By Joe DiStefano, RPh.

Intravenous immune globulin (IVIG) preparations are safe and effective treatments for a variety of medical conditions. Serious, but uncommon reactions occur, and include thromboembolic events, (e.g., pulmonary embolism, deep vein thrombosis, myocardial infarction, transient ischemic attack), renal dysfunction and acute renal failure. Mild to moderate side effects that occur during or after IVIG treatment are more common. These may include: headache, flushing, chills, myalgia, fatigue, low grade fever, changes in blood pressure and lower back pain. While many common side effects may be controlled by decreasing the IVIG infusion rate, administering physician-prescribed pre-medications can minimize or eliminate side effects and is a common practice. Of note, these reactions can occur with subcutaneous immune globulin (SCIG) but the risk appears to be much lower as compared to IVIG. Patients experiencing unmanageable IVIG side effects may better tolerate SCIG. Subcutaneous site reactions are the common SCIG side effects. This article will focus on IVIG.

The exact mechanism by which IVIG causes side effects is not known. Side effects may be related to the active ingredient, immune globulin (common to all brands), or inactive ingredients (many of which are brand-specific). Many of the common side effects are flu-like symptoms, which may be caused by immune globulins activating the complement pathway of the immune system. Hence, standard pre-medication regimens target flu-like symptoms with analgesics and anti-histamines. Because each IVIG lot is derived from blood pooled from many donors, there may be some differences in antibodies (immune globulins) from batch to batch. These variable factors together could explain toleration of one brand versus another as well as toleration of the same brand one time versus another time and supports the recommendation to always administer pre-medications.

Other pre-medications, less common than analgesics and anti-histamines, are usually ordered to specifically prevent a known problem such as migraines or after an unexpected effect occurs such as nausea or the more serious thromboembolism. The chart below lists information about some common pre-medications. Consult the manufacturer's prescribing information for full details or the NuFACTOR pharmacist.

*IVP = Intravenous Push; IVPB = IV Piggy Back; SL = Sublingual
IV medications can generally be administered 15 minutes before IVIG.

Intolerable side effects can lead to patient discouragement and the decision to discontinue quality of life improving IVIG. Many side effects can be minimized or eliminated by adherence to pre-medication administration as well as taking them at the right time in advance of IVIG administration. Often, prescribers order repeating of pre-medications if symptoms occur during IVIG administration. Another way to help minimize side effects is to maintain proper oral hydration. Unless handling fluid volume is a problem (e.g., CHF, pre-existing renal dysfunction), it is recommended patients consume 64 ounces of water daily (e.g., 8 x 8 oz.) starting a day or two before, each day of and 1 - 2 days after IVIG. Lastly, compliance with routine anti-hypertensive medications could control major fluctuations of blood pressure during IVIG administration. Bothersome and intolerable side effects, as well as serious ones, should be reported to the NuFACTOR pharmacist.

The IVIG Nurse plays a major role in side effect management. Knowing all ordered medications, encouraging compliance, identifying and managing side effects and working with the NuFACTOR pharmacist can help patients better tolerate IVIG.