By Joe DiStefano, RPh.

Anaphylaxis is a severe systemic allergic reaction resulting from exposure to allergens that is rapid in onset and can result in a life-threatening emergency. Severe hypersensitivity reactions and anaphylaxis to immune globulin (IG) are uncommon. Patients with low serum IgA with anti-IgA antibodies are at greater risk.

Anaphylaxis signs usually occur within minutes of exposure to an allergen; sometimes it can occur a half-hour or longer after exposure. NuFACTOR obtains prescriber orders for anaphylaxis treatment for all IG patients. The NuFACTOR anaphylaxis kit and orders include oral diphenhydramine, parenteral diphenhydramine (in kits for intravenous immune globulin [IVIG], but not subcutaneous immune globulin [SCIG]) and epinephrine. The kit also includes guidelines for management, when to use each medication and the weight-based dose. It is important to recognize signs of anaphylaxis, take appropriate action and administer proper medications. Before administering every IG dose, an intact anaphylaxis kit with in-date components should be readily available.

Early allergic signs may be mild such as itching, rash and nausea. If these signs occur, the administration of IG should be stopped, the patient evaluated and oral diphenhydramine administered. Mild allergy can progress to severe allergy or anaphylaxis signs such as angioedema, wheezing, difficulty in breathing and swelling of eyelids, lips or tongue. Instead of presenting with mild allergic signs initially, some patients may present with severe allergy or anaphylaxis. If severe allergy or anaphylaxis signs occur, epinephrine should be administered first, and then parenteral diphenhydramine (in kits for IVIG) or oral diphenhydramine if able (in kits for SCIG). Epinephrine can be repeated in 15 minutes if needed. As soon as possible, contact or have the caregiver call 911 and place the patient in the supine position. If the patient has problems breathing, tilt the head or thrust the jaw to relieve airway obstruction. Monitor vital signs. If the patient is hypotensive, elevate the legs. For IVIG patients with IV access, maintain the IV line with normal saline to keep the vein open. If cardiopulmonary arrest occurs, begin CPR. Remain with the patient until paramedics arrive. As soon as possible, inform the physician and then NuFACTOR.

Epinephrine is available as an auto-injector (e.g., EpiPen^®) or vial. The auto-injector is a ready to use device which can deliver up to two prescribed doses (0.15 mg or 0.3mg, depending on the product) intramuscularly. The EpiPen^® package insert states to administer the dose by swinging and pushing the device firmly into the middle of the outer thigh (upper leg) at a right angle to the thigh until it ‘clicks’, holding it in place for a count of three, removing the device from the thigh and then massaging the injection site for 10 seconds.

Doses other than 0.15 mg or 0.3 mg, including those for pediatric patients weighing less than 33 pounds (15 kg) must be withdrawn from a vial before administration. Although epinephrine can be administered intramuscularly or subcutaneously, the NuFACTOR protocol is for subcutaneous administration.

Controversy surrounding the high cost of EpiPen^® with its estimated $600 cost per device has been in the news lately. Generic auto-injectors, while less costly, are still expensive at an estimated $300 per device. Comparatively, two epinephrine vials (1 mg/1 ml) are relatively inexpensive at an estimated $30. Considering the low risk of anaphylaxis and financial burden for patients, dispensing vials can be a less costly but safe alternative to the auto-injector. Considering risk and safety while understanding administration of epinephrine from vials takes additional time, NuFACTOR has adopted guidelines for dispensing epinephrine auto-injectors and vials.

Orders for an epinephrine auto-injector will be obtained for:

• Patient-administered traditional SCIG or HyQvia for new or refill patients. This includes nurse-administered doses during training.
• Nurse-administered IVIG for new patients with a known allergic/hypersensitivity reaction to IG. It is important to understand reactions such as headache or infusion-related reactions are not considered allergic/hypersensitivity reactions.
• Nurse-administered IVIG for new patients with a history of a severe hypersensitivity or anaphylaxis to any drug.

For all other patients, orders will be obtained for epinephrine vials.

Epinephrine auto-injectors are not usually used and are typically replaced annually before expiring. At the time of replacement, if a patient receiving nurse-administered IVIG has an epinephrine auto-injector, and has not had an allergic/hypersensitivity reaction to IVIG in the previous 3 months or 3 courses, NuFACTOR will obtain orders for epinephrine vials.

The selective use of epinephrine vials is a clinically safe and cost-effective alternative to epinephrine auto-injectors. Regardless of the method of epinephrine delivery, the most important aspects of patient safety are the nurse knowing the signs and symptoms of severe allergy and anaphylaxis, being prepared, knowing treatment medications and administering them properly. NuFACTOR offers various resources and guides for responding to IVIG side effects as well as SCIG side effects. Contact us to determine what will be most helpful for you.