Nucala Prefilled Autoinjector
Nucala Prefilled Autoinjector Uses, Dosage, Side Effects, Food Interaction and all others data.
Eosinophils are involved in inflammatory immune responses, and prolonged hypereosinophilia (typically defined as absolute eosinophil levels of 1500/mm3 or more) is associated with a spectrum of diseases, including severe asthma, eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome (HES). The pathogenesis of eosinophilia is complex, but IL-5 is recognized as a key cytokine involved in the differentiation, recruitment, activation, and prolonged survival of eosinophils in peripheral tissue. Activated eosinophils further stimulate an inflammatory response and also induce tissue lesions and promote fibrosis, all of which contribute to the multifactorial symptomatology of hypereosinophilic diseases.
Nucala Prefilled Autoinjector is a fully-humanized recombinant IgG1 kappa monoclonal antibody directed against IL-5 produced in Chinese hamster ovary cells. Nucala Prefilled Autoinjector was first approved by the FDA on November 4, 2015, as an add-on therapy for severe asthma and marketed under the brand name Nucala by GlaxoSmithKline. This indication was subsequently expanded to cover EGPA on December 12, 2017, and HES on September 25, 2020.
Nucala Prefilled Autoinjector is a monoclonal antibody that acts through interleukin-5 (IL-5) antagonism to reduce blood eosinophil levels, generally in the range of 60-90% of baseline depending on dose, which in turn offers therapeutic benefit in the specific conditions for which mepolizumab is indicated. Nucala Prefilled Autoinjector has a relatively long half-life of between 16 and 22 days, which allows for long-lasting therapeutic benefit and a four-week dosing schedule. Despite a good demonstrated safety profile, mepolizumab use does act to depress part of the immune system and may be associated with increased infections, such as with herpes zoster virus; pre-existing helminth infections should be treated before starting mepolizumab therapy. Inhaled and oral corticosteroids should not be discontinued after starting mepolizumab but may be tapered as appropriate. Nucala Prefilled Autoinjector should not be used to treat acute bronchospasms or status asthmatics. Finally, hypersensitivity reactions, including anaphylaxis, have been reported in patients; mepolizumab should be discontinued in patients with suspected or confirmed hypersensitivity.
| Trade Name | Nucala Prefilled Autoinjector |
| Availability | Prescription only |
| Generic | Mepolizumab |
| Mepolizumab Other Names | Mepolizumab |
| Related Drugs | Dupixent, Xolair, Trelegy Ellipta, ProAir Digihaler, prednisone, Symbicort, Breo Ellipta, Ventolin, Xopenex, Ventolin HFA |
| Weight | 100mg, 100mg/ml |
| Type | Subcutaneous powder for injection, subcutaneous solution |
| Weight | 149000.0 Da |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Nucala Prefilled Autoinjector is a fully-humanized monoclonal IgG1 kappa anti-IL-5 antibody used in conjunction with other therapies to treat severe asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome.
Nucala Prefilled Autoinjector is an anti-IL-5 IgG1 kappa monoclonal antibody indicated as an add-on maintenance treatment in patients aged six years and older with severe eosinophilic asthma and as a treatment in adult patients for eosinophilic granulomatosis with polyangiitis (EGPA). Nucala Prefilled Autoinjector is also indicated for the treatment of hypereosinophilic syndrome (HES) in patients aged 12 and older in whom eosinophilia is present for at least six months without an identifiable non-hematologic secondary cause.
Nucala Prefilled Autoinjector is also used to associated treatment for these conditions: Eosinophilic Granulomatosis With Polyangiitis, Hypereosinophilic Syndromes, Severe Eosinophilic Asthma
How Nucala Prefilled Autoinjector works
Hypereosinophilia is typically considered as an absolute eosinophil count of 1500/mm3 or higher and is associated with aberrant immune responses in several conditions, including severe asthma, eosinophilic granulomatosis with polyangiitis, and the variable spectrum of hypereosinophilic syndrome (HES). Eosinophils are involved in the inflammatory response by secretion of molecules such as MBP, leukotrienes, matrix metalloproteinases, transforming growth factor-β, nitric oxide, and other reactive oxygen species. Interleukin-5 (IL-5) is the primary cytokine associated with the differentiation of bone marrow progenitor cells into mature inflammatory neutrophils and the subsequent migration, activation, and prolonged survival of activated neutrophils. In concert with other cells, including lymphocytes, neutrophils, mast cells, and macrophages, which themselves can secrete additional pro-inflammatory molecules, high concentrations of neutrophils are associated with tissue damage and fibrosis, leading to the symptoms of eosinophilic diseases.
Typically, eosinophils arise from both CD34+ Although there exists a population of eosinophils that are insensitive to IL-5 levels, the main population of inflammatory eosinophils proliferates and migrates into the tissue in response to IL-5. Nucala Prefilled Autoinjector is a fully-humanized monoclonal IgG1 kappa antibody that binds IL-5 with a dissociation constant of 100 pM, preventing IL-5 from binding to and subsequently activating IL-5R+ This reduction lowers circulating blood eosinophil levels and therefore exerts a beneficial effect in eosinophilic disease; the exact mechanistic nature of mepolizumab action has not been definitively determined. Not all patients will benefit from mepolizumab treatment, such as those with milder asthma or those with a sub-type of HES that is independent of IL-5 signalling.
Toxicity
Toxicity information regarding mepolizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as newly established or worsening chronic infections, including those caused by helminths, and generalized immune depression. Symptomatic and supportive measures are recommended.
Food Interaction
No interactions found.Nucala Prefilled Autoinjector Disease Interaction
Volume of Distribution
Nucala Prefilled Autoinjector has a population central volume of distribution of 3.6 L (for a 70 kg individual) in adult asthma patients.
Elimination Route
Nucala Prefilled Autoinjector is administered subcutaneously and has a bioavailability of approximately 80% based on a 100 mg dose given to both adult and adolescent subjects with asthma. With the recommended four-week dosing schedule, there is an approximately two-fold accumulation of mepolizumab at steady-state.
Half Life
Nucala Prefilled Autoinjector has a mean terminal half-life of between 16 and 22 days.
Clearance
Nucala Prefilled Autoinjector has an estimated apparent population systemic clearance of 0.28 L/day (for a 70-kg individual) in adult and adolescent subjects.
Innovators Monograph
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