Understanding What are the most common complications of IVIG?

October 11, 2025 •

3 min read

According to an Immune Deficiency Foundation survey, 98% of people using IVIG experienced side effects, with headaches, fatigue, and muscle aches being the most frequent. While many are mild, understanding what are the most common complications of IVIG, as well as the rare severe ones, is crucial for patient safety and effective management.

Quick Summary

This guide details the most common complications of IVIG, such as flu-like symptoms, headache, and fatigue, alongside less frequent but serious risks like renal failure, blood clots, and aseptic meningitis. Learn about management and risk factors.

Key Points

Common Side Effects: Mild, flu-like symptoms like headache, chills, fever, and fatigue are the most frequent, often related to the infusion rate.
Serious Risks: Rare but severe complications include acute renal failure, thromboembolic events (blood clots), and aseptic meningitis.
Risk Factors: Patients who are older, have a history of cardiovascular or kidney disease, or are dehydrated are at higher risk for severe complications.
Prevention: Staying well-hydrated, starting with a slow infusion rate, and taking premedication can help mitigate many adverse reactions.
Management: Infusion-related reactions often improve by slowing or pausing the infusion; severe symptoms require immediate medical attention.
SCIG as an Alternative: For those with persistent systemic reactions, subcutaneous immunoglobulin (SCIG) offers a lower risk of such complications.
Long-term Monitoring: Regular monitoring of kidney and liver function is recommended, especially for patients on long-term therapy.

Intravenous immunoglobulin (IVIG) is a vital therapy utilizing pooled antibodies from healthy donors to treat various autoimmune and immunodeficiency disorders. Although generally well-tolerated, adverse events can occur, ranging from minor and transient to severe. Understanding these risks, their causes, and management is essential for patients and healthcare providers.

Mild and Moderate Infusion-Related Reactions

The majority of IVIG complications are mild, temporary, and linked to the infusion process. These are often manageable through adjusting the infusion rate, premedication, or ensuring adequate hydration. They are more likely during the first infusion or with a new IVIG product.

Common signs and symptoms of mild reactions include:

Headache, a frequently reported side effect.
Flu-like symptoms such as fever, chills, fatigue, and muscle aches.
Nausea and occasional vomiting.
Flushing or temporary low blood pressure.
Mild skin reactions like rash.
Back and joint pain.

These reactions are thought to stem from cytokine release and complement activation triggered by the infusion. Slowing the infusion rate is often effective in reducing symptoms.

Rare but Serious Complications

While uncommon, certain serious complications warrant close monitoring and prompt medical attention, particularly in patients with pre-existing risk factors.

Renal (Kidney) Complications

IVIG can lead to or worsen renal dysfunction, potentially causing acute renal failure. Risk factors include advanced age, existing kidney disease, diabetes, and dehydration. While older formulations with sucrose posed a higher risk, modern sucrose-free products have significantly reduced this. Monitoring kidney function is crucial.

Thrombotic Events (Blood Clots)

Thromboembolic events are a recognized risk with IVIG. The risk is elevated in older adults or those with a history of cardiovascular issues, immobilization, or specific clotting conditions. These events are more common within 24 hours post-infusion, especially with higher doses. Staying hydrated and using slow infusion rates can help prevent them.

Aseptic Meningitis Syndrome (AMS)

AMS is a rare inflammatory reaction of the meninges. Symptoms include severe headache, stiff neck, fever, light sensitivity, nausea, and vomiting, typically occurring within 2 days. It is usually self-limiting but requires medical assessment to rule out infectious causes.

Hemolytic Anemia

IVIG can cause the breakdown of red blood cells, leading to hemolytic anemia. High doses can contain antibodies that react with blood group antigens in susceptible patients. Monitoring for signs like fatigue or jaundice is advised for those receiving high doses, particularly with blood types A, B, or AB.

Comparison of IVIG vs. Subcutaneous Immunoglobulin (SCIG)

SCIG is an alternative for patients experiencing systemic side effects with IVIG. Administered under the skin more frequently, SCIG results in more stable immunoglobulin levels and fewer systemic complications compared to IVIG.


Feature	Intravenous Immunoglobulin (IVIG)	Subcutaneous Immunoglobulin (SCIG)
Common Side Effects	Systemic (e.g., headache, chills, fatigue, fever).	Localized (e.g., redness, swelling, itching at site).
Infusion Site Reactions	Mild.	Very common, usually mild.
Infusion Rate	Careful monitoring needed; faster rates increase systemic risk.	Slower; reduces rapid systemic reactions.
Frequency	Typically monthly or every few weeks.	Often daily, weekly, or bi-weekly.
Hydration	Crucial for preventing headaches and renal issues.	Important, but less critical for managing systemic reactions.
Serious Risks	Rare but significant (thromboembolism, renal failure, meningitis).	Significantly lower risk of systemic complications.

Prevention and Management Strategies

Preventive measures and a personalized management plan can significantly reduce complications.

Hydration: Increase fluid intake before, during, and after infusion to minimize headaches and protect kidneys.
Infusion Rate: Start slowly, especially initially, and increase gradually as tolerated. Slow or pause infusion if side effects occur.
Premedication: Acetaminophen, NSAIDs, or antihistamines may be used to prevent mild reactions.
Monitoring: Vital signs should be monitored during infusion, and patients educated on signs of serious complications.
Product/Route Change: If complications persist, consider changing the IVIG brand or switching to SCIG.

Conclusion

While IVIG is effective, understanding its potential complications is crucial. Most side effects are mild and manageable with simple strategies. However, rare but serious risks require careful consideration, particularly in at-risk patients. Close collaboration with the healthcare team and preventive measures can minimize adverse events for a successful IVIG experience.

Frequently Asked Questions

These symptoms are believed to be caused by cytokine release and complement activation triggered by the infusion, and are often linked to a fast infusion rate or the specific IVIG formulation.

Yes, rarely, IVIG can cause acute renal dysfunction, especially in older or at-risk patients. The risk is lower with modern, sucrose-free formulations, but careful screening and monitoring are still needed.

Symptoms can include chest pain, trouble breathing, swelling and warmth in an arm or leg, vision changes, or weakness on one side of the body. These require immediate medical attention.

Key strategies include staying well-hydrated before and after infusions, starting the infusion at a slow rate, and taking premedications like acetaminophen or antihistamines as prescribed by your doctor.

Yes, many infusion-related reactions, particularly mild ones like headaches and chills, are more likely to occur during the first few infusions.

Aseptic meningitis is a rare inflammatory reaction of the brain's lining that can occur after IVIG. Symptoms include a severe headache, stiff neck, fever, and sensitivity to light.

You should contact your doctor for severe or persistent headaches, a stiff neck, dark-colored urine, new swelling, or any signs of a serious allergic reaction or blood clot.

Yes, if complications persist with one IVIG brand, your doctor may switch to another brand or suggest moving to subcutaneous immunoglobulin (SCIG), which generally causes fewer systemic side effects.