The incidence of adverse events associated with the administration of IVIG is reported by the manufacturers to be in the range of 1 to 15 percent, usually less than 5 percent. Most of these reactions are mild and self-limited. Severe reactions occur very infrequently and usually do not contraindicate further IVIG therapy. Neither HIV nor hepatitis B infection has been transmitted to recipients of products currently licensed in the U.S. The various IVIGs are manufactured from large numbers of donors whose plasma has been tested and found to be negative for hepatitis B surface antigen and HIV antibody. A number of adverse events have been recognized. These include the following:

• pyrogenic reactions marked by high fever and systemic symptoms;
• minor systemic reactions with headache, myalgia, fever, chills, lightheadedness, nausea and/or vomiting;
• vasomotor and/or cardiovascular manifestations, marked by changes in blood pressure and tachycardia. These may be related to occasional reports of shortness of breath and chest tightness; and
• hypersensitivity and anaphylactic reactions.

Patients with primary antibody deficiency syndromes may be at increased risk for reactions. Anaphylactic reactions induced by anti-IgA can occur in individuals who have a total absence of circulating IgA and antibodies to IgA. These are extremely rare in panhypogammaglobulinemic individuals and potentially more frequent in patients with subclass deficiencies. Frequency of reactions may be correlated with volume and/or rate of infusion. Seriously ill patients with compromised cardiac function may be at increased risk of vasomotor or cardiac complications manifested by elevated blood pressure and/or cardiac failure.

Adverse reactions often can be alleviated by reducing the rate or the volume of infusion. For patients with repeated severe reactions unresponsive to these measures, hydrocortisone, 1-2 mg/kg, intravenously, can be given 30 minutes before IVIG infusion. In those rare instances when reactions related to anti-IgA antibodies have occurred, use of IgA-depleted preparations will reduce the likelihood of further reactions. Avoidance of anaphylactic reactions may require the use of material completely devoid of IgA. Because the combination of the absence of IgA and the presence of anti-IgA antibodies is infrequent and reactions are rare, screening for IgA-deficiency is not routinely recommended for potential recipients of IVIG.

As with any biologic or pharmacological product, the potential for new or previously unrecognized adverse events should be anticipated. With IVIG these include the following:

• transmission of blood-borne pathogens, such as the newly identified hepatitis C virus.
• Immunosuppression--for example, administration of IVIG has been associated with transient effects on immune response that do not appear to have clinical significance. However, with increased dosage of IVIG or new products for the treatment of specific infections, the possibility of adverse outcomes from immunosuppression should be considered.

After nearly a decade of experience, the safety of IVIG has been established. For any potential recipient, the small risk of adverse reactions must be weighed against the likelihood of significant benefit. For those patients who require repeated courses of IVIG such as those with a primary humoral immunodeficiency home infusion by the patient or a family member after adequate training has been effectively utilized and is cost-effective.