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Immunoglobulin replacement therapy

Key points: 

  • Immunoglobulin (Ig) replacement therapy provides antibodies to protect people with primary immunodeficiency (PI) from infections.
  • Ig replacement therapy needs to be tailored to each person’s medical condition and personal preferences, including dose, infusion frequency, and route of administration, to minimize infections while also avoiding side effects.
  • Ig replacement therapy can be given intravenously (IVIG) or subcutaneously (SCIG or SubQ), and each route has its benefits and drawbacks.
  • Most people with PI need Ig replacement therapy for life.

Treating antibody deficiencies and other PIs

Immunoglobulin (Ig) replacement therapy is a standard treatment for people with PI who lack antibodies, also known as immunoglobulins, or whose antibodies do not work well. Healthcare providers most often prescribe Ig replacement therapy for antibody deficiencies like common variable immunodeficiency (CVID), X-linked agammaglobulinemia (XLA), or specific antibody deficiency (SAD). However, it can also help treat other PIs like combined immunodeficiencies (CIDs). In addition, babies with severe combined immune deficiency (SCID) often receive Ig replacement therapy in the short term before they have either a hematopoietic stem cell transplant (HSCT) or gene therapy. Ig replacement therapy has successfully treated PIs for over 40 years [1].

In all cases, Ig replacement therapy treats PI by providing people with working antibodies that allow their bodies to fight off infections. It is a form of passive immunization, similar to how mothers provide antibodies to their babies in the womb.

Note that Ig replacement therapy provides only temporary protection from germs. The antibodies are used up by the body and must be constantly replaced. People on Ig replacement therapy need repeat doses of Ig on a regular schedule to keep their Ig levels high enough to prevent infections.

In addition, Ig replacement therapy does not make the person’s immune system start producing working antibodies. Since Ig does not correct the root problem, people with PI usually need Ig replacement therapy for life or until they receive other treatment like HSCT, if appropriate.

The immunoglobulin used in Ig replacement therapy is made from donated human plasma [2], the liquid part of blood that contains antibodies. Ig can be given either directly into the bloodstream (intravenously; IVIG) or under the skin (subcutaneously; SCIG or SubQ).

There are many Ig products approved by the U.S. Food and Drug Administration (FDA) to treat PI [3]. All products are 95-98% pure IgG antibodies with only small amounts of other classes of antibodies like IgA and IgM. The products differ from each other in a number of ways, though, including the concentration of IgG (10%, 16.5%, or 20%), how much of each IgG subclass they have, which stabilizers (chemicals that prevent the Ig from breaking down) they use, and whether they are approved for IVIG, SCIG, or both. 

Whether someone uses IVIG or SCIG, the therapy must be customized to meet each person’s needs. Customizing includes:

  • The best dose and dosing schedule to prevent infections while minimizing side effects.
  • The Ig product the person tolerates best.
  • A therapy regimen that is compatible with the person’s lifestyle and any other medical diagnoses.

Ig replacement therapy reduces infections and improves quality of life for those missing or with non-working antibodies. As with any treatment, discuss your individual risks and benefits with a healthcare provider before beginning Ig replacement therapy.

Guide to Ig Therapy

This guide was developed for patients and caregivers to help increase understanding of immunoglobulin (Ig) replacement therapy.

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Immunoglobulin product booklet

This regularly updated booklet contains detailed information on all Ig products approved to treat PI in the U.S.

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Find Ig replacement therapy clinical trials

See if you qualify to participate in clinical trials evaluating Ig replacement therapy.

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Ig manufacturing and safety

All Ig products are made from donated human plasma. There are multiple steps in the production process to make sure the end product is safe.

First, plasma donation centers screen all plasma donors by asking for a detailed history of infections and risk behaviors, such as intravenous drug use. Donors also complete testing for certain viruses using very sensitive tests. Donors can only give plasma if they pass this screening. If the screening identifies any risk factors, the person is excluded from donation, or deferred. The FDA requires centers to maintain a central list of people who have been deferred to prevent them from donating at other centers or in the future [4].

As an added protection, plasma donors must return to donate a second time within a few weeks of their first donation. They are then rescreened for viruses and risk factors. If a donor does not return within that timeframe or the second screening identifies risk factors, the center throws away the plasma from their first donation.

Plasma centers then test each individual plasma donation for germs before pooling it with plasma from thousands of other donors. Once the plasma is pooled, the entire pool is tested for HIV and hepatitis A, B, and C viruses. Different separation and filtration methods help pull out IgG antibodies from the pooled plasma, and manufacturers test for viruses at multiple points throughout this process.

In the mid-1990s, some IVIG users developed non-A, non-B hepatitis (now known to be caused by the hepatitis C virus (HCV)). These rare infections caused manufacturers to add an extra step in the manufacturing process to dissolve, or inactivate, these types of viruses. More recently, manufacturers have added a final ultrafiltration or depth filtration step to remove prions, which are infectious proteins that cause diseases like mad cow disease. Notably, HIV, which is destroyed in the first step in the production of Ig, has never been spread through the use of any Ig product.

