Why does IVIG make you feel sick? Unpacking the causes of infusion reactions

October 12, 2025 •

4 min read

While considered generally well-tolerated, up to 50% of patients receiving Intravenous Immunoglobulin (IVIG) therapy experience at least one adverse event during long-term treatment. Understanding the complex reasons for why IVIG makes you feel sick? is crucial for better managing the infusion process.

Quick Summary

This article explains the various physiological responses and contributing factors, such as infusion rate, inflammatory cytokine release, and specific product formulation, that cause adverse effects like nausea, headaches, and flu-like symptoms during IVIG therapy, and outlines practical strategies for mitigating these symptoms.

Key Points

Infusion Rate Matters: A faster IVIG infusion rate is a leading cause of systemic side effects like headaches, fever, and nausea.
Immune System Overload: The body's immune reaction to the large amount of foreign proteins can trigger a cascade of inflammatory responses, causing flu-like symptoms.
Formulation Differences: The type of stabilizers and additives used by different IVIG manufacturers can affect tolerability and lead to adverse reactions.
Hydration is Key: Maintaining good hydration before, during, and after infusion can significantly reduce the severity of common side effects, especially headaches.
Premedication Can Help: Taking medications like acetaminophen or antihistamines before the infusion can prevent or lessen common side effects.
Alternative Options Exist: For patients who consistently experience severe side effects with IVIG, switching to a different product or to subcutaneous immunoglobulin (SCIG) may be recommended.
Patient Factors are Influential: Pre-existing conditions like heart or kidney disease, as well as a history of previous reactions, increase the risk of adverse events.

Understanding the complex triggers of IVIG side effects

Intravenous Immunoglobulin (IVIG) is a concentrated blood product derived from the pooled plasma of thousands of healthy donors. It is used to treat a range of conditions, including primary immunodeficiencies, autoimmune disorders, and neuromuscular diseases. Although a life-changing therapy for many, IVIG can trigger a variety of adverse reactions that make patients feel unwell, often described as having flu-like symptoms. While the exact mechanisms are not always fully understood, several factors contribute to these infusion-related side effects.

The body's immune response to infused proteins

One of the primary reasons for feeling sick during or after an IVIG infusion is the body's natural immune response to the large quantity of foreign proteins being introduced into the bloodstream. This can activate the complement system, a part of the immune system that helps clear pathogens. When complement is activated, it can cause an inflammatory cascade that leads to symptoms like fever, chills, and flu-like aches. The release of inflammatory cytokines, such as IL-6 and TNF-α, may also play a significant role in causing these generalized symptoms.

The impact of infusion rate and dosage

The speed at which IVIG is infused and the total dose administered are major determinants of adverse reactions. Rapid infusion can overwhelm the body's system, leading to a higher incidence of side effects. For this reason, healthcare providers often start with a very slow infusion rate and gradually increase it as the patient demonstrates tolerance. Similarly, higher doses of IVIG are associated with an increased risk of adverse events, including headaches, fevers, and more serious complications.

The role of product formulation

Different IVIG brands are manufactured using various stabilizers and additives, and these differences can significantly affect tolerability. Some preparations may contain sugars like sucrose or maltose, while others use amino acids such as glycine. Historically, sucrose-stabilized products were associated with renal issues and high osmolality, which could cause fluid shifts and contribute to side effects. Variations in IgA content between products can also be a factor, particularly for patients with an anti-IgA deficiency, who have a rare but serious risk of anaphylaxis.

Patient-specific risk factors

Individual patient characteristics and underlying health conditions can influence the likelihood and severity of IVIG side effects. Predisposing factors include:

A history of previous adverse reactions to IVIG
Pre-existing cardiovascular or renal diseases
Dehydration, which can exacerbate symptoms like headache and fatigue
Concurrent infections or chronic inflammation
Advanced age
A history of migraines

Common signs of an IVIG infusion reaction

Side effects can be categorized based on their timing relative to the infusion. Immediate reactions occur within the first 30 to 60 minutes, while delayed reactions can appear hours or even days after the infusion is complete.

