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Gamunex

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Gamunex

Side Effects
Interactions

SIDE EFFECTS

Adverse Drug Reaction Overview

The most serious adverse reaction observed in clinical study subjects receiving GAMUNEX (immune globulin intravenous (human) 10%) for PI was an exacerbation of autoimmune pure red cell aplasia in one subject.

The most serious adverse reaction observed in clinical study subjects receiving GAMUNEX (immune globulin intravenous (human) 10%) for ITP was myocarditis in one subject that occurred 50 days post study drug infusion and was not considered drug related.

The most serious adverse reaction observed in clinical study subjects receiving GAMUNEX (immune globulin intravenous (human) 10%) for CIDP was pulmonary embolism (PE) in one subject with a history of PE.

The most common drug related adverse reactions observed at a rate >5% in subjects with PI were headache, cough, injection site reaction, nausea, pharyngitis and urticaria.

The most common drug related adverse reactions observed at a rate >5% in subjects with ITP were headache, vomiting, fever, nausea, back pain and rash.

The most common drug related adverse reactions observed at a rate >5% in subjects with CIDP were headache, fever, chills and hypertension

Clinical Trials Adverse Drug Reactions

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.

Adverse events similar to those previously reported with the administration of intravenous and intramuscular immunoglobulin products may occur. Cases of reversible aseptic meningitis, migraine, isolated cases of reversible hemolytic anemia and reversible increases in liver function tests have been observed with GAMUNEX (immune globulin intravenous (human) 10%) . Immediate anaphylactic reactions can possibly occur (<0.01%). Epinephrine should be available for treatment of any acute anaphylactoid reaction. (see WARNINGS and PRECAUTIONS)

Treatment of Primary Humoral Immunodeficiency

The following table shows the number of subjects treated with GAMUNEX (immune globulin intravenous (human) 10%) in clinical trials to study PI, and the reason for discontinuation due to adverse events:

Table 1: Reasons for Discontinuation Due to Adverse Events: All PI Studies

Study Number Number of Subjects Treated with GAMUNEX Number of Subjects Discontinued Due to Adverse Events Adverse Event
100152 18 0 -----
100174 20 1 Coombs negative hypochromic anemia*
100175 87 1 Autoimmune pure red cell aplasia*
* Both events were considered unrelated to study drug as per the investigator.

In study 100175, 9 subjects in each treatment group were pretreated with non-steroidal medication prior to infusion. Generally, diphenhydramine and acetaminophen were used.

Any adverse events in trial 100175, irrespective of the causality assessment, are given in the following table.

Table 2: Subjects with At Least One Adverse Event Irrespective of Causality (Study 100175)

Adverse Event GAMUNEX (immune globulin intravenous (human) 10%)
No. of subjects: 87
No of subjects with AE
(percentage of all subjects)
GAMIMUNE N
No. of subjects: 85
No of subjects with AE
(percentage of all subjects)
Cough increased 47 (54%) 46 (54%)
Rhinitis 44 (51%) 45 (53%)
Pharyngitis 36 (41%) 39 (46%)
Headache 22 (25%) 28 (33%)
Fever 24 (28%) 27 (32%)
Diarrhea 24 (28%) 27 (32%)
Asthma 25 (29%) 17 (20%)
Nausea 17 (20%) 22 (26%)
Ear Pain 16 (18%) 12 (14%)
Asthenia 9 (10%) 13 (15%)

The subset of drug related adverse events in trial 100175 reported by at least 5% of subjects during the 9-month treatment are given in the following table.

Table 3: Subjects with At Least One Drug Related Adverse Event (Study 100175)

Drug Related Adverse Event GAMUNEX (immune globulin intravenous (human) 10%)
No. of subjects: 87
No. of subjects with drug related AE (percentage of all subjects)
GAMIMUNE N
No. of subjects: 85
No. of subjects with drug related AE (percentage of all subjects)
Headache 7 (8%) 8 (9%)
Cough increased 6 (7%) 4 (5%)
Injection site reaction 4 (5%) 7 (8%)
Nausea 4 (5%) 4 (5%)
Pharyngitis 4 (5%) 3 (4%)
Urticaria 4 (5%) 1 (1%)

Adverse events, which were reported by at least 5% of subjects, were also analyzed by frequency and in relation to infusions administered. The analysis is displayed in the following table.