Usually, one lot of Ig product is made from the plasma of about 10,000 donors. This pooling makes sure that all Ig lots contain a broad variety of antibodies that are found in the general population to specific germs and routine vaccinations, which then provide protection to people with PI. By law, all Ig products licensed in the U.S. must be made from source plasma that has been collected in the U.S. [5].

Starting Ig replacement therapy

The goal of Ig replacement therapy for PI—no matter the setting, dose, or route of administration—is to provide protection from germs. Being consistent with Ig replacement therapy is very important for reaching this goal. Any challenges, real or potential, need to be addressed to make sure that the person with PI remains on schedule for their infusions.

Healthcare providers set someone’s initial Ig dose based on their weight. Typically, a starting dose is between 400-600 mg/kg/month. Healthcare providers then adjust the dose to minimize the frequency and severity of infections while also minimizing any side effects from the medication.

It is important to track any side effects during or after infusions and tell the prescribing healthcare provider about them. People should also report any side effects to the product manufacturer and MedWatch at the FDA in case there is a problem with the product lot [6].

Monitoring IgG levels over time is important to track the person’s response to therapy. The goal is to keep the Ig in the bloodstream above a target level, which differs for each person, even at its lowest point right before the next infusion, which is known as the trough level.

It is also important to remember several things when starting Ig replacement therapy:

  • Ig replacement therapy can’t prevent all infections. 
    • After starting Ig replacement therapy, you may still get infections, especially if you are not yet at the dose that works best for you. However, the frequency and severity of infections should significantly decrease so that permanent organ damage, like bronchiectasis, does not develop. 
    • Because the antibody levels in Ig products mirror what plasma donors have been vaccinated against and exposed to, Ig products may not provide strong or reliable protection against fast-changing germs, such as the newest COVID-19 or influenza virus strains. Antibody levels to whooping cough (pertussis) also vary among products and may not be protective. 
    • If you are still getting multiple or severe infections after being on a steady Ig replacement therapy regimen, talk to your prescribing healthcare provider about increasing your Ig dose or the frequency of your infusions. 
  • One size does not fit all. A customized Ig replacement therapy regimen must be developed for each person and modified as needed to achieve treatment goals and meet the person’s needs.
  • Once someone has been diagnosed with an antibody deficiency, they will likely need to be on Ig replacement therapy for life. Exceptions are people who are treated with Ig replacement therapy temporarily in order to prevent infections while waiting for HSCT or gene therapy. In addition, some children may no longer need Ig replacement therapy if they “outgrow” their antibody deficiency as their immune system matures. 
  • Ig can inactivate live vaccines. If someone is on Ig replacement therapy at the time they receive a vaccine, the antibodies in Ig products can make the vaccine ineffective, especially live vaccines. The exceptions are seasonal vaccines, like the flu and COVID-19 vaccines, or vaccines for germs not typically seen in the U.S., like typhoid.
  • Ig can interfere with antibody-based laboratory tests. If someone is on Ig replacement therapy, antibody-based (serology) tests, which are often used to check for exposure to a particular germ like the hepatitis B virus, will not be accurate. They will measure the antibodies in the Ig product rather than the antibodies the person makes. Healthcare providers should use antigen or molecular tests instead.
  • In some cases, healthcare providers may need to reevaluate a diagnosis. This must be done cautiously, because Ig replacement therapy has to be paused for at least four months to get accurate results for antibody-based laboratory tests.

Tests to complete beforehand

Before starting Ig replacement therapy, it is important that a healthcare provider completes all laboratory tests needed to show that the person’s Ig levels are low and/or that they do not make working antibodies. These tests typically include a serum immunoglobulin test and a vaccine challenge test.

Insurance companies often require these test results as part of their prior authorization paperwork and will not approve Ig replacement therapy without them. You should keep a copy of the results with your other important medical information in case your insurance changes or you become eligible for Medicare. Medicare will not cover Ig replacement therapy without serum immunoglobulin and vaccine challenge test results. Once someone starts Ig replacement therapy, it is not possible to get accurate results for these important tests without stopping treatment for several months. Stopping treatment to redo these tests places you at risk of getting infections.

Insurance considerations

Ig replacement therapy typically requires the prescribing healthcare provider to get prior authorization from the person’s health insurance company. In addition, health insurance providers may not cover all Ig products and sometimes place other restrictions on Ig replacement therapy, such as limiting where a person can get their infusions. Be sure to check with your insurance plan to determine which routes of administration and/or Ig products are covered and whether there are any other restrictions on Ig replacement therapy.

