Managing IVIG-Related Side Effects
By Jean McCaslin, RN IgCN - August 5, 2022

Intravenous Immune Globulin (IVIG) infusions are generally well tolerated. Most associated side effects are mild and managed with multiple approaches which may include pre-medication, clinical consultation providing education on what to expect with infusion, ongoing monitoring of infusions, and modifications to the individualized patient infusion protocol if side effects occur.

In the blog Pre-infusion Tips and Tricks for IVIG and SCIG Infusions, we reviewed helpful information for patients receiving IgG through Nufactor. This blog will focus on actual side effects experienced during and after IVIG administration. Patient and clinician education specific to this therapy are perhaps the most essential components to safe, and relatively symptom-free IVIG infusion.

Prevention

As discussed in a prior blog, pre-infusion protocols may be implemented. All pre-infusion steps should be followed with every infusion. Ongoing patient assessment is important. Patients and nurses should be well versed in the avoidance and mitigation of actions known to contribute to poor outcomes. This should also include mindful oral hydration, avoidance of exceeding recommended infusion rates, thoughtful communication, and ongoing education. The best way to handle any side effects is to prevent them from occurring when possible.

Administration

IVIG should only be infused by a Registered Nurse (RN) specifically trained in IVIG administration:

• Verify two patient identifiers.
• Locate the anaphylaxis kit in the home prior to moving forward; if it is not present in the home, do not infuse the patient and call Nufactor to report.
• Follow physician orders, manufacturer Package Insert (PI) recommendations for each brand, and pharmacy-specific protocols.
• Administer IV hydration, oral and IV pre-medications when prescribed.
• Verify product integrity for each IgG vial (check expiration dates, ensure each vial is clear and free of particulate matter).
• Review patient history and medication profile. Obtain recent history, including updates/changes of medications, illnesses, or hospitalizations since the last infusion.
• On-site patient pre-infusion assessment.
• Controlled IVIG infusion: Follow the IVIG administration instructions provided by Nufactor on the IVIG Titration chart. Never exceed the maximum infusion rate. There should be a minimum of three rate increases with every IVIG infusion.

Monitoring

Continuous monitoring of every IVIG infusion by an RN is essential so that actions can be taken by the RN to report and decrease or eliminate potential side effects. This includes monitoring the infusion rate, conducting a patient-tolerance assessment, including vital signs throughout every infusion.

Reporting

Nurses communicate primarily via written or digital Nursing Notes. Most often, when mild symptoms are noted, it does not require a call to a Nufactor pharmacist or to the prescribing physician. While moderate side effects often warrant a call to report during an infusion, it is best to call Nufactor to report if they are non-life threatening. Using Nufactor as a conduit for all non-life-threatening calls allows for RN/pharmacist and patient/pharmacist evaluation. Oftentimes, the pharmacist can offer infusion-protocol modifications without the need to urgently contact the prescribing physician. For a life-threatening side effect stop the infusion and call 911.

After a Nufactor pharmacist has collaborated with the RN and patient, the pharmacist will call the prescribing physician to limit perceived nuisance calls from both nurses and pharmacists seeking physician orders, often for the same request. Informing the patient that Nufactor will contact the prescriber when applicable can minimize patient anxiety as well as their additional calls to the physician’s office.

Immune Globulin Therapy Side Effects Management Card

Those coded in green typically can be managed without the need to report (i.e., repeat pre-medications). Those coded in yellow typically can be managed by contacting a Nufactor pharmacist; this may result in Nufactor contacting the prescribing physician for additional orders. Please do not call the prescribing physician directly for any non-life-threatening symptoms. Those colored in red are considered serious and require immediate medical attention.

Mitigation of Mild Side Effects

Typically, can be managed without the need to report (i.e., repeat pre-medications).

