Increases in creatinine and blood urea nitrogen (BUN) have been observed as soon as one to two days following infusion. Progression to oliguria and anuria requiring dialysis has been observed, although some patients have improved spontaneously following cessation of treatment.35
Types of severe renal adverse reactions that have been seen following IGIV therapy include:
- acute renal failure
- acute tubular necrosis36
- proximal tubular nephropathy
- osmotic nephrosis18 (see also 37-39)
In general, reported adverse reactions to GAMMAGARD (immune globulin) , in patients with either congenital or acquired immunodeficiencies are similar in kind and frequency. Various minor reactions, such as mild to moderate hypotension, headache, fatigue, chills, backache, leg cramps, lightheadedness, fever, urticaria, flushing, slight elevation of blood pressure, nausea and vomiting may occasionally occur. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.
Immediate anaphylactic and hypersensitivity reactions are a remote possibility. Epinephrine and antihistamines should be available for treatment of any acute anaphylactoid reaction (See WARNINGS).
Primary Immunodeficiency Diseases
Twenty-one adverse reactions occurred in 341 infusions (6%), when using GAMMAGARD (immune globulin) (5% solution), in a clinical trial of 17 patients with primary immunodeficiency.40 Of the 17 patients, 12 (71%) were adults, and 5 (29%) were children (16 years or younger).
In a cross-over study comparing GAMMAGARD and GAMMAGARD S/D (immune globulin) (5% solutions) conducted in a small number (n=10) of primary immunodeficient patients, no unusual or unexpected adverse reactions were observed in the GAMMAGARD S/D (immune globulin) group. The adverse reactions experienced in the GAMMAGARD S/D (immune globulin) group were similar in frequency and nature to those observed in the control group consisting of patients receiving GAMMAGARD (immune globulin) .
GAMMAGARD (immune globulin) , reconstituted to a concentration of 10%, was administered intravenously at rates varying from 2 to 11 mL/kg/Hr. Systemic reactions occurred in 23 (10.5%) of 219 infusions. This compares with an adverse reaction incidence of 6% (only systemic reactions reported) for primary immunodeficient patients previously treated with a 5% solution at infusion rates varying between 2 and 8 mL/kg/Hr, as described above (see reference 40). Local pain or irritation was experienced during 35 (16%) of 219 infusions. Application of a warm compress to the infusion site alleviated local symptoms. These local reactions tended to be associated with hand vein infusions and their incidence may be reduced by infusions via the antecubital vein.
B-cell Chronic Lymphocytic Leukemia (CLL)
In the study of patients with B-cell Chronic Lymphocytic Leukemia, the incidence of adverse reactions associated with GAMMAGARD (immune globulin) infusions was approximately 1.3% while that associated with placebo (normal saline) infusions was 0.6%.9
Idiopathic Thrombocytopenic Purpura (ITP)
During the clinical study of GAMMAGARD (immune globulin) for the treatment of Idiopathic Thrombocytopenic Purpura, the only adverse reaction reported was headache which occurred in 12 of 16 patients (75%). Of these 12 patients, 11 had chronic ITP (9 adults, 2 children), and one child had acute ITP. Oral antihistamines and analgesics alleviated the symptoms and were used as pretreatment for those patients requiring additional IGIV therapy. The remaining 4 patients did not report any side effects and did not require pretreatment.
In a study of patients (n=51) with Kawasaki syndrome, no hypersensitivity-type reactions (urticaria, bronchospasm or generalized anaphylaxis) were reported in patients receiving either a single 1g/kg dose of IGIV, GAMMAGARD (immune globulin) , or 400 mg/kg of IGIV, GAMMAGARD (immune globulin) , for four consecutive days.13 Mild adverse reactions, including chills, flushing, cramping, headache, hypotension, nausea, rash and wheezing, were reported with both dose regimens. These adverse reactions occurred in 7/51 (13.7%) patients and in association with 7/129 (5.4%) infusions. Of the 25 patients who received a single 1 g/kg dose, 4 patients experienced adverse reactions for an incidence of 16%. Of the 26 patients who received 400 mg/kg/day over 4 days, 3 experienced a single adverse reaction for an incidence of 11.5%.3
The following list of adverse reaction have been identified and reported during the post-approval use of IGIV products:
Respiratory: cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm
Cardiovascular: thromboembolism, hypotension
Neurological: seizures, tremor
Hematologic: hemolysis, positive direct antiglobulin (Coombs) test
General/Body as a Whole: pyrexia, rigors
Musculoskeletal: back pain
Gastrointestinal:hepatic dysfunction, abdominal pain
Rare and Uncommon Adverse Events:
Respiratory: apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion Associated Lung Injury (TRALI)
Integumentary: bullous dermatitis, epidermolysis, erythema multiforme, Stevens- Johnson syndrome
Cardiovascular: cardiac arrest, vascular collapse
Neurological: coma, loss of consciousness
Hematologic: pancytopenia, leukopenia
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 or establish a causal relationship to exposure to the product. Such is also the case with literature reports authored independently.41 (See PRECAUTIONS)