For people on Medicare, how Ig replacement therapy is covered depends on the ICD-10 diagnostic code your provider uses to prescribe your medication. The Centers for Medicare and Medicaid Services (CMS) only allows certain ICD-10 diagnostic codes to be used for Ig replacement therapy covered under Medicare Part B; see below. Other diagnostic codes may be covered under Medicare Part D, which is the optional prescription coverage. Before purchasing a Medicare Part D plan, be sure it covers Ig replacement therapy if your healthcare provider does not use an ICD-10 covered under Part B.

Reporting side effects

It is important to track any side effects during or after immunoglobulin infusions, or when taking other medications. If your side effects are severe, get emergency medical care as soon as possible.

Please note that the Immune Deficiency Foundation cannot assist individuals experiencing side effects. Instead, please notify all of the following:

  • Your healthcare provider.
  • The product's manufacturer.
  • MedWatch at the FDA.
Notify MedWatch

Diagnostic codes for Ig replacement therapy covered by Medicare Part B

The following ICD-10 diagnostic codes are eligible for Part B coverage of Ig replacement therapy. Note that diagnoses with ICD-10 codes that are not listed below may have Ig therapy covered under Medicare Part D (optional prescription plan). Check with your plan for details.

D80 Immunodeficiency with predominantly antibody defects

  • D80.0 Hereditary hypogammaglobulinemia
  • D80.2 Selective deficiency of immunoglobulin A [IgA]
  • D80.3 Selective deficiency of immunoglobulin G [IgG] subclasses
  • D80.4 Selective deficiency of immunoglobulin M [IgM]
  • D80.5 Immunodeficiency with increased immunoglobulin M [IgM]
  • D80.6 Antibody deficiency with near-normal immunoglobulins or with hyperimmunoglobulinemia
  • D80.7 Transient hypogammaglobulinemia of infancy

D81 Combined immunodeficiencies

  • D81.0 Severe combined immunodeficiency [SCID] with reticular dysgenesis
  • D81.1 Severe combined immunodeficiency [SCID] with low T- and B-cell numbers
  • D81.2 Severe combined immunodeficiency [SCID] with low or normal B-cell numbers
  • D81.5 Purine nucleoside phosphorylase [PNP] deficiency
  • D81.6 Major histocompatibility complex class I deficiency
  • D81.7 Major histocompatibility complex class II deficiency
  • D81.82 Activated Phosphoinositide 3-kinase Delta Syndrome [APDS]
  • D81.89 Other combined immunodeficiencies
  • D81.9 Combined immunodeficiency, unspecified

D82 Immunodeficiency associated with other major defects

  • D82.0 Wiskott-Aldrich syndrome
  • D82.1 Di George's syndrome
  • D82.4 Hyperimmunoglobulin E [IgE] syndrome

D83 Common variable immunodeficiency

  • D83.0 Common variable immunodeficiency with predominant abnormalities of B-cell numbers and function
  • D83.1 Common variable immunodeficiency with predominant immunoregulatory T-cell disorders
  • D83.2 Common variable immunodeficiency with autoantibodies to B- or T-cells
  • D83.8 Other common variable immunodeficiencies
  • D83.9 Common variable immunodeficiency, unspecified

G11.3 Cerebellar ataxia with defective DNA repair

T86 Complications of transplanted organs and tissue

  • T86.01 Bone marrow transplant rejection
  • T86.02 Bone marrow transplant failure
  • T86.09 Other complications of bone marrow transplant
  • T86.5 Complications of stem cell transplant

Options for administration

Ig replacement therapy can be given either intravenously as IVIG or subcutaneously as SCIG. SCIG can be given in two ways: conventional or facilitated. Facilitated SCIG (fSCIG) uses an additional protein medication, hyaluronidase, to increase the amount of Ig that can be absorbed during each subcutaneous infusion.

The Immune Deficiency Foundation’s 2023 patient survey found that, among those receiving Ig replacement therapy in the U.S., approximately 45% use IVIG and 55% use SCIG [7]. You and your healthcare provider should have a discussion about, and come to a shared decision on, which route of administration is best for you. Studies show that patient quality of life is similar across regimens as long as they are individualized to meet the person’s needs [8]. There are advantages and disadvantages for each, but all options are effective for preventing infections.

IGRT route considerations
Use this table to discuss Ig replacement therapy options with your healthcare provider. IVIG = intravenous immunoglobulin, fSCIG = facilitated subcutaneous immunoglobulin, SCIG = subcutaneous immunoglobulin.

Intravenous immunoglobulin (IVIG) replacement therapy

A healthcare provider must administer IVIG, with each infusion scheduled in advance. IVIG is given through a single infusion site, directly into a vein, every 3-4 weeks. IVIG can be given in several settings, including inpatient or outpatient infusion suites, physicians’ offices, or at home with nursing support. Note that some insurance providers will only pay for IVIG given in specific settings, so check to be sure which settings are covered. The healthcare provider giving IVIG should stay with you for your entire infusion because of the risk of serious side effects. Typically, IVIG infusions take between 2-6 hours.

