Nivolumab is available as a 10-mg/mL concentrate for injection in 4-, 10-, 12-, and 24-mL preservative-free, single-dose vials.3879 Each mL of the concentrate contains nivolumab 10 mg with mannitol 30 mg, pentetic acid 0.008 mg, polysorbate 80 0.2 mg, sodium chloride 2.92 mg, and sodium citrate dihydrate 5.88 mg in water for injection.3879 Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.3879
The concentrate must be diluted prior to administration.3879 To prepare the drug for intravenous infusion, the appropriate dose of the concentrate should be withdrawn from the vial and added to an infusion bag followed by a volume of dextrose 5% or sodium chloride 0.9% to yield a final nivolumab concentration between 1 and 10 mg/mL.3879 The total volume of infusion must not exceed 160 mL for patients weighing 40 kg or greater; for adult and pediatric patients with body weight less than 40 kg, the total volume of infusion must not exceed 4 mL/kg of body weight.3879 The solution should be mixed by gentle inversion and should not be shaken.3879 Any unused portion remaining in vials should be discarded.3879
pH
6.3879
Trade Name(s)
Opdivo
Nivolumab is administered by intravenous infusion over 30 minutes only after dilution in dextrose 5% or sodium chloride 0.9%.3879 Diluted solutions for infusion should be administered through a 0.2- to 1.2-µm low protein-binding inline filter.3879 The infusion line should be flushed after each infusion.3879
Other drugs should not be co-administered with nivolumab through the same infusion line.3879
Intact vials of nivolumab should be stored at 2 to 8°C in the original carton to protect from light and should not be shaken or frozen.3879 The concentrate for injection is a clear to slightly opalescent, colorless to pale yellow solution that may contain a few translucent to white proteinaceous particles.3879 Vials should be visually inspected for particulate matter and discoloration prior to use; discard the solution if it is discolored, cloudy, or if particulate matter other than translucent to white protineaceous particles is present.3879
The manufacturer states diluted solutions may be stored for no more than 8 hours at room temperature in light or 7 days at 2 to 8°C and protected from light, including administration time.3879 Diluted solutions should be discarded after 8 hours at room temperature or 7 days at 2 to 8°C.3879 Product labeling states diluted solutions should not be frozen.3879
Stability of nivolumab concentrate for injection (Bristol Myers Squibb) in opened vials and diluted solutions was evaluated in a study using a variety of methods to assess physicochemical stability (spectrophotometry, pH and osmolality measurement, dynamic light scattering, steric exclusion high-performance liquid chromatography [HPLC], ion exchange HPLC, peptide mapping HPLC).4115 In addition, to determine functional activity of the drug, a competition assay was performed to determine the drug's ability to bind to programmed-death receptor-1 (PD-1).4115 Nivolumab concentrate for injection (10 mg/mL) in the original vial following puncture with a vial access spike was stable for up to 28 days when stored at 2 to 8°C or up to 7 days at 40°C.4115 Diluted solutions of nivolumab 2 mg/mL in sodium chloride 0.9% in polyolefin bags (Fresenius Kabi) also were stable for up to 28 days when stored at 2 to 8°C or up to 7 days at 40°C, with evidence of possible deamidation of the drug observed after 28 days.4115
Freezing Solutions
Diluted solutions of nivolumab (Bristol Myers Squibb) 2 mg/mL in sodium chloride 0.9% in polyolefin bags (Fresenius Kabi) were frozen at -20°C followed by thawing for 3 freeze-thaw cycles.4115 Using a variety of methods to assess physicochemical stability, nivolumab 2 mg/mL in sodium chloride 0.9% was found to be stable following 2 freeze-thaw cycles.4115 Physical instability (increased dispersity index on dynamic light scattering, indicating possible protein aggregation) was observed after the third freeze-thaw cycle.4115
Filtration
Diluted solutions for infusion should be administered through a 0.2- to 1.2-µm low protein-binding inline filter.3879
For a list of references cited in the text of this monograph, search the monograph titled References.