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 1 of this blog will focus on boxed warnings and serious ADRs.

BOXED WARNINGS

All IVIG products carry a boxed warning for thrombosis and renal dysfunction/acute renal failure. The pharmacist should conduct a thorough patient assessment before the start of IVIG therapy and collaborate with the prescriber and nurse to minimize these severe ADRs. Mitigation strategies include administering the smallest IVIG dose and slowest infusion rate practicable and ensuring adequate oral hydration (IV if unable).

Thrombosis
Monitor for signs and symptoms of thrombosis. Deep vein thrombosis (DVT) symptoms include lower leg swelling and pain in knees. Pulmonary embolism (PE) symptoms include shortness of breath (SOB)/pain with breathing, and chest pain. Myocardial infarction (MI) symptoms include chest pain. Transient ischemic attack (TIA)/cerebral vascular accident (CVA) symptoms include confusion, slurred speech, drooling, and loss of consciousness. If thrombosis is suspected, do not initiate IVIG (stop the IVIG infusion if started), contact the prescriber immediately for instruction. If the prescriber is not readily available, call 911.

Renal dysfunction/acute renal failure (ARF)
Monitor for signs and symptoms of renal dysfunction/ARF. Symptoms include decreased urine output, dark (tea-colored) urine, sudden weight gain, fluid retention/edema and SOB. If renal dysfunction/ARF are suspected, do not initiate IVIG (stop the IVIG infusion if started), contact the prescriber immediately for instruction. If the prescriber is not readily available, recommend the patient seek emergency medical care.

SERIOUS ADRS

Anaphylaxis and anaphylactoid reactions
True anaphylaxis occurs rarely and is characterized by immediate, severe hypotension and extreme breathing difficulty. Without immediate intervention, cardiopulmonary arrest may occur. Since anaphylaxis can occur with any dose, emergency drugs or kit should be readily available (within eyesight view) for all doses. Physicians or pharmacies may have different protocols, emergency drugs, routes of administration and different instructions for different symptoms so the nurse must know and understand each patient's specific orders. If anaphylaxis occurs, stop the IVIG infusion, activate the emergency medical system, administer emergency drugs as ordered, secure the airway, and initiate IV fluids if ordered. As soon as possible, inform the prescriber and then Nufactor.

Anaphylactoid reactions have a similar presentation as anaphylactic reactions (e.g., trouble breathing, chest tightness) although usually hypertension instead of hypotension occurs, the onset is gradual, and severity less. Anaphylactoid reactions can occur any time during an infusion, but usually within the first half of a dose. If an anaphylactoid reaction occurs, stop the IVIG infusion and administer ordered drug(s), which may include an oral or parenteral anti-histamine and moderate dose of corticosteroid.

After an anaphylaxis/anaphylactoid reaction, whether to restart an infusion or therapy should be decided by the prescriber, patient, nurse, and pharmacist. If therapy is resumed, mitigation strategies include pretreatment anti-histamine and corticosteroid, switching to a different brand of IVIG or changing to the subcutaneous route of administration.

Aseptic meningitis
Aseptic meningitis is characterized by severe headache generally occurring after an infusion and lasting hours to days. It is sometimes accompanied by nuchal rigidity, drowsiness, photophobia, painful eye movements, nausea and vomiting. Cerebral spinal fluid (CSF) studies usually reveal an increased white blood cell count (WBC) & protein, but negative culture (thus "aseptic"). Aseptic meningitis is often described as severe and debilitating and may require aggressive pain management if it occurs. Mitigation strategies include splitting IVIG doses over more days, alternating days, infusing at a slower rate, and ensuring adequate hydration. Pretreatment is generally ineffective, although there are some reports of success with IV corticosteroids, IV hydration, and anti-migraine medication. Another strategy is switching to the subcutaneous route of administration.

Hemolytic anemia
IVIG can cause destruction of red blood cells, leading to hemolytic anemia. Monitor for signs and symptoms of hemolytic anemia, which generally present within days or weeks. Fatigue may be the first symptom, when hemolysis is mild. As hemolysis worsens, symptoms include dark urine, jaundice of skin or eyes, heart murmur, increased heart rate, and enlarged spleen/liver. Severe hemolysis-related renal dysfunction/ARF or disseminated intravascular coagulation (DIC) have occurred.

Hemolytic anemia is likely due to the presence of anti-A and anti-B blood type antibodies in IVIG products; therefore, those with non-O blood types may be at risk. Knowing a patient's blood type and providing counseling is practical. There is little published evidence on prevention of hemolytic anemia. Prudent measures include splitting large IVIG doses over more days, alternating days, and infusing at a slower rate. For those at high risk, the prescriber may monitor Hgb/HCT prior to IVIG, within approximately 36 hours, and in 7 – 10 days.

Transfusion-related acute lung injury (TRALI)
A rare complication of IVIG, TRALI is characterized by severe respiratory distress, pulmonary edema (non-cardiogenic), hypoxemia, normal left ventricular function and fever. Symptoms typically appear within 1 - 6 hours following IVIG. Management may require oxygen therapy with adequate ventilatory support. There are no particular risk factors or mitigation strategies. If TRALI is suspected, do not initiate IVIG (stop the IVIG infusion if started), and contact the prescriber immediately for instruction. If the prescriber is not readily available, call 911.

Summary
While uncommon, IVIG can cause serious ADRs. However, thorough patient assessment, collaboration between the prescriber, nurse and pharmacist to develop and implement prevention strategies, an educated patient and a skilled, knowledgeable and perceptive IVIG nurse can minimize patient risk, enhance tolerability, and help patients receive and adhere to IVIG therapy to treat their disease.