Intended for US audiences only.

Side Effects of IVIg and SCIg Replacement Therapies

This article contains general medical information about the adverse events associated with the different routes of administration of immunoglobulin replacement therapies (IgRT). It is not intended to be applied to any individual case or to substitute for professional medical advice. Consult your healthcare provider to see which route of IgRT administration is right for you.

For the past several decades, immunoglobulin replacement therapy (abbreviated IgRT) has provided effective treatment for a variety of primary immunodeficiencies (abbreviated PI or PID), and the survival rate of patients with antibody deficiencies has increased dramatically since its introduction.1,2,3

The ABC’s of Immunoglobulin Replacement Therapy

A quick reference for commonly used acronyms
PI or PID Primary Immunodeficiency (Disease)
IgRT Immunoglobulin Replacement Therapy
Ig Purified Immunoglobulin
IgA Immunoglobulin Type A
IgG Immunoglobulin Type G
IMIg Intramuscular Therapy
IVIg Intravenous Therapy
SCIg Subcutaneous Therapy

Typically, IgRT therapy is available for use either intravenously (through a vein, abbreviated IVIg) or subcutaneously (through the skin, abbreviated SCIg). A third route, intramuscular infusion (into a muscle, abbreviated IMIg) is no longer recommended because of its high rate of infusion-related side effects.4 Both IVIg and SCIg therapies are viable for the treatment of patients with PI, and both administration routes have had a positive impact on reduction of bacterial infections, hospital stays, and days missed from work or school because of illness.3,5

Although the typical long-term safety of IgRT preparations has been well established, IgRT is not without risk.1 While both IVIg and SCIg infusions increase serum Ig levels and are effective in preventing many infections, studies have shown that some patients may receive additional benefits from SCIg versus IVIg including more stable and better-balanced serum IgG levels, better tolerability, and the convenience of scheduling home treatment to suit their lifestyle.3,6,7,8

Both IVIg and SCIg have unique qualities that may be advantages and disadvantages and may not be suitable for every patient. Continue reading to learn more about the side effects (called adverse events) and comparative safety associated with IVIg and SCIg therapies.

Table 1: SCIg vs IVIg Adverse Events — Top-line Overview of Side Effects

Local Site Reactions Common:5
Mild/moderate local injection site reactions (such as redness, swelling, pain, itching) which typically diminish over time
Mild local injection site reactions (such as itching).
Systemic Reactions – Mild/Moderate Infrequent:5,9
Mild/moderate systemic reactions (such as fatigue, dizziness, chills, nausea)
Mild/moderate systemic reactions (such as headache, migraine, fatigue, dizziness, chills, nausea, vomiting)
Systemic Reactions - Severe Rare:3
Severe systemic reactions (such as anaphylaxis, aseptic meningitis)
Severe systemic reactions (such as anaphylaxis, aseptic meningitis)

Terminology Tips

Quick definitions of terms used in this article
Adverse event Unwanted harmful side effect
Anaphylaxis A severe allergic reaction
Antibody An infection-fighting protein, or immunoglobulin, in blood plasma
Aseptic Not a result of infection
Blanching Turning white
Catheter Needle
Circulatory system Bloodstream
Clinical Outcomes Desired health results
Dysesthesia An abnormal sensation – burning, prickling, or aching
Erythema Redness
Local At the injection site
Lot A preparation batch
Malaise Depression or listlessness
Metabolize Use up
Mitigation Steps to reduce risk
Myalgia Muscle pain
Peak Highest level of Ig in the system
Systemic In the body
Trough Lowest level of Ig in the system
Washout Experience of fatigue and/or increased susceptibility to illness at trough

What Are the Side Effects of Intravenous Ig (IVIg) Therapy?