IgG levels over time
Example IgG levels in the bloodstream over time for IVIG, fSCIG, and SCIG. In the example, IVIG and fSCIG are given every three weeks, while SCIG is given every week.

IVIG requires less frequent infusions than SCIG, but longer periods between doses may cause peaks and valleys (troughs) in your bloodstream Ig levels. Troughs that are too low can lead to fatigue known as “wear-off” or breakthrough infections. In these cases, your IVIG dose may not be high enough.

Most immunologists strongly discourage using central venous catheters (also known as ports) to administer IVIG due to the increased risk of serious blood infections and blood clots. Given the very serious risk involved with the use of implantable ports, people with poor access to veins should instead consider switching to SCIG.

Side effects of IVIG

Although IVIG has been safely and effectively used since the early 1980s, IVIG can cause side effects, both at the infusion site (local) and throughout the body (systemic). Systemic side effects occur in up to 34% of IVIG infusions, although most are mild and do not interfere with daily life. Only about 1% of IVIG infusions result in serious systemic side effects [9, 10]. There is a higher risk of developing systemic side effects with IVIG than SCIG [10], and people are at the highest risk during their first IVIG infusion, if they have an active infection or pre-existing condition (such as pneumonia or bronchiectasis), or if they are switching Ig products [9].

Common systemic side effects include: 

  • Headache. 
  • Nausea or vomiting.
  • Fever or chills. 
  • Flushing.
  • Wheezing.
  • Back, muscle, or joint aches.
  • Chest tightness. 
  • Fluid overload (hypervolemia) symptoms like high blood pressure or swelling of the limbs. Those with kidney problems or congestive heart failure are at higher risk for fluid overload with IVIG and should consider SCIG instead.

Side effects that happen during the infusion are almost always related to infusing too fast or the Ig product not being at room temperature.

Rarely, more serious side effects can happen up to 72 hours after IVIG. These delayed side effects are not usually caused by the rate of infusion or the temperature of the product.

Some people have had aseptic meningitis headaches (inflammation of the covering of the brain and spinal cord) up to 72 hours after IVIG [11]. Hydrating prior to IVIG can prevent this side effect. Note that not every person who develops a post-infusion headache has aseptic meningitis. Notify the prescribing healthcare provider if you develop severe headaches that do not respond to over-the-counter medications.

Anaphylaxis, a severe, whole-body allergic reaction, is very rare and may be caused by antibodies against human IgA in some people who have low or no IgA [12]. Currently, there are no tests for these antibodies. Liquid IVIG products have low concentrations of IgA to avoid this reaction. In addition, reactions due to anti-IgA antibodies do not occur with SCIG, and SCIG has been safely given to people with PI suspected of having anti-IgA antibodies.

Some people have had acute kidney (renal) failure after IVIG infusions. However, 90% of these cases happened with sucrose-stabilized Ig products [13]. No Ig products currently on the market contain sucrose. Individuals over age 65 or who have pre-existing kidney disease may be at an increased risk of kidney-related side effects from IVIG.

Blood clots causing stroke, heart attack, or pulmonary embolism (when a clot blocks blood flow in the lungs) have also happened after both IVIG and SCIG infusions. The increased risk of blood clots may be because of traces of the clotting protein, factor XIa, in Ig products [14]. Manufacturers now test for and get rid of factor XIa in the final product to reduce this risk. Individual risk factors for blood clots include heart disease, advanced age, previous clotting event, clotting disorder, high blood pressure, diabetes, high cholesterol, kidney disease, obesity, and lack of mobility.

Hemolytic anemia, which is when red blood cells burst, leading to low red cell counts, is a rare but reported side effect of IVIG. The risk of hemolytic anemia seems to be higher in those who receive high-dose IVIG for autoimmune disorders than in those receiving Ig replacement therapy.

These types of severe, systemic reactions after IVIG are medical emergencies, and people who experience symptoms of them should get medical care immediately. 

Improving the IVIG experience

To prevent side effects, hydrate well before and during IVIG. Not only will being hydrated help the healthcare provider get an IV started, it will also decrease the risk of headaches and other, more serious side effects afterward. Also, make sure that the Ig product is at room temperature before starting the infusion. If it has been refrigerated, the product needs to warm to room temperature for at least 30 minutes to one hour.

Pre-medicating with acetaminophen (Tylenol), diphenhydramine (Benadryl), non-steroidal anti-inflammatory drugs (NSAIDs like aspirin or ibuprofen), or corticosteroids can also help prevent side effects during and after an infusion. It is important to note, however, that repeated use of corticosteroids for managing side effects may lead to long-term problems.

Sometimes, individuals have to switch Ig products to prevent side effects because they tolerate one brand of Ig better than another. Switching to SCIG can also help because SCIG generally has a lower rate of systemic side effects [9].

