Understanding What Are the Side Effects of Gamma Globulin Injections?

October 13, 2025 •

3 min read

While most patients tolerate immunoglobulin therapy well, a 2018 survey reported that 98% of intravenous immunoglobulin (IVIG) users experienced some side effect. Understanding what are the side effects of gamma globulin injections is essential for patients and caregivers to ensure safe and effective treatment.

Quick Summary

Immune globulin (IG) therapy, or gamma globulin injections, can cause various side effects, which differ based on whether the medication is administered intravenously (IVIG) or subcutaneously (SCIG). Common reactions include headaches, fatigue, and chills, while more serious complications like kidney problems or blood clots are rare but possible. Management strategies, such as premedication and adjusting infusion speed, can help mitigate these adverse effects.

Key Points

Two Primary Methods: Gamma globulin is delivered intravenously (IVIG) or subcutaneously (SCIG), with each method having a different side effect profile.
Common Side Effects Differ: IVIG is associated with higher rates of systemic reactions like headaches, fever, and chills, while SCIG primarily causes local site reactions such as redness and swelling.
Hydration is Key: Drinking plenty of fluids before, during, and after infusion can significantly help prevent common side effects and reduce the risk of more serious complications like kidney problems.
Infusion Rate Matters: Slowing down the infusion rate for both IVIG and SCIG can reduce the occurrence and severity of side effects, especially during initial treatments.
Watch for Serious Symptoms: While rare, complications like blood clots, aseptic meningitis, and kidney problems require immediate medical attention, with specific symptoms to watch for like severe headaches, dark urine, or chest pain.
Preparation is Protective: Using premedication and correct administration techniques are important strategies for managing and preventing adverse reactions.

What Are Gamma Globulin Injections?

Gamma globulin injections, also known as immune globulin (IG) therapy, provide concentrated antibodies from healthy donors to support weakened immune systems in conditions like primary immunodeficiency diseases (PIDD) or autoimmune disorders. The two main administration methods, intravenous (IVIG) and subcutaneous (SCIG), have different side effect profiles. IVIG, given into a vein, has a higher risk of systemic side effects due to rapid bloodstream entry. SCIG, injected under the skin more frequently, typically causes fewer systemic reactions but more local site issues.

Common Side Effects

Side effects vary by administration method, infusion rate, and individual patient factors. They are most common during the initial treatments.

Common IVIG Side Effects: Include flu-like symptoms such as headache, fever, chills, fatigue, muscle and joint aches, back pain, and gastrointestinal issues like nausea, vomiting, or diarrhea. Changes in blood pressure may also occur.

Common SCIG Side Effects: Primarily involve localized infusion site reactions like redness, swelling, itching, bruising, or lumps, which often improve over time. Mild headache, nausea, and diarrhea are also possible but less frequent than with IVIG.

Less Common but Serious Side Effects

Serious complications are rare but require attention, especially in older or patients with existing conditions. These include Aseptic Meningitis Syndrome (AMS), characterized by severe headache and stiff neck; kidney problems, particularly with certain IVIG products and risk factors; Thromboembolic Events (Blood Clots), which carry a boxed warning; Hemolytic Anemia, involving red blood cell destruction; Transfusion-Related Acute Lung Injury (TRALI); and rare Severe Allergic Reactions (Anaphylaxis), especially in patients with IgA deficiency.

Comparison of IVIG and SCIG Side Effects


Feature	Intravenous Immune Globulin (IVIG)	Subcutaneous Immune Globulin (SCIG)
Route of Administration	Into a vein	Under the skin (fatty tissue)
Common Local Side Effects	Infusion site pain, redness, or swelling	Most common side effect; redness, swelling, itching, bruising, and hard lump at injection site
Common Systemic Side Effects	High incidence of headache, chills, fever, fatigue, muscle aches	Milder and less frequent systemic side effects; mild headache, nausea, diarrhea possible
Infusion Rate Effects	Faster rates can increase the risk of systemic side effects	Slower, more controlled absorption results in fewer systemic reactions
Risk of Serious Adverse Events	Higher risk of systemic issues like kidney problems, blood clots, and AMS	Lower risk of serious systemic adverse events compared to IVIG
Management of Side Effects	Often requires premedication and careful monitoring of vitals during infusion	Local site reactions can be managed with compresses; hydration is still important

Management and Prevention of Side Effects

Strategies to reduce adverse effects include maintaining proper hydration before, during, and after infusion. Adjusting the infusion rate, particularly starting slowly, can decrease systemic reactions for IVIG and minimize local discomfort for SCIG. Premedication with acetaminophen, antihistamines, or NSAIDs can help manage flu-like symptoms and allergic reactions. Monitoring vital signs during IVIG is standard, and patients using SCIG at home should be aware of when to seek medical help. For SCIG, using correct needle length, rotating sites, and proper line priming can prevent site irritation.

Conclusion

Understanding the potential side effects of gamma globulin injections is vital for patient safety. Both IVIG and SCIG have different risk profiles. While common side effects like headaches and fatigue are usually manageable, it's crucial to be aware of rare but serious risks such as blood clots and kidney dysfunction. Effective management involves open communication with healthcare providers, proper preparation, hydration, and careful monitoring to optimize outcomes from immunoglobulin therapy. For further information, consult resources like the Immune Deficiency Foundation.

Frequently Asked Questions

For intravenous (IVIG) administration, the most common side effects include headache, fever, chills, fatigue, muscle aches, and gastrointestinal upset such as nausea and vomiting.

Subcutaneous (SCIG) infusions are typically associated with milder systemic side effects than IVIG. However, SCIG can frequently cause localized reactions at the injection site, including redness, swelling, itching, and bruising.

To prevent headaches, healthcare providers often recommend staying well-hydrated before and during the infusion and may administer pre-medications like acetaminophen (Tylenol). Slowing the infusion rate can also be effective.

Yes, acute renal dysfunction or kidney failure is a potential, though rare, side effect, particularly with certain IVIG products and in high-risk patients (elderly, diabetic, or dehydrated). Staying hydrated is crucial to minimize this risk.

Signs of a blood clot to watch for include pain, swelling, warmth, or redness in an arm or leg, sudden shortness of breath, or chest pain. These require immediate medical attention.

Local reactions at the subcutaneous injection site can be managed with cold or warm compresses. Rotating injection sites and ensuring a slow infusion rate can also help minimize irritation.

You should contact a healthcare provider immediately if you experience a severe headache with a stiff neck, dark urine, significant swelling, chest pain, or difficulty breathing.

Severe allergic reactions (anaphylaxis) are rare but possible. The risk is higher for patients with IgA deficiency and anti-IgA antibodies. Signs include hives, swelling in the mouth or throat, and trouble breathing.