well-controlled studies in pregnant women. Therefore, Pegex should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Lactation: It is not known whether Pegex is secreted in human milk. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. Caution should be exercised when administered to a nursing woman.
Contraindication
Do not administer Pegex to patients with a history of serious allergic reactions to Pegex or Filgrastim.
Acute Overdose
The maximum amount of Pegex that can be safely administered has not been determined.
Storage Condition
Pegex should be stored at 2-8° C & avoid shaking before injection. Don’t store it at room temperature for more than 48 hours. Do not administer this product if discoloration or particulates are observed.
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