• Headache (1-3/10 on pain scale), mild malaise, aches, pains, backaches, leg cramps: If not yet taken, encourage patient to take pre-medications/repeat pre-meds if adequate time has elapsed since the last dose. Assess nutritional status/encourage the patient to eat something. Encourage a more vigorous intake of oral hydration.^*
• Mild chills: Verify IgG vials are at room temperature; use only body heat if coaxing product to the proper temperature. If not yet taken, encourage the patient to take pre-medications/repeat pre-meds if adequate time has elapsed since the last dose. Encourage a more vigorous intake of oral hydration. Don blanket, socks or sweater.
• Mild non-sustained hypertension: Repeat BP at rest on both arms. Verify that the patient has taken their daily anti-hypertensive medications as prescribed. Follow BP parameters on the Nufactor Nursing Note and call Nufactor to report values above those denoted.
• Mild nausea: Take prn anti-nausea medications when prescribed. Review nutritional status to assess if non-IgG oral intake has contributed. Avoid greasy, fatty, spicy foods before and during the infusion course. Encourage frequent, small sips of oral hydration throughout the infusion cycle as well as small snacks of food items known to decrease GI upset (ginger, soda crackers, toast).

Mitigation of Moderate Side Effects

Contact a Nufactor pharmacist. Typically, moderate side effects can be managed by decreasing the infusion rate or repeating pre-medications. Nufactor may contact the prescribing physician for additional orders. Please do not call the prescribing physician directly for any non-life-threatening symptoms.

• Headache (4-5/10 on pain scale): Decrease the infusion rate by 50%, encourage increased oral hydration, and repeat pre-medications. Call Nufactor if not improved by decreased infusion rate.
• Significant malaise, aches, pains, backaches, leg cramps: Decrease infusion rate by 50%, encourage increased oral hydration, repeat pre-medications.
• * Moderate fever (<100.5 degrees F): Decrease infusion rate by 50%, encourage increased oral hydration, repeat pre-medications and call Nufactor.
• Chills with shivering: Decrease infusion rate by 50%. Check the patient’s temperature. Verify IgG vials are at room temperature; use only body heat if coaxing product to the proper temperature. If not yet taken, encourage the patient to take pre-medications/repeat pre-meds if adequate time has elapsed since the last dose. Encourage a more vigorous intake of oral hydration. Don blanket, socks or sweater. Call Nufactor.
• Verified sustained hypertension: Decrease infusion rate by 50%, repeat prn antihypertensives when prescribed. Call Nufactor if BP is not improved by decreased infusion rate. Stop infusion if acutely elevated and call Nufactor.
• Significant nausea (no longer able to orally hydrate/visibly uncomfortable): Decrease infusion rate by 50%. If not improved by decreased rate, call Nufactor. The infusion may be discontinued.
• Allergy (non-anaphylactoid) rash, hives, itching: Stop infusion, administer Benadryl, and call Nufactor. Remain in the home for 30 minutes longer to assess antihistamine response. Prior to leaving the home, review anaphylaxis signs and symptoms as well as the use of the epinephrine device and when to dial 911. Remind the patient to contact their physician or go to an urgent care facility if the rash persists and is not controlled by their prn antihistamine medication.

Mitigation of Significant Side Effects

STOP INFUSION AND CALL NUFACTOR for all non-life-threatening side effects. The prescribing physician will be called by a Nufactor pharmacist for further direction.

• Significant headache (6-7/10 on pain scale): Stop infusion and call Nufactor. Repeat pre-medications as prescribed. Encourage vigorous oral hydration. Assess for neck stiffness, light sensitivity, and nausea; when present, seek immediate medical attention to rule out Aseptic Meningitis. Infusion modifications are likely. This may include decreasing the daily IgG dose, non-consecutive day dosing, amending the titration, modifying the pre-medications, or adding IV hydration.
• Significant/persistent malaise, aches, pains, backaches, leg cramps: Stop infusion and call Nufactor. Repeat pre-medications as prescribed. Encourage vigorous oral hydration. Modifications to the infusion regimen are likely.
• * High fever (>101 degrees F): Stop infusion and call Nufactor. Repeat pre-medications as prescribed. Encourage vigorous oral hydration.
• Significant chills unresolved by rate decrease: Stop infusion, check the patient’s temperature, and call Nufactor. Repeat pre-medications as prescribed. Encourage vigorous oral hydration.
• Acute hypertension: Stop infusion and call Nufactor. Repeat prn antihypertensives when prescribed.
• Severe nausea: Stop infusion. Repeat anti-nausea/anti-emetics when prescribed. Call Nufactor.
• Allergy with significant skin rash: Stop infusion, repeat antihistamine, and call Nufactor. Immediate medical attention may be necessary for symptoms not resolved by antihistamines. Remain in the home to monitor for 30-60 minutes when warranted.

