By Joe DiStefano, RPh

Intravenous immune globulin (IVIG) is safe and effective treatment for a variety of medical conditions. Overall IVIG is well-tolerated in most patients. However, it is not without adverse drug reactions (ADRs), ranging from mild to severe. Thorough clinical assessment prior to start of care, astute monitoring during the infusion, post-infusion follow-up, and knowing potential ADRs and how to manage them are key to good patient experience and quality care. A thorough patient assessment should include the patient's health status and vital signs, hydration status, risk factors and co-morbidities, previous immune globulin regimen, and history of ADRs.

ADRs can be categorized into the less common but consequential boxed warnings and serious ADRs and the more common mild to moderate ADRs. Part 2 of this blog will focus on the more common mild to moderate ADRs.

IVIG Products & ADR Considerations

While the primary component of IVIG products (IgG) is the same and the clinical efficacy is comparable, products are not interchangeable. Manufacturing differences, such as the molecule structure of the IgG (e.g., monomer, dimer), IgA and IgM content, stabilizers, additives, impurities, pH, and osmolarity/osmolality could result in different tolerability.

The nurse should be aware of circumstances when the risk of IVIG-related ADRs may be increased and take additional precautions. Circumstances include during initial treatment, when switching brands of IVIG and with treatment interruptions of more than 8 weeks. Precautions include slowly titrating the infusion rate, infusing at a lower maximum rate for the first couple of infusions, and vigilant monitoring.

Infusion-related reactions (IRR)

ADRs related to the infusion rate include headache, chills, flushing, and changes in blood pressure and pulse. If IRRs occur, stop the IVIG infusion to determine the ADRs are not the beginning of a more serious ADR which may subsequently escalate. If symptoms resolve, resume the IVIG infusion at a lower rate and titrate as tolerated. The lower infusion rate may indicate the maximum tolerated rate for the patient with the specific IVIG product. In addition, if enough time has passed, repeat ordered anti-histamine & analgesic pre-medications.

Headache

Headache is the #1 ADR reported with IVIG. Those occurring during an infusion are often due to mild/moderate blood pressure changes and may be rate-related. Re-check blood pressure. Slowing the IVIG infusion rate may cause relief. If enough time has passed, repeat ordered analgesic pre-medication.

Post-infusion ADRs

IVIG may cause post-infusion fatigue, low grade fever, nausea, myalgia, diarrhea, and other flu-like symptoms and may last up to 72 hours. The patient should be educated about the possibility of these ADRs and instructed on symptomatic treatment with rest, oral hydration, analgesics, anti-histamines, or other symptom-specific medications as appropriate. Before infusing IVIG, the nurse should inquire about post-infusion reactions to the previous dose. For future infusions, titrating more slowly may be prudent.

Rash/hives

Rash/hives can occur during or several days or weeks after an IVIG infusion. If rash/hives occur during an infusion, stop the infusion to ensure a severe allergic/anaphylactic reaction is not occurring. Usually administration of a single dose of anti-histamine and/or corticosteroid resolves rash/hives. If symptoms resolve, resume the IVIG infusion at a lower rate and titrate as tolerated. If not ordered, procure anti-histamine pre-medication orders and encourage adherence. Moderate to severe cases of rash may require a prolonged course of anti-histamine and/or corticosteroid treatment. In severe cases or ineffective pre-treatment, treatment strategies may include a different IVIG brand or switching to the subcutaneous route of administration.

Blood pressure changes

Minor blood pressure fluctuations during infusion of IVIG are common. Various possible short-term factors affecting blood pressure should be considered and addressed when possible, including anxiety with a first dose, needle phobia, "white coat" syndrome, emotions, stress, pain, and consumption of a large meal. Caffeine, smoking and physical activity should be avoided for at least 30 minutes before blood pressure measurement. The bladder should be empty and talking avoided. Repeat measurements should be separated by 1 – 2 minutes. Ensure patients with concomitant underlying hypertension are compliant with blood pressure medications.

Nufactor recommends measuring vital signs at baseline, 15 minutes into an infusion, at every rate change, hourly once the maximum rate is reached and at the end of the infusion. If vital signs fluctuate, monitor every 15 minutes until stable.

Contact Nufactor before initiating an IVIG infusion if baseline SBP ≥140 mm Hg (in patients ≤60 years old), SBP ≥150 mm Hg (≥ 60 years old) or DBP ≥90 mm Hg. Contact Nufactor during an IVIG infusion if there is an increase or decrease in SBP ≥20 mm Hg or DBP ≥10 mm Hg from baseline. Also contact Nufactor during an infusion if the patient is symptomatic of elevated blood pressure (e.g., dizziness, flushed face, headache, epistaxis, nervousness) or symptomatic of low blood pressure (e.g., faintness, light-headedness, dizziness, confusion, or blurred vision).

Management includes slowing the IVIG infusion rate or stopping the infusion. Once blood pressure normalizes, a stopped infusion can be restarted at a lower infusion rate and gradually titrated based on response. Similarly, an infusion rate that was lowered can also be gradually titrated based on response. Whenever possible, underlying hypertension should be controlled. The prescriber may order fast-acting clonidine for specific elevated blood pressure parameters.

General ADR Prevention Strategies and Summary

Actions to prevent or minimize IVIG-related ADRs include conducting a thorough patient assessment, pre-medication use and adherence, ensuring adequate oral hydration, compliance with maintenance medications (e.g., for hypertension, CHF), rest, proper nutrition, communication between the patient and nurse during the infusion, and a nurse having detailed knowledge of IVIG and sharp monitoring skills.

Proper pre-medication use includes taking oral medications in enough time to take effect. In general, oral medications should be taken 30 – 60 minutes before IVIG administration. Adequate oral hydration, preferably water, should be spread over the course of a day starting 1 – 2 days prior to, each day of, and 1 - 2 days post-IVIG therapy. Daily recommendations are: adults - 8 x 8 ounces, children 9 – 17 years old - 6 x 8 ounces, children 1 – 8 years - 8 x 4 ounces. Recommended amounts may be contraindicated and require reduction for diseases such as CHF, cirrhosis, kidney disease or pre-existing renal insufficiency, nephrotic syndrome and pregnancy.

Intolerable side effects can lead to patient discouragement and the decision to discontinue quality of life improving IVIG. The IVIG nurse plays a major role in side effect management and collaborating with the Nufactor pharmacist to help patients better tolerate and adhere to IVIG therapy.