Commonly reported symptoms include:

Headache, which is one of the most frequent side effects
Nausea and vomiting
Chills and fever
Fatigue and malaise
Muscle aches (myalgia) and joint pain
Flushing and dizziness
Rash or itching (urticaria)

Management and prevention strategies

To mitigate and prevent IVIG side effects, a combination of strategies may be employed by a healthcare provider. These approaches aim to make the infusion experience more comfortable and safe for the patient.

Comparison of strategies for managing IVIG reactions


Strategy	Description	Efficacy	Best for	Notes
Slowing the Infusion Rate	Reducing the speed at which IVIG is administered, especially at the start of the infusion.	High	All patients, particularly those with a history of reactions.	Often the first line of defense to prevent or stop immediate reactions.
Premedication	Administering drugs like acetaminophen, NSAIDs, or antihistamines before the infusion.	High	Managing headaches, fever, and mild allergic reactions.	Acetaminophen and diphenhydramine are common choices for prophylaxis.
Staying Hydrated	Encouraging vigorous oral hydration before, during, and after the infusion.	High	Preventing headaches and kidney-related side effects.	Use water, not sugary or caffeinated drinks.
Switching IVIG Products	Changing to a different brand or formulation of IVIG.	Moderate to High	Patients who have persistent reactions to a specific product.	Different stabilizers and osmolality can affect tolerability.
Switching to SCIG	Changing the route of administration to subcutaneous (under the skin) immunoglobulin.	High	Patients with a high rate of systemic reactions to IVIG.	Side effects with SCIG are typically milder and localized to the injection site.
Ensuring Room Temperature	Allowing the IVIG product to warm up to room temperature before administration.	High	All patients to prevent chills.	Cold infusions can induce chills and other flu-like symptoms.

Conclusion

While feeling sick from IVIG is a common side effect, it is important to remember that most adverse reactions are mild, transient, and manageable. By understanding the underlying causes—including infusion rate, product formulation, and individual patient factors—healthcare providers can tailor the treatment protocol to minimize discomfort and ensure a safer, more effective therapy. For patients, communication with their care team and adhering to preventative measures like hydration and premedication are key steps in managing their infusions successfully. Serious adverse reactions are rare, but it is vital to be aware of the signs and seek immediate medical attention if they occur. To learn more about IVIG therapy, consider visiting the Immune Deficiency Foundation's website for educational resources and support.

Commonly reported symptoms during IVIG therapy:

Headache and migraine: Frequent and often related to infusion rate or dehydration.
Flu-like symptoms: Chills, fever, fatigue, and muscle aches are common inflammatory responses.
Nausea and vomiting: Can occur during or shortly after the infusion.
Skin reactions: Rashes, itching, or flushing are often mild and temporary.
Blood pressure changes: Both hypotension (low) and hypertension (high) are possible.
Dizziness: Can be caused by blood pressure fluctuations or fluid shifts.

Frequently Asked Questions

Most side effects from IVIG, such as headaches and flu-like symptoms, are transient and typically last for a few hours to a few days following the infusion. More serious reactions are rare but can persist longer.

Yes, headaches are one of the most common side effects of IVIG. Severe headaches can be managed by slowing the infusion rate, ensuring proper hydration, and using premedication with analgesics like acetaminophen or NSAIDs.

Adequate hydration before, during, and after an IVIG infusion is crucial for preventing side effects like headaches and reducing the risk of rare, but serious, complications affecting the kidneys.

While serious adverse reactions like anaphylaxis, aseptic meningitis, or blood clots are possible, they are very rare. Healthcare providers monitor patients closely during infusions to identify and manage any complications.

Yes, because different brands of IVIG use varying stabilizers and manufacturing processes, switching products can sometimes improve tolerability for patients who react poorly to a specific formulation.

Subcutaneous immunoglobulin (SCIG) is generally associated with fewer systemic side effects than IVIG, although local reactions at the injection site (redness, swelling) are more common with SCIG.

Yes, it is common to experience more frequent or intense side effects during the first infusion of IVIG or with a new brand. Reactions often lessen with subsequent infusions as the body becomes more accustomed to the treatment.