Overview
11 DESCRIPTION Inebilizumab-cdon is a CD19-directed humanized afucosylated IgG1 monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. The molecular weight is approximately 149 kDa. UPLIZNA (inebilizumab-cdon) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution, free from visible...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism by which inebilizumab-cdon exerts its therapeutic effects in NMOSD, IgG4-RD, and gMG is presumed to involve binding to CD19, a cell surface antigen presents on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, inebilizumab-cdon results in antibody-dependent cellular cytolysis. 12.2 Pharmacodynamics Pharmacodynamics of UPLIZNA were assessed with an assay for CD20+ B-cells, since UPLIZNA can interfere with the CD19+ B-cell assay. Treatment with UPLIZNA reduces CD20+ B-cell counts in blood by 8 days after infusion. In Study 1 [see Clinical Studies (14.
Indications
- 1 INDICATIONS AND USAGE UPLIZNA is a CD19-directed cytolytic antibody indicated for the treatment of: Neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. ( 1.1 ) Immunoglobulin G4-related disease (IgG4-RD) in adult patients. ( 1.2 ) Generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle specific tyrosine kinase (MuSK) antibody positive. ( 1.2 ) 1.
Common Doses
- 250 mL
- 300 mg
- 80 mg
- 125 mg
Dosage
2 DOSAGE AND ADMINISTRATION Hepatitis B virus, quantitative serum immunoglobulins, and tuberculosis screening is required before the first dose. ( 2.1 ) Prior to every infusion: Determine if there is an active infection ( 2.2 , 5.2 ) Premedicate with a corticosteroid, an antihistamine, and an antipyretic ( 2.2 , 5.1 ) UPLIZNA must be diluted in 250 mL of 0.9% Sodium Chloride Injection, USP prior to administration. ( 2.3 , 2.4 ) UPLIZNA is administered as an intravenous infusion titrated to completion, approximately 90 minutes.
Contraindications
- 4 CONTRAINDICATIONS UPLIZNA is contraindicated in patients with: A history of a life-threatening infusion reaction to UPLIZNA [see Warnings and Precautions (5.1) ] Active hepatitis B infection [see Warnings and Precautions (5.2) ] Active or untreated latent tuberculosis [see Warnings and Precautions (5.2) ] Previous life-threatening reaction to infusion of UPLIZNA ( 4 ) Active hepatitis B infection ( 4 ) Active or untreated latent tuberculosis ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Infusion Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Reduction in Immunoglobulins [see Warnings and Precautions (5.3) ] The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were NMOSD: urinary tract infection and arthralgia. ( 6.1 ) IgG4-RD: urinary tract infections and lymphopenia. ( 6.1 ) gMG: headache and infusion-related reactions. ( 6.
Interactions
- 7 DRUG INTERACTIONS 7.1 Immunosuppressive or Immune-Modulating Therapies Concomitant usage of UPLIZNA with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when co-administering immunosuppressive therapies with UPLIZNA.