openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Adverse reactions sections page 1 of 3 · 12 matching rows.
adverse reactions
6 ADVERSE REACTIONS The most common adverse reactions observed at a rate ≥5% in subjects treated with IV GAMUNEX-C for PI were headache, cough, injection site reaction, nausea, pharyngitis and urticaria. The most common adverse reactions observed at a rate ≥5% of subjects treated with SC GAMUNEX-C for PI were infusion site reactions, headache, fatigue, arthralgia and pyrexia. The most common adverse reactions observed at a rate ≥5% in subjects treated with GAMUNEX-C for ITP were headache, vomiting, fever, nausea, back pain and rash. The most common adverse reactions observed at a rate ≥5% in subjects with GAMUNEX-C for CIDP were headache, fever, chills, hypertension, rash, nausea and asthenia. PI - The most common adverse reactions (≥5%) with intravenous use of GAMUNEX-C were headache, cough, injection site reaction, nausea, pharyngitis and urticaria. The most common adverse reactions (≥5%) with subcutaneous use of GAMUNEX-C were infusion site reactions, headache, fatigue, arthralgia and pyrexia. ( 6.1 ) ITP - The most common adverse reactions during clinical trials (reported in ≥5% of subjects) were headache, vomiting, fever, nausea, back pain and rash. ( 6.1 ) CIDP - The most common adverse reactions during clinical trials (reported in ≥5% of subjects) were headache, fever, chills, hypertension, rash, nausea and asthenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Talecris Biotherapeutics, Inc. at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to rates in other clinical trials of another drug and may not reflect the rates observed in clinical practice. Treatment of Primary Humoral Immunodeficiency by the Intravenous Route The most serious adverse event observed in clinical study subjects receiving GAMUNEX-C IV for PI was an exacerbation of autoimmune pure red cell aplasia in one subject. In four different clinical trials to study PI, out of 157 subjects treated with GAMUNEX-C, 4 subjects discontinued due to the following adverse events: Coombs negative hypochromic anemia, Autoimmune pure red cell aplasia, arthralgia/hyperhidrosis/fatigue/myalgia/nausea and migraine. In a study of 87 subjects, 9 subjects in each treatment group were pretreated with non-steroidal medication prior to infusion, such as diphenhydramine and acetaminophen. Table 2 lists all adverse events occurring in greater than 10% of subjects irrespective of the causality assessment. Table 2: Adverse Events Occurring in >10% of Subjects Irrespective of Causality Adverse Event GAMUNEX-C ® GAMIMUNE ® N, 10% No. of subjects: 87 No. of subjects: 85 No. of subjects with AE No. of subjects with AE (percentage of all subjects) (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%) Table 3 lists the adverse reactions reported by at least 5% of subjects during the 9-month treatment. Table 3: Adverse Reactions Occurring in ≥5% of Subjects Adverse Reactions GAMUNEX-C ® GAMIMUNE ® N, 10% No. of subjects: 87 No. of subjects: 85 No. of subjects with adverse reaction No. of subjects with adverse reaction (percentage of all subjects) (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%) Table 4 lists the frequency of adverse reactions, which were reported by at least 5% of subjects, and their relationship to infusions administered. Table 4: Adverse Experience Frequency GAMUNEX ® -C GAMIMUNE ® N, 10% Adverse Experience No. of infusions: 825 No. of infusions: 865 Number (percentage of all infusions) (percentage of all subjects) 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 rela ted 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 reactions per infusion that occurred during or on the same day as an infusion was 0.21 in both the GAMUNEX-C and GAMIMUNE ® N, Immune Globulin Intravenous (Human), 10%, 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-C, 4 GAMIMUNE N, 10%) 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-C or GAMIMUNE N, 10% in clinical trials. In the IV efficacy and safety study, 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. Treatment