This is an article I found in the IG Living magazine (available free at www.igliving.com - just sign up). This article is in the past issue April-May 2010 on page 26.

It makes most people chuckle:
A television commercial touts the
benefits of a wondrous new drug;
the patient is smiling and laughing,
obviously enjoying a newfound
healthy lifestyle while spending
time with family and friends. Then,
the announcement: “Side effects
include …” Wow, the viewer thinks,
no thanks!
Knowing what side effects, from mild
to serious, to expect during and after
immune globulin infusions can prepare
patients and their caregivers for treatment
changes to mitigate their impact.
By Ronale Tucker Rhodes, MS,
and Kris McFalls
Understanding and Treating
IG Side Effects

The truth is that there is nothing funny about a drug’s
side effects — especially when it comes to a life-sustaining
drug like immune globulin (IG). IG patients either undergo
the treatments or they forgo them, which brings on far
worse consequences than those caused by side effects.
Fortunately, many IG patients never experience any
effects, and while those who do often think they are
having a severe reaction, by definition, the reaction is
typically a moderate or mild side effect. And, the good
news is that in almost all cases, the effects can be controlled
or even eliminated.
Side Effects Defined
Side effects, also referred to as adverse drug reactions
(and considered one and the same by the Federal Drug
Administration [FDA]), are those that are expected,
although undesired, and are listed on the package insert
for each medication. Mild or moderate side effects typically
occur due to the manner in which the treatment is
administered, and they can be managed. Serious side
effects, on the other hand, also can be a result of the
components of the drug itself and result in hospitalization
or prolongation of an existing hospitalization and
can be life-threatening.
The Mayo Clinic has an exhaustive list of side effects
available at www.mayoclinic.com/health/drug-information/
DR601705/DSECTION=side-effects. Most of these effects
often can be eliminated by stopping the infusion temporarily
and then restarting at a lower infusion rate, and even by
switching the treatment modality.

Mild and Moderate Side Effects and Treatments
Mild and moderate side effects of intravenous IG (IVIG)
are headache, flushing, chills, myalgia, wheezing, tachycardia,
lower back pain, nausea and hypotension. Headaches
and their more severe form, migraines, tend to be one of
the more common side effects. Patients can overcome
both forms of headaches by treating with antihistamines,
NSAIDS and steroids both before and after an infusion. In
addition, hydrating before, during and after an infusion
can help alleviate these discomforts.
Other forms of treatment also can be tried. For example,
a patient just beginning IVIG treatments experienced
a mild migraine the day following her first treatment. As
a further preventative, she increased hydration and took
Tylenol before her next two treatments. Regardless, on
her third treatment, she experienced a severe migraine
lasting three days. For her next infusion, her doctor
ordered a small dose of prednisone to be taken the day
before the infusion, the day of the infusion and the day after
the infusion. In addition, the rate of the infusion was
decreased. With these treatment adjustments, the patient
still experienced occasional mild headaches, but she no
longer had migraines.
In another instance, a patient experienced severe
migraines following IVIG infusions. The patient was given
Tylenol, Benadryl and steroids, as well as a migraine prophylaxis,
prior to treatment, but the headache symptoms
persisted. Different formulations of IVIG 5% and 10%
were then tried, but the migraines continued. So, the
patient switched to subcutaneous IG (SCIG), which has
eliminated the problem, and no premedications are needed.
For SCIG patients, the most common side effects include
headaches and local irritation (redness, swelling, itching,
blanching) at the needle site. Some reactions, especially
for patients new to SCIG therapy, are expected, and most
decrease with time once the body becomes accustomed to
the therapy. For patients bothered by reactions, applying
ice or heat to the needle sites can help decrease some of
the symptoms. Using a topical anesthetic cream 30 to 60
minutes prior to starting the infusion also can be helpful.
Patients with persistent symptoms should explore needle
placement as a possible cause. If the needle is not properly
placed, it is possible that some of the fluid is leaking into
surrounding tissue rather than into the subcutaneous
space. A provider experienced in SCIG therapy should be
able to help patients troubleshoot and eliminate possible
causes to site reactions. However, in some cases, patients
are simply unable to tolerate the side effects of SCIG and
need to switch back to IVIG treatment.
Mild or moderate side
effects typically occur
due to the manner in
which the treatment is
administered and can be
managed.