A healthcare provider trained in IVIG and an appropriate setting for administering IVIG are also important. The healthcare provider should have experience infusing Ig and know when to slow down or stop the infusion, if necessary. If you start experiencing side effects during an infusion, ask the healthcare provider to slow down the infusion rate.

You should record each infusion experience in an infusion log (available from many Ig manufacturers) to track any side effects. Report all side effects, no matter how minor, and any discomfort during or after an infusion, to:

  • The healthcare provider giving the IVIG, so that they can slow down or stop the infusion, or otherwise provide immediate medical care.
  • The prescribing healthcare provider, so that they can change the infusion rate, Ig dose, or other variables in their order, prescribe pre-medication, or prescribe a different Ig product.
  • The product’s manufacturer and MedWatch at the FDA [6]. In some cases, Ig product lots have been recalled because of increased reported side effects.

Subcutaneous immunoglobulin (SCIG or SubQ) replacement therapy

Subcutaneous immunoglobulin replacement therapy (SCIG or SubQ) has gained popularity in the U.S. since the approval of the first SCIG Ig product in 2006. In general, SCIG requires the person with PI or a caregiver to learn how to give infusions at home. Both forms of SCIG allow for self-administration, but facilitated SCIG can also be given at home or in-office by a healthcare provider, depending on insurance coverage.

SCIG provides the freedom to infuse anywhere at any time because it does not require medical supervision. College students and those whose jobs require frequent travel should consider SCIG. While this flexibility and control appeal to many individuals, the ability of the person to stick to the treatment regimen is an important consideration for SCIG since there are no fixed appointments.

In addition, fear of needles and poor manual dexterity, or an inability to coordinate hand and finger movements to manipulate objects, can make SCIG difficult. For fear of needles, strategies like using topical numbing creams can help. SCIG requires manual dexterity in order to administer the Ig and manage the pump.

SCIG does not require access to veins and results in the slow release of Ig from the subcutaneous tissues into the blood. More frequent dosing and a slower rate of absorption allow Ig levels to remain more consistent between infusions with SCIG than IVIG. With conventional SCIG, there is a steady level of Ig present in the bloodstream (no peaks or troughs like IVIG). With facilitated SCIG, there are peak and trough levels, but the peak levels are not as high, and the trough levels are not as low as with IVIG.

SCIG also has a lower rate of systemic side effects [10], making this route of administration a good option for those who have side effects from IVIG. The smaller volumes for SCIG also decrease the risk of fluid overload, which can cause high blood pressure and problems breathing.

There are 10%, 16.5%, and 20% IgG products for conventional SCIG, and 10% IgG plus a protein called hyaluronidase for facilitated SCIG. The Ig is infused under the skin, into the subcutaneous fat layer of the abdomen, thighs, back of the arms, or lateral hips (love handle area) at one or more sites.

SCIG infusion sites
Infusion sites for SCIG include the abdomen, thighs, back of the arms, and love handle area.

For SCIG, the prescribing healthcare provider calculates the total monthly Ig dose based on the individual’s weight, then divides it according to the length of time between infusions (from daily to every two weeks). Larger periods of time between infusions require the infusion of larger volumes for the same total Ig dose per month. Typically, conventional SCIG infusions take between 1-2 hours.

In general, SCIG is delivered using a small needle attached to tubing and a syringe, which is placed in a pump. The Ig products come in a variety of vial sizes or pre-filled syringes, depending on the manufacturer. There are several needle and tubing sizes available, and troubleshooting problems with SCIG often involves changing the equipment being used, such as needle sets, tubing, and pump. Some individuals may prefer or better tolerate SCIG delivered by subcutaneous push instead of a pump, meaning that a small amount of SCIG is injected daily under the skin without using a pump.

Facilitated SCIG is given every 3-4 weeks to deliver the total monthly Ig dose all at once. This is “facilitated” by hyaluronidase, a protein naturally found in subcutaneous tissues. Hyaluronidase is injected into the subcutaneous space before the Ig to expand the space and allow more medication to be infused into each site. The effects of the hyaluronidase are short-lived, and the tissues go back to normal in 24-48 hours. In facilitated SCIG, about 300-600mL can be delivered at one site or divided between two sites.

The benefit of facilitated SCIG is fewer infusions, as it allows for an entire 3-4 week dose to be given at one time. The length of the infusion varies depending on the volume infused, but generally takes 1-3 hours.

Side effects of SCIG

In general, people using SCIG have fewer side effects than those using IVIG, and any systemic side effects are typically mild [10]. SCIG is an option to consider if you do not tolerate IVIG well, when there is poor access to veins (for example, from scarring), or when your lifestyle is more compatible with SCIG than IVIG. SCIG is an option for children, adults, pregnant women, the elderly, and individuals with antibodies against IgA (very rare).

