Udenyca

Uses

Patients With Cancer Receiving Myelosuppressive Chemotherapy: Udenyca 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

Udenyca is not used for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Patients With Hematopoietic Subsyndrome Of Acute Radiation Syndrome: Udenyca is used to increase survival in patients acutely exposed to myelosuppressive doses of radiation

Udenyca is also used to associated treatment for these conditions: Chemotherapy Induced Neutropenia, Hematopoietic Subsyndrome of Acute Radiation Syndrome, Infection

How Udenyca 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. Udenyca 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

Udenyca dosage

Cancer patients receiving Myelosuppressive Chemotherapy: The recommended dosage of Udenyca 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 Udenyca between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Hematopoietic Subsyndrome of Acute Radiation Syndrome: The recommended dose of Udenyca 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 Udenyca and other drugs have been performed.

Food Interaction

Udenyca 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

Udenyca Disease Interaction

Major: glomerulonephritis, myeloid tumors, leukocytosis

Volume of Distribution

Udenyca appears to have a volume of distribution of approximately 170L.[A33290]

Elimination Route

Udenyca 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 Udenyca 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

Udenyca 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. Udenyca 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, Udenyca 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 Udenyca 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 Udenyca to patients with a history of serious allergic reactions to Udenyca or Filgrastim.

Acute Overdose

The maximum amount of Udenyca that can be safely administered has not been determined.

Storage Condition

Udenyca 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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