Serious Side Effects and Treatments
Serious side effects are rare, and most can be
reduced by screening the patient for factors predisposing
them to complications.2 Serious side effects can
include acute renal failure, thrombosis, Stevens-
Johnson syndrome, serum sickness, aseptic meningitis
and anaphylaxis. The most severe form of IG-related
headache comes from aseptic meningitis, and in fact,
patients with a history of migraines appear to be more
susceptible to aseptic meningitis. Symptoms, which are
severe and similar to meningitis, usually begin a few
hours after treatment but can occur up to two days
later. They can include severe headache, photo sensitivity,
chills, nausea, vomiting, fever and painful eye
movement. Although cerebrospinal fluid (CSF) can
show increased white blood cells and proteins, cultures
are generally negative, thus resulting in the aseptic
diagnosis.1 Treatment to prevent aseptic meningitis
includes antihistamines, NSAIDS and steroids both
before and after an infusion.
Anaphylaxis, a rapidly progressing, life-threatening allergic
reaction, can be a side effect of both IVIG and SCIG.
Anaphylactic reactions may require administration of
corticosteroids and antihistamines, and in very severe
cases, administration of epinephrine.3
A case in point: One patient who experienced anaphylaxis
is a child named Julia. At 7 months old, Julia was
diagnosed with pertussis, despite having been vaccinated.
Julia’s health deteriorated so rapidly that she was sent by
ambulance to a hospital where she stayed for nearly three
weeks. At age 5, she was diagnosed with a primary
immune deficiency, and at age 6, IVIG treatments were
started. Unfortunately, her infusion days rarely went
smoothly. From the beginning, Julia was plagued with
flu-like symptoms, and by age 9, she experienced severe
migraines lasting three days. Doctors treated Julia with
Benadryl and prednisone prior to her infusions, as well as
with intravenous Benadryl during her infusions. In addition,
the rate of infusions was slowed down so much that they
took eight hours to complete.
When she turned 10, Julia’s doctors decided to try
another brand of immune globulin, hoping to shorten
infusion time and decrease side effects. Unfortunately,
Julia’s side effects worsened. During the infusion, Julia felt
her chest tightening and told her mother she was having
trouble breathing. Overcome by an analphylactoid
reaction, Julia went into respiratory arrest, so the doctors
quickly stopped the infusion and administered valium and
epinephrine. At this point, Julia’s parents considered
halting all treatments; it seemed their daughter’s life was
threatened with or without IG. But, after weighing the
risks and benefits, doctors successfully resumed therapy
with the original brand of IVIG. When Julia was 13,
doctors suggested subcutaneous infusions in hopes of
giving Julia her life-saving IG without risking her life. This
worked; Julia was soon free of the side effects that
plagued her with every treatment.
Anaphylactic and anaphylactoid reactions (both
referred to as anaphylaxis) are life-threatening events that
Serious side effects are rare,
and most can be reduced
by screening the patient
for factors predisposing
them to complications.
result from an overreactive and misdirected immune
response to a substance that is viewed by the body as
foreign (an antigen). An anaphylactic reaction is an acute
fatal, or potentially fatal, hypersensitivity reaction that
requires the patient to be sensitized and their reaction
mediated through immunoglobulin E (IgE) antibodies.
An anaphylactoid reaction doesn’t need the presence of
IgE antibodies for a hypersensitivity reaction to occur.
Thus, an anaphylactic reaction occurs only after the
patient has been previously exposed at least once to
the antigen and is sensitized. And, it can occur following
a single, first-time exposure to certain agents in
nonsensitized patients.4
Anaphylactic and anaphylactoid reactions to IVIG
therapy are relatively rare, but they can occur in any
patient at any time. Some IgA-deficient patients produce
certain IgA antibodies that can increase the potential for
anaphylaxis. For those patients, it is prudent to use an IVIG
product that has a very low IgA content. Alternatively,
many patients who experience anaphylaxis have had good
success by switching their route of infusion from intravenous
to subcutaneous.4
Documenting and Reporting Side Effects
Both the FDA and European regulatory authorities are
encouraging patients and healthcare professionals to
report adverse drug reactions so that any unknown serious
side effects, such as those that occurred with Vioxx,
can be discovered more quickly. (Vioxx and related pain
medications were taken off the market in 2004 because
they caused dangerous heart problems in some people.)
The purpose of documenting and reporting these
effects is to prevent future injuries for patients. Of particular
importance to the FDA are suspected adverse
drug reactions for a new drug (i.e., within three years of
entry to market) and suspected severe adverse drug
reactions for any drug, no matter when the drug
entered the market.5
The FDA also requires many manufacturers of
newly licensed drugs to perform post-marketing risk
management (pharmacovigilance studies) to collect
information on adverse reactions in a more proactive
manner. Additional information on serious adverse
drug reactions and instructions for reporting an
adverse drug reaction to the FDA can be obtained at
www.fda.gov/Safety/MedWatch/HowToReport/default.htm.
Benefits Outweigh Risks
IG is one of the safest biological products available, and
although severe side effects have been reported, they are
rare. The good news is that almost all side effects can be
safely controlled and often eliminated altogether. And,
with the growing number of diseases being treated today
with IG, as well as the stringent testing and reporting
standards mandated by the FDA, patients who rely on this
life-saving treatment can rest assured that they can be
safely treated.
Sources
1. Gamunex Prescribing Information. Accessed at
www.gamunex.com/media/Gamunex_Prescribing_Info.pdf.
2. Duhem, C, Dicato, MA, and Ries, F. Side-effects of intravenous
immune globulins. Clinical & Experimental Immunology. 1994: 97
(Suppl 1), 79-83.
3. Siegel, J. Case Management of the Challenging IgG Patient: Clinical
Considerations for the Most Effective and Safe Therapy. Breakfast
symposium, National Home Infusion Association (NHIA) Meeting,
March 1-5, 2009.
4. Limmer, DD, Mistovich, JJ, and Krost, MS. Anaphylactic and
Anaphylactoid Reactions: Prehospital Pathophysiology.
EMSResponder.com. Accessed at publicsafety.com/article/article.jsp?
id=2165&siteSection=6.
5. VA Center for Medication Safety and VHA Pharmacy Benefits
Management Strategic Healthcare Group and the Medical Advisory
Panel (November 2006). Adverse Drug Events, Adverse Drug
Reactions and Medication Errors: Frequently Asked Questions.
Accessed at www.pbm.va.gov/vamedsafe/Adverse%20Drug%20
Reaction.pdf.
RONALE TUCKER RHODES, MS, is the editor of IG Living
magazine, and KRIS MCFALLS is the full-time patient advocate
for IG Living magazine, written for patients who depend
upon immune globulin products and their healthcare
providers.
Anaphylactic and
anaphylactoid reactions
to IVIG therapy are
relatively rare, but they
can occur in any
patient at any time.
30 April-May 2010 www.IGLiving.com IG Living!
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