Intravenous Immunoglobulin Manufactured Using a Novel Caprylate and Chromatography-Based Method (IGIV-C, Gamunex®) Was Safe and Well Tolerated When Administered at an Increased Maximum Rate in Patients with Idiopathic Thrombocytopenic Purpura (ITP).

The objective of this study was to determine the safety and tolerability of a novel intravenous immunoglobulin preparation (IGIV-C; Gamunex^®, 10%) when infused at two different infusion rates. The standard maximum licensed rate (0.08 mL/kg/min) for IGIV-C was compared with a maximum rate almost twice as high (0.14 mL/kg/min). Eight patients with a confirmed diagnosis of idiopathic thrombocytopenic purpura (ITP) were enrolled and randomized in this single center, open label, cross-over study. IGIV-C (dose 1.0 g/kg) was given on two occasions as a single daily infusion (for platelet counts <30 Giga/L), at maximum intervals of six weeks. Patients randomized to Group 1 received their first infusion of IGIV-C at the standard maximum rate; their second infusion at the higher rate. Conversely, patients randomized to Group 2 received their first infusion of IGIV-C at 0.14 mL/kg/min; their second infusion at a rate of 0.08 mL/kg/min. All infusions were started at an initial infusion rate of 0.02 mL/kg/min, with a stepwise increase to 0.04 mL/kg/min, then to 0.08 or 0.14 mL/kg/min. Infusions were maintained for at least 15 minutes at each infusion rate, and if well tolerated, increased to the target rate. All 8 patients were valid for the safety analysis. Eight patients received the standard infusion rate (0.08 mL/kg/min) and 7 patients received the faster infusion rate (0.14 mL/kg/min) (one patient did not require a second infusion due to the unexpected maintenance of platelet counts). The incidence of infusion related adverse events was similar for both infusion rates; only acetaminophen and diphenhydramine premedication were allowed. The most commonly reported adverse event was headache (62.5% of patients infused at 0.08 mL/kg/min; 57.1% at 0.14 mL/kg/min). Only headaches and urticaria were deemed by the investigator to be drug-related. None of the treatment emergent events were severe, in fact 84% were mild in nature, in spite of the difference in fluid loading over a shorter period of time for patients infused at the higher rate. Analysis of laboratory findings did not reveal any clinically important changes in parameters that distinguished between the two infusion rates, and there were no signs of hemolysis (Day 7 hemoglobin change from baseline, −0.58 ± 0.60 g/dL, 0.08mL/kg/min; and −0.99 ± 0.73 g/dL, 0.14 mL/kg/min). The mean duration of study drug infusion was 97.86 ± 6.36 minutes for the 0.14 mL/kg/min infusion rate compared with 146.25 ± 5.82 minutes for the 0.08 mL/kg/min rate, a time savings of 48.4 minutes (approximately one-third of the infusion time). These results are consistent with our previous multicenter 3-part crossover study (n = 28 patients enrolled,