Overview
11 DESCRIPTION Emapalumab-lzsg is an interferon gamma (IFNγ) neutralizing antibody. Emapalumab-lzsg is produced in Chinese Hamster Ovary cells by recombinant DNA technology. Emapalumab-lzsg is an IgG1 immunoglobulin with a molecular weight of approximately 148 kDa. GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Emapalumab-lzsg is a monoclonal antibody that binds to and neutralizes interferon gamma (IFNγ). Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of HLH by being hypersecreted. 12.2 Pharmacodynamics IFNγ Inhibition Emapalumab-lzsg reduces the plasma concentrations of CXCL9, a chemokine induced by IFNγ. Cardiac Electrophysiology At a dose of 3 mg/kg GAMIFANT does not prolong the QT interval to any clinically relevant extent. 12.3 Pharmacokinetics The pharmacokinetics of emapalumab-lzsg were evaluated in healthy adult subjects and in patients with HLH. Following a 1 mg/kg emapalumab-lzsg dose, median steady state peak concentration was 44 mcg/mL, which was 2.9 times higher than after the first dose.
Indications
- 1 INDICATIONS AND USAGE GAMIFANT is indicated for the treatment of: adult and pediatric patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. adult and pediatric patients with HLH/macrophage activation syndrome (MAS) in known or suspected Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA), with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS.
Common Doses
- 1 mg
- 6 mg
- 3 mg
- 10 mg
Dosage
2 DOSAGE AND ADMINISTRATION For intravenous infusion only: Primary HLH recommended starting dosage: 1 mg/kg as an intravenous infusion over 1 hour twice per week. ( 2.1 ) HLH/MAS in Still’s disease recommended dosage schedule: 6 mg/kg, followed by 3 mg/kg every 3 days for 5 doses, then 3 mg/kg twice per week. Given as an intravenous infusion over 1 hour. ( 2.2 ) For both indications, the dose may be titrated up to a maximum of 10 mg/kg. ( 2.5 , 2.6 ) 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions ( 5.1 )] Increased Risk of Infection with Use of Live Vaccines [see Warnings and Precautions ( 5.2 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.3 )] In patients with primary HLH, the most common adverse reactions (≥ 20%) were: infections, hypertension, infusion-related reactions, and pyrexia. ( 6.
Interactions
- 7 DRUG INTERACTIONS 7.1 Effect of GAMIFANT on Cytochrome P450 Substrates The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (such as IFNγ) during chronic inflammation. By neutralizing IFNγ, use of GAMIFANT may normalize CYP450 activities which may reduce the efficacy of drugs that are CYP450 substrates due to increased metabolism. Upon initiation or discontinuation of concomitant GAMIFANT, monitor for reduced efficacy and adjust dosage of CYP450 substrate drugs as appropriate.