Serious Side-Effects

STOP INFUSION! Considered serious and requires immediate medical attention. Call 911 and the prescribing physician directly when life-threatening. Call Nufactor for non-life-threatening events.

• Headache/Aseptic Meningitis: Headache 8-10/10 on pain scale, stiff neck, light sensitivity, nausea, vomiting, and fever are all possible symptoms. Stop infusion, call Nufactor, and assist the patient to seek emergency medical care. Call 911 when symptoms are severe or life-threatening.
• Renal insufficiency/failure: Not identifiable during infusion typically. Scant, concentrated urine may denote renal concerns/insufficiency. Call Nufactor to discuss. Typically, BUN/Creatinine testing is routinely monitored in high-risk patients; elevated results may necessitate discontinuation of IVIG therapy or a revision in daily infusion doses, titration, or result in non-consecutive daily dosing. More frequent renal function monitoring is typical as well as follow-up/clearance from a nephrologist if IVIG is to be continued; based on risk vs. benefit consultation.
• Thrombotic events: Those considered high-risk for clotting are carefully screened; infusion regimens are conservative. Observe the patient for signs and symptoms of stroke/CVA, Myocardial Infarction (MI), DVTs, or Pulmonary Emboli (PE). Call 911 and call prescribing physician. Notify Nufactor.
• Transfusion-Related Acute Lung Injury (TRALI): Sudden and acute shortness of breath (SOB), typically accompanied by fever. Stop infusion. Call 911 and the prescribing physician. Notify Nufactor.
• Hemolytic Anemia: Breakdown of red blood cells (RBCs). Not typically detected during infusion. Symptoms include pallor, fatigue, fever, confusion, lightheadedness, weakness, dark-colored urine, jaundice, increased heart rate, and enlarged spleen. Confirmed by complete blood count (CBC) when symptoms are reported. IVIG may be discontinued.
• Rigors: Shaking or exaggerated shivering; often accompanied by fever and/or teeth chattering. Stop infusion and check the patient’s temperature. Call Nufactor.
• Anaphylaxis: Swollen throat, wheezing, stridor, chest tightness, passing out, difficulty breathing, hoarse voice, difficulty swallowing. Stop infusion, call 911, and follow anaphylaxis protocol (give Benadryl, administer epinephrine, start a KVO IV).

*Note: Considering the COVID-19 pandemic, any fever is suspect for COVID-19 positivity. When warranted, a COVID-19 test should be considered; when positive, take appropriate actions.

Potential Post-Infusion Side-Effects

Some side effects may not be reported during the actual IVIG infusion or may recur post-infusion. Patient Education on this topic is an essential aspect of IVIG patient care.

• Prior to leaving the home, RNs must review the patient teaching materials provided by Nufactor. These are included in the Nufactor New Patient Package; it includes the Immune Globulin Therapy Side Effects Management Card, Infusion Journal, and Anaphylaxis Management Plan.
• Encourage the patient to continue oral hydration with 64 ounces of water-based fluids unless the patient has a specific fluid restriction. This protocol should be followed for at least 24 hours post-last infusion day and continued for another 1-2 days if flu-like symptoms persist.
• Repeat pre-medications every 4-6 hours as prescribed post-infusion. APAD dosage should not exceed 1 gm every 6 hrs/4,000 mg every 24 hours in average-weight adults, or as recommended by the prescribing physician.
• Reference the Immune Globulin Therapy Side Effects Management Card to determine when to call Nufactor or the prescribing MD, or to seek immediate medical attention.
• Remind the patient that Nufactor is available by phone 24/7. They have access to pharmacists, nurses, and Client Service Specialists by calling (800) 323-6832. Encourage the verbalization of infusion-related symptoms in a timely manner to Nufactor staff members to facilitate continuity of care and optimal outcomes.

IVIG as discussed is generally well tolerated. Astute assessment, infusion monitoring, pre-medication, and rate adjustments often are the only actions needed. Timely consultation with a Nufactor pharmacist is recommended when side effects are identified. Infusion protocol modifications are common and will be facilitated by Nufactor pharmacy staff.

While serious infusion-related side effects are uncommon, knowledge is essential to the identification and associated actions taken by RNs in the home.