Overview
11 DESCRIPTION Eculizumab-aeeb, a complement inhibitor, is a recombinant humanized monoclonal IgG2/4κ antibody produced by Chinese Hamster Ovary (CHO) cell culture and purified by standard bioprocess technology. Eculizumab-aeeb contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light-...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Eculizumab-aeeb, the active ingredient in BKEMV, is a monoclonal antibody that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. Eculizumab products inhibit terminal complement-mediated intravascular hemolysis in PNH patients and complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. The precise mechanism by which eculizumab exerts its therapeutic effect in gMG patients is unknown, but is presumed to involve reduction of terminal complement complex C5b-9 deposition at the neuromuscular junction. 12.
Indications
- 1 INDICATIONS AND USAGE BKEMV is a complement inhibitor indicated for: The treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. ( 1.1 ) The treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. ( 1.2 ) Limitation of Use BKEMV is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). The treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. ( 1.3 ) 1.
Common Doses
- 600 mg
- 900 mg
- 200 mg
- 300 mg
Dosage
2 DOSAGE AND ADMINISTRATION For intravenous infusion only; recommended dosage for: PNH: ( 2.2 ) aHUS and gMG in adults: ( 2.3 ) aHUS in pediatric patients: ( 2.4 ) 2.1 Recommended Vaccination and Prophylaxis for Meningococcal Infection Vaccinate patients against meningococcal infection (serogroups A, C, W, Y and B) according to current ACIP recommendations at least 2 weeks prior to initiation of BKEMV [ see Warnings and Precautions (5.1) ].
Black Box Warning
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS Eculizumab products, complement inhibitors, increase the risk of serious infections caused by Neisseria meningitidis [see Warnings and Precautions (5.1) ] . Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of BKEMV, unless the risks of delaying therapy with...
Contraindications
- 4 CONTRAINDICATIONS BKEMV is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection [ see Warnings and Precautions (5.1) ]. BKEMV is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Serious Meningococcal Infections [ see Warnings and Precautions (5.1) ] Other Infections [ see Warnings and Precautions (5.3) ] Monitoring Disease Manifestations after BKEMV Discontinuation [ see Warnings and Precautions (5.4) ] Thrombosis Prevention and Management [ see Warnings and Precautions (5.5) ] Infusion-Related Reactions [ see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS 7.1 Plasmapheresis, Plasma Exchange, Fresh Frozen Plasma Infusion or IVIg Concomitant use of eculizumab products with plasma exchange (PE), plasmapheresis (PP), fresh frozen plasma infusion (PE/PI), or in patients with gMG on concomitant IVIg treatment can reduce serum eculizumab product concentrations and requires a supplemental dose of BKEMV [see Dosage and Administration (2.5) ] . 7.2 Neonatal Fc Receptor Blockers Concomitant use of eculizumab products with neonatal Fc receptor (FcRn) blockers may lower systemic exposures and reduce effectiveness of eculizumab products.