Table 4: Adverse Event Frequency (Study 100175)

Adverse Event GAMUNEX (immune globulin intravenous (human) 10%)
No. of infusions: 825
Number of AE (percentageof all infusions)
GAMIMUNE N
No. of infusions: 865
Number of AE (percentageof all infusions)
Cough increased
  All 154 (18.7%) 148 (17.1%)
  Drug related 14 (1.7%) 11 (1.3%)
Pharyngitis
  All 96 (11.6%) 99 (11.4)
  Drug related 7 (0.8%) 9 (1.0%)
Headache
  All 57 (6.9%) 69 (8.0%)
  Drug related 7 (0.8%) 11 (1.3%)
Fever
  All 41 (5.0%) 65 (7.5%)
  Drug related 1 (0.1%) 9 (1.0%)
Nausea
  All 31 (3.8%) 43 (5.0%)
  Drug related 4 (0.5%) 4 (0.5%)
Urticaria
  All 5 (0.6%) 8 (0.9%)
  Drug related 4 (0.5%) 5 (0.6%)

The mean number of adverse events per infusion that occurred during or on the same day as an infusion was 0.21 in both the GAMUNEX (immune globulin intravenous (human) 10%) and GAMIMUNE N treatment groups.

In all three trials in primary humoral immundeficiencies, the maximum infusion rate was 0.08 mL/kg/min (8 mg/kg/min). The infusion rate was reduced for 11 of 222 exposed subjects (7 GAMUNEX (immune globulin intravenous (human) 10%) , 4 GAMIMUNE N) at 17 occasions. In most instances, mild to moderate hives/urticaria, itching, pain or reaction at infusion site, anxiety or headache was the main reason. There was one case of severe chills. There were no anaphylactic or anaphylactoid reactions to GAMUNEX (immune globulin intravenous (human) 10%) or GAMIMUNE N.

In trial 100175, serum samples were drawn to monitor the viral safety at baseline and one week after the first infusion (for parvovirus B19), eight weeks after first and fifth infusion, and 16 weeks after the first and fifth infusion of IGIV (for hepatitis C) and at any time of premature discontinuation of the study. Viral markers of hepatitis C, hepatitis B, HIV-1, and parvovirus B19 were monitored by nucleic acid testing (NAT, Polymerase Chain Reaction (PCR), and serological testing. There were no treatment emergent findings of viral transmission for either GAMUNEX (immune globulin intravenous (human) 10%) , or GAMIMUNE N. [1, 3, 4]

Treatment of Idiopathic Thrombocytopenic Purpura

The following table shows the number of subjects treated with GAMUNEX (immune globulin intravenous (human) 10%) in clinical trials to study ITP, and the reason for discontinuation due to adverse events:

Table 5: Reasons for Discontinuation Due to Adverse Events: All ITP Studies

Study Number Number of Subjects Treated with GAMUNEX Number of Subjects Discontinued Due to Adverse Events Adverse Event
100213 28 1 Hives
100176 48 1 Headache, Fever, Vomiting

One subject, a 10-year-old boy, died suddenly from myocarditis 50 days after his second infusion of GAMUNEX (immune globulin intravenous (human) 10%) . The death was judged to be unrelated to GAMUNEX (immune globulin intravenous (human) 10%) .

No pre-medication with corticosteroids was permitted by the protocol. Twelve (12) ITP subjects treated in each treatment group were pretreated with medication prior to infusion. Generally, diphenhydramine and/or acetaminophen were used. More than 90% of the observed drug related adverse events were of mild to moderate severity and of transient nature.

The infusion rate was reduced for 4 of the 97 exposed subjects (1 GAMUNEX (immune globulin intravenous (human) 10%) , 3 GAMIMUNE N) on 4 occasions. Mild to moderate headache, nausea, and fever were the reported reasons. There were no anaphylactic or anaphylactoid reactions to GAMUNEX (immune globulin intravenous (human) 10%) or GAMIMUNE N.

