SIDE EFFECTS

General

Various mild and moderate reactions, such as headache, fever, fatigue, chills, flushing, dizziness, urticaria, wheezing or chest tightness, nausea, vomiting, rigors, back pain, chest pain, muscle cramps, and changes in blood pressure may occur with infusions of Immune Globulin Intravenous (Human). In general, reported adverse reactions to GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) in patients with Primary Immunodeficiency are similar in kind and frequency to those observed with other IGIV products. Slowing or stopping the infusion usually allows the symptoms to disappear promptly. Although hypersensitivity reactions have not been reported in the clinical studies with GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) immediate anaphylactic and hypersensitivity reactions are a remote possibility. Epinephrine and antihistamines should be available for treatment of any acute anaphylactic reactions (see WARNINGS).

Clinical Study

Adverse experiences were examined among a total of 61 enrolled subjects with Primary Immunodeficiency who received at least one infusion of GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) during the Phase 3 multicenter clinical study. For this study, temporally associated adverse events are defined by the FDA as those occurring during or within 72 hours of completion of an infusion. Adverse drug reactions (ADR's) are those adverse events that were deemed by the investigators as causally related to the infusion of GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) .

Of all adverse experiences, 15 events in 8 subjects were serious. Two serious events, two episodes of aseptic meningitis in one patient, were deemed to be possibly related to the infusion of GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) .

Among the 896 non-serious adverse experiences, 258 were judged by the investigator to be possibly or probably related to the infusion of GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) . Of these, 136 were mild, 106 were moderate, and 16 were severe. All of the severe non-serious adverse experiences were transient, did not lead to hospitalization, and resolved without complication. One subject withdrew from the study due to a non-serious adverse experience (papular rash).

Of the 345 temporally related adverse experiences, those occurring in > 5% of subjects are shown in Table 5. Of these events, only headache occurred in association with more than 5% of infusions. All events were expected based on past experiences with intravenous gammaglobulin products.

Table 5: Adverse Events*, Regardless of Causality, that Occurred within 72 Hours of Infusion

The majority (227/258) of the non-serious adverse experiences deemed related to study product were considered expected based on previous experience with IGIV products and 31 were considered unexpected. In virtually every case, these unexpected events were either consistent with the subject's specific type of immunodeficiency or with the subject's medical history prior to entering the study. A total of 14 hospitalizations occurred during the study but none were related to infection. Hematology and clinical chemistry parameters were monitored in all subjects prior to each infusion throughout the 12-month period of study. Mean values for all laboratory parameters remained consistent throughout the study period. Three of the hematology values in one subject were outside of the normal range and reported as non-serious adverse experiences that resolved completely. These were a red cell count of 3.9 x106/jL, hematocrit of 31%, and white cell count of 3.88 x 103/jL. All spontaneously returned to baseline. One subject had an elevated BUN (45 mg/dL) and creatinine (1.4 mg/dL) on one occasion that were reported as non-serious adverse experiences and resolved completely. These values improved to 30 mg/dL and 0.8 mg/dL, respectively, by the next infusion. Six of the patients had a single, transient elevation in serum transaminases. Two additional patients had persistent elevations in transaminases, ALT and AST, which were present at the initiation of the study, prior to the infusion of GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) . There was no other evidence of liver abnormalities. None of the hematology or chemistry laboratory abnormalities that occurred during the course of the study required clinical intervention and none had clinical consequences. During the Phase 3 clinical study, viral safety was assessed by serological screening for HBsAg and antibodies to HCV and HIV-1 and HIV-2 prior to, during, and at the end of the study and by Polymerase Chain Reaction (PCR) tests for HBV, HCV, and HIV-1 genomic sequences prior to and at the end of the study. None of the 61 treated subjects were positive prior to study entry and none converted from negative to positive during the 12-month period of study.

Postmarketing:

The following is a list of adverse reactions that have been identified and reported during the post-approval use of IGIV products:

Rare and Uncommon Adverse Events:

Because postmarketing reporting of these reactions is voluntary and the at-risk populations are of uncertain size, it is not always possible to reliably estimate the frequency of the reaction to establish a causal relationship to exposure to the product. Such is also the case with literature reports authored independently⁴⁵ (see PRECAUTIONS).

Read the entire FDA prescribing information for Gammagard Liquid (Immune Globulin Intravenous (Human) 10%) »