Pre-medication is usually not needed for SCIG. Overall, severe reactions rarely occur with SCIG, but individuals who have had severe reactions to IVIG may be at a higher risk of severe reactions to SCIG. However, SCIG products carry the same warnings for rare, systemic blood-clotting reactions (such as stroke, heart attack, or pulmonary embolism) as IVIG products. The increased risk of blood clots may be because of traces of the clotting protein, factor XIa, in Ig products [14], which manufacturers now test for and get rid of in the final product. Individual risk factors for blood clots include heart disease, advanced age, previous clotting event, clotting disorder, high blood pressure, diabetes, high cholesterol, kidney disease, obesity, and lack of mobility.

The most common side effect of SCIG is local redness, swelling, and irritation at the infusion site(s). Usually, these mild, localized reactions improve with repeated infusions. In rare cases, the infusion site reactions can be severe.

The individual with PI or a caregiver should report all side effects and any discomfort experienced during or after an infusion of SCIG to the prescriber, the product's manufacturer, and MedWatch at the FDA [6]. 

Improving the SCIG experience

Several factors allow individuals to optimize their SCIG experience, including the number and location of infusion sites, the volume infused per site, needle length, and pump type (or manual push instead of a pump).

The number of infusion sites depends on the volume and concentration of Ig being infused. Increasing the volume of Ig infused at each site or using more concentrated 16.5% or 20% IgG products reduces the number of needle sticks. 16.5% and 20% IgG products require 1.6 and 2 times less volume, respectively, than 10% IgG products to deliver the same dose of Ig. For some individuals, SCIG with 10% IgG is not practical because of the large volume required for each infusion, even when split between several sites. People without much subcutaneous tissue cannot absorb large volumes and may experience leakage of Ig at their infusion site(s).

Individuals can choose to rotate between the abdomen, thighs, lateral hips, or the back of the arms for SCIG infusions. Each person has areas on the body with different amounts of subcutaneous tissue. It's important to avoid bony areas, bruises, scar tissue, and stretch marks.

To improve or avoid infusion site reactions, individuals need to be trained to make sure they use proper technique to access subcutaneous tissue. Local skin reactions can be caused by using needles that are too short, causing the Ig to be infused into the skin instead of the subcutaneous tissue. Several needle lengths are available; the important thing is to use a needle long enough to ensure that the Ig is being administered into the subcutaneous tissues rather than the skin. It’s also important to “prime” or push the Ig into the infusion tubing only up to the needle hub (where the tubing and needle connect). Ig droplets at the tip of the needle while inserting it can also cause a skin reaction. Note that air in the tubing is fine for a SCIG infusion.

Those who have issues tolerating infusions can try smaller volumes of SCIG given more frequently. Some SCIG users even infuse daily. A variety of infusion pumps are also available, ranging from simple, portable mechanical pumps to more complicated programmable pumps. 

Monitoring and adjusting Ig replacement therapy

It's important to monitor IgG levels and infections closely when starting Ig replacement therapy or if the dose or route of administration changes. The prescribing healthcare provider will recheck your IgG levels a few weeks after starting or changing treatment. It may take up to 8-12 weeks to reach a steady, protective IgG level.

The prescribing healthcare provider will also order routine blood tests, such as complete blood counts (CBC) and tests of kidney and liver function. Experts differ on how often individuals on Ig replacement therapy should have follow-up visits, from monthly to annually. However, they all agree that each person has their own biological level of IgG that protects against infection and that infections and IgG levels are the most important data to track [15].

The goal of therapy is to prevent severe, life-threatening infections. Infections may still occur, especially if you have organ or tissue damage, such as bronchiectasis, or other conditions like the loss of protein in the gastrointestinal tract (protein-losing enteropathy). However, if you continue to have frequent or serious infections, your Ig dose or regimen may need to be adjusted. A study looking at more than 600 people on IVIG found that people with trough IgG levels of 1000 mg/dL were five times less likely to get pneumonia compared to those with trough IgG levels of 500 mg/dL [16].

Your dose or regimen may also need to be adjusted for changes in weight, other health conditions, or how well you absorb and break down Ig over time. Each person is unique, and so is their Ig treatment regimen.

