Product Information
Registration Status: ActiveFASENRA SOLUTION FOR INJECTION 30MG/ML (AUTOINJECTOR PEN) is approved to be sold in Singapore with effective from 2020-11-18. It is marketed by ASTRAZENECA SINGAPORE PTE LTD, with the registration number of SIN16043P.
This product contains Benralizumab 30mg/ml in the form of INJECTION, SOLUTION. It is approved for SUBCUTANEOUS use.
This product is manufactured by Catalent Indiana LLC in UNITED STATES, andCatalent Indiana LLC in UNITED STATES, and.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Benralizumab is a humanized recombinant monoclonal antibody of the isotype IgG1k immunoglobulin that specifically binds to the alpha chain of the interleukin 5 receptor (IL-5R) expressed on eosinophils and basophils.[A31294] It inhibits the binding of IL-5 as well as the hetero-oligomerization of the alpha and beta subunits of the IL-5R, thus blocking, signal transduction. Besides, it is an afucosylated IgG which gives it high affinity for the FcγRIIIα receptor in natural killer cells, macrophages and neutrophils.[A31293] Benralizumab, FDA approved on November 14, 2017, was developed by MedImmune, the AstraZeneca's global biologic research and development arm.[L1019]
Indication
Benralizumab is indicated as a maintenance treatment of patients 12 years or older with severe asthma and an eosinophilic phenotype.[L1020] The pathology of severe asthma with eosinophilic phenotype is also denotated as TH2-high phenotype. The patients with this phenotype are characterized by the expression of IL-5 and IL-13, airway hyperresponsiveness, responsiveness to inhaled corticosteroids, high serum IgE and eosinophilia in blood and airway. In the TH2-high phenotype, IL-5 presents a central role as it is responsible for eosinophil differentiation, survival, activation and migration to the lungs.[A31295]
Mechanism of Action
Interleukin-5 (IL-5) induces an eosinophil-mediated inflammatory response by binding to the IL-5 receptor (IL-5R) expressed in eosinophils, basophils and some mast cells. Benralizumab, unlike IL-5 low-affinity binding, binds with high affinity to the domain I of the α-chain of IL-5R and blocks its signaling and the proliferation of IL-5-dependent cell lines. On the other hand, Benralizumab is an afucosylated antibody in the CH2 region which gives it a high affinity for the FcγRIIIa on natural killer cells, macrophages and neutrophils. This binding triggers a magnified apoptosis response in eosinophils via antibody-dependent cell-mediated cytotoxicity.[A31293, A31295]
Pharmacokinetics
- Absorption
- Subcutaneous administration of Benralizumab presented a dose-proportional pharmacokinetic profile. The administration of 20-200 mg presented an absorption half-life of 3.6 days with a bioavailability of 58%.[FDA label] It is also reported for Benralizumab a Cmax of 82 mcg/ml and AUC of 775 mcg day/ml.[A31293]
- Distribution
- Pharmacokinetic reports of Benralizumab showed a volume of distribution in a range of 52-93ml/kg. For a 70kg individual, the central volume of distribution of Benralizumab is 3.2 L while the peripheral volume of distribution is reported to be 2.5 L.[A31297]
- Metabolism
- As any monoclonal IgG antibody, Beralizumab is degraded by proteases widely spread in the body. [FDA label]
- Elimination
Clearance
For a subject weighting 70kg, the typical systemic clearance is 0.29L/day.[FDA label]
Toxicity
There are not reports of long-term studies regarding tumorgenesis or carcinogenesis. Fertility studies performed in aminal trials showed no adverse histopathological findings.[FDA label]
Active Ingredient/Synonyms
Benralizumab | Benralizumab |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.