IVIg is considered safe, which is why it is indicated for several medical conditions requiring Ig therapy.5 Every 3 or 4 weeks, a nurse administers the full dose of IVIg directly into the patient’s bloodstream (or circulatory system), using an IV catheter.5,11 Thus, a large amount of antibodies enters the circulation in a short time and is used up (or metabolized) over the next few weeks.11 This causes the IgG levels to be at their highest (called a peak) right after an infusion and at their lowest (a trough) just before the next dose is due.3 The trough period is often referred to as “washout”. Fluctuations in IgG levels (peaks and troughs) can put IVIg patients at risk of infection as they approach their trough serum levels. These fluctuations can also cause some adverse events when the patient reaches their trough levels.5

Adverse events associated with IVIg can occur both locally and systemically.1,3 Local injection site reactions with IVIg are rare and usually mild or moderate.11 They can include pain or swelling from the medication leaking into the tissues around the site of infusion.11 Systemic reactions, on the other hand, tend to be more common with IVIg than SCIg and can be mild, moderate, or severe.1,11 They are frequently observed in patients who are new to IVIg treatment, especially with the first infusion.5,12 Systemic reactions to IVIg commonly include mild to moderate headache, nausea, fever, fatigue, and “flu-like” symptoms.1,10 More rarely, patients may experience more serious systemic side effects, including hypertension, aseptic meningitis, stroke, and renal (kidney) problems, as well as a severe allergic reaction (called anaphylaxis).10 Some factors predispose patients to a higher than average rate of systemic reactions to IVIg.1 (See Table 2.) At some point during the long-term use of IVIg therapy, up to half of all patients experience at least one adverse event.13

Table 2: Some factors that may contribute to systemic side effects in patients receiving IVIg1

Adverse events Possible cause
Flu-like symptoms High dose, rapid infusion rate, accompanying infection, previous adverse reactions
Skin reactions High dose, rapid infusion rate, accompanying infection, male patients with pre-existing inflammatory neuropathy
Cardiac (heart-related) events Pre-existing heart disease or conditions
TRALI (transfusion-related acute lung injury) Rapid infusion rate
Thrombotic (blood-clotting-related) events High dose; rapid infusion rate; advanced age; being bedridden; diabetes mellitus, high blood pressure, or other pre-existing vascular diseases and conditions; oral contraceptives
Aseptic (non-infection-related) meningitis High dose
Renal (kidney-related) impairment Rapid infusion rate, advanced age, dehydration, other drugs, IVIg preparation containing sucrose, diabetes mellitus, and other pre-existing kidney conditions
Hemolysis (rupture of red blood cells) High dose, rapid infusion rate, non-O blood group, pre-existing inflammatory condition

*TRALI, transfusion-related acute lung injury

IVIg is administered either in a medical setting or at home, but always with a healthcare professional present.5 Because of the risk of systemic reactions with IVIg, healthcare providers must be able to recognize and manage complications.14 They should have access to an emergency center (or call 911) in the rare event that a severe reaction might occur.10

For some patients, pre- and post-infusion medications, pre-hydration, and infusion rate adjustments may be used to help control adverse reactions to IVIg. For other patients, venous access may be a challenge. If patient tolerability remains a challenge, healthcare providers may consider changing the treatment to a different IVIg product or switching the patient from IVIg to SCIg.10

What Are the Side Effects of Subcutaneous Ig (SCIg) Therapy?

SCIg has been considered a safe and effective alternative to IVIg since the 1980s in Europe and since 2006 in the US.3,9 Particular product specifics and patient requirements are used to determine the frequency of SCIg administrations, which are often administered weekly, but may be adjusted for a patient’s needs.3,12 SCIg’s alternative dosing schedules can result in more stable and consistent Ig serum concentration levels, making the wash-out (trough) periods associated with IVIg limited.5,9 (See Figure 2.) Furthermore, SCIg is administered under the skin rather than into a vein, which can also help to reduce the complications associated with difficult venous access.3

Figure 1: With SCIg, there is a steady level of IgG present in the bloodstream due to the more frequent dosing regimens (Figure 1.1). With IVIg, the dosing at longer intervals may cause peaks and valleys (Figure 1.2)14