of Primary Humoral Immunodeficiency by the Subcutaneous Route (SC PK and Safety Study) Adverse experiences were divided into 2 types: 1) Local infusion site reactions, and 2) Non-infusion site adverse events. Table 5 lists those adverse events occurring in ≥ 2% of infusions during the SC phase of the study. Table 5: Most Frequent Adverse Experience (≥ 2% of infusions) by Infusion Irrespective of Causality in the SC Phase Adverse Experience (≥2% of infusions) Number (Number of infusions: 725) (Rate Rate is calculated by the total number of events divided by the number of infusions received (725) ) Local Infusion Site reactions 427 (0.59) Mild 389 (0.54) Moderate 29 (0.04) Severe 9 (0.01) Non-infusion site adverse events Headache 37 (0.05) Sinusitis 11 (0.02) Table 6 lists the adverse reactions occurring in ≥5% of subjects and the frequency of adverse reactions per infusion. All local infusion site reactions were a priori considered drug-related. Table 6: Most Frequent Adverse Reactions (≥5% of subjects) by Subject and Infusion in the SC phase Adverse Reactions No. of Subjects No. of Adverse Reactions (≥5% of subjects) n=32 (% ) (Rate Rate is calculated by the total number of events divided by the number of infusions received (725) ) Local Infusion Site Reactions 24 (75%) 427 (0.59) Non-infusion Site Adverse Reactions Headache 4 (13%) 21 (0.03) Arthralgia 2 (6.3%) 4 (0.01) Fatigue 2 (6.3%) 3 (≤0.01) Pyrexia 2 (6.3%) 2 (≤0.01) There were no serious bacterial infections in the SC phase of the PK and safety study. Local Infusion Site Reactions Local infusion site reactions with SC GAMUNEX-C consisted of erythema, pain and swelling. The majority of local infusion site reactions resolved within 3 days. The number of subjects experiencing an infusion site reaction and the number of infusion site reactions decreased over time as subjects received continued weekly SC infusions. At the beginning of the SC phase (week 1), a rate of approximately 1 infusion site reaction per infusion was reported, whereas at the end of the study (week 24) this rate was reduced to 0.5 infusion site reactions per infusion, a reduction of 50%. Treatment of Idiopathic Thrombocytopenic Purpura In two different clinical trials to study ITP, out of 76 subjects treated with GAMUNEX-C, 2 subjects discontinued due to the following adverse events: Hives and Headache/Fever/Vomiting. One subject, a 10-year-old boy, died suddenly from myocarditis 50 days after his second infusion of GAMUNEX-C. The death was judged to be unrelated to GAMUNEX-C. 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-C, 3 GAMIMUNE N, 10%) on 4 occasions. Mild to moderate headache, nausea, and fever were the reported reasons. Table 7 lists any adverse events, irrespective of the causality, reported by at least 5% of subjects during the 3-month efficacy and safety study. Table 7: Adverse Events Occurring in ≥ 5% of Subjects Irrespective of Causality GAMUNEX ® -C GAMIMUNE ® N, 10% Adverse Event No. of subjects: 48 No. of subjects: 49 No. of subjects with AE No. of subjects with AE (percentage of all subjects) (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%) Table 8 lists the adverse reactions reported by at least 5% of subjects during the 3-month efficacy and safety study. Table 8: Adverse Reactions Occurring in ≥5% of Subjects GAMUNEX ® -C GAMIMUNE ® N, 10% Adverse Event No. of subjects: 48 No. of subjects: 49 Number (percentage of all subjects) Number (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 ® -C, Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified or GAMIMUNE ® N, Immune Globulin Intravenous (Human), 10%. Treatment of Chronic Inflammatory Demyelinating Polyneuropathy In the CIDP efficacy and safety study, 113 subjects were exposed to GAMUNEX-C and 95 were exposed to Placebo. (see Clinical Studies [14.3] ) As a result of the study design, the drug exposure with GAMUNEX-C was almost twice that of Placebo, with 1096 GAMUNEX-C 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. Table 9 shows the numbers of subjects per treatment group in the CIDP clinical trial, and the reason