Any adverse events in trial 100176, irrespective of the causality assessment, reported by at least 5% of subjects during the 3-month trial are given in the following table.

Table 6: Subjects with At Least One Adverse Event Irrespective of Causality (Study 100176)

Adverse Event GAMUNEX (immune globulin intravenous (human) 10%)
No. of subjects: 48
No of subjects with AE
(percentage of all subjects)
GAMIMUNE N
No. of subjects: 49
No of subjects with AE
(percentage of all subjects)
Headache 28 (58%) 30 (61%)
Ecchymosis, Purpura 19 (40%) 25 (51%)
Hemorrhage (All systems) 14 (29%) 16 (33%)
Epistaxis 11 (23%) 12 (24%)
Petechiae 10 (21%) 15 (31%)
Fever 10 (21%) 7 (14%)
Vomiting 10 (21%) 10 (20%)
Nausea 10 (21%) 7 (14%)
Thrombocytopenia 7 (15%) 8 (16%)
Accidental injury 6 (13%) 8 (16%)
Rhinitis 6 (13%) 6 (12%)
Pharyngitis 5 (10%) 5 (10%)
Rash 5 (10%) 6 (12%)
Pruritis 4 (8%) 1 (2%)
Asthenia 3 (6%) 5 (10%)
Abdominal Pain 3 (6%) 4 (8%)
Arthralgia 3 (6%) 6 (12%)
Back Pain 3 (6%) 3 (6%)
Dizziness 3 (6%) 3 (6%)
Flu Syndrome 3 (6%) 3 (6%)
Neck Pain 3 (6%) 1 (2%)
Anemia 3 (6%) 0 (0%)
Dyspepsia 3 (6%) 0 (0%)

The subset of drug related adverse events in trial 100176 reported by at least 5% of subjects during the 3-month trial are given in the following table.

Table 7: Subjects with At Least One Drug Related Adverse Event (Study 100176)

Drug Related Adverse Event GAMUNEX (immune globulin intravenous (human) 10%)
No. of subjects: 48
No. of subjects with drug related AE (percentage of all subjects)
GAMIMUNE N
No. of subjects: 49
No. of subjects with drug related AE (percentage of all subjects)
Headache 24 (50%) 24 (49%)
Vomiting 6 (13%) 8 (16%)
Fever 5 (10%) 5 (10%)
Nausea 5 (10%) 4 (8%)
Back Pain 3 (6%) 2 (4%)
Rash 3 (6%) 0 (0%)

Serum samples were drawn to monitor the viral safety of the ITP subjects at baseline, nine days after the first infusion (for parvovirus B19), and 3 months after the first infusion of IGIV and at any time of premature discontinuation of the study. Viral markers of hepatitis C, hepatitis B, HIV-1, and parvovirus B19 were monitored by nucleic acid testing (NAT, PCR), and serological testing. There were no treatment related emergent findings of viral transmission for either GAMUNEX (immune globulin intravenous (human) 10%) , or GAMIMUNE N [11].

Treatment of Chronic Inflammatory Demyelinating Polyneuropathy

In study 100538, 113 subjects were exposed to GAMUNEX and 95 were exposed to Placebo (See Clinical Studies). As a result of the study design, the drug exposure with GAMUNEX (immune globulin intravenous (human) 10%) was almost twice that of Placebo, with 1096 GAMUNEX (immune globulin intravenous (human) 10%) infusions versus 575 Placebo infusions. Therefore, adverse reactions are reported per infusion (represented as frequency) to correct for differences in drug exposure between the 2 groups. The majority of loading-doses were administered over 2 days. The majority of maintenance-doses were administered over 1 day. Infusions were administered in the mean over 2.7 hours.