References

References

  1. Nolte MT, Pirofsky B, Gerritz GA, Golding B. Intravenous immunoglobulin therapy for antibody deficiency. Clin Exp Immunol. 1979;36: 237–243. Available: https://pubmed.ncbi.nlm.nih.gov/477026/ 
  2. What is plasmapheresis? [cited 23 Oct 2025]. Available: https://primaryimmune.org/resources/news-articles/what-plasmapheresis
  3. Immune Globulins. In: U.S. Food and Drug Administration [Internet]. FDA; 8 Mar 2023 [cited 23 Oct 2025]. Available: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/immune-globulins
  4. Have You Given Blood Lately? In: U.S. Food and Drug Administration [Internet]. FDA; 20 Feb 2025 [cited 23 Oct 2025]. Available: https://www.fda.gov/consumers/consumer-updates/have-you-given-blood-lately
  5. 21 CFR Part 640 -- Additional Standards for Human Blood and Blood Products. [cited 23 Oct 2025]. Available: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-F/part-640
  6. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. In: U.S. Food and Drug Administration [Internet]. FDA; 26 Sep 2025 [cited 23 Oct 2025]. Available: https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program
  7. 2023 national patient survey. [cited 23 Oct 2025]. Available: https://primaryimmune.org/advancing-pi-research-and-clinical-care/idf-surveys/2023-national-patient-survey
  8. Pulvirenti F, Cinetto F, Pecoraro A, Carrabba M, Crescenzi L, Neri R, et al. Health-related quality of life in patients with CVID under different schedules of immunoglobulin administration: Prospective multicenter study. J Clin Immunol. 2019;39: 159–170. Available: https://pubmed.ncbi.nlm.nih.gov/30644015/ 
  9. Ness S. Intravenous and Subcutaneous Immunoglobulin Treatment Options. American Journal of Managed Care. 2019;25. Available: https://www.ajmc.com/view/intravenous-and-subcutaneous-immunoglobulin-treatment-options 
  10. Wasserman RL, Gupta S, Stein M, Rabbat CJ, Engl W, Leibl H, et al. Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases. Immunotherapy. 2022;14: 215–224. Available: https://pubmed.ncbi.nlm.nih.gov/34931880/ 
  11. De Felice ELT, Toti GF, Gatti B, Gualtieri R, Camozzi P, Lava SAG, et al. Acute aseptic meningitis temporally associated with intravenous polyclonal immunoglobulin therapy: A systematic review. Clin Rev Allergy Immunol. 2024;66: 241–249. Available: https://pubmed.ncbi.nlm.nih.gov/38739354/ 
  12. Rachid R, Bonilla FA. The role of anti-IgA antibodies in causing adverse reactions to gamma globulin infusion in immunodeficient patients: a comprehensive review of the literature. J Allergy Clin Immunol. 2012;129: 628–634. Available: https://pubmed.ncbi.nlm.nih.gov/21835445/ 
  13. Lin RY, Rodriguez-Baez G, Bhargave GA, Lin H. Intravenous gammaglobulin-associated renal impairment reported to the FDA: 2004 - 2009. Clin Nephrol. 2011;76: 365–372. Available: https://pubmed.ncbi.nlm.nih.gov/22000556/ 
  14. Germishuizen WA, Gyure DC, Stubbings D, Burnouf T. Quantifying the thrombogenic potential of human plasma-derived immunoglobulin products. Biologicals. 2014;42: 260–270. Available: https://pubmed.ncbi.nlm.nih.gov/25096922/ 
  15. Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Allergy Clin Immunol. 2008;122: 210–212. Available: https://pubmed.ncbi.nlm.nih.gov/18602574/ 
  16. Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical studies. Clin Immunol. 2010;137: 21–30. Available: https://pubmed.ncbi.nlm.nih.gov/20675197/ 

Products approved for IVIG and/or SCIG in the U.S.

All products can be stored either refrigerated or at room temperature (not to exceed 77°F or 25°C) for at least four weeks; check package inserts to see if your specific product can be stored for longer. Once a product has reached room temperature, it should not be returned to refrigerated temperature. 

Products should never be frozen and should be discarded if they become frozen. Refer to product package inserts for additional storage details.

Download Ig product booklet

Alyglo

(Manufacturer: GC Biopharma )

Administration: IVIG   
Concentration: 10% (100 mg/mL)
Approved for: Ages 17+ 

Report side effects/adverse reactions at medicalinfo@gcbiopharmausa.com or 1-833-426-6426.

Package insert Product website Copay assistance

Asceniv

(Manufacturer: ADMA Biologics )

Administration: IVIG 
Concentration: 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at PV@admabio.com or 1-800-458-4244, option 2.

Package insert Product website Copay assistance

Bivigam

(Manufacturer: ADMA Biologics )

Administration: IVIG 
Concentration: 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at PV@admabio.com or 1-800-458-4244, option 2.

Package insert Product website Copay assistance

Cutaquig

(Manufacturer: Octapharma )

Administration: SCIG 
Concentration: 16.5% (165 mg/mL) 
Approved for: Ages 2+

Octapharma and Pfizer both distribute Cutaquig. Each company has its own product website and may have its own copay assistance program. If your infusion center or hospital supplies Cutaquig, it is typically distributed by Octapharma. If you get Cutaquig through a specialty pharmacy/for home care, it is distributed by Pfizer. 

Report side effects/adverse reactions at 201-604-1137.

Package insert Copay assistance (Octapharma) Copay assistance (Pfizer)

Cuvitru

(Manufacturer: Takeda )

Administration: SCIG 
Concentration: 20% (200 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at pvsafetyamericas@takeda.com or 1-877-825-3327.

Package insert Product website Copay assistance

Flebogamma DIF

(Manufacturer: Grifols )

Administration: IVIG 
Concentration: 5% (50 mg/mL) or 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at https://www.grifols.com/en/notification-of-adverse-reaction. 

