The most common adverse reactions observed in ≥5% of clinical study subjects receiving GAMMAGARD LIQUID for CIDP were headache, pyrexia, anemia, leukopenia, neutropenia, illness, blood creatinine increased, dizziness, migraine, somnolence, tremor, nasal dryness, abdominal pain upper, vomiting, chills, nasopharyngitis, and pain in extremity.
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
Treatment of Primary Immunodeficiency (Intravenous)
The safety of GAMMAGARD LIQUID intravenous infusion was evaluated in 61 subjects.
Fifteen adverse reactions in 8 subjects were serious. Of these, two episodes of aseptic meningitis in one subject were deemed possibly related to infusion of GAMMAGARD LIQUID.
There were 400 non-serious adverse reactions. Of these, 217 were rated as mild (transient discomfort that resolves spontaneously or with minimal intervention), 164 were rated as moderate (limited impairment of function and resolves spontaneously or with minimal intervention with no sequelae), and 19 were rated as severe (marked impairment of function or can lead to temporary inability to resume normal life pattern; requires prolonged intervention or results in sequelae). 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).
Adverse reactions with a frequency of ≥5% (defined as adverse events occurring during or within 72 hours of infusion or any causally related event occurring within the study period) are shown in Table 8.
Pooled analysis of 4 short term clinical studies with 106 subjects (total of 854 infusions) showed no differences in the safety profile of GAMMAGARD LIQUID. These short-term studies were designed to stabilize the immune globulin treatment or as a safety follow-up study. They were not designed to study the safety, efficacy and tolerability of GAMMAGARD LIQUID. No additional adverse reactions were reported during the study periods.
Treatment of Primary Immunodeficiency (Subcutaneous)
The safety of GAMMAGARD LIQUID in subcutaneous infusion was evaluated in 47 subjects.
Adverse reactions with a frequency of ≥5% (defined as adverse events occurring during or within 72 hours of infusion or any causally related event occurring within the study period) are shown in Table 9.
Of the 348 non-serious adverse reactions, 228 were rated as mild (transient discomfort that resolves spontaneously or with minimal intervention), 112 were rated as moderate (limited impairment of function and resolves spontaneously or with minimal intervention with no sequelae), and 8 were rated as severe (marked impairment of function or can lead to temporary inability to resume normal life pattern; requires prolonged intervention or results in sequelae). Neither of the severe adverse reactions required hospitalization or resulted in sequelae.
Local Adverse Reactions:
Local adverse reactions reported as mild (transient discomfort that resolves spontaneously or with minimal intervention) were rash, erythema, edema, hemorrhage, and irritation. Local adverse reactions reported as mild or moderate (limited impairment of function and resolves spontaneously or with minimal intervention with no sequelae) were pain, hematoma, pruritus, and swelling.
One subject withdrew from the study after 10 treatments with GAMMAGARD LIQUID subcutaneous infusion (2.5 months) due to increased fatigue and malaise.
The overall rate of local adverse reactions (excluding infections) during subcutaneous treatment was 2.4% per infusion. In subcutaneous naïve subjects, the incidence of local adverse reactions (N=1757 infusions) was 2.8% (2.2% mild and 0.6% moderate with no severe adverse reactions). In the subjects who were subcutaneous experienced (N=537 infusions), the incidence of local adverse reactions was 1.1% (1.1% mild, and no moderate or severe adverse reactions).
After all subcutaneous doses were adjusted, only one subject did not reach the maximum rate allowed in the protocol for one or more infusions, 20 mL/site/hour if weight was below 40 kg and 30/mL/hour for weight 40 kg and greater. Overall, 70% (31 of 44) of subjects opted for the highest rate for all infusions. No subject limited the infusion rate due to an adverse reaction. Median duration of each weekly infusion was 1.2 hours (range: 0.8-2.3 hours). The rate set on the pump was the rate per site multiplied by the number of sites, with no maximum.
During subcutaneous treatment, 99.8% of infusions were completed without a reduction, interruption, or discontinuation for tolerability reasons. The proportion of subjects who experienced local adverse reactions (excluding infections) was highest immediately following the switch from intravenous to subcutaneous treatment in all age groups. The rate of local adverse reactions per infusion immediately after switching from intravenous to subcutaneous treatment was 4.9% (29/595), decreasing to 1.5% (8/538) by the end of the study and to 1.1% (10/893) in the Study Extension. There was a decrease of local adverse reactions over subsequent subcutaneous infusions.
Eight (17%) subjects experienced a local adverse reaction during the first infusion, but that decreased to 1 (2.2%) for subsequent infusions, ranging from 0 to 4 (8.7%) during the first year of subcutaneous treatment. No subject reported a local adverse reaction from week 53 to end of study at week 68.
Analysis of a short-term follow-up safety study of 10 subjects who were treated with subcutaneous administration of GAMMAGARD LIQUID (total of 218 infusions) showed no differences in the safety profile. The follow-up safety study was not designed to study the safety, efficacy and tolerability of GAMMAGARD LIQUID and no additional adverse reactions were reported during the study period.
Treatment of Multifocal Motor Neuropathy (Intravenous)
The safety of GAMMAGARD LIQUID was evaluated in 44 subjects with MMN who received a total of 983 infusions. Two serious adverse reactions, pulmonary embolism and blurred vision, occurred.
In the study, among the 317 non-serious adverse reactions, 176 were considered ARs. Of these, 126 were mild (transient discomfort that resolves spontaneously or with minimal intervention), 37 were moderate (limited impairment of function and resolves spontaneously or with minimal intervention with no sequelae) and 13 were severe (marked impairment of function or can lead to temporary inability to resume normal life pattern; requires prolonged intervention or results in sequelae).
Adverse reactions with a frequency ≥5% (defined as adverse events occurring during or within 72 hours of infusion or any causally related event occurring within the study period) are shown in Table 10.
Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (Intravenous)
The safety of GAMMAGARD LIQUID was evaluated in a clinical study of 20 adult subjects with CIDP. A total of 389 infusions of GAMMAGARD LIQUID were administered during the study.
Fourteen out of the 20 subjects reported 60 adverse events; 9 experienced mild events (transient discomfort that resolves spontaneously or with minimal intervention), 3 had moderate events (limited impairment of function and resolves spontaneously or with minimal intervention with no sequelae), and 2 experienced severe events (marked impairment of function or can lead to a temporary inability to resume normal life pattern; requires prolonged intervention or results in sequelae). There were 39 ARs in 13 subjects (65%), and 31 related to GAMMAGARD LIQUID in 11 subjects (55%). One subject (5%) experienced one severe AR (headache) related to GAMMAGARD LIQUID. No AR resulted in early discontinuation or death, and no serious AR was reported.
Adverse reactions with a frequency ≥5% (defined as adverse events occurring during or within 72 hours of infusion or any causally related event occurring within the study period) are shown in Table 11.