The following table shows the numbers of subjects per treatment group in the CIDP clinical trial, and the reason for discontinuation due to adverse events:

Table 8: Reasons for Discontinuation Due to Adverse Events: CIDP

Number of Subjects Number of Subjects Discontinued due to Adverse Events Adverse Event
GAMUNEX 113 3 (2.7%) Urticaria, Dyspnea, Bronchopneumonia
Placebo 95 2 (2.1%) Cerebrovascular Accident, Deep Vein Thrombosis

Adverse events reported by at least 5% of subjects in any treatment group irrespective of causality are shown in the following table.

Table 9: Subjects with At Least One Adverse Event Irrespective of Causality (Study 100538)

MedDRA Preferred Term a GAMUNEX
No. of subjects: 113
Placebo
No. of subjects: 95
  No. of Subjects (%) No. of Adverse Events Incidence density b No. of Subjects (%) No. of Adverse Events Incidence density b
Any Adverse Event 85 (75) 377 0.344 45 (47) 120 0.209
Headache 36 (32) 57 0.052 8 (8) 15 0.026
Pyrexia (fever) 15 (13) 27 0.025 0 0 0
Hypertension 10 (9) 20 0.018 4 (4) 6 0.010
Rash 8 (7) 13 0.012 1 (1) 1 0.002
Arthralgia 8 (7) 11 0.010 1 (1) 1 0.002
Asthenia 9 (8) 10 0.009 3 (3) 4 0.007
Chills 9 (8) 10 0.009 0 0 0
Back pain 9 (8) 10 0.009 3 (3) 3 0.005
Nausea 7 (6) 9 0.008 3 (3) 3 0.005
Dizziness 7 (6) 3 0.006 1 (1) 1 0.002
Influenza 6 (5) 6 0.005 2 (2) 2 0.003
a Reported in ≥ 5% of subjects in any treatment group irrespective of causality.
b Calculated by the total number of adverse events divided by the number of infusions received (1096 for GAMUNEX (immune globulin intravenous (human) 10%) and 575 for Placebo)

Drug-related adverse events reported by at least 5% of subjects in any treatment group are reported in the following table. The most common drug-related events with GAMUNEX (immune globulin intravenous (human) 10%) were headache and pyrexia:

Table 10: Subjects with At Least 1 Drug Related Adverse Event (Study 100538)

MedDRA Preferred term a GAMUNEX
No. of subjects:113
Placebo
No. of subjects: 95
No. of Subjects (%) No. of Adverse Events Incidence density b No. of Subjects (%) No. of Adverse Events Incidence density b
Any drug-related adverse event 62 (55) 194 0.177 16 (17) 25 0.043
Headache 31 (27) 44 0.040 6 (6) 7 0.012
Pyrexia (fever) 15 (13) 26 0.024 0 0 0
Chills 8 (7) 9 0.008 0 0 0
Hypertension 7 (6) 16 0.015 3 (3) 3 0.005
Rash 6 (5) 8 0.007 1 (1) 1 0.002
Nausea 6 (5) 7 0.006 3 (3) 3 0.005
Asthenia 6 (5) 6 0.005 0 0 0
a Reported in ≥ 5% of subjects in any treatment group.
b Calculated by the total number of adverse events divided by the number of infusions received (1096 for GAMUNEX (immune globulin intravenous (human) 10%) and 575 for Placebo).

Laboratory Abnormalities

During the course of the clinical program, ALT and AST elevations were identified in some subjects.

  • For ALT, in the primary humoral immunodeficiency (PI) study (100175) treatment emergent elevations above the upper limit of normal were transient and observed among 14/80 (18%) of subjects in the GAMUNEX (immune globulin intravenous (human) 10%) group versus 5/88 (6%) of subjects in the GAMIMUNE N group (p = 0.026).
  • In the ITP study which employed a higher dose per infusion, but a maximum of only two infusions, the reverse finding was observed among 3/44 (7%) of subjects in the GAMUNEX (immune globulin intravenous (human) 10%) group versus 8/43 (19%) of subjects in the GAMIMUNE N group (p = 0.118).
  • In the CIDP study (100538), 15/113 (13%) of subjects in the GAMUNEX (immune globulin intravenous (human) 10%) group and 7/95 (7%) in the Placebo group (p=0.168) had a treatment emergent transient elevation of ALT.