for discontinuation due to adverse events: Table 9: Reasons for Discontinuation Due to Adverse Events Number of Subjects Number of Subjects Discontinued due to Adverse Events Adverse Event GAMUNEX ® -C 113 3 (2.7%) Urticaria, Dyspnea, Bronchopneumonia Placebo 95 2 (2.1%) Cerebrovascular Accident, Deep Vein Thrombosis Table 10 shows adverse events reported by at least 5% of subjects in any treatment group irrespective of causality. Table 10: Adverse Events Irrespective of Causality Occurring in in ≥ 5% of Subjects MedDRA Preferred Term Reported in ≥5% of subjects in any treatment group irrespective of causality. GAMUNEX ® -C No. of subjects: 113 Placebo No. of subjects: 95 No. of Subjects (%) No. of Adverse Events Incidence density Calculated by the total number of adverse events divided by the number of infusions received (1096 for GAMUNEX-C and 575 for Placebo) No. of Subjects (%) No. of Adverse Events Incidence density 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 The most common adverse reactions with GAMUNEX-C were headache and pyrexia. Table 11 lists adverse reactions reported by at least 5% of subjects in any treatment group. Table 11: Adverse Reactions Occurring in ≥ 5% of Subjects MedDRA Preferred Term Reported in ≥5% of subjects in any treatment group irrespective of causality. GAMUNEX ® -C No. of subjects: 113 Placebo No. of subjects: 95 No. of Subjects (%) No. of Adverse Events Incidence density Calculated by the total number of adverse events divided by the number of infusions received (1096 for GAMUNEX-Cand 575 for Placebo) No. of Subjects (%) No. of Adverse Events Incidence density Any 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 The most serious adverse reaction observed in clinical study subjects receiving GAMUNEX-C for CIDP was pulmonary embolism (PE) in one subject with a history of PE. Laboratory Abnormalities During the course of the clinical program, ALT and AST elevations were identified in some subjects. For ALT, in the IV PI study treatment emergent elevations above the upper limit of normal were transient and observed among 14/80 (18%) of subjects in the GAMUNEX-C group versus 5/88 (6%) of subjects in the GAMIMUNE N, 10% group (p = 0.026). In the SC PI study treatment emergent laboratory abnormalities during the SC phase occurred in several subjects. Four subjects (4/32, 13%) had elevated Alkaline Phosphatase and one subject (1/32, 3%) had a low Alkaline Phosphatase. One subject (1/32, 3%) had an elevated ALT and three subjects (3/32, 9%) had an elevated AST. No elevations were >1.6 times the upper limit of normal. 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-C group versus 8/43 (19%) of subjects in the GAMIMUNE N, 10% group (p = 0.118). In the CIDP study, 15/113 (13%) of subjects in the GAMUNEX-C 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-C may contain low levels of anti-Blood Group A and B antibodies primarily of the IgG 4 class. 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. 6.2 Postmarketing Experience Because adverse reactions are voluntary and reported post-approval from a population of uncertain size, it is not always possible to reliably estimate their frequencies or establish a causal relationship to product exposure. GAMUNEX-C Postmarketing Experience The following adverse reactions have been identified and reported during the post marketing use of GAMUNEX-C: Hematologic: Hemolytic anemia Infections and Infestations: Aseptic meningitis The following adverse reactions have been identified and reported during the overall post marketing use of IGIV products [17]: Respiratory: Apnea, Acute Respiratory Distress Syndrome (ARDS), TRALI, cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm Cardiovascular: Cardiac arrest, thromboembolism, vascular collapse, hypotension Neurological: Coma, loss of consciousness, seizures/convulsions, tremor Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis Hematologic: Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs test) General/Body as a Whole: Pyrexia, rigors Musculoskeletal: Back pain Gastrointestinal: Hepatic dysfunction, abdominal pain