Figure 1.1: SCIg Weekly

Figure 1.2: IVIg Every 3-4 Weeks

Systemic reactions to SCIg therapy are rare, but can be severe (including, aseptic meningitis).15 Mild or moderate systemic reactions can include headache, fever, or diarrhea.15 Less common mild-to-moderate reactions can include dermatitis or asthma.15

Mild local-infusion-site reactions, on the other hand, are typically more common than systemic reactions. Local site reactions can include redness, pain, itching, or swelling. Such local site reactions have been known to decrease over time as the patient adjusts to the treatment.3,5,9,16 Moderate local reactions such as blanching (turning white) of the swelling and a ring of erythema (redness) have also been reported.3 (See Figure 4.) Most mild and moderate reactions, however, have been reported to resolve spontaneously within 24 hours.9,16 Local adverse reactions can be reduced with established mitigation strategies.5

Figure 2: Mild and moderate local injection-site reactions after SCIg therapy.16

Mild local site reactions with redness and swelling

Moderate local site reactions with blanching of the swelling and a ring of erythema (redness)

Both SCIg patients and their doses are carefully monitored over time.14 Dose, rate, and infusion intervals are adjusted to minimize the frequency and severity of infections and adverse events.10 IgG levels are monitored to achieve the desired state of health (clinical outcomes).14

Which Ig Therapy (IgRT) Administration Route is Right For me?

Choosing the route of administration of your IgRT therapy goes well beyond considerations about potential side effects. It also includes thinking about your lifestyle needs and preferences. Although either route of Ig administration may be appropriate for patients with PI, each one has its unique qualities, impacting both treatment experience and way of life.

For the most part, after a patient or caregiver has been properly trained, SCIg can be self-administered at home without the need for a nurse’s supervision.3 On the other hand, although IVIg can also be infused at home (or in a healthcare or hospital setting), it must be administered by an infusion nurse or other healthcare provider trained in the administration of IVIg infusions.5,14 Studies have shown that patients often prefer the convenience, flexibility, and comfort of home-based Ig administration.17 Many who switched from in-hospital IVIg to at-home SCIg reported greater independence, fewer restrictions on activities, and increased treatment satisfaction.17 The ability to self-administer treatment can greatly improve the lifestyle for patients who are eligible, and the compliance associated with convenient self-administration reduces the frequency of hospitalizations and the need for home care.8

In the end, the choice of which route of Ig administration you would prefer will be up to you.5 Whether you choose IVIg or SCIg, the success of your Ig therapy experience not only depends on the knowledge, expertise, and support of your medical team but also on your spirit of collaboration and participation.5

Be sure to talk to your healthcare provider about your options so that you can make the best decision for your medical needs and lifestyle.

Below (Table 3) is an overview of some of the primary differences between SCIg and IVIg therapies.

Table 3: A simplified overview of SCIg and IVIg therapies

Who (lifestyle)5 Self-administered or administered by a caregiver
Administered by a healthcare provider (Structured/by appointment)
Where5 At home (or office, vacation, etc.) At home or in a healthcare facility with nurse supervision
When3,5,12 Daily, weekly, or every 3 to 4 weeks Usually every 3 to 4 weeks
Administration (challenges)5 Subcutaneous (under the skin)
(Fear of self-administration; problematic if cognitive or fine motor ability are lacking)
Intravenous (into a vein)
(Self-administration is not an option; problematic if venous access is difficult)
Time to Infuse11 1 to 2 hours 2 to 6 hours
Absorption Rate5 Slow (Ig first has to diffuse through subcutaneous space into lymphatic system before entering the circulatory system via the thoracic duct) Fast (Ig is administered directly into the circulatory system via a vein)
Ig Levels5 Steady state Ig levels Peaks and troughs in Ig levels
Systemic Side Effects9 Infrequent Common
Local Site Reactions9 Common Infrequent

To learn more about the safety of IgRT as a treatment for patients with PI, see Is IgRT Safe?

The page contains general medical information that cannot safely be applied to any individual case. Medical knowledge and practice can change rapidly. Therefore, this page should not be used as a substitute for professional medical advice.


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