Elevations of ALT and AST were generally mild (<3 times upper limit of normal), transient, and were not associated with obvious symptoms of liver dysfunction.

GAMUNEX (immune globulin intravenous (human) 10%) class. may contain low levels of anti-Blood Group A and B antibodies primarily of the IgG4

Direct antiglobulin tests (DAT or direct Coombs tests), which are carried out in some centers as a safety check prior to red blood cell transfusions, may become positive temporarily. Hemolytic events not associated with positive DAT findings were observed in clinical trials.[1, 3, 4, 11, 36]

Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

GAMUNEX (immune globulin intravenous (human) 10%) Postmarketing Experience

The following adverse reactions have been identified and reported during the post marketing use of GAMUNEX (immune globulin intravenous (human) 10%) :

  • Hematologic:Hemolytic anemia
  • Infections and Infestations: Aseptic meningitis
General

The following adverse reactions have been identified and reported during the post marketing use of IGIV products [37]:

Read the Gamunex (immune globulin intravenous (human) 10%) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

GAMUNEX (immune globulin intravenous (human) 10%) may be diluted with 5% dextrose in water (D5/W). Admixtures of GAMUNEX (immune globulin intravenous (human) 10%) with other drugs and intravenous solutions have not been evaluated. It is recommended that GAMUNEX (immune globulin intravenous (human) 10%) be administered separately from other drugs or medications which the patient may be receiving. The product should not be mixed with IGIVs from other manufacturers.

The infusion line may be flushed before and after administration of GAMUNEX (immune globulin intravenous (human) 10%) with 5% dextrose in water. Various passively transferred antibodies in immunoglobulin preparations can confound the results of serological testing.

Antibodies in GAMUNEX (immune globulin intravenous (human) 10%) may interfere with the response to live viral vaccines such as measles, mumps and rubella. Physicians should be informed of recent therapy with IGIVs, so that administration of live viral vaccines, if indicated, can be appropriately delayed 3 or more months from the time of IGIV administration. (See Patient Counseling Information)

REFERENCES

1. Kelleher J, F.G., Cyrus P, Schwartz L,, A Randomized, Double-Blind, Multicenter, Parallel Group Trial Comparing the Safety and Efficacy of IGIV-Chromatography, 10% (Experimental) with IGIV-Solvent Detergent Treated, 10% (Control) in Patients with Primary Immune Deficiency (PID), 2000. Report on file.

3. Bayever E, M.F., Sundaresan P, Collins S, Randomized, Double-Blind, Multicenter, Repeat Dosing, Cross-Over Trial Comparing the Safety, Pharmacokinetics, and Clinical Outcomes of IGIV-Chromatography, 10% (Experimental) with IGIV-Solvent Detergent Treated, 10% (Control) in Patients with Primary Humoral Immune Deficiency (BAY-41-1000-100152). MMRR-1512/1, 1999.

4. Lathia C, E.B., Sundaresan PR, Schwartz L, A Randomized, Open-Label, Multicenter, Repeat Dosing, Cross-Over Trial Comparing the Safety, Pharmacokinetics, and Clinical Outcomes of IGIV-Chromatography, 5% with IGIV-Chromatography 10% in Patients with Primary Humoral Immune Deficiency (BAY-41-1000-100174). 2000.

11. Cyrus P, F.G., Kelleher J, Schwartz L,, A Randomized, Double-Blind, Multicenter, Parallel Group Trial Comparing the Safety, and Efficacy of IGIV-Chromatography, 10% (Experimental) with IGIV-Solvent Detergent Treated, 10% (Control) in Patients with Idiopathic (Immune) Thrombocytopenic Purpura (ITP), 2000. Report on file.

36. Kelleher J, S.L., IGIV-C 10% Rapid Infusion Trial in Idiopathic (Immune) Thrombocytopenic Purpura (ITP), 2001. Report on file.

37. Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Trans Med Rev 2003; 17,241-251.

Last reviewed on RxList: 10/2/2008
This monograph has been modified to include the generic and brand name in many instances.

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