Package insert (5%) Package insert (10%) Product website

Gammagard Liquid

(Manufacturer: Takeda )

Administration: IVIG or SCIG
Concentration: 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at pvsafetyamericas@takeda.com or 1-877-825-3327.

Package insert Product website Copay assistance

Gammagard Liquid ERC

(Manufacturer: Takeda )

Administration: IVIG or SCIG
Concentration: 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at pvsafetyamericas@takeda.com or 1-877-825-3327.

Package insert

Gammagard S/D

(Manufacturer: Takeda )

NOTE: Takeda is discontinuing Gammagard S/D in December 2027.

Administration: IVIG
Concentration: 5% (50 mg/mL) or 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at pvsafetyamericas@takeda.com or 1-877-825-3327.

Package insert

Gammaked

(Manufacturer: Kedrion )

Administration: IVIG or SCIG
Concentration: 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at 1-855-353-7466 or https://www.kedrion.us/ pharmacovigilance/.

Package insert Product website Copay assistance

Gammaplex

(Manufacturer: Kedrion )

Administration: IVIG 
Concentration: 5% (50 mg/mL) or 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at 1-855-353-7466 or https://www.kedrion.us/ pharmacovigilance/.

Package insert (5%) Package insert (10%) Product website Copay assistance

Gamunex - C

(Manufacturer: Grifols )

Administration: IVIG or SCIG
Concentration: 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at https://www.grifols.com/en/notification-of-adverse-reaction. 

Package insert Product website Copay assistance

Hizentra

(Manufacturer: CSL Behring )

Administration: SCIG 
Concentration: 20% (200 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at Adverse.Events.Global@cslbehring.com or 1-866-915-6958. 

Package insert Product website Copay assistance

HyQvia

(Manufacturer: Takeda )

Administration: Facilitated SCIG 
Concentration: 10% (100 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at pvsafetyamericas@takeda.com or 1-877-825-3327.

Package insert Product website Copay assistance

Octagam

(Manufacturer: Octapharma )

Administration: IVIG   
Concentration: 5% (50 mg/mL) or 10% (100 mg/mL)*  
* Octagam 10% is approved for chronic immune thrombocytopenia and dermatomyositis. 
Approved for: Ages 6+ 

Octapharma and Pfizer both distribute Octagam. Each company has its own product website and may have its own copay assistance program. If your infusion center or hospital supplies Octagam, it is typically distributed by Octapharma. If you get Octagam through a specialty pharmacy/for home care, it is distributed by Pfizer. 

Report side effects/adverse reactions at 201-604-1137.

Package insert (5%) Package insert (10%) Copay assistance (Pfizer)

Panzyga

(Manufacturer: Octapharma )

Administration: IVIG 
Concentration: 10% (100 mg/mL) 
Approved for: Ages 2+

Octapharma and Pfizer both distribute Panzyga. Each company has its own product website and may have its own copay assistance program. If your infusion center or hospital supplies Panzyga, it is typically distributed by Octapharma. If you get Panzyga through a specialty pharmacy/for home care, it is distributed by Pfizer. 

Report side effects/adverse reactions at 201-604-1137.

Package insert Copay assistance (Pfizer)

Privigen

(Manufacturer: CSL Behring )

Administration: IVIG 
Concentration: 10% (100 mg/mL) 
Approved for: all ages

Report side effects/adverse reactions at Adverse.Events.Global@cslbehring.com or 1-866-915-6958.

Package insert Product website Copay assistance

Qivigy

(Manufacturer: Kedrion )

Administration: IVIG
Concentration: 10% (100 mg/mL) 
Approved for: Ages 18+

Report side effects/adverse reactions at 1-855-353-7466 or https://www.kedrion.us/ pharmacovigilance/.

Package insert Product website

Xembify

(Manufacturer: Grifols )

Administration: SCIG 
Concentration: 20% (200 mg/mL) 
Approved for: Ages 2+

Report side effects/adverse reactions at https://www.grifols.com/en/notification-of-adverse-reaction. 

Package insert Product website Copay assistance

Yimmugo

(Manufacturer: Biotest AG )

Administration: IVIG   
Concentration: 10% (100 mg/mL)
Approved for: Ages 2+ 

Kedrion distributes Yimmugo in the U.S. 

Report side effects/adverse reactions at 1-855-353-7466 or https://www.kedrion.us/ pharmacovigilance/.

Package insert Product website

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This page contains general medical and/or legal information that cannot be applied safely to any individual case. Medical and/or legal knowledge and practice can change rapidly. Therefore, this page should not be used as a substitute for professional medical and/or legal advice. Additionally, links to other resources and websites are shared for informational purposes only and should not be considered an endorsement by the Immune Deficiency Foundation.

Adapted from the Patient & Family Handbook for Primary Immunodeficiency Diseases, Sixth Edition.  
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