While both IVIG and SCIG infusions increase serum IgG levels and are effective in preventing many bacterial and viral infections, systemic adverse events occur less frequently with SCIG. The most common side effects of IVIG infusions include headache, fever, fatigue, vomiting, chills, dizziness, and hives. Drug-related and temporarily related adverse events have been reported to occur in 9%–29% of IVIG infusions.68
Headaches occurring after IVIG infusion and lasting 24–72 hours are one of the most common side effects. Serious adverse events have been noted in up to 20% of patients receiving IVIG, although many of these adverse events may have been unrelated to the study drug.70
The majority of adverse events occur during or within 48 hours of the infusion, and may be related to the rapid increase in serum IgG concentration. Most of the data regarding adverse events with IVIG administration come from clinical trials of new products where subjects are generally not permitted to use premedication to prevent adverse reactions. One prospective review of 459 PIDD patients who were self-infusing IVIG in the home showed an overall reaction rate of 0.8%; however, 50% of these patients routinely used premedication prior to infusion to prevent infusion reactions.72
In contrast, serious systemic adverse events rarely occur with SCIG infusions. Most studies report a rate of less than 1%,21
although one study reported a higher rate of 3.3% for serious adverse events.36
Local reactions with redness, pain, or swelling at the site of infusion were reported by the majority of subjects participating in the US trials. Most of these local reactions were considered mild, with only slight swelling and redness, or moderate, with some blanching of the swelling and a ring of erythema. The incidence of these local reactions, however, decreases over time and very few patients discontinue SCIG therapy due to local reactions.21
One additional consideration is the complication of using indwelling catheters for vascular access to facilitate administration of IVIG. In young children, the elderly, and patients with other medical conditions, monthly venous access can become increasingly difficult. Indwelling catheters have been used to provide a reliable portal for administration of IVIG however, due to the risks of infection this practice is discouraged.57
In 1999, the FDA required manufacturers of IVIG products licensed in the US to add a “black box” warning to advise patients of the risk of acute renal failure.75
The development of acute renal failure was most associated with IVIG products that contained sucrose, products that were given in large doses in older patients, and in patients with renal insufficiency prior to the infusion.76
To date, renal insufficiency has not been noted after SCIG administration and the products currently available in the US for SC administration do not contain sucrose.
Thrombotic events (TE) occurring after IVIG infusion using high doses to treat patients with neurologic conditions have been thought to be related to the increase in serum viscosity sometimes seen after IVIG infusion.77
A large retrospective review of TE after IG infusion demonstrated a significant increase in the risk of TE with Octagam®
(Octapharma, Lachen, Switzerland; IVIG), Vivaglobin®
(CSL Behring, Kankakee, IL; SCIG) with an odds ratio of 2.03 and 3.56, respectively.78
The risk of TE appears to be related to increased factor XI procoagulant activity, possibly related to specific manufacturing processes.78
This risk is further increased in older patients and those with a hypercoagulable state.78
is no longer manufactured for use in the US, and Octagam®
, initially removed from the market, has now been reintroduced following changes in the manufacturing process intended to minimize the procoagulant activity of the product.
Two additional important adverse events that have been seen after IVIG therapy are hemolysis and transfusion-related acute lung injury. Hemolysis may be triggered by the presence of red blood cell antibodies and is more likely to occur in patients with neurologic disorders. Transfusion-related acute lung injury reactions are rare and have not been reported in PIDD patients receiving IVIG.76
Many of the acute adverse events appear to be related to the rate of IV infusion, and may be attenuated by slowing the rate of infusion in addition to use of pretreatment with antihistamines and acetaminophen. Pretreatment before IVIG infusion with antihistamines, acetaminophen, and sometimes systemic steroids is widely used, but is rarely needed with SCIG infusions.